Stereoisomerically pure trisubstituted vinylaluminum reagents and their utility in Copper-Catalyzed enantioselective synthesis of 1,4-Dienes containing Z or e alkenes

Article abstract of DOI:10.1002/anie.200905223

"Chemical Equation Presented" The desired isomer of a chiral 1,4-diene containing an E or Z double bond can be accessed readily by a regio- and stereoselective hydroalumination of silyl-substituted alkynes and subsequent enantioselective copper-catalyzed

Full text of DOI:10.1002/anie.200905223

Angewandte
Chemie
DOI: 10.1002/anie.200905223
Enantioselective Synthesis
Stereoisomerically Pure Trisubstituted Vinylaluminum Reagents and
their Utility in Copper-Catalyzed Enantioselective Synthesis of 1,4-
Dienes Containing Z or E Alkenes**
Katsuhiro Akiyama, Fang Gao, and Amir H. Hoveyda*
Catalytic enantioselective addition of vinyl groups to C-based
ꢀ
electrophiles constitutes a versatile class of C C bond
forming processes.[1–3] We recently reported that vinylalumi-
num reagents, generated through reactions of alkyl- or
alkenyl-substituted terminal alkynes with commercially avail-
able and inexpensive diisobutylaluminum hydride (dibal-H),
can be used in site- and enantioselective Cu-catalyzed allylic
alkylations.[4] The above protocol, however, suffers from two
notable deficiencies. First, cis vinylmetals cannot be accessed
Scheme 1. Projected diastereo- and enantioselective synthesis of
nyasol through Cu-catalyzed allylic alkylation with a cis vinylaluminum
reagent. NHC=N-heterocyclic carbene, PG=protecting group.
ꢀ
(> 98% trans product formed due to syn addition of Al H to
terminal alkynes). Second, aryl-substituted vinylaluminums
cannot be utilized since the corresponding hydroaluminations
are inefficient.[5] Herein, we present solutions to the above
shortcomings through efficient, site- and stereoselective
preparation of vinylaluminum reagents by reactions of Si-
substituted alkynes with dibal-H. The vinylmetals can be used
in situ in site- and enantioselective Cu-catalyzed allylic
alkylations.[6] Enantiomerically enriched vinylsilanes are
proto-desilylated with trifluoroacetic acid (TFA), affording
the derived Z or E alkenes typically as a single stereoisomer
in up to > 99:1 enantiomeric ratio (e.r.).
The present investigations originated partly from consid-
Scheme 2. Synthesis of a cis- or trans-disubstituted alkene may be
accomplished through hydroalumination/desilylation of a Si-substi-
tuted alkyne.
erations regarding application of the enantioselective allylic
alkylations of vinylaluminum reagents,[4] catalyzed by chiral
bidentate N-heterocyclic carbene (NHC) Cu complexes,[7] to
synthesis of nyasol.[8] The proposed plan (Scheme 1) demands
the efficient and selective formation of a Z vinylaluminum
from an aryl-substituted alkyne. Consequently, addressing the
aforementioned drawbacks, namely identification of a proto-
col allowing efficient access to a cis vinylmetal derived from
an aryl-substituted alkyne, was required.
We surmised that a silyl substituent at the alkyne terminus
(I, Scheme 2) would allow hydroaluminations of aryl-substi-
tuted substrates to proceed readily and with minimal byprod-
uct formation. Efficiency would arise from stabilization of the
low-lying s* orbital of the adjacent C Si.[9] Accordingly, site-
and stereoselective hydrometallation of a silyl-substituted
alkyne[10] (I, Scheme 2), reaction of the resulting vinylmetal
(II) with an electrophile (!III), followed by protonation of
ꢀ
ꢀ
the C Si bond (!IV) would deliver the desired product
bearing a trans alkene. The corresponding Z olefin could be
obtained stereoselectively (via V–VII, Scheme 2) if the initial
hydroalumination adduct (II) could be induced to undergo
isomerization, positioning the large aryl and silyl substituent
trans to one another.
