Rearrangements of unnatural steroids

•

CHEMISTlW

Di:PT't. UI:!R.

i)

2b),

)

64a)

5.

5,'¥

,,

5,

5.

( )

•

)

o:n

)

1

2

6

9

9

24

of .5,6oc-epoxy-9J ...

cholest-7-en-3fo (69)

for of structures to

3f·~-diacetoxy-.5d-hydroxy-9f­

\'.d th

3.5

37

42

.50

1.

2e)

(?)a)

111i th H2

so

₄-.tw20-AcOH2 and BF

3-ethera.te-Ac2

o

hydroxy-diacetate (?)a) also

) )

,

and/or ether. The

to be A s

The and role carbonium

in has su.bj a vast

• concerned

acyclic compounds,

or

bridged _•

been an ever growing

studies been 1. Coordination rupture, deficient 2. skeletal

e 'lllhere

c

sition.

types

4,5-a. <:lCid

to the

centre. (

the course

the

" 1.)

•

"

of an

of

Sci-alcohol is

involves sulphation of

virtually • (i.e. consumes almost all of

or

concentration) followed reversible

the a

ionisation to

)

..

5ci.-acetoxy with

in _•

is

this case

..

this

will

to

ion.

steroids

57 the

), 5,6p-epoxy-( },

steroid

.2.)

~Tith

7

Compound

2min

Producta

Sp-6-one ( )

oil

5a-6-one(9a)

, 14hr

5j3-6 ... one (

Jb)

:

.

,,'

AcO' , ,,'

0''

~

w

AcO ~ ,,, 0''

4.

B-nor { } 5.

5p-6-one{ ) • O;lh

~{9) (•7)

s.

o! a trisubstitu.ted occurs

preferentially centre.

b) favourable molecular

substituents the

the

mechanism)

-coordinated

comes

of the

..

consistent

ions.

fully

4p,5p-which

c

carbonium. ion.

group.

.)

6 ..

at

on the

the

17

7·

A concerted :process would the formation only one

aldehyde from each In some epoxide

aldehJ'de in the minor even it

the more stable in conflict

with postulate ·which that

in state are mirrored by

in

..

postulatedt

". as an

, occur

process and same

the

, in

as

can _•

by

a trisubstituted

For to

by

for bond

ion

by the

the

6;a-:P(l4a), 6f-Cl(

0 _{~ for}

f-value

•4.8

can

as

5cX.-acetoxy

ions as

four

as

tertiary carbonium is

lobes on

8 ....

ctronic •

c:a:

3

o-cR2

a

-ve

_f

ion

in 80% ethanol 2

are both to

in

transition

cently Blackett eta122 have established the comparability

of the constant for a hjrdride shift kHa or Kab ~ 1. 71 to

that the k1 , k-1:£; 1.84 for ·the symtem

ShO\I!n in results of studies the

of steroidal rearrangements involving

_G-5

ion intermediates in the light of the posed bili·ty thnt the conforraational from the initial conformation

ion and the of es

(with the molecule in the most favourable co:n.for.matio:n for reaction i.n case) might

1)

from

steroids _H2

so

₄ in are

the orientation of the elec·tron of the 10,;3-methyl path 6p-compounds4(14}

~·

proton ex:clusiv·ely for the 6a-acetate24'( 20). of ·the 5ci-aceV)l.sulpha te deri va.t:i va Lt- to

.5tX.-hydroxy-C-4 occurs During the

the c5_

on

..

from to (planar)

" justment \'lill o ccu.r more or

to

(15)

10.

lOj3 ... methyl

in the of

p .... orbital to

of

can

(15).

c

2)

the

(17)7,

(16)

to

(18) 2

5

reaction

(19 }26 "rl th

).

occurs.

ion

( )

.

01:1

c::

on

a)

(

)

)

(30)

(

).

(

)

to (

can occur

b)

)

..

can occur

( )

( )

can

( ) (J7)

...

...,.,.,

..

.,.,.., )

.

in (34) (35)

!Yl (44)

boat not

ion B

an

E can. occur

1)

C~M2H!!!

by

on

)

(lr7)

( )

)

..

on

(

)

)

"

14.

2)

e

•

:.Pa,rt I.

Rea:rrgngement ofr 5q,,6C(-ewv-2a-cholestan-Ja-ol(ld)

d.,

over 2.5 sees

onto deactivated

(3:2)

(

).

on

was

)

_).

4 .. 375 ( J =J ' = 4., 5 Hz ) the

'a consistent with the

(J)j3,2ot • J3fo,4ti = 4.5 Hz,

¢

= 40o; J'Jf3,2j3 •

JJp,4p

<= 0 Hz,

¢ •

80°).

by

J

'I'•

₇ d.. =: 0 Hz 9

¢ •

87°).

the

(J 6(3 ,. ₇

~

• 5. 5 Hz ,

¢

=

c

6 ...

H

4.J?5

( c)~

( J

=

J • = 5 Hz ' J II • J 1/1 = 1

Hz )

out on the

(J = 7 B;z } .. This

J'Jf

t4f->= OHz J 3f ,4d..= 7 Hz ;

J)j3,₂ot •

JJf3,'Zf3

= 1 .. 5 Hz ) c3-proton.

can be

5fo""'"6

of the )o:

model

)c<

a 4-,. or ""-"'n:rn

or

6-o:f

lOp-methyl

a one to

resonance in

can

compou:nd.

a

resonance.

a~~>

).14 (

).

resonance

()b) .•

could ( '7

0%)

t.Yae

( ) by

an

to

Ll(lO)_

on to

as one a

a five

to

A

(1)

(

).

(ii)

can

over on

(1:1) an

o.

(

)

Hz ) an

(41")

more

more

an

§(10) Ol' ~(14)"

1)

(

m .. p •

(51) '\'Ti th the d.-epoxide (ld)

;yield .. 21 was a ~unc:~.•• ~mt'ltt'l'!d:

( ; 4%). It was w.J..I::.a.~.

)cX.•hJdroxy-5,

tound.

ot Jp-hydroxy-5.

(2d;

tosyloxy-chlorohydrina

(53, 54).

(KOH/methanol)

Light.

