Original citation:
Kothandaraman, Prasath, Zhao, Yichao, Lee, Bo Ra, Le Ng, Clarrisa Jia, Lee, Jun Yi, Ayers, Benjamin James and Chan, Philip Wai Hong. (2016) Gold-Catalyzed Aminoalkenylation of β-Amino-1, n -Diynols to Cycloalkyl-, Piperidinyl- and Pyranyl-Fused Pyrroles. Advanced Synthesis & Catalysis, 358 (9). pp. 1385-1391.
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COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Gold-Catalyzed Aminoalkenylation of β-Amino-1,n-Diynols to
Cycloalkyl-, Piperidinyl- and Pyranyl-Fused Pyrroles
Prasath Kothandaraman,
[c]Yichao Zhao,
[a]Bo Ra Lee,
[a]Clarrisa Jia Le Ng,
[c]Jun Yi
Lee,
[c]Benjamin James Ayers
[c]and Philip Wai Hong Chan
[a,b]*
[a] School of Chemistry, Monash University, Clayton, Victoria 3800, Australia
[b] Department of Chemistry, University of Warwick, Coventry, CV4 7AL, United Kingdom
[c] Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang
Technological University, Singapore 637371, Singapore
Fax: (+61)-3-9905-4597; e-mail: [email protected] or [email protected]
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please delete if not appropriate))
Abstract. A synthetic method to prepare cycloalkyl-, piperidinyl- and pyranyl-fused pyrroles efficiently by gold(I)-catalyzed dehydrative aminoalkenylation of -amino-1,n-diynols under mild conditions at room temperature is described.
Keywords: 1,2-amino alcohols; gold; homogeneous catalysis; nitrogen heterocycles; synthetic methods
Functionalized pyrroles are present as a structural motif in many bioactive natural products and pharmaceutically interesting compounds.[1,2]
They also feature in many optoelectronic functional materials and are versatile building blocks in organic synthesis and drug discovery programs. For this reason, the development of facile catalytic methods for pyrrole synthesis with selective control of substitution patterns by using readily accessible substrates continues to be actively pursued.
Gold-catalyzed alkyne cycloisomerizations have come to represent one of the most efficient synthetic methods for rapidly increasing molecular complexity and diversity.[3–6] In the last decade, the field has
expanded exponentially, with a myriad of elegant approaches to synthetically valuable compounds being established. Included in this has been the recent emergence of a small handful of examples describing the assembly of 1- and 2-naphthyl ketones, phenanthrenes and 8H-indeno[1,2-c]furans from the corresponding 1,n-diynols (Scheme 1, eq 1).[6,7] We envisioned that if 1,n-diynols bearing an appropriately placed β-amino group were explored, such as the type 1 shown in Scheme 1, eq 2, a
Scheme 1. Gold-Catalyzed Reactivities of 1,n-Diynols.
reaction sequence initiated by CN rather than CC bond formation might instead prevail to give the putative (4,5-dihydro-1H-pyrrol-3-yl)gold species
I.[4,8–10] Subsequent dehydrative aromatization
followed by trapping of the ensuing cycloadduct by the remaining alkyne moiety may then be anticipated to deliver pyrrole-containing bicyclic molecules 2–8
in a straightforward manner.[11–14] Achieved under
mild conditions at room temperature, we report herein the realization of this unprecedented aminoalkenylation chemistry in gold catalysis that provides a facile and chemoselective approach to cycloalkyl-, piperidinyl- and pyranyl-fused pyrroles in good to excellent yields and as single regioisomers.
[Au]+
R'' O O R''
R'
O R R'
O R'''
R''
O R'''
(R' = H)
(R'' = H) with
-[Au]+
previous works:
[Au]+ this work:
X
OH NHTs
R1
N Ts
X R1
N Ts
Me R1
( )n
N Ts R1
N Ts R1
( )n
X = NTs, O
n = 1
X = CH2 n = 0-2 [Au]+
-[Au]+
(1)
(2)
1 I
2, X = NTs
3, X = O
4, n = 0 5, n = 1
6, n = 2
7, n = 1
8, n = 2 Ref 6
( )n OH R
R'
R or R' = R'' ( )n
OH R
R'
H/SnnBu3
( )n
N R1OH[Au]
Ts H R2
R2
R2
R2 R2
Our present study began by examining the gold-catalyzed cycloisomerizations of -amino-1,6-diynol
1a in orderto establish the reaction conditions (Table 1).[15] This initially revealed that treating the substrate
with 5 mol % of gold(I) phosphine catalyst A in THF at room temperature for 1 h afforded piperidinyl-fused pyrrole 2a in 70% yield (entry 1). The structure of the nitrogen-containing cycloadduct was determined by NMR spectroscopic measurements and X-ray crystallography.[16] Lower product yields of
14–60% were observed when the transformation was conducted with the gold(I) phosphine complex B, AuCl and AuCl3 as the catalyst (entries 2, 10 and 11).