ꢀ
incipient electron density at the carbon of the C Al bond by
the d orbitals of silicon, or through hyperconjugation with the
To access the requisite cis vinylmetals, we turned to the
pioneering investigations of Eisch, disclosed nearly four
decades ago, in connection with hydroaluminations of silyl-
substituted alkynes.[11] Treatment of trimethylsilyl-substituted
phenylacetylene 1 with dibal-H in 5:1 hexanes:THF (558C,
2 h) leads to vinylaluminum 2 in > 98% Z-selectivity
(Scheme 3). When hydrometallation is performed in hexanes,
3 is formed with > 98% E-selectivity (> 98% conv.). A
mechanistic scheme, related to that suggested by Eisch,[11] is
illustrated in Scheme 3. In the absence of Lewis basic THF,
alkene isomerization occurs readily (VIII!IX!X) due to
the energetically accessible and unoccupied p orbital of the Al
metal. When THF is present, its coordination to the Lewis
[*] Dr. K. Akiyama, F. Gao, Prof. A. H. Hoveyda
Department of Chemistry, Merkert Chemistry Center
Boston College, Chestnut Hill, MA 02467 (USA)
Fax: (+1)617-552-1442
E-mail: amir.hoveyda@bc.edu
[**] The NIH (Grant GM-47480) provided financial support. Mass
spectrometry facilities at Boston College are supported by the NSF
(CHE-0619576).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200905223.
Angew. Chem. Int. Ed. 2010, 49, 419 –423
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
419

Communications
Table 1: Catalytic enantioselective allylic alkylations with vinylaluminum
reagent 3 promoted by NHC–Cu complex derived from 5.[a]
Entry Substrate [R]
Yield [%][b] SN2’:SN2[c] E:Z[c]
e.r.[d]
99:1
99:1
98:2
1
4a [Ph]
93
96
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
2
3
4
5
6
7
8
9
4b [oMeC6H4]
4c [oMeOC6H4]
4d [oNO2C6H4]
4e [mBrC6H4]
4 f [pClC6H4]
4g [pNO2C6H4]
4h [pTsOC6H4]
4i [pMeC6H4]
4j [(CH2)2C6H5]
4k [Cy]
82
Scheme 3. Stereoselective hydroalumination of trimethylsilylphenylace-
tylene with dibal-H, and a rationale for the effect of a Lewis base
(THF). dibal-H=(iBu)2AlH.
89
>98:2 >99:1
95
94
87
>98
92
>98:2
>98:2
>98:2
>98:2
99:1
98.5:1.5
97.5:2.5
99:1
acidic Al inhibits isomerization of the initially generated Z-
vinylmetal. In both cases, hydroaluminations proceed with
> 98% site-selectivity.
>98:2 >99:1
10
11
88
88
>98:2
>98:2
94:6
94:6
Next, we examined the related NHC-Cu-catalyzed enan-
tioselective allylic alkylations. Subjection of 1.5 equivalents of
vinylaluminum 3, prepared and used in situ, to aryl and alkyl-
substituted allylic phosphates 4a–k, in the presence of 1.0
mol% NHC-AgI complex 5 and 2.0 mol% CuCl2·2H2O,
results in complete substrate consumption (Table 1). 3-Sub-
stituted 1,4-dienes 6a–k are generated with > 98% site-
selectivity (SN2’), in 82% to > 98% yield and in 94:6 to
> 99:1 e.r. Selectivities are high, regardless of the steric or
electronic attributes of aryl substituents of the allylic phos-
phates. Alkyl-substituted substrates (entries 10–11, Table 1)
can be used effectively in the hydroalumination/allylic
alkylation process, albeit with somewhat lower enantioselec-
tivity (94:6 e.r.). In all the transformations examined, there is
> 98% E-selectivity, and products derived from the addition
of an iBu unit of the Al-based reagent are not detected (< 2%
[a] Reactions were performed under N2 atmosphere; >98% conversion
and <2% iBu addition product in all cases (400 MHz 1H NMR analysis
of unpurified product mixtures). [b] Yields of isolated purified products.
[c] Site-selectivities and alkene stereoselectivities established by analysis
of 400 MHz H NMR spectra of product mixtures prior to purification.
[d] Enantiomer ratios determined by HPLC analysis; see the Supporting
Information for details.
1
Table 2: Catalytic enantioselective allylic alkylations with various vinyl-
aluminum reagents promoted by NHC–Cu complex derived from 5.[a]
Entry Product [R]
t [h] Yield [%][b] SN2’:SN2[c] E:Z[c]
e.r.[d]
1
2
3
4
5
7a [oMeOC6H4] 12
94
82
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2 92:8
>98:2 99:1
>98:2 97:3
88:12 97:3[e]
>98:2 99:1
1
by 400 MHz H NMR analysis). It is thus a notable attribute
7b [mMeC6H4]
7c [pFC6H4]
6
12
12
6
of this class of transformations that the overall process,
beginning with the silyl-substituted alkyne and ending with
the enantiomerically enriched dienes, requires five distinct
issues of selectivity to be addressed: site- and stereoselectivity
in generation of the vinylaluminum (Scheme 3), followed by
site- (SN2’ vs. SN2), group- (vinyl- vs. iBu addition) and, finally,
enantioselectivity of allylic alkylation. In reactions summar-
ized in Table 1, there is complete (> 98%) control of
selectivity in all aspects except product enantiomeric purity,
which varies between 94:6 and > 99:1 e.r.