(52; 8 ..

as a

c

2-H,

..

on

two

( 5 )

a better

(

)

(2b)

(J = 2.1 Hz )

with an

22.

(J:2)

compound

triplet centred at 4,.)0 (J = J ~ •

z.;

Hz) for tl:u;

The

as

oxidation ( )

..

(2~))

•

• 2.5

Hz)

=

8 Hz).

(19. which were

( _•

was

in

s ..

so

C -H, C -B).,

3

4

to in

feature[5 (/}•4 )

+

9 Hz structure

to the J.tnc)wn /} '4

-~

polt~.r

one

can down to

6p-ol (.55a) and cholest-4-e:n-6-one (6e),.

,2:~ti1jation of cholesrta-2₁4-.t!ien-~§-ol (61)

(55b;

only the

6 .. 825

to

(5

( was

to

(55a) .. were

..

on

~~!?.&;:~~~~~~~it! ( 57b)

300

llll (~.

5t400).

(0 ... 01 )

(

(

on

(15g) the

•

5 nm (~.

ooo)

by

EiHi!Hl ... )

two

30

er

,

trV

ally lie

(1:1) (

oJ.:I.\.Iw~::::u a. one

06 _{a one}

(J I = 4., 5 a~

)

f'or

lTere also ill

(48a).

.Den,zente ... er&ne~r ( 2)

one (9e; 19%).

The

same

)

..

6d-hyclroxy-are

).

on

(

Hz)

\'lith a

·Hz···

(

the

), '760)

by

(

( f 207 nm 7, 0; 8

to 9(10)

c

;

..

)

..

8

(48b)

_·5

19 7 .. 5

)6

nm 6,200; f;

)

)

) -as

)

" dJ(l?)_

)

sole

7.6

19

4

41 .. 5

..

3(( -h;rdroxy-epoxide)

not

only one

..

( 5

( ; 88~}.

---

5

Hz)

function:3°.,

(4 .. 6.5

are Oxidation with

t

to ( 6;). III.

10f3 -methyl Hydride

)-substituted 5cl, )migration(%)

J•H 9 la 29 50

)o(-OAe 64

17

Jd_-OH

14

5f3

10 _{46 20}

)cl-OH 2e

70

21

J~-OH 2b

_.5

)d-OAc no

•

caae of

3f-hydroxy-5f,

(2b)

of

1<'

.5a,6p-triol(50) waa

)0.

lOp-meth.yl )

(41). a

)

Jl ... ·

·was as an

to

a.n

=

)

).91 an

=

7

).

-( no

5

(Wh/2 •

)

( t .

257 nm 21,)00) is

(9:1)

are

on

;3-:face

c

1

.5-

₁₃R.

it

use a :more

to reduce

(64a). was

(69; 78%).

•

wa.s

on

as ),

(~v

1

• s

h 2

chro:mophore

43.

-uv

( 6

221

nm

8,4oo)

'7

( _{. t:ne}

Je

_,s~

,oe-and

:3f3

,5« ,

o/3-triol was

but a.n

,JjO)

(7lc;

(?ld; 75%)

"""""""----

_{as 11 )}

the triol

'lt\'l<>t"l,Ph~i">"f" by

afforded

;p

.6£ ....

diacetoxy-5o(. .. hydroxy ... 9&""'oholestane ( ; 70%)

~ - , r

(7le)

as

as a

.0.?

•5 .•

6tX.•epo:x:ide ( ) on _.._.,~, ... ,..,.""'

-the

3j3.5f ,6o<. .... d-tr1ol {72)

7

:}3

.5!i-.6CX:-L:l -triol )

7

'f3•5d.6(3-!J,-triol .(¥(lb)

would

the

(?la)

(

)

(

_}.

(7:3a) the

)

= 6

).

"

)

(4).

(

(2)

Acetylation

(73

a}

deactivated

c6

(1), (2). (3)

{4).

(

)

(?)b) by

o ..

(?ld)

o:r

(Lv. ?O

(l) or

of

one

the

10, nm

(1.

..

)

on

..

a

1754

)

(

..

(

(e 197 nm

)

were

).. of

(

( Y

max 1741

c

( _{( E 200.7 nm}

40 ..

dio1 to

one

(

( 6 197 ·5 nm. fl,600)

of

(

~(11)

showed th~

{1700

{74;

(

occurs

)

more

)

..

5

-=

7

to

9p

iJ-double

; ) was

(

)

).

of

by

mixture

one

moves,

was

II"\

(

)

sec one

(

8

(

)

..

(

)

..

" (

(P ..

54 .. )

)

(

).

( 80a).

( )

..

9

" v!fere

on

tJ.(

) _{( )}

e ( b) ..

( 50),.

TLO both

occur 5 :no

an

no

..

( 85a) '\<ras

..

an ( )

to

!fhe

c proton nor the

ch

{J • ).9 Hz)

was a

\1as

(f:l96.5 :nm ,240) ..

an

with

to

as

the

at 5) .. 25

(

_{• 1714}

₎

..

will

on

on

•

as

(

_,270).

was a

(J a 4"'8

,

G

, mass

an ever

51.

in

) in

ettYI.zeJne-4,t?-n;zd.roxz Ll

1

J(l7)-~~:!!l;~~.:.::.ss~~( ) •

are

the can

a)

( 92)' b)

of d(ll)_

(74)

(92).

010-o.5

05_010 bond

ion

c

19-H occurs to the

in

can

one in

(i.e.

96)

of

(9J).

\'lith

A

(94)

can

the

to

N(lO

the c9_01o

the C=O

• 86a)

( ) is

) by (3-face

the during ot

..

on the

·the

or

a<

_•

bring

bond

'

,

)

of the

•

or

( ) (

• ) 7J(iih/2=5

"'"7"'"-"') • (J=ll,

5.22

5• _(Wh/2

=4.

)

;.

_•

)

)

5

)

;.

evidence assignments was based on a detailed comparison of the. data (!able III).

stable conformation for these spirans in whieh ring B is in the chair form.