An increase in product yield from 70 to 82 to 90% was subsequently achieved when the reaction was repeated with Ph3PAuCl/AgOTf and Ph3PAuNTf2 in
place of gold(I) complex A as the catalyst (entries 4 and 5). With Ph3PAuNTf2 as the catalyst, changing
[image:3.595.68.301.334.693.2]the solvent from THF to acetone, toluene, dichloro-
Table 1. Optimization of Reaction Conditions.[a]
Entry Catalyst Solvent 2a
[%][b]
9a
[%][b]
1 A THF 70 −
2 B THF 60 −
3 C THF −[c] −
4 Ph3PAuCl/
AgOTf
THF 82 −
5 Ph3PAuNTf2 THF 90 −
6 Ph3PAuNTf2 acetone 98 −
7 Ph3PAuNTf2 toluene 92 −
8 Ph3PAuNTf2 CH2Cl2 82 −
9 Ph3PAuNTf2 (CH2Cl)2 52 −
10 AuCl THF 27 −
11 AuCl3 THF 14 −
12 AgOTf[d] THF − 80
13 Tf2NH[d] THF − [c] −
14 TfOH[d] THF − [c] −
[a] All reactions were performed at the 0.18 mmol scale with catalyst:1a ratio = 1:20 at room temperature for 1 h. [b] Isolated yield. [c] No reaction based on TLC and 1H NMR analysis of the crude mixture. [d] Reaction performed with 10 mol % of the catalyst.
methane or 1,2-dichlororethane led to 2a being obtained in yields of 52–98% (entries 6–9). However, no reaction was detected in control experiments catalyzed by the gold(I) phosphine complex C or 10 mol % of the Brønsted acids TfOH or Tf2NH (entries
3, 13 and 14). In a final control reaction mediated by 5 mol % of AgOTf with THF as the solvent, the exclusive formation of the monocyclic pyrrole 9a in 80% yield was found (entry 12). On the basis of the above results, the procedure described in entry 6 with 5 mol % of Ph3PAuNTf2 as the catalyst in acetone at
room temperature for 1 h was deemed to provide the optimum reaction conditions.
With the reaction conditions established, we next sought to evaluate the generality of the methodology for a series of β-amino-1,n-diynols 1b–s. As illustrated in Table 2, we found the reaction conditions to be broad, with a variety of substituted fused-pyrroles 2–8 furnished in 52–96% yield. Starting β-amino-1,6-diynols (1b–e) bearing alkyl or aryl substituents at the carbinol carbon center were found to react well to afford the corresponding piperidinyl-fused pyrrole adducts 2b–e in up to 95% yield. Likewise, comparable product yields of 92 and 83% were obtained in the reaction of substrates bearing two adjacent phenyl groups (1f) or an ethereal diyne linker (1h). The only instance where a lower product yield of 52% was obtained was when the β-position of the substrate bore an aliphatic isopropyl moiety (1g). The reaction of β -amino-1,5-diynols (1i–m) containing a -(CH2)2- tethered diyne
also furnished the corresponding cyclohexenyl-fused pyrroles 4i–m in up to 78% yield. The β -amino-1,6-diynol homologues 1n and 1o were initially found to afford mixtures of 5n and 7n, and 5o and 7o of the corresponding endo- and exo-alkenylated products, in 2:1 and 1:1 ratios, and in 67 and 69% yield, respectively. An increase in the product yield of the
5n and 7n mixture to 88%, and that of 5o and 7o to 85%, was observed when the reaction time was increased from 1 to 3 h. A slight fine-tuning of the conditions in the analogous experiments of these substrates with the introduction of 4 Å molecular sieves (MS) for 2 h subsequently led to the exo -alkenylated pyrroles 7n and 7o being chemoselectively afforded in respective yields of 89 and 94%. Likewise, in the presence of 4 Å MS, the