Sequential hydroalumination/Cu-catalyzed allylic alkyla-
tion can be performed with silyl-substituted alkynes bearing
different aryl units (Table 2). Products are isolated with
complete site- and group-selectivity and in 92:8–99:1 e.r.
Hydroaluminations proceed with exceptional site-selectivity,
irrespective of the steric or electronic characteristics of the
alkyne substituent. Only in one instance is the final product
isolated as a mixture of E and Z isomers (entry 4, 88:12 E:Z).
The incomplete vinylaluminum isomerization may be due to
70
7d [pCF3C6H4]
7e [pMeC6H4]
70[e]
91
[a-d] See Table 1. [e] Data pertain to the major E isomer.
destabilization of the zwitterionic structure (IX in Scheme 3)
by the electron withdrawing p-CF3 unit.
The representative example, illustrated in Equation (1),
underlines the exceptional efficiency of this single-vessel class
of transformations. Approximately 0.5 gram of 6a (90%
yield) can be synthesized in 98.5:1.5 e.r. and 95:5 site-
selectivity (SN2’:SN2) through a reaction that proceeds with
otherwise complete (> 98%) selectivity, requiring only 0.05
mol% (1.1 mg) of chiral NHC-AgI complex 5.
The first enantioselective synthesis of nyasol was subse-
quently realized (Scheme 2). Pd-catalyzed cross-coupling[12]
of commercially available trimethylsilylacetylene with 4-
iodophenol delivers the substrate (8) required for site- and
420
www.angewandte.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 419 –423

Angewandte
Chemie
relative facility with which such entities undergo allylic
ꢀ
alkylation (i.e., only C C bond formation may be
irreversible).
2) Allylic alkylations with Ag complex 5, used in reactions of
E vinylaluminum reagents (Tables 1–2 and Scheme 4),
furnish similar efficiency and site-selectivity (vs. 12). With
complex 12, however, enantioselectivity is improved
significantly. As an example, the transformation shown
in entry 1 of Table 3 generates 14 in 86.5:13.5 e.r. when 5 is
used, whereas in the presence of 12 the desired 1,4-diene is
isolated in 97:3 e.r. The amount of product derived from
isobutyl addition is slightly lower with complex 5 (96:4 vs.
91:9 with 12). Similarly, when 12 is used to promote
addition of E-vinylsilane 3 to 4a, under otherwise identical
conditions, only 53% conversion is observed and 6a is
obtained in 94.5:5.5 e.r. (vs. > 98% conv. and > 99:1 e.r.
with 5). The rationale for such selectivity differences is
unclear.
3) Vinylaluminums 13a–g, bearing a dimethylsilyl hydride
(vs. trimethylsilyl), are employed because the correspond-
ing Cu-catalyzed allylic alkylations proceed with a stron-
ger preference for the transfer of the vinyl unit (vs. iBu
group). For example, when trimethylsilyl 2 (see Scheme 3)
is used for the reaction in entry 1 of Table 3, 40% isobutyl
addition is observed (vs. 9% with 13a).
stereoselective hydroalumination in 76% yield (Scheme 4).[13]
Treatment of 8 with dibal-H (558C, 2 h) delivers vinylalumi-
num 9, which is used in Cu-catalyzed allylic alkylation of
allylic phosphate 10. The one-pot process furnishes silyl-
substituted 1,4-diene 11 with complete control of alkene
selectivity (> 98% E), as well as > 98% group- (< 2% iBu
addition) and site-selectivity (< 2% SN2) in 76% yield and
98.5:1.5 e.r. (ꢀ)-Nyasol is obtained in 73% yield from 11 by a
three-step procedure that includes proto-desilylation with
trifluoroacetic acid (42% overall yield from commercially
available trimethylsilylacetylene).[14]
The Z-vinylaluminum reagents, such as 2 (Scheme 3),
obtained site-selectively through syn aluminum hydride
addition to silyl-substituted aryl alkynes, allow us to obtain
products that cannot be efficiently accessed by direct hydro-
alumination of aryl-substituted alkynes.[5] An assortment of
enantiomerically enriched 1,4-dienes can be obtained through
enantioselective Cu-catalyzed allylic alkylation with this set
of stereochemically defined organometallic reagents
(Table 3). Similar to reactions with E vinylaluminum reagents
(Tables 1–2 and Scheme 4), when 13a–g are used (Table 3),
high site- (> 98% SN2’) and enantioselectivity are observed
(95.5:4.5–98.5:1.5 e.r.).[15] In all instances except one (Z:E =
90:10, entry 7),[16] there is > 98% Z-selectivity.
