Synthetic Reagents

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Dr

. Bap

u R. Tho

rat

Assit. Professor of Chemistry

Govt. of M

Govt. of Maharashaharashtra,tra,

Ismail Yusuf Arts, Science and Commerce College, Jogeshwari (E),

Maharashtra 400060

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Reagent

Substrate

Substrate Reagent & ReactionReagent & Reaction _Product_Product

cond. cond.

A group of organic molecules serve as

substrates

for a particular type of reaction

when treated with specific reagent.

e. g. Nitration of aromatic compounds by using

nitrating mixture

; the aromatic

compounds are substrates and nitrating mixture is reagent for nitration reaction.

Types of reactions

1.

1. Ad

Ad

di

ti

on r

ea

ct

io

n;

2.

2. El

El

im

in

at

io

n r

ea

ct

io

n;

3.

3. Su

Su

bs

ti

tu

ti

on r

ea

ct

io

n;

4.

4. Re

Re

ar

ra

ng

em

en

t;

1.

1. Pe

Pe

ri

cy

cl

ic

r

ea

ct

io

n;

2.

2. Ph

Ph

ot

oc

hem

ic

al

an

d

f

r

ee

radical reaction

;

3.

3. Ox

Ox

i

d

a

t

i

o

n

;

4

4 .

.

R

e

d

u

c

t

i

o

n

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Nitration Nitration Sulfonation Sulfonation Acylation Acylation Alkylation Alkylation Bromination Bromination Halogination Halogination Carbonylation Carbonylation Formylation Formylation Oxidation Reduction Oxidation Reduction

Oxidation of an organic compound involves Oxidation of an organic compound involves one or more of the

one or more of the following changes:following changes: (1)

(1) an increase in the multiple bond order ofan increase in the multiple bond order of the C

the C (2)

(2) addition of O to a Caddition of O to a C (3)

(3) replacemreplacement of an H on a C ent of an H on a C by O.by O.

Reduction of an organic compound involves Reduction of an organic compound involves one or more of the following changes:

one or more of the following changes: (1)

(1) an decrease in the an decrease in the multiple bond order ofmultiple bond order of the C the C (2) (2) addition of H to a Caddition of H to a C (3) (3) rereplacement of an placement of an O on a C.O on a C.

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Oxidizing agents

Cr

Cr(V(VII ) Re) Reageagents:nts: Sodium or potassium dichromate (NaSodium or potassium dichromate (Na₂₂Cr Cr ₂₂OO₇₇ or K or K ₂₂Cr Cr ₂₂OO₇₇), or), or chromium trioxide (

chromium trioxide (CrOCrO₃₃), to), to aqueous solutions of sulfuricaqueous solutions of sulfuric or acetic or acetic acidacid.. Modified reagents: PCC (Pyridinium chlorochromate); PDC (Pyridinium Modified reagents: PCC (Pyridinium chlorochromate); PDC (Pyridinium dichromate); chromium trioxide pyridine (CeO

dichromate); chromium trioxide pyridine (CeO₃₃.py.py₂₂););

Jones Jones reagent reagent M M nnO O ₂₂ S

Sododiuiu m Hm H ypypocochlhl oriori tete (NaOCl) (NaOCl) K M n O K M n O ₄₄ Peroxycarboxylic acids Peroxycarboxylic acids H

H ₂₂O O /N /N aOH ₂₂ aOH

Triiosproxide aluminium Triiosproxide aluminium

Oppena

Oppenauer uer oxidationoxidation DMDM SSO/oO/oxalyl xalyl chlorichlori dede:: Swern oxidation Swern oxidation Osmium tetroxide Osmium tetroxide (OsO (OsO₄₄)) Ozone (O Ozone (O ) ) ₃₃ H H II O O ₄₄ Pb(OAc) Pb(OAc) ₄₄ chromyl chlor chromyl chlor ii dede (C (Cl l ₂₂CrCr O O ) ) ₂₂ s

seell eenini uum dim di oxioxi de de (Se(SeO O ) ) ₂₂

Frem

Fremy's salt y's salt ((KSO((KSO )) N-O.)N-O.) K K [Fe(CN)[Fe(CN) ]]

O O ₂₂

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Metals used for reduction

Metals used for reduction: Copper (low valent), Chromium (low valent), Fe, Indium (low: Copper (low valent), Chromium (low valent), Fe, Indium (low valent), Iron, Lithium, Magnesium, Manganese, Neodymium (low valent), Nickel, Niobium valent), Iron, Lithium, Magnesium, Manganese, Neodymium (low valent), Nickel, Niobium (low valent), Potassium, Red-Al, Sodium, Stronti

(low valent), Potassium, Red-Al, Sodium, Strontium, Tum, Titanium (low valent), itanium (low valent), Zinc, Samarium.Zinc, Samarium. Hydrides

Hydrides: Potassium tetrahydro: Potassium tetrahydroborateborate, Potassium, Potassium boroborohydride, Sodiumhydride, Sodium boroborohydride, Sodiumhydride, Sodium cyano

cyanoboroborohydride, Sodium tetrahydrohydride, Sodium tetrahydroborateborate, Sodium triacetoxy, Sodium triacetoxyboroborohydride, Decahydride, Decaboraneborane,, Diisopropylamino

Diisopropylaminoboraneborane, Dimethylsulfide, Dimethylsulfide boraneborane, Di, Diboraneborane, LiTE, LiTEBBH, NickelH, Nickel boroborohydridehydride Sodium bis(2-methoxyethoxy)

Sodium bis(2-methoxyethoxy)aluminumaluminumhydride, hydride, DIBDIBALAL-H, -H, LLAAH,H, AluminiumAluminium triisopropoxide/isopropanol

triisopropoxide/isopropanol Tin

Tin hydrides, Tributyl hydrides, Tributyltintin hydride hydride Tributyl

Tributylstannanestannane,, Trichloro

Trichlorosilanesilane, , Silanes, TriethySilanes, Triethyllsilanesilane, , TrTris(trimethylsilyis(trimethylsilyl)l)silanesilane, Diethoxymethyl, Diethoxymethylsilanesilane Zircon

Zirconocene chloride hydrideocene chloride hydride Copper

Copper hydridehydride Hydrogen

Hydrogen Formic

Formic acid acid Hydrazine Hydrazine Sodium Sodium dithionatedithionate Reducing agents

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Organom

Organometallic etallic reagents in organic synthesisreagents in organic synthesis

Organomet

Organometallic allic chemistchemistry ry timelinetimeline

1827 Zeise's salt is the first platin

1827 Zeise's salt is the first platinum-olefin complexum-olefin complex:: K[PtClK[PtCl₃₃(C(C₂₂HH₄₄)]H)]H₂₂O Zeise's saltO Zeise's salt 1863 C. Friedel & J. Crafts prepare

1863 C. Friedel & J. Crafts prepare organochlorosilanesorganochlorosilanes 1890 L. Mond discovers

1890 L. Mond discovers Nickel carbonylNickel carbonyl 1899 Introduction of

1899 Introduction of Grignard reactionGrignard reaction

1900 P. Sabatier works on hydrogenation organic compounds with metal catalysts: 1900 P. Sabatier works on hydrogenation organic compounds with metal catalysts:

Hydrogenation of fats Hydrogenation of fats 1909 P. Ehrlich introduces

1909 P. Ehrlich introduces SalvarsanSalvarsan for the treatment of syphilis, an early arsenic based for the treatment of syphilis, an early arsenic based organometallic compound. (As

organometallic compound. (As₃₃Ar Ar ₃₃) [Ar) [Ar – – 3-amino-4-hydroxypheny] 3-amino-4-hydroxypheny] 1912 Nobel Prize:

1912 Nobel Prize: Victor GrignardVictor Grignard and Paul Sabatierand Paul Sabatier 1930 Henry Gilman works on

1930 Henry Gilman works on lithium cuprates:lithium cuprates: RX RX + + 2Li 2Li RLi RLi + + LiXLiX 1951

1951 FerroceneFerrocene is discovered is discovered

1963 Nobel prize for K. Ziegler and G. Natta on

1963 Nobel prize for K. Ziegler and G. Natta on Ziegler-NZiegler-Natta atta catalystcatalyst 1965 Discovery of cyclobutadieneiron tricarbonyl Ferrocene

1965 Discovery of cyclobutadieneiron tricarbonyl Ferrocene (C (C ₄₄H H )F )F e₄₄ e(C(CO) O) ₃₃

1968

1968 Heck reactionHeck reaction

1973 Nobel prize G. Wilkinson and E. O. Fischer on

1973 Nobel prize G. Wilkinson and E. O. Fischer on sandwich sandwich compoundscompounds

2005 Nobel prize Y. Chauvin, R. Grubbs, and R Schrock on metal-catalyzed

2005 Nobel prize Y. Chauvin, R. Grubbs, and R Schrock on metal-catalyzed alkenealkene metathesis

metathesis

2010 Nobel prize Richard F. Heck, Ei-ichi Negishi, Akira Suzuki.

2010 Nobel prize Richard F. Heck, Ei-ichi Negishi, Akira Suzuki. "for palladium-catalyzed"for palladium-catalyzed cross couplings in organic synthesis"

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Organom



 Materials Materials which which possess possess direct, direct, more more or or less less polar polar bonds bonds MM++_—_— C_C--_{between metal}_{between metal}

and carbon atoms. and carbon atoms.



 In In addition addition to to the the traditional traditional metals, metals, lanthanides, lanthanides, actinides, actinides, and and semimetals,semimetals, elements such as

elements such as boronboron, silicon, arsenic, and selenium are considered to form, silicon, arsenic, and selenium are considered to form organom

organometallic etallic compounds.compounds.



 e.g. e.g. Organoborane Organoborane compounds compounds such such as as triethylborane triethylborane (Et(Et₃₃B).B).



 OrganomOrganometallic etallic chemistry chemistry combines combines aspects aspects of of inorganic inorganic chemistry chemistry and and organicorganic chemistry.

chemistry.

Classification of organometallics based on the bond type:

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Organom

Covalent,

Covalent, multicentermulticenter,, σ

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Organo borane

Organo borane compoun

compounds

ds

Organoborane or organoboron compounds are

Organoborane or organoboron compounds are organic derivatives oforganic derivatives of BHBH₃₃. Organoboron. Organoboron compounds are important reagents in organic chemistry enabling many chemical compounds are important reagents in organic chemistry enabling many chemical transformations, the most important one called

transformations, the most important one called hydroborahydroborationtion.. Characteristics

Characteristics::

•• C-B bondC-B bond, low polarity (electronegativity C 2.55, B 2.04), low polarity (electronegativity C 2.55, B 2.04)

•• Electron-rich groupsElectron-rich groups like vinyl or phenyl provide the like vinyl or phenyl provide the C-B bond with partialC-B bond with partial double bond character

double bond character.. •

• Organoboron Organoboron hydrides hydrides R R ₂₂BH and RBHBH and RBH₂₂ form dimers which always display form dimers which always display hydride bridges rather than alkyl bridges

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Organo borane

Organo borane compoun

compounds

ds

Hydroborat

Hydroboration: Syion: Synthesis of alkylborane (mono, di, tri-)nthesis of alkylborane (mono, di, tri-)

Borane (BH

Borane (BH₃₃ in dimer form) reacts rapidly to alkenes and alkynes forming alkyl and alkenyl in dimer form) reacts rapidly to alkenes and alkynes forming alkyl and alkenyl boranes

boranes are are called called as as calledcalled hydroborationhydroboration. This concept was discovered by. This concept was discovered by HerbertHerbert Charles Brown

Charles Brown at Purdue University with help from at Purdue University with help from George WittigGeorge Wittig.. Number of alk

Number of alkenes of widely differenes of widely different structures except most hindered alkenes.ent structures except most hindered alkenes.



 The simple alkenes gives (mono- and di The simple alkenes gives (mono- and di-substituted ethylenes) gives-substituted ethylenes) gives trialkylboranetrialkylborane..



 Tr Tri-substituted i-substituted ethylenes givesethylenes gives dialkylboranedialkylborane, and, and



 Tetra-substituted ethylenes forms Tetra-substituted ethylenes forms monoalkylboranesmonoalkylboranes..



ThThe e mono- mono- and diand di-al-alkkylborylboranes anes arare e lleesss res reactiactive ve and morand more e sseelleectictive ve ththan an ththe e boranboranee

itself

itself ..

In case of

In case of allyl derivatives and nuclear substituted styrenesallyl derivatives and nuclear substituted styrenes, the proportion of product, the proportion of product formed by addition of boron to the

formed by addition of boron to the αα-carbon (more substituted carbon) atom increases with-carbon (more substituted carbon) atom increases with the electronegativity of the substituents.

the electronegativity of the substituents.

δ

δ-

-δ

δ++

Less substituted C has Less substituted C has δδ-

-More substituted C has More substituted C has δδ++

Asymmetric alkenes

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Organo borane

Organo borane compoun

compounds

ds

CH CH₃₃(CH(CH₂₂))₃₃CH=CHCH=CH₂₂ (CH(CH₃₃))₂₂C=CHCHC=CHCH₃₃ CHCH₃₃CH=CH(CHCH=CH(CH₃₃))₂₂ CH CH₂₂=CHCH=CHCH₃₃ CHCH₂₂=CHCH=CHCH₂₂OCOC₂₂HH₅₅ CHCH₂₂=CHCH=CHCH₂₂ClCl CH CH₃₃OO ClCl 5% 5% 18%18% 82% 82% 25% 25% 94% 94% 6%6% 19%19% _40%_40% 6% 6% 94%94% _2%_{2% 98%}_98% _{58% 42%}_58% _42% Mechanism Mechanism Hydroborations

Hydroborations take place take place stereoselective in astereoselective in a ssyn yn mode mode that isthat is on the same face of theon the same face of the alkene

alkene. The reaction proceeds through. The reaction proceeds through transition statetransition state is represented as a square with theis represented as a square with the corners occupied by carbon, hydrogen and boron with

corners occupied by carbon, hydrogen and boron with maximum overlap between the twomaximum overlap between the two

olefin p-orbitals and the empty boron orbital

olefin p-orbitals and the empty boron orbital..