exo-alkenylated pyrroles 8p–s were exclusively provided from the corresponding β-amino-1,7-diynols
1p–s in 85–93% yield. Intriguingly, repeating the reactions of these substrates 1p–s in the absence of 4 Å MS gave the endo-alkenylated pyrroles 6p–s as the sole adduct. The structure of the cycloheptenyl-fused pyrrole 6r was ascertained by NMR spectroscopic measurements and X-ray crystallography.[17]
TsN
Ph OH NHTs
N Ts
NTs Ph
catalyst (5 mol %)
1a 2a
N Ts
NTs Ph
9a
P Au NCMe
tBu tBu SbF6
-A
P AuX R1R1
B, R1 = Cy, R2 = iPr, X = NTf 2
C, R1 = tBu, R2 = H, X = Cl
R2
R2
R2
Table 2. Aminoalkenylation of β-Amino-Diynols 1b–
s Catalyzed by Ph3PAuNTf2 [a]
[a] All reactions were performed at the 0.18 mmol scale with a Ph3PAuNTf2:1 ratio of 1:20 in acetone at room temperature for 1 h. Values in parentheses denote isolated yields and product ratios for mixtures. [b] Reaction conducted in toluene at 80 °C. [c] Reaction time = 2 h. [d] Reaction time = 3 h. [e] Reaction with 4 Å MS. [f] Reaction time = 18 h.
The mechanistic premise outlined in Scheme 1, eq 2, predicted that the gold(I)-catalyzed cycloisomerization may proceed through an aminoalkenylation pathway comprised of tandem hydroamination and alkenylation steps. While the isolation of 9a in Table 1, entry 12, under catalysis by AgOTf was fortuitous, the outcome suggests that this may be an intermediate in the gold(I)-catalyzed transformation. This was corroborated by the formation of fused-pyrrole 2a in 96% yield from the aromatic N-heterocycle under the optimized gold(I) catalysis conditions (Scheme 2, eq 1). The likelihood of this catalytic reaction pathway was further exemplified by the isolation of 9p on repeating the Au(I)-mediated rearrangement of β-amino-1,7-diynol
1p under the conditions described in Scheme 2, eq 2 for 3 h. Resubmission of the pyrrole intermediate to the same reaction conditions for a further 18 h afforded the fused-pyrrole adduct 8p in 90% yield. In contrast, repeating the analogous transformation of
9p with 5 mol % of Tf2NH instead of Ph3PAuNTf2 as
the catalyst was found to the near quantitative recovery of the pyrrole substrate.
Scheme 2. Control Experiments with 1p and 9a.
A tentative mechanism for the present gold(I)-catalyzed aminoalkenylation of β-amino-1,n-diynols is outlined in Scheme 3. We postulate that this could involve the initial activation of the internal alkyne moiety in the substrate to give the organogold complex II. This might consequently trigger the formation of vinyl gold intermediate I by an intramolecular CN bond-forming hydroamination step. Ensuing protodemetalation and Brønsted acid-assisted dehydrative aromatization of the resultant 2,3-dihydro-1H-pyrrol-3-ol adduct III would deliver isolable pyrrole 9 via the iminium species IV.[10]
Further activation of the pendant alkyne in this newly formed compound may afford the gold(I)-coordinated complex V. In the instances of 1,5-diynol substrates (1i–m), this may lead to 5-endo-dig alkenylation to the spirocyclic gold species VI and succeeding 1,2-alkyl migration to give the second vinyl gold intermediate VII.[13] Rearomatization and