Proto-desilylation of the enantiomerically enriched 1,4-
dienes shown in Table 3, obtained from the single-vessel
process, can be utilized to access the products expected from a
sequence beginning with hydroalumination of aryl-substi-
tuted terminal alkynes, which, as mentioned before,[5]
undergo hydrometallation inefficiently.[5] The example pro-
vided in Equation (2) is a case in point.
Several points regarding the data in Table 3 merit further
discussion:
1) In contrast to reactions of E-vinylaluminums (Tables 1–2
and Scheme 4), 7–28% of the products derived from
addition of an isobutyl group are observed (Table 3). The
origin of such group-selectivity differences is likely due to
subtle variations in equilibria involving the formation of
vinyl- versus isobutylcopper complexes as well as the
Scheme 4. Enantioselective synthesis of (ꢀ)-nyasol, featuring a one-pot alkyne hydroalumination/Cu-catalyzed enantioselective allylic alkylation.
TFA=trifluoroacetic acid.
Angew. Chem. Int. Ed. 2010, 49, 419 –423
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
421

Communications
b) J.-R. Kong, C.-W. Cho, M. J.
Krische, J. Am. Chem. Soc. 2005,
127, 11269 – 11276; c) M.-Y. Ngai,
A. Barchuk, M. J. Krische, J. Am.
Chem. Soc. 2007, 129, 12644 –
12645; d) S. Lou, S. E. Schaus, J.
Am. Chem. Soc. 2008, 130, 6922 –
6923; e) Y. Nakao, M. Takeda, J.
Chen, L. Salvi, T. Hiyama, Y.
Ichikawa, R. Shintani, T. Hayashi,
Chem. Lett. 2008, 37, 290 – 291.
Table 3: Catalytic enantioselective allylic alkylations with Z-vinylaluminum reagents 13 promoted by
NHC–Cu complex derived from 12.[a]
[3] For examples of catalytic enantio-
selective vinyl conjugate additions
to unsaturated carbonyls, see: a) S.
Oi, A. Taira, Y. Honma, Y. Inoue,
Org. Lett. 2003, 5, 97 – 99; b) S. Oi,
T. Sato, Y. Inoue, Tetrahedron Lett.
2004, 45, 5051 – 5055; c) Y. Oto-
maru, T. Hayashi, Tetrahedron:
Asymmetry 2004, 15, 2647 – 2651;
d) K. C. Nicolaou, W. Tang, P. Dag-
neau, R. Faraoni, Angew. Chem.
2005, 117, 3942 – 3947; Angew.
Chem. Int. Ed. 2005, 44, 3874 –
3879; e) Y. Nakao, J. Chen, H.
Imanaka, T. Hiyama, Y. Ichikawa,
W.-L. Duan, R. Shintani, T. Hay-
ashi, J. Am. Chem. Soc. 2007, 129,
9137 – 9143; f) M. Vuagnoux-dꢀAu-
gustin, A. Alexakis, Chem. Eur. J.
2007, 13, 9647 – 9662; g) K.-s. Lee,
Entry 4 [R]
13 [Ar]
Product Yield Vinyl:iBu SN2’:SN2[c] E:Z[c]
e.r.[d]
[%][b] addition[c]
1
2
3
4
5
6
7
8
9
10
4a [Ph]
13a [Ph]
14
78
68
61
86
71
85
75
81
81
84
91:9
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2 97:3
4a [Ph]
4a [Ph]
4a [Ph]
4a [Ph]
4a [Ph]
4a [Ph]
4g [pNO2C6H4] 13a [Ph]
4h [pTsOC6H4] 13a [Ph]
4i [pMeC6H4]
13b [oMeOC6H4] 15
13c [oMeC6H4] 16
13d [mCF3C6H4] 17
13e [pCF3C6H4]
13 f [pFC6H4]
72:28
76:24
91:9
75:25
90:10
80:20
93:7
>98:2 97.5:2.5
>98:2 97:3
>98:2 95.5:4.5
>98:2 96.5:3.5
>98:2 98:2
18
19
13g [pMeOC6H4] 20
>98:2 98.5:1.5
>98:2 97:3
21
22
23
90:10
87:13
>98:2 98:2
>98:2 98:2
13a [Ph]
[a–d] See Table 1.