+

H H BB solvent solvent H H BB _H_H _H_H protonolysis protonolysis

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Organo borane

Organo borane compoun

compounds

ds

Hydrobora

Hydroboration: Synthesis of tion: Synthesis of alkylborane (mono, di, tri-)alkylborane (mono, di, tri-)

H H BB H H BB H H BB H H B B HH H H B B B B + + + + alkene alkene alkyne alkyne organoborane organoborane organoborane organoborane alkylborane alkylborane alkenylborane alkenylborane e.g. e.g. 1 1 2 2 3 3 C C H H₃₃ C C H H₃₃ HH CH CH₃₃ CH CH₃₃ CH CH₃₃ C C H H₃₃ C C H H₃₃ 4 4 B-H B-H B B₂₂HH₆₆/THF/THF B B₂₂HH₆₆/THF/THF B B₂₂HH₆₆/THF/THF B B₂₂HH₆₆/THF/THF [(CH [(CH₃₃))₂₂CH-CH(CHCH-CH(CH₃₃)])]₂₂BHBH [(CH [(CH₃₃))₂₂CH-C(CHCH-C(CH₃₃))₂₂]BH]BH₂₂

no reaction because of steric hinderence no reaction because of steric hinderence

disiamylborane disiamylborane thexylborane thexylborane 9-BBN 9-BBN Hydride source Hydride source

The hydroboration of alkenes and alkynes is highly stereospecific and takes place by addition to The hydroboration of alkenes and alkynes is highly stereospecific and takes place by addition to the

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Organo borane

Organo borane compoun

compounds

ds

Hydrobora

Hydroboration: tion: LimitationsLimitations

1.

1. The reThe regio-sgio-selectivelectivity in the hyity in the hydroboradroboration of tion of termterminal alkeinal alkenes, althounes, although higgh high, is noh, is nott complete and in

complete and in 1,2-disubstututed alkenes1,2-disubstututed alkenes there are little discrimination between thethere are little discrimination between the two termini of the double bond.

two termini of the double bond. 2

2.. TThheerre e iiss little difference in the rate of reaction of boranelittle difference in the rate of reaction of borane with differently substitutedwith differently substituted double bonds, so that it is

double bonds, so that it is rearly possible to carry out selective hydroboration of onerearly possible to carry out selective hydroboration of one bond in presence of another

bond in presence of another .. 3

3.. TThhee hydrobhydroboration oration of teof termirmi nal nal alkyne is alkyne is diffdiff iculicul t to cot to contrntr olloll eed at the d at the ssii ngle angle addddii tiontion but but the desired alkenylborane undergoes second addition of a second molecule of borane to the desired alkenylborane undergoes second addition of a second molecule of borane to the 1,1-dibora-alkane.

the 1,1-dibora-alkane.

1-alkylcy

1-alkylcycloalkanes cloalkanes on hydroboration followed by oxidation on hydroboration followed by oxidation gives -gives -Problems:

Problems:

4-chlorostyrene on hydroboration followe

4-chlorostyrene on hydroboration followed d by oxidation gives -by oxidation gives -4-chlorostyrene on hy

4-chlorostyrene on hydroboration followed by heating and then droboration followed by heating and then oxidation gives -oxidation gives -Hydroboration of 2-pentene gives

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Organo borane

Organo borane compoun

compounds

ds

From Grignard Reagent: Synthesis of alkylborane (tri-)

This method is generally used for the

This method is generally used for the synthesis of trialkylboranesynthesis of trialkylborane such as trimethylborane andsuch as trimethylborane and triethylborane. triethylborane. RMgX + BX RMgX + BX₃₃ _R_R 3 3B B + + MgXMgX22 3 3 ₃₃ By exchange

By exchange methmethod:od: Synthesis of alkylborane (tri-)Synthesis of alkylborane (tri-)

The organoborane ex

The organoborane exchange their alkyl group with change their alkyl group with more reactive alkene alkyl.more reactive alkene alkyl.

R

R₃₃B B + + 33AlkeneAlkene R'R'₃₃B B + + 33 Alkene'Alkene' more reactive

more reactive less less reactivereactive Isomerisation:

Isomerisation:

The organoborane compounds undergo isomerisation on heating if and only if

The organoborane compounds undergo isomerisation on heating if and only if αα-carbon atom with respect-carbon atom with respect

to boron atom bearing atleast one hydrogen atom. Such organoborane compound undergoes isomerisation

to stable organoborane compound (to organoborane compound in which boron has less substituents) by

addition-elimination mechanism. addition-elimination mechanism. 200 C 200 Coo e.g. e.g. HH _B_B B B

+

BHBH₃₃ THFTHF

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Organo borane

Organo borane compoun

compounds

ds

Organo-Borane Reagents used organic synthesis

Many of these reagents, such as thexylborane, disiamylborane, dipinylborane, Many of these reagents, such as thexylborane, disiamylborane, dipinylborane, 9-borabicyclo-[3.3.1] nonane, catecholborane, chloroborane etherates, haloborane-dimethyl sulfides, [3.3.1] nonane, catecholborane, chloroborane etherates, haloborane-dimethyl sulfides, IPCBH

IPCBH₂₂, ICP, ICP₂₂BH, RBClBH, RBCl₂₂ and R and R ₂₂BCl.BCl.

B-H B-H [(CH [(CH₃₃))₂₂CH-CH(CHCH-CH(CH₃₃)])]₂₂BHBH _[(CH_[(CH 3 3))22CH-C(CHCH-C(CH33))22]B]BHH22 disiamylborane

disiamylborane thexylboranethexylborane

9-BBN 9-BBN

catecholborane

catecholborane monohaloboranemonohaloborane dihaloboranedihaloborane thexylmonochloroboranethexylmonochloroborane [(CH [(CH₃₃))₂₂CH-C(CHCH-C(CH₃₃))₂₂]BHCl]BHCl O O O O BH BH H H₂₂BXBX HBXHBX22 (X- Cl, Br) (X- Cl, Br) mono-isopinocampheylborane mono-isopinocampheylborane BH BH₂₂

))

22 di-isopinocampheylborane di-isopinocampheylborane BH BH [ICPBH ]

[ICPBH ] [ICP BH][ICP 22BH]

2 2

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Organo borane

Organo borane compound

compounds:

s: Disiamylborane

Disiamylborane

It is

It is dialkylboranedialkylborane used selectively for the used selectively for the hydrobhydroboratiorati on of C=C bond in on of C=C bond in ssuch a way uch a way thatthat boron atom attach to less stericaly hindered carbon

boron atom attach to less stericaly hindered carbon . It is used selectively for. It is used selectively for mon

monohydroboration ohydroboration of alkynesof alkynes..

C C H H₃₃ C C H H₃₃ HH CH CH₃₃ B B₂₂HH₆₆/THF/THF [(CH [(CH₃₃))₂₂CH-CH(CHCH-CH(CH₃₃)])]₂₂BHBH disiamylborane disiamylborane 2-methyl-2-butene 2-methyl-2-butene [(CH [(CH₃₃))₂₂CH-CH(CHCH-CH(CH₃₃)])]₂₂BHBH B(C B(C₅₅HH₁₁₁₁))₂₂ B(C B(C₅₅HH₁₁₁₁))₂₂ + + 3% 3% 97%97% e.g.1. e.g.1. 2, 2, B(C B(C₅₅HH₁₁₁₁))₂₂ OHOH [(CH [(CH₃₃))₂₂CH-CH(CHCH-CH(CH₃₃)])]₂₂BHBH oxidation oxidation Examples: Examples:

Steric interactions betwee

Steric interactions between methyl ann methyl andd

Siamyl group

Preparation: Preparation:

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Organo borane

Organo borane compounds

compounds:: 9-BBN

9-BBN

It is more sensitive to the structure of the alkene.

It is more sensitive to the structure of the alkene. Terminal alkenes react more rapidly thanTerminal alkenes react more rapidly than the internal alkene and Z-alkene

the internal alkene and Z-alkene also react more also react more rapidly than the E-isomer.rapidly than the E-isomer. These are also used for

These are also used for monohydroboratimonohydroboration of alon of alkynes kynes whiwhich on oxidatich on oxidation to keon to ketone tone . The. The acid catalyzed hydrolysis of terminal alkyne gives methyl ketone while by using acid catalyzed hydrolysis of terminal alkyne gives methyl ketone while by using disiamylborane or 9-BBN followed by oxidation gives aldehyde.

disiamylborane or 9-BBN followed by oxidation gives aldehyde. These reagents are used to

These reagents are used to reduce mono- and di-substituted alkenereduce mono- and di-substituted alkene preferentially preferentially thanthan the tri- and tetra-substituted alkene.

the tri- and tetra-substituted alkene.