The

The diacetate (?6b) from the H₂SOJ/Ac

20/AcOR reaction

of the 5<i-hydroxy-compound. C?Ja) must have the Jj3,6j3-etructu_re as no rin.g fragmentation can occur ..

accord with this structure.

The is in

A comparison the data for this

(?6b) to the ( 76d) from the lE!.lcohol

no in position or

cou.pling of the c3 ~R.. Little difference would be expected between the coupling of a

c

2- H and a

(p_

H "VIith the jaeent m.ethylene protons as both are similarly positioned "VIi th

to the methylene , but the can

only formed via a Jj3-0H, so this (76d) from alcohol-epoxide is to have a 3p-substituent.

However the Jp,6~-compound (?6b) the

c6-H

in an equatorial conformation (Wh/Z

=

5 Hz) the

(?6d) what to be an

c

6 • This in

(76e)

(

for

c

3j3.6p-At~l'i">A for the

-a:11

or 15j3-0Ac on

case

).

that

a:re were

li, _{• or} or

of v/v or

, or

on an

•

was

are

a

as smears

an

(,g, 1.11),

~

rnax

h

1.

(

o ..

1 .. 00

)

..

(

' 4.

) ; 1. 5

..

'

a

..

~·

o.

(

(1:1)

•

.

,.

_c

'

.6

) ; )

..

(

(

(2:))

)

,

[o(\)

+

) ; o ..

i ...

•

was

II • .,

)

.

; )

0

•

> .• VJna.'l: •

1;oo

(COlq)

S

).48 (c18 ) ; o.

; c3-rr); o.ss

(

) ;

(

).

an •

1704

. [Lit.

8 m •. p.

(COl!~)

b

4. 58

(ol8

); o.

142-14)0

~max

1?3), 1?0:3

0.6;

::.,l;H

lZ)-!n!l ( 1le; 10%) was

an

[cxJ

₀ +

50°.]

(

(Wh/z•b

); 1

c

1

_{4-cH3), 1.oo}

o.aa

• 'Y

max

(56;

100

o..

)

~max

1716

; H, 11 ..

..

;

c'~H);

o.85 (c19-tl

3);

(

)

..

and

em'""1 •

[Lit~

2

7

m.p. 146-l!t8°

"

'

•

0.79

(CDCl;)

6

4,.JJ

); 0.73

ppm (

(Wh/Z a 12

); and

of ~:!11JIES:U:.:~:.!.2~~t::.2~~!.§D!.\ 62;

"'"""~~.~, .... ( .50m.l) was (1,.25g)

U<::U~V.Z.. ( )

was

(49b;

(.£

o. ) •

~

[O(JD

+

59J

(KBr)

(CD<n

3)

5

4.51,

(

), o.

was not

(

, was

0

( }

), o ..

a

(5

•

J4JO.- J076, 1640 910

(

( )

,

5

~~~~~~~~~~ ( ( " )

( )

was

•

<s

..

m • )

₅

_{J ..}

( 6

'i

o ..

o.

l

..

( (

~~( ;

[~] (c 1,0)

'

(d.] -

6o]

(

..

(

)

) " m.

..

[Lit..

m.

(

03)" .

1)

"

61.

(

(34 ..

wa.s onto

with

~~~~~~~~~~~~~ 2d; 15. as

(

(nuj

{Found: 09

iiJl

m.p.

1179 • {

c

₃₄

n

53

so

4

cn

140.

"

$

c,

99.

1170

..

• 7.74, 7.

); 2.

(

.. 08; H.

0.5°, [oL]D + .. 9° (Q

o.

),

..

(

)

..

{

); o.

,

_)JH!.<9..X { 8 • "

s.

5 ..

"

)

.

( ) ;

{

..

( )

_b

_7.91,

_1·11.

_?.4:;,

_7.

( H);

s.oz

(\V'h/2=8

); 4.27

( );

2 (

₉₆

(ol8

) ;

o.

(

₎

..

m. ₎

_'

~max

'

1370.

"

c.

II,

• ?;

s.o •

• " • f

..

_c,

_H,

_{9.00; 5.1;0").}

'

"

(

) s

_7.91,

_7.77t

_{?.4), 7.}

( H)J

5

( {l )

'

2.46

( ( );

o.

{ ) ;

0.91,

o.

( • '\'Jas

( ; 1.52-153°)

(31) to ( _•

( ) in ( )

maj

of was

(

_•

\'!18.8 (?50g)

•

( )

s

2. (

o.

o ..

(

(

'

vm.ax { )

H, 11.

} £

4 ..

1 ..

(

'"

;

5.80

5.??,

5 (

- (d)D

+

·cci.JD

+

' 6

•

(;

~

c,

{

( _);

_J.Ol,

) ;

o.

);

(4:1)

( )

'

L.07)~~

..

)

.

():2)

),

( ~

o.

" •

..

I'

84.

)

,.

4 ..

'

);

o ..

( ) ;

oro~me1;11al:le), m.. ,

[C(]D

+1.

)2 ;

u,

..

1-t ,l.. l:

c '

[Lit. 165-167°] ·

v.wv • ..__)

b

h

(

₍

₎ ;

..

{ )

o. ) ..

0.5 "

'

