Exceptionally E- and β-selective NHC-Cu-catalyzed proto-silyl additions to terminal alkynes and site- and enantioselective proto-boryl additions to the resulting vinylsilanes: Synthesis of enantiomerically enriched vicinal and geminal borosilanes

Article abstract of DOI:10.1002/chem.201203803

An exceptionally site- and E-selective catalytic method for preparation of Si-containing alkenes through protosilylation of terminal alkynes is presented. Furthermore, the vinylsilanes obtained are used as substrates to generate vicinal or geminal borosilanes by another catalytic process; such products are derived from enantioselective protoborations of the Si-substituted alkenes. All transformations are catalyzed by N-heterocyclic carbene (NHC) copper complexes. Specifically, a commercially available imidazolinium salt, cheap CuCl (1.0 mol %) and Me₂PhSi-B(pin), readily and inexpensively prepared in one vessel, are used to convert terminal alkynes to (E)-β-vinylsilanes efficiently (79-98 % yield) and in >98 % E and >98 % β-selectivity. Vinylsilanes are converted to borosilanes with 5.0 mol % of a chiral NHC-Cu complex in 33-94 % yield and up to 98.5:1.5 enantiomeric ratio (e.r.). Alkyl-substituted substrates afford vicinal borosilanes exclusively; aryl- and heteroaryl-substituted alkenes deliver the geminal isomers preferentially. Different classes of chiral NHCs give rise to high enantioselectivities in the two sets of transformations: C₁-symmetric monodentate Cu complexes are most suitable for reactions of alkyl-containing vinylsilanes and bidentate sulfonate-bridged variants furnish the highest e.r. for substrates with an aryl substituent. Working models that account for the observed trends in selectivity are provided. Utility is demonstrated through application towards a formal enantioselective total synthesis of naturally occurring antibacterial agent bruguierol A. Different NHCs for different tasks: Three classes of N-heterocyclic carbene(NHC)-Cu complexes serve to promote two sets of reactions. Catalysts with an achiral monodentate NHC convert terminal alkynes to (E)-β-vinylsilanes with exceptional selectivity through efficient protosilylation. Cu-based catalysts bearing a chiral monodentate NHC bring about protoborations of alkyl-substituted vinylsilanes, generating enantiomerically enriched vicinal borosilanes; however, it is the sulfonate-bridged bidentate NHC-Cu complexes that deliver geminal silylborons with the highest e.r. values. Copyright