The same result is obtained by using catacholborane, dibromoborane or The same result is obtained by using catacholborane, dibromoborane or thexylmonochlorborane. thexylmonochlorborane. B-H B-H BH BH₃₃/THF/THF B-H B-H H-B H-B R' R' R R R' R' R R H H BB HH R R H H R' R' e.g. e.g. 9-BBN9-BBN THF THF protonolysis protonolysis C C₂₂HH₅₅ H H₅₅CC₂₂ C C₂₂HH₅₅ H H₅₅CC₂₂ H H BB _H_H H H₅₅CC₂₂ OH OH C C₂₂HH₅₅ e.g.1. e.g.1. 9-BBN9-BBN THF THF oxidation oxidation 2. 2. H H H H₅₅CC₂₂ H H H H₅₅CC₂₂ H H BB _H_H H H₅₅CC₂₂ OH OH H H 9-BBN 9-BBN THF THF oxidation oxidation _H_H 5 5CC22-CH-CH22CHOCHO

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Organo borane

Organo borane compound

compounds:

s: Thexylborane

Thexylborane

It is most radialy available of

It is most radialy available of monoalkylboranemonoalkylborane. It is useful for cyclic hydroboration of. It is useful for cyclic hydroboration of

diene

diene. Hydroboration of diene itself by using. Hydroboration of diene itself by using borane gives polymerborane gives polymer but but with with thexylboranethexylborane gives

gives cyclic or bicyclic cyclic or bicyclic organoboranesorganoboranes.. Thexylborane is also used for the

Thexylborane is also used for the synthesis of trialkylboranessynthesis of trialkylboranes containing three differentcontaining three different

alkyl groups. This process has limited scope because the

alkyl groups. This process has limited scope because the first first alkene alkene must must be be relativelyrelatively

unreactive

unreactive..

This difficult can be overcome by using

This difficult can be overcome by using thexylchloroboranethexylchloroborane The thexylchloroborane react The thexylchloroborane react

with an

with an alkenealkene gives an gives an chloroalkylthexylboranechloroalkylthexylborane which may be converted to which may be converted to

dialkythexylborane by reaction with

dialkythexylborane by reaction with one equivalentone equivalent Grignard’sGrignard’s reagent reagent or anor an alkyl-lithiumalkyl-lithium

or

or by hydridation wiby hydridation with LAH in presenth LAH in presence of ce of alkenealkene..

Dialkylthexylboranes are useful for the synthesis of cyclic or

Dialkylthexylboranes are useful for the synthesis of cyclic or acyclic ketones.acyclic ketones.

CH CH₃₃ CH CH₃₃ C C H H₃₃ C C H H₃₃ B B₂₂HH₆₆/THF/THF [(CH [(CH₃₃))₂₂CH-C(CHCH-C(CH₃₃))₂₂]BH]BH₂₂ thexylborane thexylborane 2,3-dimethyl-2-butene 2,3-dimethyl-2-butene B B O O _OH_OH Thexylborane Thexylborane THF THF 1.CO 1.CO 2. 2. NaBH NaBH₄₄ H H₂₂O/OHO/OH --e.g.1. e.g.1. 2. 2. B B H H Thexylborane Thexylborane THF THF B B COOEt COOEt COOEt COOEt 1.CO 1.CO 2. 2. H H₂₂O/OHO/OH --COOEt COOEt

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Organo borane compounds

Organo borane compounds: Optical active reagents (Ipc: Optical active reagents (Ipc₂₂BH and IpcBHBH and IpcBH₂₂))

Diisopinacamphenylborane (Ipc

Diisopinacamphenylborane (Ipc₂₂BH) and monopinacamphenylborane (IpcBHBH) and monopinacamphenylborane (IpcBH₂₂) are prepared) are prepared in either form by reaction of

in either form by reaction of borane with (+) or (-)-borane with (+) or (-)-αα-pinene-pinene under appropriate conditions. under appropriate conditions. These reagents are used for t

These reagents are used for the synthesis ofhe synthesis of optical active alcoholsoptical active alcohols..

H H BH BH H H BH BH H H BH BH₂₂ BH BH₃₃ THF THF

))

22

))

22

purification with 15% purification with 15% a-pi-nene and stand it over nene and stand it over night night a-pinene a-pinene TMEDA TMEDA (+)-a-pinene

(+)-a-pinene _{IPC BH}_{IPC BH} IPC IPC BHBH IPCBHIPCBH 2

2 93% ee93% ee 22 22

100%ee

100%ee 100%ee100%ee

The Z-alkene is converted into optical active secondary alcohol of high optical purity by using The Z-alkene is converted into optical active secondary alcohol of high optical purity by using Ipc

Ipc₂₂BH followed by oxidation. But with E-substituted alkene best result will obtained by usingBH followed by oxidation. But with E-substituted alkene best result will obtained by using IpcBH

IpcBH₂₂, the success of reaction is depends on the bulk of the alkyl substituents of the double, the success of reaction is depends on the bulk of the alkyl substituents of the double bond. bond. BH BH _B_B H H BH BH₂₂ _B_BHH H H

))

₎₎

2 2 H H O O H H O O H H HH H H₂₂OO₂₂/NaOH/NaOH H H₂₂OO₂₂/NaOH/NaOH (R, 87% optical pure) (R, 87% optical pure) (S, 73% optical pure) (S, 73% optical pure) 2 2

(20)

Reactions of

Reactions of organoboranesorganoboranes

Protonolysis

Protonolysis of organoborane compounds by using organic acid is the

Protonolysis of organoborane compounds by using organic acid is the convenient method forconvenient method for the

the reduction of carbon-carbon multiple bondsreduction of carbon-carbon multiple bonds..

Boiling with propaonic acid

At RT with acetic acid At RT with acetic acid

R R B B R R R R H H O O O O R' R' R R B B R R R R OO O O R' R' H H

+

-- ++ R-HR-H

+

RR₂₂B(OCOR')B(OCOR') 22R-HR-H B(OCOR')

+

B(OCOR')₃₃

Alkenylborane

Alkenylborane are more reactive than the alkylborane. This are more reactive than the alkylborane. This reaction takes place with

reaction takes place with retensation of configurationretensation of configuration at the at the carbon atom attach to the boron atom. The

carbon atom attach to the boron atom. The alkalkyneynes as arre ce clleeanlanlyy conve

converrteted intd into Z-alo Z-alkenekenes s ..

Advantageous

- the reduction of the double bond or triple bond in compound containing - the reduction of the double bond or triple bond in compound containing

other reducible functional groups can be easily occurs such as compounds containing ester,

sulphide, protected carbonyl group, nitro group, etc

CH CH₂₂ C C₄₄HH₉₉ 1. 1. 2. 2. CC22HH55 CC22HH55 C C₂₂HH₅₅ CC₂₂HH₅₅ B B H H C C₂₂HH₅₅ CC₂₂HH₅₅ (C (C₄₄HH₉₉CHCH₂₂CHCH₂₂))₃₃BB _C_C 4 4HH99CHCH22CHCH33 BH BH₃₃/THF/THF (C (C₅₅HH₁₁₁₁))₂₂BHBH Diglyme Diglyme CH CH₃₃COOHCOOH propionic acid propionic acid reflux reflux 25 C 25 Coo 91% 91%

(21)

Diastereoselect

Diastereoselective hydration ive hydration of the double bond of acyclic of the double bond of acyclic alkenes.alkenes.