We therefore demonstrate that trisubstituted vinylalumi-
num reagents, accessed by hydroalumination of silyl-substi-
tuted alkynes, offer a practical protocol for stereoselective
synthesis of alkenes. The application to Cu-catalyzed enan-
tioselective allylic alkylation represents one of several other
A. H. Hoveyda, J. Org. Chem. 2009, 74, 4455 – 4462.
[4] Y. Lee, K. Akiyama, D. G. Gillingham, M. K. Brown, A. H.
Hoveyda, J. Am. Chem. Soc. 2008, 130, 446 – 447.
[5] Treatment of aryl-substituted terminal alkynes with dibal-H
leads to the generation of significant amounts ( ꢁ 30%) of the
derived alkynylalanes. See: G. Zweifel, J. T. Snow, C. C. Whit-
ney, J. Am. Chem. Soc. 1968, 90, 7139 – 7141.
ꢀ
possible C C bond forming processes feasible through the use
of these vinylmetal reagents. Such considerations, together
with continuing advances in catalytic cross-coupling reactions
of vinylsilanes,[17] augur well for upcoming developments
regarding diastereo- and enantioselective synthesis of mole-
cules bearing a trisubstituted alkene.
[6] For reviews on catalytic allylic alkylation reactions with “hard”
alkyl- or arylmetal-based reagents, see: a) A. H. Hoveyda, A. W.
Hird, M. A. Kacprzynski, Chem. Commun. 2004, 1779 – 1785;
b) H. Yorimitsu, K. Oshima, Angew. Chem. 2005, 117, 4509 –
4513; Angew. Chem. Int. Ed. 2005, 44, 4435 – 4439; c) C. A.
Falciola, A. Alexakis, Eur. J. Org. Chem. 2008, 3765 – 3780.
[7] For other examples of catalytic enantioselective allylic alkyla-
tions promoted by chiral bidentate NHC-Cu complexes, see:
a) A. O. Larsen, W. Leu, C. Nieto-Oberhuber, J. E. Campbell,
A. H. Hoveyda, J. Am. Chem. Soc. 2004, 126, 11130 – 11131;
b) J. J. Van Veldhuizen, J. E. Campbell, R. E. Giudici, A. H.
Hoveyda, J. Am. Chem. Soc. 2005, 127, 6877 – 6882; c) Y. Lee,
A. H. Hoveyda, J. Am. Chem. Soc. 2006, 128, 15604 – 15605;
d) M. A. Kacprzynski, T. L. May, S. A. Kazane, A. H. Hoveyda,
Angew. Chem. 2007, 119, 4638 – 4642; Angew. Chem. Int. Ed.
2007, 46, 4554 – 4558; e) D. G. Gillingham, A. H. Hoveyda,
Angew. Chem. 2007, 119, 3934 – 3938; Angew. Chem. Int. Ed.
2007, 46, 3860 – 3864. For reactions promoted by the correspond-
ing ZnII- and AlIII-based complexes, see: f) Y. Lee, B. Li, A. H.
Hoveyda, J. Am. Chem. Soc. 2009, 131, 11625 – 11633.
Received: September 17, 2009
Published online: December 3, 2009
Keywords: allylic alkylation · enantioselective catalysis ·
.
hydroalumination · N-heterocyclic carbenes ·
vinylaluminum reagents
[1] For examples of catalytic enantioselective vinyl additions to
carbonyls, see: a) W. Oppolzer, R. N. Radinov, J. Am. Chem.
Soc. 1993, 115, 1593 – 1594; b) K. M. Miller, W.-S. Huang, T. F.
Jamison, J. Am. Chem. Soc. 2003, 125, 3442 – 3443; c) H. Li, P. J.
Walsh, J. Am. Chem. Soc. 2004, 126, 6538 – 6539; d) D. Tomita,
R. Wada, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2005, 127,
4138 – 4139; e) Y. Yang, S.-F. Zhu, C.-Y. Zhou, Q.-L. Zhou, J.
Am. Chem. Soc. 2008, 130, 14052 – 14053; f) M. H. Kerrigan, S.-J.
Jeon, Y. K. Chen, P. J. Carroll, P. J. Walsh, J. Am. Chem. Soc.