Full text of DOI:10.1002/chem.201203803

DOI: 10.1002/chem.201203803
Exceptionally E- and b-Selective NHC–Cu-Catalyzed Proto-Silyl Additions
to Terminal Alkynes and Site- and Enantioselective Proto-Boryl Additions to
the Resulting Vinylsilanes: Synthesis of Enantiomerically Enriched Vicinal
and Geminal Borosilanes
Fanke Meng, Hwanjong Jang, and Amir H. Hoveyda*[a]
Abstract: An exceptionally site- and E-
selective catalytic method for prepara-
tion of Si-containing alkenes through
protosilylation of terminal alkynes is
presented. Furthermore, the vinylsi-
lanes obtained are used as substrates to
generate vicinal or geminal borosilanes
by another catalytic process; such
products are derived from enantiose-
lective protoborations of the Si-substi-
tuted alkenes. All transformations are
catalyzed by N-heterocyclic carbene
(NHC) copper complexes. Specifically,
a commercially available imidazolinium
salt, cheap CuCl (1.0 mol%) and
sively prepared in one vessel, are used
to convert terminal alkynes to (E)-b-vi-
nylsilanes efficiently (79–98% yield)
and in >98% E and >98% b-selectivi-
ty. Vinylsilanes are converted to borosi-
lanes with 5.0 mol% of a chiral NHC–
Cu complex in 33–94% yield and up to
98.5:1.5 enantiomeric ratio (e.r.).
Alkyl-substituted substrates afford vici-
nal borosilanes exclusively; aryl- and
heteroaryl-substituted alkenes deliver
the geminal isomers preferentially. Dif-
ferent classes of chiral NHCs give rise
to high enantioselectivities in the two
sets of transformations: C1-symmetric
monodentate Cu complexes are most
suitable for reactions of alkyl-contain-
ing vinylsilanes and bidentate sulfo-
nate-bridged variants furnish the high-
est e.r. for substrates with an aryl sub-
stituent. Working models that account
for the observed trends in selectivity
are provided. Utility is demonstrated
through application towards a formal
enantioselective total synthesis of natu-
rally occurring antibacterial agent bru-
guierol A.
Keywords: boron
· borosilanes ·
copper · enantioselective catalysis ·
silicon · synthesis
Me2PhSi–BACHTUNGTRENNUNG(pin), readily and inexpen-
Introduction
nome and their co-workers have led to the development of
inter-[6] as well as intramolecular[7] Pt-catalyzed boron–sili-
con additions to alkyl-substituted alkenes. Another notewor-
thy advance by Ito, Toyoda, and Sawamura illustrates that
Cu–phosphine catalysts can promote copper–boron addition
to aliphatic vinylsilanes.[8] More recently, it has been shown
that activation of a B–Si bond with KOtBu in the presence
of aryl alkenes results in the formation of the corresponding
borosilanes.[9,10] The above transformations take place with
high site selectivity. Although a limited number of catalytic
enantioselective methods for generation of borosilanes has
been disclosed,[11] protocols leading to the formation of
products of the type presented here (cf. Scheme 1) have not
been described.
We have reported that aryl alkenes[1] and vinylborons[2] un-
dergo highly enantioselective copper–boron additions with
chiral NHC–Cu–BACHTUNGTRENNUNG(pin) complexes (pin=pinacolato); in situ
protonation of the resulting C–Cu bond, which occurs with
retention of stereochemistry, leads to the formation of the
corresponding protoboration products[3] in high enantiomer-
ic purity.[4] A notable attribute of the above transformations
is their exceptional site selectivity. Reactions entail prefer-
ential placement of the NHC–Cu at the carbon bearing the
aryl or the (pinacolato)boron,[5] allowing the accumulated
electron density at the carbon of the incipient Cu–C bond to
be stabilized by the adjacent aryl or BACTHNUTRGNEUNG(pin) group (hyper-
conjugation with aryl p* or boron p orbital, respectively).
Cu-catalyzed H–B additions to vinylsilanes can afford vi-
cinal or geminal enantiomerically enriched borosilanes.
Within this context, pioneering investigations by Ito, Sugi-
Our interest in examining Cu-catalyzed copper–boron ad-
ditions to vinylsilanes derives not only from their potential
utility in chemical synthesis, but also from several funda-
mental mechanistic questions. Based on previous studies, as
illustrated in Scheme 1, we predicted that in reactions of
alkyl-substituted substrates there would be a strong prefer-
ence for the generation of vicinal borosilyl products (elec-
tron density at Cu–C stabilized by silyl unit); in such instan-
ces, it was unclear whether transformations would take
place with high efficiency and enantioselectivity. With aryl-
substituted vinylsilanes, on the other hand, two additional
questions present themselves: Does formation of the Cu–C
[a] F. Meng, H. Jang, Prof. A. H. Hoveyda
Department of Chemistry
Boston College
Chestnut Hill, MA 02467 (USA)
Fax : (+1) 617-552-1442
E-mail: amir.hoveyda@bc.edu
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203803.
3204
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Chem. Eur. J. 2013, 19, 3204 – 3214