room

(

)

~~~~~:!:::E::.2!!.£ ( ) ;

5); [.

Y

max

0 (

) ; o.

o.

5

, E

₃₁₄ nm 7620]

(C4-H);

); 1 .. 02

:Elution

(5?a; 60mg) as a (

£

264 run 4,380,

Y

max 1666

by _{) , [ 234 nm H,lOO}

(

) s

,

6. , 6. f 6.?6 (

6. 07_"'" ~. ~. _{v . ,} 6 _• o~ _,./J 6 01 _"'

) f (

1. ( (

o.

(side chain ).

(2ml) was

{2 ),

'"i

th (1:1) non

(6

..

6(3-hydroxy-Jo(,lOd:-oxido-¥

~~..;:;;;._;;:;;...;_-=--.:~=:;;;..:::.;:;;;.;;;;;;;.;::;; (48b' 5 as (

), m.p. 168-169°, vmax (KlJr) 3460, 917 _•

: c,

..

4;

(ODOlJ)

s

4.)4 _(Wh/2=12 ); ;.89, ).

).62 (C6 ) ; 1.075 (cl9_u3); 0.66 ( ) ;

0.92 0.82 ( sic1e CH

3)"

elution

,,,1

th

);

) ;

with

~~ (9c; as

{c 1.05),

v:max

)466, 1713

[c<1:a

+

z.6j

(

) 5

4 .. 1) (

( ; 72mg) as

(

_0.5),

(;

195 nm

_'

), m.

[Lit.

(Wh/2=6 ;

0.92

'

t:

200 _nm

, ,

); O .. ?J

(

f/ 205 nm

12

7400.

( ..

o,

_.60;

_H"

210 nm • •

{

(W11; 2

=14

(c5-cH

3); o.

).

WB.S

• •

(\th/2=20 ); 1.01

o.

(c1Lt-_mr

3), 0.905

•

( (

) _•

(

;

);

:; ..

(c21-H

3

);

0.905

0.795

{

res

)

..

•

)

..

an

..

"

( J)

,.;t....:~~~!:.Z:~~~~C.Z.~'J.:.}.~ ( ;

(

~ 205 nm 81

5°, [,

207 (

[

(

-dj(l?)

an

(

;

C, 80 .. 48; H11 11.

[o<. ]1}

+

100°

J

..

) b

J.

•

'

m.In .. p .. 102-10)0

l. 09),

J)

max ( )

7530, (; ₂₁₀ nra 6200,

f

..

{C

)

.

( ~1)

)

(

"

'

).575

,

in

) ;

J<X t

), m ..

, l

CX:JD + 44.,

..

"

(£ 1. ) _{[Llt .. t}

_(o<.JD

₊

( (C

{

)

( 0 .. 005rn1)

by

..

( 25ml) WlM3

room

\\fith T\ll>T'"'I'I

~:o.;;;;.;::;~;;;;,;;;.;;;. ( ; 2 .. as

(.Q, 1 .. 175), (Found.: C, 78 .. 2; , 11.00 ..

( )

s

_{5 (lrlh/2=8}

(06 _{) ; 1 .. 00 (cl9_HJ);}

_0.66

0 .. 825 (side methyl) ..

) ;

)

..

(

].

0.81 (

) waa

( ;2 ..

5g)

(2 ..

5ml)

(2 ..

) ;

on

) ' m.

(KBr) 1740, 1245

: c,

; H,

}; 0.92

(

..

..

(

with ) for 1 min.

~~~~~~~~~~~~~~~ ( ; as

~~~

... " m.. 181-182° • [<X] D

+

6.1°

\£

1,.015), Ymax ( 3414. 1734 cm-1• : G, 75.15; H, 10. ..

•

c,

'75.4;

#

( )

s

( ,. ) ;

'

{ ) ; ( 1..

);

0.,69 (e18 -HJ);

o ..

0.82 ( chain

)

..

116-diol (.59 ;

( 60"

'

as ( ) t 160-1

(£,

o.

)

..

[Lit.

39

m.p. 165-166°, [oe]D +

J ..

7o]

(CDC1₃)82. 5 { ); 1.04 ( ) ;

o.

( ) ; 0

A ( )

(

(

(

..

( ( " !I

c

).

_J• f

s ..

)

,

1 ..

f.

o.

(

),

o .. (

)

( 1., )

.

)}

m~:t:x:

) _"

) 5

s .. s?,

s ..

5 .. 2) ( 6 ) t

"'

,

_'

f

1

(200ml)

colour

the

(c

1

9a

3

), o.s6

).

m. 118 .... 119°, [ci] D +

'

(

., "

c,

c,

)

..

s.

( ); 1.08

o ..

(

( ) 'I'

o. , o.

was added

•

(1:1)

( 66a; 2. ) as

"

.65;

(

(

( 1 .. 128),

v

,

..

'

)

.

)

.

) ; j .

(

(

had

)

,

) 3306,

(2 ..

a u ... ~~'"" to 9j3 .... oholest-7-e:n-:y3-ol ( ( )

20°

( _{means of}

..

( : C, 84,. ; H~ 11 ; H11 11 ..

"

'

), 1 .. )1

(

)

..

onto 2

"'

4 .. 5hr·.

on

of'

(

); o.

t

o.

(l.OOml)

l~hr).

(

) (5 lOOml)

1 hr·.

( )

(lOOml), was

(3lml;

..

the

( ) was

(lOOg).,

with

{

(

)

.

(50g) was

( U'V'LIJ<L.L.

over

..

c

onto d

to

74.

( • as ( )

,.

'

(

o.

),

_•

f

;oo.

• 10 • ;

'

•

•

o •

_•

) s

_5·

( )

( (

),

( )

.

o.

),

o.

).

( t1)

1 ( )

(

) )

..

re8,

),

)

.

)t }

< 20°

(

_l)

( )

to

{

(

o.

( )

,

_{f 84~}

~ ,400 (Found:

c 77.

,

..

.oo.

I

C, 77.46; H, 11.07%).

(CC14)

b

5.42

(

( ~v'

11

;

2

=Z:J ; c3 ... H). 2. 91

1720

c.

80.

(

(

1.

m.eans

•

(

(

).

wa.s

(4:1)

• )

,

'·

,

;

).

:).

)

o.

(

( in ) \vas

)

,

Hz; C

LiAlH

₄

-product

was (0.2ml)

(2ml)

20° for

J6

(

.

_as 0

f m.p •

lJO-lJl ,

'

[o<JD ...

llo

(f.

o.

585)

ll

~nax

{ )

-

1726

,

( : 0

,

7B. • H, 10.

_c29a48oJ

•

o.

'

• •

H~ 10. )

..

(GDClJ)

b

5 .. 09

( _" c7 -H); Lh

'

(\1/h/2=25

•

cJ-H);

_{2 ..} ) ;

1.0?5

'

0.705

) ; 0.92,

o.

).

1.

(69;

lg)

(lOOml)

'"as

c acid ( ;

lOOml)

at 20° for

JO

reaction '!f!aS quenched. with

product was

(

•

..

(70;

740mg)~

m.p.

9~-cholest-6,(8,14)-dien-Jp,Sd-diol

m.m.p. 123-124.5° ..

2.. The ( 69; 100111g) ) 1'/aS

with perohlorio acid ( ; J

cn

₂

c1

₂ was

(70).

"

'

) ;

(lOOrttg) ) was 'Vii th

reflux lhr no reaction.

no was obtained under the following

4.

{lOOmg) in

{ 10m1) lhr.

5.. Epoxide (lOOm~:s) i:n

(10%; lOml) tor lhr.

(lOOmg) dimethyl sulphoxide (2 )

for lhr ..

(lOOmg) in {lOml) acid

(.024ml) 20°

; 5.12g) i:n

onto active _•

Elution ( )

.

(19:1)

(?0;

..

(4:1)

Elution

Jl~t5ea6!3-fl-triol

(7lb)

r '

~

1

5ot,6d-L:l-triol

( ) in

ratio ?:2 (by ).

pure ~&,5o:,64 .... ~7 ... triol (

(acetone),m.p .. 164.5 - 165. , [o(lD

...

H, 11

was

on

(

_•

(1:1)

as ( ) f

) _{:3472, 'I}

,

t f;

'

" 'I .. 29;

_'

10.29 ..

• ; 10 • _•

"

..

'

'

)

s

_5- (

.

,.

) ; 4 .. 23

(

..

,.

) ; 0

,,

( f'

,

)

..

of

(

)

in (

(

)

..

blo

( 0.465),

( (

); 4 ..

); 2.1,,

2.00

);

); 5- ppm

); 2

... v:u .... \1- ) ;

(

₎

..

.!1,!."-'""J'""" ( 1; 1)