CH CH₃₃ R R H H R R R R C C H H₃₃ HH RR HH _H_H RR R R CH CH₃₃ H H

+

major

major _minor_minor

L L M M M M M M L L L L 1. 1. 2. 2. R R₂₂BHBH H H₂₂OO₂₂/NaOH/NaOH Terminal alkene

Terminal alkene in which R in which R _L_L and R and R _M_M are stericaly large and medium sized substituent are stericaly large and medium sized substituent

groups respectively. The

groups respectively. The stereochemistrystereochemistry of the hydroboration appears to be controlled of the hydroboration appears to be controlled

primarily by the

primarily by the size of the groupssize of the groups on the nearby chiral carbon.on the nearby chiral carbon.

Reactions of

Protonolysis

Intramolecular hydroboration

Intramolecular hydroboration takes place viatakes place via boatboat

like transition state

like transition state rather than the chair. Therather than the chair. The formation of boat like transition state is preferred formation of boat like transition state is preferred because

because thethe boron-hydrogen bond eclipses theboron-hydrogen bond eclipses the ππ-

-system of the double bond

system of the double bond but it is not a case in chair but it is not a case in chair form formation. This indicates that intramoleculer form formation. This indicates that intramoleculer hydroboration reaction takes place through planar four hydroboration reaction takes place through planar four

1. 1. 2. 2. thexylborane thexylborane H H₂₂OO₂₂/NaOH/NaOH e.g. e.g. CHCH33 C C H H₃₃ CH CH₃₃ C C H H₃₃ CH CH₃₃ OH OH CH CH₃₃ OH OH CH CH₃₃ C C H H₃₃ OHOH CH CH₃₃ OH OH

+

(81%, 6:1 selectivity) (81%, 6:1 selectivity) B B C C H H₃₃ H H H H B B H H C C H H₃₃ H H

boat transition state boat transition state is preferred.

is preferred.

chair transition state chair transition state not prefered.

(22)

Reactions of

Oxidation

Oxidation of organoboranes to alcohol

Oxidation of organoboranes to alcohol can be easily carried out can be easily carried out by using alkalineby using alkaline

hydrogen peroxide

hydrogen peroxide.. In overall reaction the

In overall reaction the water molecule can be added (overall is cis-/syn-addition) acrosswater molecule can be added (overall is cis-/syn-addition) across the double bond by using anti-Markownikoff rule

the double bond by using anti-Markownikoff rule. This also used to. This also used to convert alkyne intoconvert alkyne into ketone

ketone and aldehyde (by using terminal and aldehyde (by using terminal alkyne)alkyne) rather than to the methyl ketone.rather than to the methyl ketone.

R R B B R R R R O O OO H H B B R R R R R R O O OHOH R R B B R R O O R R R R B B R R O O RR O O HH RR B B R R O O

₊

+

ROROHH ROH ROH + + B(OH)B(OH)₃₃

OH OH

--

--H H₂₂OO₂₂ + + NaOHNaOH

--The reaction path involving

The reaction path involving intramoleculer transfer of alkyl group from boron to carbonintramoleculer transfer of alkyl group from boron to carbon inin an intermediate ate compound.

an intermediate ate compound.

1. 1. 2. 2. CH CH₃₃ CH CH₃₃ CH CH₃₃ OH OH CH CH₃₃ OH OH CH CH₃₃ CH CH₃₃ H H (C (C₅₅HH₁₁₁₁))₂₂BHBH Diglyme Diglyme 1. 1. 2. 2. // H H₂₂OO₂₂/NaOH/NaOH (C (C₅₅HH₁₁₁₁))₂₂BHBH Diglyme Diglyme 1. 1. 2. 2. // H H₂₂OO₂₂/NaOH/NaOH OH OH CH CH₃₃ H H CH CH₃₃ CH CH₃₃ OH OH

(23)

Reactions of

Oxidation

The

The direct oxidation of primary trialkylborane into aldehyde and secondarydirect oxidation of primary trialkylborane into aldehyde and secondary

trialkylborane into ketone

trialkylborane into ketone, without isolation of the alcohol is possible by using, without isolation of the alcohol is possible by using pyridiniumpyridinium

chlorochromate (PCC) or aqueous chromic acid

chlorochromate (PCC) or aqueous chromic acid..

BSia

BSia₂₂ _BSia_BSia

2 2 H H CHO CHO O O H H Sia Sia₂₂BHBH PCC PCC PCC PCC or chromic or chromic acid acid chromic chromic acid or acid or

(24)

Reactions of organoboranes

Amine formation

The

The trialkylboranestrialkylboranes are converted into are converted into primary amineprimary amine by by reaction reaction withwith hydroxylamine-O-

hydroxylamine-O-sulphonic acid or N-chloroamine

sulphonic acid or N-chloroamine..dialkylchloroborane with organic azide gives secondarydialkylchloroborane with organic azide gives secondary

amine

amine. Only one alkyl group can be migrate towards the nitrogen atom therefore, yield of the. Only one alkyl group can be migrate towards the nitrogen atom therefore, yield of the

product is less which can be increased by

product is less which can be increased by using 9-BBN or Siausing 9-BBN or Sia₂₂BH.BH.

R R₃₃BB

+

HH₂₂N-Cl/HN-Cl/H₂₂NOSONOSO₄₄HH RR _B_B R R R R _NH_NH 2 2 Cl Cl RR B B R R NHNH₂₂ R R R-NH R-NH₂₂ + + RR₂₂B-ClB-Cl + + ClCl ₊₊

--

--.

.dialkylchlorodialkylchloroborane wborane withith N-chloroamine /N-chloroamine /organic azide gives secondary amineorganic azide gives secondary amine..

R R₂₂B-ClB-Cl ++

--

--+

+

R'NR'N₃₃ R R B B R R Cl Cl N N R' R' N N₂₂ R R B B Cl Cl N N R R R' R' R R NNHH R' R' OH OH OHOH22

(25)

Primary bromides and iodides are also obtained by the reaction of trialkylboranes

derived form terminal alkenes with bromine and iodine in presence of base such

as NaOH, methanoic sodium methoxide, etc.

Primary brom

Primary bromide an

ide an

d iodide formation

R R₃₃BB

₊

_X_X 2 2 MeONa/MeOH MeONa/MeOH _R_R-X_-X

+

BXBX₃₃ organoborane organoborane of terminal alkene of terminal alkene bromine bromine or iodine

or iodine primary halideprimary halide

+ + ++

--

_OH_OH

--R R₃₃BB

+

XX₂₂ _R_R-X_-X

₊

R R B B R R R R _X_X XX R R B B R R X X R R R R₂₂BOHBOH

Mechanism

(26)

Carbonylation

The reaction of organoborane with

The reaction of organoborane with carbon monoxidecarbon monoxide under appropriate conditions is veryunder appropriate conditions is very important for the synthesis

important for the synthesis primary alcohol, secondary alcohol and tertiary alcohols,primary alcohol, secondary alcohol and tertiary alcohols,

aldehydes and open, cyclic and polycy

aldehydes and open, cyclic and polycyclic ketonesclic ketones..