FULL PAPER
menced by developing a proto-
col for synthesis of gram quan-
tities of vinylsilanes that is cost-
effective, reliable, and selec-
tive.[15] Complete (vs. high) site-
as well as stereoselectivity (i.e.,
>98%) is critical for the prepa-
ration of this valuable class of
organosilicon molecules,[16] as it
is virtually impossible to sepa-
rate the a- and b-vinylsilane
isomers. Our desire to intro-
duce a new catalytic method for
synthesis of vinylsilanes was
therefore based on the fact
that, although there are extant
methods for E- and b-selective
Scheme 1. NHC–Cu-catalyzed Cu–B additions to alkyl- and aryl-substituted vinylsilanes: Similar or opposite
trends in site selectivity?
bond preferentially occur at the aryl- or silyl-substituted
carbon? Can the chiral catalyst influence site selectivity?[12]
We will begin by outlining an exceptionally efficient, gen-
eral and exceptionally site- and stereoselective protocol for
net protosilylation of terminal alkynes that is easily amena-
ble to gram-scale preparations;[13] substantial quantities of
vinylsilanes can be obtained through the use of a readily
and inexpensively prepared reagent with complete stereo-
and site selectivity [>98% terminal C–Si (b) and E; minor
isomers undetected by 400 MHz 1H NMR spectroscopy].
We then disclose methods for catalytic site- and enantiose-
lective protoboration [i.e., Cu–B(pinacolato) additions/Cu–
C protonation] of the resulting (E)-b-vinylsilanes,[14] which
are converted to enantiomerically enriched vicinal or gemi-
nal borosilanes by mono- or bidentate chiral NHC–Cu cata-
lysts. Reactions proceed in the presence of commercially
available bis(pinacolato)diboron (1), affording the desired
borosilyl products in up to >98% site selectivity and
98.5:1.5 enantiomeric ratio (e.r.).
We will demonstrate that the enantioselective Cu–B addi-
tions to vinylsilanes involve two distinct modes of reaction
catalyzed by two different types of N-heterocyclic carbene
(NHC) copper complexes. Additions to alkyl- and alkenyl-
substituted vinylsilanes require monodentate chiral NHC li-
gands and afford enantiomerically enriched vicinal silylbor-
on species. In contrast, it is the chiral sulfonate-bridged bi-
dentate NHC–Cu complexes that furnish optimal selectivity
for protoborations of aryl-substituted substrates, which react
with the opposite sense of site selectivity and deliver gemi-
nal silylborons predominantly. Mechanistic models account-
ing for the observed site- and enantioselectivities, as well as
representative functionalization demonstrating the methodꢁs
utility, including a formal enantioselective synthesis of anti-
bacterial agent bruguierol A, will be presented.
alkyne hydrosilylation,[17] a broadly applicable and practical
approaches, particularly one that reliably delivers >98%
site- and stereoselectivity, was lacking. In addition, the re-
ported protocols suffer from limited substrate range and/or
require the use of rare and costly metals (e.g., Rh,[18] Pt,[19]
or Ru[20,21] complexes). A more recent procedure allows
access to a wide array of silyl-substituted alkenes with high
E selectivity, but calls for the use of stoichiometric amounts
of chromium salts and dihalomethyl silanes, which must be
synthesized separately.[22]
A
titanocene-based strategy
(Cp2TiCl2/nBuLi) has been outlined, but reactions are limit-
ed to n-alkyl-substituted terminal alkynes.[23] Finally, we find
that vinylaluminum reagents, obtained through reactions of
terminal alkynes with diisobutylaluminum hydride (dibal–
H)[24] cannot be reacted efficiently with PhMe2SiCl (<10%
yield).
Alkyl- or aryl-substituted (E)-b-vinylsilanes are readily
obtained in 79–98% yield with complete stereo- and site se-
lectivity (>98% E and b) through NHC–Cu-catalyzed pro-
tosilylation of alkynes (Table 1); in none of the reactions
1
were we able to detect any a or Z isomers by H NMR anal-
ysis (400 MHz).[25] Transformations, which have been per-
formed on 0.6–2.0 gram scale, proceed in the presence of
1.0 mol% of imidazolinium salt 3, CuCl, and 4.0 mol%
NaOtBu, all of which are commercially available and inex-
pensive. Moreover, the borosilane reagent [Me2PhSi–B-
AHCTUNGTREG(NNNU pin)], which can be purchased if so desired, can simply be
prepared[26] on multi-gram quantities easily through a one-
vessel procedure with commercially available reagents in-
cluding inexpensive phenyldimethylsilyl chloride. Indeed, we
have synthesized Me2PhSiBACTHNURGTNE(UNG pin) on ~20 gram scale without
any complications and from cheap starting materials pur-
chased from common vendors. The borosilane generated
need not be purified prior to use: it can be employed direct-
ly, after simple filtration (to remove lithium hydride byprod-
uct), in NHC–Cu-catalyzed protosilylation reactions.
Results and Discussion
Exclusive generation of the b isomer (>98%), regardless
of the electronic attributes of the alkyne substituent, indi-
cates that high site selectivity is controlled by steric factors,
where the sizeable dimethylphenylsilyl group is placed at
Site- and stereoselective synthesis of vinylsilanes by NHC–
Cu-catalyzed protosilylation of terminal alkynes: We com-
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3205