~~~~~~~~~~~r~,~-~~~<

)

Y

max (

(

was

i

"'"'"''>""''t'<a);

[qi}D

i' 91.

a ( I C7

?4.

H, ,.00,.

•

,

..

(

_•

); 2 .. t

..

(

);

2 ..

);

) was

(7.

)

..

(1.,

9B-cbolest-7-ene _I (7lc)

ratio 1:).,

compounci

~~~~~~~~--~~~~~~~~~~~~)

as a (CS₂)

3428, 1738,

1236 cm-1 , ( 11'~"'~11'""~"~;

c,

73.57; H, 10 .. )4..

c

31H52

o

₅

(Wh/z=24

(CD01

3)

b

5 .. 07

o

6 ); 2.

(\th/2=6

(c

1 9H

3);

o ..

(C

, 1 .. 99 ( ); 0 .. 92,

o.

" ) \'las

'

(73a;

l. Ac

2

o

(2ml) 0014 (

left 20° for

3

The reaction

the

The product (1 .. 792g) was

alumina (lOOg) ..

Elution petroleu.m

of

Elution with solvent

to petroleum-benzene (1:1)

; c3-H); 4 .. 82

); 1 .. 17

(

) the

( _" 1 .. as a (

),

[~XJD

₊

'

(5! 1.17)' { ) f

'

1206

•

(

c,

_" 11. •

_{c •}

_.49;

'

..

..

( (J '

_·5

_" 1 ) ; _5-09

0 ); 2 ( _1.21

" 0.665 ); 0.91,

o.

(

).

'

) was

an

results are

i)

103 [steroid] 103

[ll

so

J

2 14.

No. 1-1 1 ...

l.

_5-7

0.25

2. _5-6 0 ..

25

J.

6.0 0.25

ii)

•

l. 5.67 0.25

2. 5.61 0 .. 25

3. 5.)9 0.25

4.

_5.55

0.25

Compound

9~10f3 3f3.6j3- 14d)

9d.l0f J}acetoxy-6j3-methoxy(14c)

9f10f

3f ,6f-

d.iacetoxy( 7Ja)

14c)

[Ac2

o]

mole

!}

1

1-1

sec ·

0.5

3 .. 64

1

o.s

:;.45

3.5

0.5

J ..

56

[Ac₂

o]

mole 1 -1 mole _{1_1} -1

sec

0 .. 5

0 ..

5

o.s

0.5

1.67

1.88

{

was

(

"

'

as a

(c

-

o .. 42)

. 3410, :)100, 16)7.

e

210 mn (

),

(

"

c.

~

80.54;

,

11

5 ..

(

_{.. 5}

) ; _:3~

_<w:n;z•5.5

•

'

(656mg)

on

D t . (:-199 5 :nm 6600

69; H,. 11.. ..

); 4

..

_);

'·

) I>'

)

)

.::::.ru~£!!.'J~::§!!:)~~~!1,2d;;, { ; , E:lS ""';"'"~"'""'"

+ 31° (<1 0 .• 3-9),

Y

max 3366, 0

m ..

p. 165·166 ,

1631 ,

e

0

nm 8560,

.6

nm 10950,

e

200 nm 10700, (: 205 nm 9:310,

0 210 nm 7420 •

e

220 run :359°' ( ) ..

..

19)-(

{

'

+

60°)

s

4.51

(\llh/2=11.5

,

" ) ;

).56

(J •11.5 " J

=1.5

• ); 1 ..

75

( );

'

'

1 .. (

..

);

_0.76

( clBH;); 0 .. 91,

o ..

'

( ).

elution (19:1)

mixtures ( 60mg) which \Frere not

) pyridine {lml) was 24 hr ..

ster'C>idal ether

Jfi=.cholest-:-J.0(19) ... en-6,&-ol ( ?6c; 42

) , [oe]

+ ( Q

0.85),

V

rnax )4'70,

6

(

-1 em ,

19? nm

7060,

~ 198 nm '7020, [ 200 nm 6,?00

f-

210 nm 2190 w..L'-1.u.c:A<:J.t!c:) 11 (E1ound: 011 78.,26; , 10.91,. C29H480J

• ; H, 10,. _•

( _{,5 ..} 1) ppm (~ih/z=4.5 ;

); ).,50

ppm

(Wh/z=6.5

;

o.6?

(c

18

:a:

3);

o.9o, o •. a1

) 5.01 1 .. 97

1(10 _...

(side chain CH 3) .. (19)-ene(?6b)

monoacetate (?6c; ) in pyridine ( ) wa.s

" The crude product (3

(?6f;

vma:x

f

{39~·1)

1{10- 5rJ.

as D +

174J, 1702 , E .. _{7 nm} _. 6

nm 49?5, ~ ₂₀₇ nm 4650,

r;

₂₁₀ nm 40JOt 6 ( cJ.<:)nexatle), ( : C, 81.. ; H~ 10 .. 65 ..

I O, 81.)5; H, 10.

..

nm.

run 1480

(

) b

5-14 ) ; 0.72

0.91, 0 .. 82 ( _{) "}

(

_-6o

0• l'lfas

• \'i'f:LS

the

(50mg) in AcOH ( ) for 90 min. ether was a

..

);

:room

1( 10 ___,_50(

seven

product indicated no

ste:roid-diol

(77a;

57mg)

(Oblml) at 100° for 2

ether

{lml)

Jlhial ol.u:t.a.~::::cu at of the

(lml) "'as

as

) 17:38, 1228

t:

₁₉₇.6 nm 12820, 12- ₂₀₀ nm 12520,

e-

₂₀₅ nm 9050, E ₂₀₇ nm 7120,

G ₂₁₀ nm 4450, [ _{220 nm} 1420 (cyclohexane).. ( :

c,

76.,Lt-7; H., 10.. •

c

31H50

o

4 C., 76 .. 50; H, 10 ) ..

(J

1 .. 69

followed

(

) S

5.16 (vlh/Z ~· 18 Hz;

, J =J

( cl9HJ);

; ); 2 .. 04, 2 .. 01 ( o,.76

(c

18H

3); 0.,905,

o •.

Bl ppm

)

of the dio1

(7?a;

98mg) with chromic filtration of crude product

deactivated

[cLJ

D

-

17° (Q

0.5).

~max

6 E

•

:run

•

nm

H• 10.

..

{ )

₅

1 .. 70

o ..

(

₎

..

1(10-->.

5

diol (??a;

l05mg)

'VIi th a

(150mg) in

<~-

....

-~:::>

of' ozone

)

..

( ) _{1?5lr• 1712}

'

e-

206.7

•

e

307

nm

• • ,.

c •

c.,

; H, 10 .. )<41

( ); ₇₆ ( );

_{o ..}

)

in (lOml) V'las

2hr ... 6o0 .. \vas

(3:1)

1(10--::!t!~:.E~~~~~~~~~:!!l.2!!.!! (?8; 34rng) as a

(g_ 1 .. 145),

)/max

17301 1700

(pure by

>.

( C, 74 ..

46;

H 10 .. 70.

c

₂₇H₄₆

o

4 ;

c,

7l~<.61;

H., 10. ) ..

(CDC1J)

b

4 ..

47

_(vlh/2=17 ; c6 );

4.

(Wh/z=9·5 ; c:-5-H); 3 .. 07 ; by D_{20); 2.,)0}

.. 24;

'

,10

( ); 0.74 ( ); 0 .. 91, 0 .. 82 (side CH

3}.

a solution of the

(74; lg) in

(17ml)

( ;

~

max

6750, 12

l

run

5360, ~

(

an (

nm

nm 970~

f?

( -.. ... "' ...

""'"'""~

) , [ 1•1'*'

0.67

1242

f:

3286:35]

) s

5

); t

5

I!

5·

t

.. 04, 2.01 (2 X UH:,-C-0-h II l •

(

)

;

);

_{" o.}

₍

, [a]D

+ ( <!

o • ) •

, e

200 ..

7

nm '

e

205 nm 4860; f: nm 21.50,.

e

(

'"'J·"'"'' .... """' CHJ).

(9:1)

an

) 1740,

' 6

207 nm

nm 560, (

: c,

75.25; H, "

'

;.

l(

(

[o(]

€

(

(

+

.. 5

nm

210 run

..

_f

..,5

..

'

..

If

);

0" (

(~ 1 ..

'

~

200 mn ll

e

~ 215 nnt 1070?

e

..

);

2 .. ( _"

'

h

o.

J

o ..

(

) ;

:))

(

was

(

{ :1)