2009, 131, 8434 – 8445; g) D. B. Biradar, H.-M. Gau, Org. Lett.
2009, 11, 499 – 502.
[8] For a previous enantioselective synthesis of di-O-methyl ether of
nyasol, involving a Wittig olefination that proceeds with 3:2 Z:E
selectivity, and related natural products, see: W.-G. Quan, B.-X.
Yu, J.-Y. Zhang, Q.-R. Liang, Y.-Q. Sun, X.-G. She, X.-F. Pan,
Chin. J. Chem. 2007, 25, 688 – 693.
[9] Both mechanisms, delocalization through Si d orbitals and
ꢀ
hyperconjugation with a neighboring s* C Si bond, have been
put forth to account for stabilization of electron density adjacent
[2] For examples of catalytic enantioselective vinyl additions to
aldimines, see: a) S. J. Patel, T. F. Jamison, Angew. Chem. 2004,
116, 4031 – 4034; Angew. Chem. Int. Ed. 2004, 43, 3941 – 3944;
to a Si substituent. See: M. A. Brook, Silicon in Organic,
422
www.angewandte.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 419 –423

Angewandte
Chemie
Organometallic, and Polymer Chemistry, Wiley-VCH, Wein-
heim, 2006, pp. 31 – 34 and 500–503, and references therein.
[10] For a review regarding stereoselective synthesis through the use
of Si-containing compounds, see: I. Fleming, A. Barbero, D.
Walter, Chem. Rev. 1997, 97, 2063 – 2192.
[11] a) J. J. Eisch, M. W. Foxton, J. Org. Chem. 1971, 36, 3520 – 3526;
b) J. J. Eisch, S-G. Rhee, J. Am. Chem. Soc. 1975, 97, 4673 – 4682.
For a related review, see: c) J. J. Eisch in Comprehensive Organic
Synthesis, Vol. 8 (Eds.: B. M. Trost, I. Fleming, S. L. Schreiber),
Pergamon, Oxford, 1991, pp. 733 – 761.
of the stereochemical identity of the chiral NHC ligands in 12
versus 5.
[16] Generation of a minor amount of E alkene (20 formed with
90:10 Z:E selectivity) in the reaction shown in entry 7 of Table 3
might be caused by olefin isomerization facilitated by the p-
methoxy substituent, as shown below. The inability of the
substrate in entry 2 (Table 3), containing an o-methoxyphenyl
group (15 formed with > 98% Z selectivity) might be because
the corresponding resonance structure suffers from destabiliza-
tion as a result of the attendant allylic strain.
[12] For a review of Sonogashira-type coupling processes, see: R.
Chinchilla, C. Nꢁjera, Chem. Rev. 2007, 107, 874 – 922.
[13] E. Yashima, S. Huang, T. Matsushima, Y. Okamoto, Macro-
molecules 1995, 28, 4184 – 4193.
[14] A plausible rationale for the retention of stereochemistry might
involve hyperconjugative assistance of the protonation process
ꢀ
by the C Si bond. It is likely that a stepwise mechanism that
includes the formation of a carbocation would lead to isomer-
ization and generation of substantial amounts of the lower
energy trans alkene. For a similar explanation provided to
account for the stereochemical outcome of the reaction of
deuterium chloride with trans-b-trimethylsilylstyrene, a process
which proceeds with retention of stereochemistry, see: K. E.
Koenig, W. P. Weber, J. Am. Chem. Soc. 1973, 95, 3416 – 3418.
[15] The absolute stereochemistry of major enantiomers in reactions
in Table 3 are opposite to those shown in Tables 1 and 2 because
[17] For representative examples, see: a) Y. Hatanaka, T. Hiyama, J.
Org. Chem. 1988, 53, 918 – 920; b) K. Tamao, K. Kobayashi, Y.
Ito, Tetrahedron Lett. 1989, 30, 6051 – 6054; c) S. E. Denmark, W.
Pan, Org. Lett. 2003, 5, 1119 – 1122; d) S. E. Denmark, S. A.
Tymonko, J. Am. Chem. Soc. 2005, 127, 8004 – 8005; e) Y. Nakao,
H. Imanaka, A. K. Sahoo, A. Yada, T. Hiyama, J. Am. Chem.
Soc. 2005, 127, 6952 – 6953; f) S. E. Denmark, J. D. Baird, Chem.
Eur. J. 2006, 12, 4954 – 4963.
Angew. Chem. Int. Ed. 2010, 49, 419 –423
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
423