protodemetalation would then furnish the cyclohexenyl-fused adduct 4. In contrast, 1,6- and 1,7-diynol substrates (1a–h and 1n–s) may undergo the respective preferential 5-exo-dig and 6-exo-dig
cyclizations to produce spirocyclic vinyl gold adduct
VIII from Au(I)-activated complex V. Subsequent 1,2-alkyl migration of this adduct to give the bicyclic gold species IX followed by rearomatization and protodemetalation would deliver the exo-alkenylated pyrroles 2, 3, 7 and 8. For the piperidinyl- and pyranyl-fused adducts 2 and 3, we propose that stabilization through non-conjugation of the heteroatom lone pair may rationalize the exclusive isolation of these exo-alkenes.[18] However, without this heteroatomic interaction, the greater stability offered by an internal alkene moiety may explain the isolation of pyrroles 7 and 8, and isomerization to the
endo-tautomers 5 and 6 under the mild acidic conditions generated when in the presence of water. A redistribution of product isomers in control experiments with the exo-alkenylated pyrrole 8p under the various conditions described in Scheme 4 would support this latter posited role of water. Treatment of 8p with an equivalent of water for 18 h was found to give a 1:1 mixture of 6p and 8p, which
X
R1OH
NHTs
N Ts
X R1
Ph3PAuNTf2 (5 mol %)
1
2, X = NTs, n = 1
3, X = O, n = 1
N Ts R1 N Ts R1
( )n ( )n
Me
5, X = CH2, n = 1
6, X = CH2, n = 2
7, X = CH2, n = 1
8, X = CH2, n = 2
R2
( )n
R2 R2 R2 N Ts NTs R
2b, R = Bn (95%)
2c, R = Me (94%)
2d, R = Et (85%)
2e, R = o-tolyl (81%) N Ts
NTs Ph
2f, R = Ph (92%)
2g, R = i-Pr (52%)
R N
Ts O Ph
3h, (83%)
N Ts R1
4i, R1 = Me, R2 = H (78%)[b,c]
4j, R1 = Et, R2 = H (72%)[b,c]
4k, R1 = Ph, R2 = H (64%)[b,c]
4l, R1 = Me, R2 = Ph (76%)[b,c]
4m, R1 = Ph, R2 = Ph (57%)[b,c]
N Ts R1
4, X = CH2, n = 0
R2
N Ts R
5n+7n, R = Ph (67%, 2:1)[b,d]
5n+7n, R = Ph (88%, 2:1)[b]
7n, R = Ph (89%)[b,c,e]
5o+7o, R = Me (69%, 1:1)[b,d]
5o+7o, R = Me (85%, 1:1)[b]
7o, R = Me (94%)[b,c,e]
N Ts R + Me N Ts R1
6p, R1 = Et, R2 = H (92%)[b,f]
6q, R1 = Me, R2 = H (92%)[b,f]
6r, R1 = Ph, R2 = H (81%)[b,f]
6s, R1 = Me, R2 = Ph (96%)[b,f]
N Ts R1
Me
R2
R2 R2
8p, R1 = Et, R2 = H (91%)[b,e,f]
8q, R1 = Me, R2 = H (90%)[b,e,f]
8r, R1 = Ph, R2 = H (85%)[b,e,f]
8s, R1 = Me, R2 = Ph (93%)[b,e,f]
acetone, RT, 1 h
or PhMe, 80 °C, 2-18 h Et OH
NHTs 1p N Ts NTs R N Ts Et N Ts Et N Ts NTs Ph
9a 2a, 96% yield
9p, 95% yield Ph3PAuNTf2: 8p, 90% yield
(1)
(2) Ph3PAuNTf2
(5 mol %) acetone, RT, 1 h
Ph3PAuNTf2
(5 mol %)
catalyst (5 mol %) PhMe, 4 Å MS
80 °C, 3 h
PhMe, 4 Å MS 80 °C, 18 h
Scheme 3. Proposed Mechanism for the Gold(I)-Catalyzed Aminoalkenylation of β-Amino-1,n-Diynols.
was observed to further increase to 11:1 on repeating the reaction with an extended reaction time of 48 h. A similar outcome was achieved after 18 h when the control experiment was repeated in the presence 5 mol % of Ph3PAuNTf2 with the endo- and exo
-alkenylated pyrroles being obtained in a ratio of 17:1. Likewise, the analogous reaction with 5 mol % of Tf2NH in place of Ph3PAuNTf2 as the catalyst was
found to give a 4:1 distribution of 6p and 8p. In contrast, a ratio of 12:1 in favor of the disubstituted alkene product was observed on conducting the isomerization process for a final time with 5 mol % of Ph3PAuNTf2 and 5 mol % of K2CO3.