~~~~~~~( (£

1.09)-II _nm

'

t2

nm

..

E

241 nm nm 173, f::

~ run 75, J98

79b)

10%

10(9 ~ 5r:t.

, ( 2

( )

( _{" 11} J., ) 267,

I

..

31846~

(

(

as an

)

'

nm 7860,

e

220 nm

o,

•

)

_b

.,5

( •

,

J

0.605

( was

(9 1)

(

)

..

'

• o.

dey ( ) ltas

1

onto

the ~~~(24

). m.p.

145-146°,

-1

e

em ' 199 nm

[c<~

+

'G

)

.

nm 7JOO' <2 210 nrn

•

5.4:-;

"'

,

0

,

•

(

h

_{o. , o.Sl}

(

_).

•

Ao<LJt"J'.llH:> ( 3: l)

[o<]

D ... ( Q. 0 .. 4 5 ) 11 .

)J

max (

f _f

219 nm ' 278 mn

f_ :nm ~"i+: ..

..

(

) s

_5. (

1 .. ( ); 0.67 (

( )

.

; l05mg)

(

..

)

~§-ol(SOd)

diol (

10% (lOg).

) _1726,

"'

_'

o ..

(

1707

,

, o ..

7510, f: _nm

'

~

215 nm

)

..

.)18464] ..

G

t

( to

with

as a (

(J:J

•7

• ll

2 .. 02 ( (-OJl,.

.8 ( ) ;

o ..

(

l(

dial (SOb; 47mg) was

1(10--SeX)

(SOc; 27mg) as a

~

max

1746, 1711

• 318464].

.

(

) s

5-52 {

),

.)18089 •

1734, 1242

);

s ..

.s

• 06 );

'

D?O); 1.0'{ ""'

II

o ..

•

!!!!!.JWI.~~~~~~l:£~b!.!.l:J~U. ( ;

)

~t )Jm~uc

e

2oo • f

nm 7ltO, f 220 nut

: c,

"

'

(

(

); o.

).

in

339199].

) 5

5

( )

..

room

20

as (

1727.

;

f

2,51 nm

..

318464

J

(

) s

6.48 (

.5

) 1 ..