R R₃₃BB

+

_CO_CO R R B B R R R R OO RR _B_B R R _R_R O O B B R R OH OH R R R R R R OHOH R R HH O O R R BB RR R R O O R R B B O O H H R R R R OH OH R R R R OHOH R R O O R R O O BB RR R R R R O O O O B B R R R R R R R R R R OH OH R R ketone ketone sec-alcohol sec-alcohol prim-alcohol prim-alcohol tert-alcohol tert-alcohol aldehyde aldehyde Bora-ketone Bora-ketone Bora-epoxide Bora-epoxide polymer

polymer _monomer_monomer 1atm., r.t. 1atm., r.t. dry atmosphere dry atmosphere + +

--

HH₂₂OO₂₂ H H₂₂OO₂₂ NaOH/H NaOH/H₂₂OO NaOH NaOH NaOH/H NaOH/H₂₂OO NaOH NaOH NaOH NaOH NaOH NaOH OH OH₂₂ LiAlH(OMe) LiAlH(OMe)₃₃ OH OH OH OH R

R ₃₃B with one mole ofB with one mole of CO

CO presence of small

presence of small amount of water & amount of water &

NaOH NaOH in presence of in presence of some hydride some hydride reducing reducing agent agent H H₂₂OO

(27)

Reactions of organoboranes Reactions of organoboranes Synthesis of Synthesis of tertiary alcohol tertiary alcohol R R₃₃BB ₊₊ COCO R R B B R R R R OO RR _B_B R R _R_R O O R R BB RR R R O O O O BB R R R R R R O O O O B B R R R R R R R R R R OH OH R R tert-alcohol tert-alcohol Bora-ketone

Bora-ketone Bora-epoxideBora-epoxide

polymer polymer monomer monomer 1atm., r.t. 1atm., r.t. dry atmosphere dry atmosphere + + --NaOH NaOH OH OH₂₂ OH OH OH OH R R R R OH OH R R tert-alcohol tert-alcohol R

RCOCOOORR' '

+

22RRMMggXX dehydrationdehydration alkene alkene (R is bulky substituent) (R is bulky substituent)

High temperature

30 alcohol in high yield

Low yield

Low yield The migration of alkyl group from boron to carbon atom intramoleculerly The migration of alkyl group from boron to carbon atom intramoleculerly Synthesis of

Synthesis of trialkylmethanolstrialkylmethanols: The trialkylborane react with dichloromethyl methyl ether in: The trialkylborane react with dichloromethyl methyl ether in presence of strong hindere

presence of strong hindered base lithium triethylcarboxide.d base lithium triethylcarboxide.

R R₃₃BB _B_B R R Cl Cl Cl Cl R R R R _OMe_OMe RR_B_B R R R R Cl Cl OMe OMe R R BB CR CR₂₂ClCl OMe OMe R R₃₃CC B B Cl Cl OMe OMe R R₃₃C-OHC-OH [O] [O] Li Li CH CH₃₃OCClOCCl₂₂LiLi THF THF

--+ + ₊₊ R R₃₃BB _B_B R R Cl Cl R R R R OMe OMe _R_R B B R R R R Cl Cl OMe OMe R R BB CR CR₂₂ClCl OMe OMe R R₃₃CC B B Cl Cl OMe OMe R R₃₃C-OHC-OH [O] [O] THF THF

--

++ H H₃₃COCClCOCCl H

H₃₃COCHClCOCHCl₂₂ + Base + Base

....

E.g. Carbonilation of equimolar mixture of

E.g. Carbonilation of equimolar mixture of triethylboranetriethylborane and and tributylboranetributylborane gives after gives after

(28)

oxidation-Reactions of organoboranes Reactions of organoboranes Synthesis of Synthesis of secondary secondary alcohol alcohol R R₃₃BB ₊₊ COCO R R B B R R R R OO RR _B_B R R _R_R O O R R BB RR R R O O R R B B O O H H R R R R OH OH R R R R OHOH R R O O R R ketone ketone sec-alcohol sec-alcohol Bora-ketone

Bora-ketone Bora-epoxideBora-epoxide 1atm., r.t. 1atm., r.t. dry atmosphere dry atmosphere + + --H H₂₂OO₂₂ NaOH NaOH NaOH/H

NaOH/H₂₂OO NaOHNaOH

Carbonylation reaction carried in presence of small amount of Carbonylation reaction carried in presence of small amount of

water which resist migration of third alkyl group. water which resist migration of third alkyl group.

oxidation

oxidation alkaline hydrolysis

alkaline hydrolysis

Unsymmetrical ketones by using mixed organoboranes prepared from thexyl or Unsymmetrical ketones by using mixed organoboranes prepared from thexyl or thexylchloroborane (The

thexylchloroborane (Thexyl group has xyl group has very low migratory aptivery low migratory aptitude value).tude value).

BH BH₂₂ _BHR_BHR B B R R R R alkene A

alkene A _{alkene B}_{alkene B}

A A B B A A COCO B B O O R R R R_B_B A A _B_B R R R R OHOH OHOH B B A A R R RR O O B B A A [O] [O]

Dienes similarly used for the synthesis of cyclic ketones.

O O HH _B_B H H H H H H O O Thexylborane Thexylborane THF THF CO/H CO/H₂₂OO H H₂₂OO₂₂/NaOH/NaOH 1. 1. 2. 2. /5O C/70atm /5O C/70atmoo Thexylborane Thexylborane THF THF CO/H CO/H₂₂OO H H₂₂OO₂₂/NaOH/NaOH 1. 1. 2. 2. B B O O H H

(29)

Synthesis of

primary alcohol

primary alcohol Carbonylation is carried out inCarbonylation is carried out in presence of some hydride reducing_agent_agent_{such as lithium trimethoxyaluminium hydride.}_{such as lithium trimethoxyaluminium hydride.}presence of some hydride reducing

R R₃₃BB

+

COCO R R B B R R R R OO RR _B_B R R _R_R O O B B R R OH OH R R R R R R OHOH R R HH O O prim-alcohol prim-alcohol aldehyde aldehyde 1atm 1atm., r.t., r.t.. dry atmosphere dry atmosphere + +

--

HH₂₂OO₂₂ NaOH/H NaOH/H₂₂OO NaOH NaOH LiAlH(OMe) LiAlH(OMe)₃₃ Main

Main disadvantagedisadvantage of this procedure is that only-one alkyl group of trialkylborane is of this procedure is that only-one alkyl group of trialkylborane is converted into the required derivative and other

converted into the required derivative and other two are effectively wastedtwo are effectively wasted. This difficulty. This difficulty can be overcome by the hydroboration of alkene

can be overcome by the hydroboration of alkene by using 9-BBN or disiamylborane.by using 9-BBN or disiamylborane.

CH CH₃₃(CH(CH₂₂))₇₇ BB COCO CHCH33(CH(CH22))77CHOH BCHOH B CHCH33(CH(CH22))77CHCH22 BB LiAlH(OCH LiAlH(OCH₃₃))₃₃ LiAlH LiAlH₄₄ HH22OO22 CHCH₃₃(CH(CH₂₂))₇₇CHCH₂₂OHOH NaOH NaOH CHO CHO H H₂₂C=CHCHC=CHCH₂₂COCO₂₂EtEt HOC(CHHOC(CH₂₂))₃₃COCO₂₂EtEt ;;

(30)

Reaction of

Reaction of B-alkylboronic esterB-alkylboronic ester withwith methoxy(phenylthio)methyl-lithiummethoxy(phenylthio)methyl-lithium forming forming intermediate which react with

intermediate which react with mercurmercurous ous chloridechloride, induces transfer of the, induces transfer of the alkyl group fromalkyl group from boron to carbon

boron to carbon and subsequent oxidation by using alkaline hydrogen peroxide gives and subsequent oxidation by using alkaline hydrogen peroxide gives corresponding aldehyde in good yield.

corresponding aldehyde in good yield.