Scheme 4. Control Experiments with 8p.
In summary, we have described an efficient synthetic strategy to diversely functionalized cycloalkyl-, piperidinyl- and pyranyl-fused pyrroles by aminoalkenylation of β-amino-1,n-diynols. The observed results and isolation of the pyrrole intermediates shed light on the possible mechanistic pathway, supporting a tandem CN/CC bond forming sequence, and a gold-mediated isomerization of the alkenylated products formed. The substrate scope proved general, furnishing a range of functionalized pyrroles which may prove of interest in both pharmaceutical and materials chemistry.
Experimental Section
To a stirred acetone (1 mL) solution of Ph3PAuNTf2 (4.7 mol) was added a solution containing 1 (0.18 mmol) in acetone (1 mL) in a drop-wise manner at room temperature under atmospheric conditions (for substrates 1i–s, the reaction was stirred at 80 °C and 4Å MS (100 mg) were added for substrates 1p–s). The reaction progress was monitored by TLC analysis to completion. The reaction mixture was then quenched with saturated NaHCO3 (2 mL) and extracted with EtOAc (2 × 25 mL). The organic layer was then washed with brine (20 mL), dried over Na2SO4, filtered, concentrated under reduced pressure and purified by flash column chromatography (eluent: nhexane/EtOAc = 6:1) to afford the desired product.
Acknowledgements
This work was supported by a Discovery Project Grant (DP160101682) from the Australian Research Council and a Tier 2 Grant from the Ministry of Education of Singapore (MOE2013-T2-1-060). We thank Dr. Yongxin Li (Nanyang Technological University) for providing the X-ray crystallographic data reported in this work.
References
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X
R1OH
R2 NHTs II [Au]+ N Ts
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IV
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for n = 0
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for n = 1, 5-exo-dig
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5, X = CH2, n = 1
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( )n
( )n ( )n
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( )n
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( )n
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R2
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R1 H [Au]
[Au]+/H 2O N Ts R1 4 R2 X
R1OH
R2
NHTs
( )n
VI
5-endo-dig
I
( )n
N R2
HO R1
H Ts [Au] X [Au]+ N Ts Et 8p
H2O (1 equiv)
N Ts Et 6p Me + 1 11 17 1 4 N Ts Et 8p
PhMe, 80 °C
: 1
: 1
: 1
: 12
: 1 18h:
48h: + Ph3PAuNTf2 (5 mol %), 18h:
+ Ph3PAuNTf2 (5 mol %), K2CO3 (5 mol %), 18h:
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2002, 124, 4178.
[8] Selected recent reviews concerning transition
metal-catalyzed hydroamination reactions: a)
Hydrofunctionalization; (Eds.: V. P. Ananikov, M. Tanaka), Springer GmbH, Berlin, 2013. b) B. Alcaide, P. Almendros, Adv. Synth. Catal.2011, 353, 2561. c) K. D. Hesp, M. Stradiotto, ChemCatChem, 2010, 2, 1192. d) T. E. Müller, K. C. Hultzsch, M. Yus, F. Foubelo, M. Tada, Chem. Rev.2008, 108, 3795.
[9] Selected examples of transition metal-catalyzed hydroamination of β-amino-alkynes in the formation of pyrroles: a) W. Van Rossom, Y. Matsushita, K. Ariga, J. P. Hill, RSC Adv. 2014, 4, 4897. b) B. Gabriele, L. Veltri, P. Plastina, R. Mancuso, M. V. Vetere, V. Maltese, V. J. Org. Chem.2013, 78, 4919. c) Y. Karibe, H. Kusama, N. Iwasawa, Angew. Chem., Int. Ed.2012, 51, 6214. d) J. H. Kim, S. B. Lee, W. K. Lee, D.-H. Yoon, H.-J. Ha, Tetrahedron 2011, 67, 3553. e) H. Yamamoto, I. Sasaki, M. Mitsutake, A. Karasudani, H. Imagawa, M. Nishizawa, Synlett2011, 2815. f) E. Ko, K. Burgess, Org. Lett.2011, 13, 980. g) B. Alcaide, P. Almendros, M. T. Quirós, Adv. Synth. Catal.2011, 353, 585. h) A. Blanc, A. Alix, J.-M. Weibel, P. Pale, Eur. J. Org. Chem.2010, 1644. i) D.-D. Chen, X.-L. Hou, L.-X. Dai, Tetrahedron. Lett.