96 ..

t ... -BuOH) was

(

" _~ ( ) \11:.1,8

..

'\liaS

(

"' 1)

(

..

₎

_'

as

)

( a,

( (

) 2

(

..

•

c,

'

..

( )

₅

_{5 ..} (

_.?

(. Q l . ) _{- '} '\l _{),\nax ·} (

).

..

)

,

...

t J

)

•

.. 2

( )

.

..

• t

-,

5 .. ( ( ) ; ); 4.70 ( Hz,

J

_·5

); 2 .. 03, _1" );

o.

(c18_H3); 0.91, 0.81 (

}

..

), (£ 1.01), vmax 17lt4, 1?39. 1235 t

E 195 nm 8860, E: 200 nm 7940, (: 205 run 6)00, f- 207 nm 514,00, E l1lll 3970, f nm ll~BO, f run , ( :

c,

•

'

H, 10 ..

..

H,

..

) "

( ); _{5 .. 05}

( L$,,. 72 • ); 2 .. 2.00

'

,

(2 ); 1 .. ( _" 9 );

o ..

( ) ;

o ..

(

)

..

( , 1740, 1240 ) :

384 .. 337626 ( ) or _{" "} )8lt. 3391991·

(CD01

3)

D

5.30 (Wh/2=7 •

_'

) ; 5.08

(~lh/2=13

.

,

).55 ( ~ ) ; 2.01

'

( _1.01 ( 0.62 ( ) ;

0.91" (

)

.

on of the the

of the product on

( 4'0g) the (7 $ 4Jmg), 9(11)-olefin

( ; 2

9(11)

)

(c 1..4))

'F

f 200 :nm 5240~ f 205 mn 41)0, ( _run

(

(

nm 650, f mn 400, (-n₂o): ..

o:r l J81t-., ).

( _.6 • =:: );

'

( ) ; )

..

(J=ll

,

J

_=5.5

,

o ..

(

) _(lml)

( \<tas a

for seven

..

no

..

1(10 ----...5(){

( (2

90min ..

(

..

mn 2

4 ..

• e6 ) ;

'

) "

room

(80f)