CH CH₃₃ CH CH₃₃ BBr.(CH BBr.(CH₃₃))₂₂SS CH CH₃₃ B B O O O O CH CH₃₃ B B O O O O SPh SPh OMeOMe CH CH₃₃ B B B B B B OMe OMe CH CH₃₃ CHO CHO HBBr HBBr ₂₂.(CH.(CH₃₃))₂₂SS CH CH₂₂ClCl₂₂ (CH

(CH₃₃))₃₃SiO(CHSiO(CH₂₂))₃₃OSi(CHOSi(CH₃₃))₃₃

LiCH(OCH LiCH(OCH₃₃)SPh)SPh Hg Hg₂₂ClCl₂₂ H H₂₂OO₂₂ NaOH NaOH

--Alkyl Alkyl shift shift

(31)

Cyanation

T

Trialkylborane treated rialkylborane treated withwith sodium cyanidesodium cyanide formingforming trialkylcyanoboratetrialkylcyanoborate. Addition of. Addition of oneone molar equivalent

molar equivalent of benzoyl chloride or trifluoroacetic unhydride induces of benzoyl chloride or trifluoroacetic unhydride induces two successivetwo successive

migrations of alkyl groups from boron to the adjacent carbon atom of cyanide group

forming the

forming the cyclic organoboranecyclic organoborane intermediate whichintermediate which on oxidation without isolation giveson oxidation without isolation gives ketone

ketone in high yield. In presence ofin high yield. In presence of excess anhydrideexcess anhydride formingforming trialkylmethanoltrialkylmethanol.. Asy

Asymmetric mmetric ketone can be easily ketone can be easily obtained from two different alkene.obtained from two different alkene.

R R₃₃BB

₊

_CN_CN RR _B_B R R R R NN R R O O R R R R R R OH OH R R ketone ketone tert-alcohol tert-alcohol

--H H₂₂OO₂₂ NaOH/H NaOH/H₂₂OO NaOH NaOH F F₃₃CC O O O O O O F F₃₃CC R R B B R R _N_N R R O O CF CF₃₃ B B O O R R N N CF CF₃₃ R R RR 2. 2. 1. 1.CFCF₃₃COOHCOOH

--F F₃₃CC O O O O F F₃₃CC B B O O R R N N R R RR B B O O R R N N CF CF R R RR O O F F₃₃CC B B O O F F₃₃CC CR CR₃₃ O O NCOCF

NCOCF₃₃ HH22OO22 RR₃₃COHCOH NaOH

NaOH

(32)

--Reactions of organoboranes

Ketone and tertiary alcohol

can be synthesized by the reaction of

trialkylboranes with anion of tri(phenylthio)-methane

. Two alkyl groups are

migrates from boron to carbon in the initial adduct to give an intermediate which

can further oxidized to ketone.

A

third migration of alkyl group

for the synthesis of tertiary alcohol can be

induced by the

treatment of mercuric ion

; oxidation of the product gives tertiary

alcohol.

R

R₃₃B + LiC(SPh)B + LiC(SPh)++ ₃₃ [R[R₃₃

--

B-C(SPh)B-C(SPh)₃₃]Li]Li++

PhS PhS B-SPh B-SPh R R RR R R R R O O R R X X BB SPh SPh R R R R R R RR₃₃COHCOH

--

RR

--B B R R SSPPhh SPh SPh R R SPh SPh H H₂₂OO₂₂ NaOH NaOH Hg Hg2+2+ or CH or CH₃₃OO₂₂SFSF H H₂₂OO₂₂ NaOH NaOH

(33)

Reaction with α

Reaction with α-bromoketone-bromoketone and αand α-bromoester-bromoester

Organoborane

Organoborane react radialy with react radialy with αα-bromoketone-bromoketone and and αα-bromoester-bromoester in presence of in presence of potassium t-butoxide or hindered base

potassium t-butoxide or hindered base forming correspondingforming corresponding ketoneketone and and esterester

respectively. The

respectively. The alkalkyl or yl or aryl aryl grougroup of organoborane dp of organoborane diissplaceplaces s bromibrominene atom from itsatom from its position. position. RCOCH RCOCH₂₂Br Br ₊₊ t-Ct-C₄₄HH₉₉OKOK O O R R Br Br R R O O Br Br B B R' R' R' R' R' R' RR O O R' R' B B R' R' R' R' R R O O R' R' BR' BR'₃₃ _t-C_t-C 4 4HH99OHOH

--

-- Nucleophilic substitution Nucleophilic substitution Limitations Limitations --a) Organoborane having

a) Organoborane having highly branched groups do not react.highly branched groups do not react. b)

b) Only-one Only-one of of the the three three alkyl alkyl groups groups in in the the trialkylborane trialkylborane is is used used in in the the reaction reaction andand remaining is wasted therefore yield of the reaction is decreased.

remaining is wasted therefore yield of the reaction is decreased. This difficulties are overcome by using an alkyl derivatives of

This difficulties are overcome by using an alkyl derivatives of 9-BBN9-BBN. This reaction can be. This reaction can be extended to

extended to dibromoacetatesdibromoacetates and can be and can be controlled at thecontrolled at the αα-alkyl--alkyl-αα-bromoacetates or-bromoacetates or

dialkylacetates. dialkylacetates. B B _CH_{CH COOEt}_COOEt BH BH₃₃/THF/THF BrCH BrCH₂₂COOEtCOOEt

(34)

Reaction wi

Reaction with diazo-compoundsth diazo-compounds

It is

It is nucleophilic substitution reactionnucleophilic substitution reaction of organoborane compound. Theof organoborane compound. The ketones and estersketones and esters are synthesized from the

are synthesized from the diazo-compound and organoboranediazo-compound and organoborane in presence of base.in presence of base.

The mechanism studies have been suggested that the

The mechanism studies have been suggested that the migration of alkyl or aryl groupmigration of alkyl or aryl group from boro

from boron to carbon n to carbon atom is occurring watom is occurring with eliminith elimination ation of nitrogen gas.of nitrogen gas. It is also used for the

It is also used for the synthesis of nitrile or cyanide derivativesynthesis of nitrile or cyanide derivative.. Yield of the reaction can be increased by using

Yield of the reaction can be increased by using dialkylchloroboranedialkylchloroborane instead of instead of trialkylborane. trialkylborane. R R₃₃B B + + NN₂₂-CHCOCH-CHCOCH₃₃ _R_RRR _B_B R R CH CH₃₃ O O N N₂₂ R R B B R R CH CH₃₃ O O R R R R O O CH CH₃₃ + + + +

--

--hydrolysis hydrolysis

Suggest the mechanism of following:

(35)

Synthesis of

Synthesis of cyclopropanecyclopropane

Cyclopropane or its derivatives are synthesized from

Cyclopropane or its derivatives are synthesized from dialkylboranedialkylborane such as thexylborane such as thexylborane or 9-BBN and

or 9-BBN and allylic chlorideallylic chloride in presence of base.in presence of base.