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2009, 351, 1371. o) D. J. Gorin, N. R. Davis, F. D. Toste, J. Am. Chem. Soc.2005, 127, 11260.
[11] For selected reviews of transition metal-catalyzed alkenylation reactions of arenes with alkynes: a) P. de Mendoza, A. M. Echavarren, Pure Appl. Chem.2010, 82, 801. b) X. Wang, L. Zhou, W. Lu, Curr. Org. Chem. 2010, 14, 289. c) T. Kitamura, Eur. J. Org. Chem.2009, 1111. d) C. Nevado, A. M. Echavarren, Synthesis2005, 167.
[12] Selected examples of transition metal-catalyzed alkenylation reactions of pyrroles with alkynes: a) A. Kumar, D. D. Vachhani, S. G. Modha, S. K. Sharma, V. S. Parmar, E. V. Van der Eycken, Synthesis2013, 45, 2571. b) S. G. Modha, A. Kumar, D. D. Vachhani, S. K. Shamra, V. S. Parmar, E. V. Van der Eycken, Chem. Commun.2012, 48, 10916. c) A. S. K. Hashmi, W. Yang, F. Rominger, Chem. Eur. J.2012, 6576. d) M. R. Bhandari, M. Yousufuddin, C. J. Lovely, Org. Lett. 2011, 13, 1382. e) M. Gruit, D. Michalik, K. Krüger, A. Spannenberg, A. Tillack, A. Pews-Davtyan, M. Beller, Tetrahedron2010, 66, 3341. f) G. Buscemi, A. Biffis, C. Tubaro, M. Basato, C. Graiff, A. Tiripicchio, Appl. Organometal. Chem. 2010, 24, 285. g) M. Gruit, D Michalik, A. Tillack, M. Beller, Angew. Chem., Int. Ed.2009, 48, 7212. h) C. S. Yi, Zhang, J. Chem. Commun. 2008, 2349. i) A. S. K. Hashmi, J. P. WeyrauchE. Kurpejović, T. M. Frost, B. Miehlich, W. Frey, J. W. Bats, Chem. Eur. J. 2006, 5806. j) V. Mamane, P. Hannen, A. Fürstner, Chem. Eur. J.2004, 4556.
[13] Selected examples of gold-catalyzed pyrrole alkenylations, see refs [12a–e], and [12i].
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[15] For the synthesis of -amino-1,n-diynol 1, see the Supporting Information for details.
[16] CCDC 1018529 (2a) contains the supplementary crystallographic data for this paper. This data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[17] CCDC 1018530 (6r) contains the supplementary crystallographic data for this paper. This data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
COMMUNICATION
Gold-Catalyzed Aminoalkenylation of β -Amino-1,n-Diynols to Cycloalkyl-, Piperidinyl- and Pyranyl-Fused Pyrroles
Adv. Synth. Catal.Year, Volume, Page – Page
Prasath Kothandaraman, Yichao Zhao, Bo Ra Lee, Clarrisa Jia Le Ng, Jun Yi Lee, Benjamin James Ayers and Philip Wai Hong Chan*
N Ts
O R1
R2
N Ts
NTs R1
R2 N
Ts
R1
R2
N Ts
R1
R2
N Ts
R1
Me
R2
N Ts
R1
R2
N Ts
R1
R2
Me
X R1OH
NHTs
( )n
Ph3PAuNTf2
(5 mol %) acetone, RT or PhMe, 80 °C
1-18 h R2
![Table 1. Optimization of Reaction Conditions.[a]](https://thumb-us.123doks.com/thumbv2/123dok_us/9474066.453746/3.595.68.301.334.693/table-optimization-of-reaction-conditions-a.webp)
![Table 2. Aminoalkenylation of β-Amino-Diynols 1b–s Catalyzed by Ph3PAuNTf2 [a]](https://thumb-us.123doks.com/thumbv2/123dok_us/9474066.453746/4.595.71.306.85.346/table-aminoalkenylation-b-amino-diynols-catalyzed-ph-pauntf.webp)