(

~~~~~~~~~~~(

( _{(~ 1 ..}

_145),

(

h) ..

_·5

o..

(

(

_).

) (80f).

"'

'

) or

6

.,

_c

'

•

o ..

(lml) )

..

) ; )

4 ..

1 .. 06

)

..

101 •

. l"!i th

..

{40g).

$

'

vmax

,

' 0

205 nm '

f

nm ' (:: 0 m1 JL~40 '

[tvi•( : .)39199].

)

s

_{) .. 57}

(J=l2 ..

,,

J

.4

0

'

); o .. 79

(

,

o ..

)

..

an (ca.

_-·

>

an ) :,

(19:1} l:'tn

102 •

• (1:1)

( _were

nzene .. (

..

on (

:-( )

1

, as·

(

(

_{}; o ..}

₎

_"

"

:

402. _•

) s

s ..

"'

_'

( ( _"

'

(

{

902

( )

); '70

..

)

) ;

( ₅ •

_•

_{'" J}

( ) ;

;

.. ;

);

u.

1. J

•

_'

).

.

..

..

..

..

,

..

,

•

..

,

c

..

J *' ..

19

13.

J,

14 ..

•

..

2). J _•

" l'L.P,.

25 ..

J

..

..

•

f

•

!i

3307 ..

(

!i •

•

,

f ;

2574;

2077.

to be shed ..

"

..

"

26 ..

" R ..

_'

•

2{. 0

_•

..

•

·-29·

J., _""

'

'

,

:3195-;}0.:

"

)1.

'

•

)2 ..

'

'

2 •

JJ.

'

,

•

-:J

)Li<. L

..

m J.:• Goto,

'

8

) t' _;)f.

t

195:3.

f 4'7 ..

)6 ..

,

..

J7 ..

o .. vL.

'

..Ji ..

,

If

..

,

1.9

_..

o ..

•

1 •

"'

•

,

19.55-.

• ;

..

•

"

"

I:t,. 0

•

.u.

Ill tJ

•

• J $

•

•

•

J,.

•

..

'

T •

,

t 51). 49 ..

..

so ..

_•

J

76,

..

51.

_•

..

•

53.

J

..

1969;

A cO

~---_fast

A cO A cO

.. products 4 fast

+

R _R

1

a. R =

j3

-HI cl-H

₂

_{a. R}

₌

_{<i-H, P-H}

b. _{R ""' d.} -OAc ,

f3 ...

H _{b. R}

_{"" j3}

_{-OH , c( -H}

c. R =

j3

-OAc , d.. -H _{c. R = cJ... -OH, (3 -H}

d. R "' c( -OH, j3-H d. R =

j3

-OTs, oL -H

e. _R = d_ -OAc,

j3

-H

0

3 a. R • G(-H.

j3

-H _{4 5}

b. R = d.. -OAc, j3 -H c. R ₌ d.. -OH,

f3

-H

R CH3 i

6H R

6 a. R

=

<£-OH, j3 -H 7 _{8 a. R =CHO.-ol}

b. R = d... -'0Ac,

f'

-H _{b. R}

_=f

_-CHO

R

9

a.

b. c.

12

··'

ACO'''

'

R

.. j3

-H, ol.-H. R = jJ -OH,

ci

-H. R = ct-OHt

jJ

-H.

R

11 a. R = c{ -H, f3 -H

b. R ,. p(. -H, j3-H

c. R ... d.. -OAc j3 ,...,. H • .

'

'

d. R "'(3 -OH, cJ.. -H ;

'

e. R =- d. -OH

' P~H;

f. _{R"' d..} ~OH, _(3-H~

F

A cO

a. R = d - OAc , (3 -H .

b. R =- f3, -OAc, <.{-H.

c. R :: rh.-OH, (3-H.

CH3i OH 10

R' = d.. -OH, j3-H.

R' =

p

-OH, d-_.!H.

R' _"' d... .,...OH,. j3-H.

R' _{= (3} -OH, o( -H . R'"' c{ -OH,

(3

-H.

R' ..

_j3

-OH, d.-H. CaH17

R

1

Energy

hydride.., shift.

CH=O

~ki~n~e~t~ic~~c~on~t~r~o~l ____

_..r ____

~----~

1 thermodynamic

1 control I

I

:~

I

products·

I

R'

_____... \:Jz.

· COR"

R1 _{,'axial' ....,}

A cO

14 a. R "j3 -F, o(-H

b. R " j3 -c I , d - H

c. R .. j3 _{-ocH 3 ,} d -H

0 _O§F'3

l

Hb

Me

~t.-Bu

"-./" Ha

Ha

lkHb

jkHo

aldehyde .aldehyde

15.

17.

_18.

20.

22.

21.

23.

16.

OH OAc

24.

H

2 8. 30.

32.

36. 38.

H

33. 35.

40.

CH~

RO

H

42.

44.

47.

41.

OBF3

4 5.

HO

48. a. R =d.-OH,j3-H.

SO.

53.

b. R = j3-oH, d-H.

c. R .. =0

OH

HO

~·

••

..

51.

OH ~ Cl

54.

R

49. a.

R

=

oZ-OH, j3-H.

b. R = d... - H,

f

-H,

Cs

c,

52. '

R

55. a. R ~

j3

-OH,o(-H.

••

•••

HO'

56.

59.

TsO

R

62.

57.

a. R .. H .

b. R oQH

60.

58.

51. lSI. R "' cl-QHtf-H;R'=.f-0H,

b. R

=

R' • =0 ( cl-H

HO

R

64.

a. R .., Ca H17

b. R = _{C9 H17}

66. ·a. R •j3-0H, c<.-H

b.

R -.

(3 -

OAc, a{ - H

·o

68.

a. R _{= H}

b. R ... OH;

c. R == OH ; HO

HO

R' R'

R'

65, a. R =CaH

17

b. R

=

C9H17

6.7.

" ;3-H, d. -H ,13-H, oC -H

HO

HO

oj

69.

R

· HO

70.

71.

a . R ""

(3

-OH • d. - H ~ R' .,. d.-OH , (3 - H. b . R ,. (3 - 0 H , v<. - H ; R' = (3 -0 H , d.. - H .

C R .. /3 - OA c . A - H • R' :: cA -OA c ' ~ - H .

• , . ' V\. ' r

d . R .. (3 -oAc, rJ.. - H ; R' "' (l -OAc, d.. - H:

e. R •

f -

OAc , d.. - H ; R' =

f -

H , d.. - H .

A cO

12.

73.

a. R =(3-0Ac, c{-H

b. R : rl.. - OAc , {J - H ;

R "~-H.

H _OAc

5cl.,6f3.

I

~

A cO

FIG. 10

-A cO

H

R R

. 76.

a. R = j3-0H, oC.- H; R' "(3 -OH• <{-H 77.a. R•f-01-1, ~-H; R'=j3-0H, d.-H

b. R :

f3-

OAc, J. - H ; R' • j3 -OAc, ~ - H b. R •

f

-OAc_, <( -1:1 ; R' =

f -

0Ac , d.. -H

c. R •(3-0Ac, c;<.-H; R" = j3 -OH, d.-H c. R •f -OH, ~_.H; R•: ol -OH , f3 -H

d. R = jl-OAc, oL-H; R' " d.. -OAc.,

f'

-H d. R •

fJ

-OAc, li-H; R'= d. -0H ,

f

-H

e. R =

f

~oH , o<..-H ; · R' "' d. -OH,

f'

-H e. R

:p

-0Ac, d.-H; R'" d. -OAc, j3 -H

f. R • R"• =0 f. R • R'" "'='0

OH _78.

A cO

:

_ _ .., AcO

H

. 75.

77b ... __

6

I

so

₂oAc

A cO

H

FJ G. 11

If

H / .H C H

-6so

₂0Ac 2

75a

H _OAc

H

c,

H

/

5oC.) 60£ .

_\

_I

5«,6p.

_~

l:lt.p A cO

H'l1

c5

Ht..c

Ht.«

(1)

H7~

(3)

(4)

FIG. 10

-A cO

R R

76.

o. R "j3-0H, a(-H; R'" (3 -OH, c{-H

b. R •

f3 -

OAc, c>\ - H ; R' = j3 -OAc, ~ - H

~. R = (l-OAc, o<.- H; Rq • j3 -OH, li -H .

d .. R =

f

-OAc., ol-H; R' " d., -OAc,

f

-H

7 7. a. R •

f

-QH , ~--:-H ; Rf"'

f3

-OH , ci -H

b. R •

f

-OAc., <{ -t-J ; R' "f3 -OAc, d -H

c. R•f-OH,<£.:H; R'=«-OH ,(J-H

d. R •

f3

-OAc, <k-H; R'= cl-QH ,

f

-H

e. R =

f

-OH , o<..-H 9 · R' "' d.. -OH,

f

-H e. R =f-3 -OAc., d..-H; R'• <i -OAc,

f

-H

f. R = R1• =0 f. R=R'" -=0

OH _78.

A cO _{--.a...'"' AcO}

l:

H / H C H

-0S020Ac 2

75a H

/

. 75.

R

R

R

79 a. R : (3 -OAc, rt - H

b. R :: j3 -OH , d - H

c. R = =0

CH3

R

. 81 a. R = ,f3 - OAc , o(-H

b. R = j3 -OH, o<.-H

c. R=

=

0

82

a; R ,. ,f3 -OH, c.(-H

b. R "f -OAc, oc-H

A cO _84.

R

80. a. R : {J -OAc. o(..,H;

b. R = j3 -oH , ()..- H ;

c. R • R• • =0

d. R:: j3-0Ac, c{-H;

e. R •

f

-OAc, c{-H ; f. R =

f3

-OH ., ct-H ;

g . R :

j3 -

OAc 'I ti -H ;

R ~ A -OAc ci -H

r --'

R • j3 -oH ., 11..-H

R = j3 -OH , d.- H

R= d.-OAc,

f3

-H

R = d. -OH ,

f3 -

H

R = ti..:. OH ,

f -

H

83.

85. a R >£ (3 -OAc, (:( -H