--ClCH ClCH₂₂CH=CHCH=CH₂₂ SiaSia22BHBH THF THF Cl Cl B B Cl Cl B B O O H H OH OH allyl chloride allyl chloride cyclopropane cyclopropane

(36)

Alkenylborane and trialkylalkynylborates are used for the synthesis of

Alkenylborane and trialkylalkynylborates are used for the synthesis of conjugated dienesconjugated dienes and

and diynesdiynes,, saturated andsaturated and α,βα,β-unsaturated ketones-unsaturated ketones by by the the migration migration of of an an alkenyl alkenyl oror alkyny

alkynyl l group from boron to carbon instead of alkyl group from boron to carbon instead of alkyl group.group. Reactions of organoboranes Reactions of organoboranes + + -- --Et Et B B H H Et Et )) 3 3 II E Et t EEtt H H BB R R R R II R R H H B B Et Et Et Et II R R II B B H H Et Et R R Et Et II R R H H Et Et Et Et E Et t EEtt H H Et Et H H Et Et R R II OHOH II₂₂,NaOH,NaOH THF THF BH BH₂₂

+

ClCl CC₆₆HH₁₁₁₁ Cl Cl B B HH C C₆₆HH₁₁₁₁ H H B B C C₄₄HH₉₉ H H C C₆₆HH₁₁₁₁ H H Cl Cl H H C C₆₆HH₁₁₁₁ H H B B H H CC₄₄HH₉₉ H H MeO MeO C C₆₆HH₁₁₁₁ C C₄₄HH₉₉ C C₆₆HH₁₁₁₁ C C₄₄HH₉₉ C C H H CC₄₄HH₉₉ C C₂₂HH₅₅COOHCOOH H H₂₂OO₂₂/NaOH/NaOH CH CH₃₃ONaONa Thexylborane Thexylborane THF THF -78 C -78 Coo (C (C₄₄HH₉₉))₃₃B B ++ Li LiC C CCCC66HH55 BB CCCC₆₆HH₅₅ C C₄₄HH₉₉ C C₄₄HH₉₉ C C₄₄HH₉₉ CC44HH99 (C (C₄₄HH₉₉))₂₂BB II C C₆₆HH₅₅ C C₄₄HH₉₉C C CCCC₆₆HH₅₅ II₂₂

(37)

--Reactions of organoboranes

Reaction with conjugated Aldehyde and

Reaction with conjugated Aldehyde and ketonesketones:: T

Trialkylboranes reacts with rialkylboranes reacts with vinyl aldehyde or ketone, forming anvinyl aldehyde or ketone, forming an ate-complexate-complex 1, in which pi-1, in which pi-electrons move with the migration of

electrons move with the migration of R on BR on B to the vinyl carbon to give enolborinateto the vinyl carbon to give enolborinate 2,2, which is then hydrolyzed w

which is then hydrolyzed with water to theith water to the correspondingcorresponding saturated aldehyde or ketone saturated aldehyde or ketone.. The yields and conditions are changed according to the substitution at

The yields and conditions are changed according to the substitution at αα- and- and ββ-position. The-position. The yield was drastically change with

yield was drastically change with ββ-substitution.-substitution.

The conjugated ester and nitril

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Examples

B B H H C C₅₅HH₁₁₁₁ CH CH₃₃CHOCHO _B_B C C₅₅HH₁₁₁₁ C C₂₂HH₅₅OO CH CH₃₃ H H CC55HH1111 O O CH CH₃₃ H H carbonylation carbonylation 1 1 BH BH

))

₂₂ H H₂₂OO₂₂/NaOH/NaOH H H H H OH OH (92%ee) (92%ee) H H₂₂N-Cl/THFN-Cl/THF H H H H NH NH₂₂ (90%ee) (90%ee) 2 2 )) 2 2

+

HH22BBr.(CHBBr.(CH33))22SS (( 22 BBr.(CHBBr.(CH₃₃))₂₂SS (( ))22 B-OCHB-OCH₃₃ H H₉₉CC₄₄ CC₄₄HH₉₉ O O CH CH₃₃ONaONa CH CH₃₃OHOH Cl Cl₂₂CHOCHCHOCH₃₃ (C (C₂₂HH₅₅))₃₃COLiCOLi 3 3 BH BH₂₂ BB C C₅₅HH₁₁₁₁ CH CH₃₃ H H _B_B ₊₊ C C₂₂HH₅₅OO C C₅₅HH₁₁₁₁ H H CHCH33 C C₅₅HH₁₁₁₁ O O C C H H₃₃ HH CH CH₃₃CHOCHO Cl

Cl₂₂CHOCHCHOCH₃₃/Et/Et₃₃COLiCOLi

H H₂₂OO₂₂/NaOH/NaOH 1. 1. 2. 2. 1. 1. 2. 2. 4 4

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Exercise

1 1 2 2 3 3 4 4 5 5 6 6 7 7

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6 6 7 7

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Organocopper reagents Organocopper reagents Organocopper compounds

Organocopper compounds in organometallic chemistry contain in organometallic chemistry contain carbon to copper chemicalcarbon to copper chemical

bonds

bonds. e.g. R . e.g. R ₂₂CuLi, RCu(CN)Li or R CuLi, RCu(CN)Li or R ₂₂Cu(CN)LiCu(CN)Li₂₂..



 The The first first organocoppeorganocopper r compound, compound, thethe explosive dicopper acetylide Cuexplosive dicopper acetylide Cu₂₂CC₂₂ waswas synthesized by Bottger in 1859.

synthesized by Bottger in 1859.



 Henry Henry Gilman Gilman preparedprepared methylcoppermethylcopper in 1936. in 1936.



 In In 1941 1941 Kharash Kharash discovered discovered that that reaction reaction of of aa Grignard’sGrignard’s reagent with reagent with cyclohexenone in presence of Cu(I) resulted in

cyclohexenone in presence of Cu(I) resulted in 1,4-addition1,4-addition instead of 1,2- instead of

1,2- addition.

addition.



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Organocopper reagents Organocopper reagents

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Organocopper Compounds

α,β

-Unsaturated carbonyl compounds have two reaction sites:

The composition of the product can be

varied with

sterric bulk of

R’

in the Grignard

reagent and

R group in the

carbonyl compound

.

Also as size of

R’

group of the Grignard reagent increases, the amount of 1,4-

group of the Grignard reagent increases, the amount of

1,4-addition product increases.

addition product increases.

The 1,4-addition of the Grignard reagent was proceeds though six membered

transition state, whereas the 1,2-addition reaction proceeds through four

membered transition state.

Also if

electron withdrawing group

attached to alkene

moiety, increases the yield of

1,4-addition product.

R'-MgX R'-MgX O O R R R''' R''' R R'''' R R OMgX OMgX R''' R''' R R'' R R'''' OMgX OMgX R R R R'' R R'''' R''' R''' + + + + (1,4- addition)

(1,4- addition) (1,2- (1,2- addition)addition)

1,2-addition

1,4-addition

What is the major product obtained by the treatment of Grignard reagent on

What is the major product obtained by the treatment of Grignard reagent on α,βα,β-unsaturated-unsaturated

aldehyde?

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Organomagnesium Compounds

Grignard’s

Reagent:

Reactivity

The cuprous salts (Cu

₂₂

X

₂₂

) was added to the

Grignard’s

reagents forming less

reactive product such as [

R

₂₂

MgCu or RCu

) containing

copper (I) which forming

co-ordinate bond strongly with carbonyl oxygen atom in

six membered transition

state

.

Grignard reagent shows 1,4-addition reaction with carbonyl compound except

α,β

-unsaturated aldehyde.

R'-MgX R'-MgX HH33OO O O R R R''' R''' R'' R'' R R R''' R''' R' R' R'' R'' O O R'' R'' R''' R''' R R O O Mg Mg R' R' X X + + + +