A. H. Hoveyda et al.
Table 1. (E)-b-Vinylsilanes through NHC–Cu-catalyzed protosilylation of alkynes per-
ing to Cu–C bond formation do not exert as signifi-
cant an influence on the course of addition.[28]
formed on 0.6–2.0 gram scale.[a]
Site- and enantioselective protoboration [Cu–B ad-
dition/Cu–C protonation] of vinylsilanes: Examina-
tion of various chiral NHC–Cu complexes: We then
probed the ability of chiral Cu–NHC complexes to
promote efficient enantio- and site-selective proto-
borations. We examined the reactions of alkyl-sub-
stituted vinylsilane 4a (Table 2, entries 1–7) and es-
tablished that mono- and bidentate NHC–Cu com-
plexes can be used to catalyze site-selective trans-
formations to generate 10a (Table 2).[29] As predict-
ed (see above), Cu–B addition occurs such that the
transition metal is placed at the Si-substituted
carbon. Importantly, it is the C1-symmetric com-
plexes,[30] derived from imidazolinium salts 6a and
6b (Table 2, entries 2 and 3: ꢀ98% conv., 93% and
85% yield, 85:15–87:13 e.r.), that catalyze C–B
bond formation with higher enantioselectivity than
their C2-symmetric (5; Table 2, entry 1: 57:43 e.r.)
Entry
G
E:Z[b]
b:a[b]
Yield [%][c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
nBu
ACHTUNGTRENNUNG
a
b
c
d
e
f
g
h
i
j
k
l
m
n
>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
>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
94
98
82
80
97
94
93
87
85
82
80
90
79
87
ACHTUNGTRENNUNG
CH
Cy
Ph
oMeC6H4
oFC6H4
oF3CC6H4
oMeOC6H4
mFC6H4
pFC6H4
2ACHTUNGTRENNUNG(pentenyl)
3-thienyl
[a] Reactions were performed under N2 atmosphere; >98% conv. in all cases. See the
Supporting Information for details. [b] Determined through analysis of 400 MHz or bidentate variants (7–9; Table 2, entries 4–7:
1H NMR spectra of unpurified product mixtures. [c] Yield of isolated and purified
products (Æ5%).
34.5:65.5–78.5:21.5 e.r.). The aforementioned trend
is unlike the previously reported cases with aryl ole-
fins[1] and vinylboron substrates,[2] where NHC–Cu
complexes derived from sulfonate-bridged ligands
the terminal carbon; this suggests that formation of the Cu–
C bond, protonation of which affords the protosilylation
product,[27] is likely less developed in the transition state,
compared to the C–Si bond and thus steric factors pertain-
(e.g., 8 and 9) are the most effective.
The trends in site selectivity as well as the identity of the
most effective chiral catalysts are entirely different with
aryl-substituted vinylsilane 4g (Table 2, entries 8–14). All
Table 2. Evaluation of site- and enantioselectivities obtained through the use of various chiral NHC–Cu complexes.[a]
Entry
Vinylsilane
Imid. Salt
Conv. [%][b]
Yield [%][c]
10:11[b]
e.r. (major isomer)[d]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
4a
4a
4a
4a
4a
4a
4a
4g
4g
4g
4g
4g
4g
4g
5
32
>98
98
74
92
53
87
92
90
>98
93
>98
>98
>98
30
93
85
61
78
44
84
74
75
81
79
80
90
81
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
37:63
30:70
30:70
35:65
52:48
8:92
57:43
85:15
87:13
78.5:21.5
60:40
34.5:65.5
45:55
62:38
56:44
63:37
6a
6b
7
8a
8b
9
5
6a
6b
7
8a
8b
9
44:56
87.5:13.5[e]
98:2
10:90
95:5
[a] Reactions were performed under N2 atmosphere. [b] Determined through analysis of 400 MHz 1H NMR spectra of unpurified mixtures. [c] Yields of
isolated and purified products (Æ5%); values for entries 8–14 correspond to total yield for both borosilane isomers. [d] Enantiomeric ratio (e.r.) deter-
mined by HPLC analysis; see the Supporting Information for details. [e] Enantioselectivity relates to geminal borosilane 11g.
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Chem. Eur. J. 2013, 19, 3204 – 3214

Enantiomerically Enriched Vicinal and Geminal Borosilanes
FULL PAPER
Table 3. Site- and enantioselective NHC–Cu-catalyzed protoboration of alkyl- and aryl-substituted
vinylsilanes.[a]
catalysts offer similar efficiency
(90% to >98% conv., 74–90%
yield). Monodentate carbene
complexes derived from 5 or
6a,b (Table 2, entries 8–10),
however, deliver only a small
preference for formation of
geminal borosilane 11g, and re-
action with phenol-containing 7
takes place with low selectivity
(Table 2, entry 11: 65% 11g).
In sharp contrast, sulfonate
salts 8b and 9 catalyze addi-
tions that afford the geminal
Entry Vinylsilane; G
Imid. Salt T [8C] Conv. [%][b] Yield [%][c] 10:11[b]
e.r.
(major isomer)[d]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
4a; nBu
6b
6b
6b
6b
À15
À15
À15
À15
À15
À15
22
22
22
22
22
91
95
>98
71
96
34
>98
68
77
>98
81
>98
90
84
89
94
59
92
33
90
62
75
94
69
90
84
84
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
8:92
11:89
8:92
<2:>98 93:7
15.5:84.5 93:7
91:9
91.5:8.5
92:8
4b; (CH2)3Cl
4c; (CH2)3CO2Me
4d; CH2OTBS
4e; CH2(cyclopentenyl) 6b
4 f; Cy
84:16
91.5:8.5
96.5:3.5
98:2
96.5:3.5
93.5:6.5
6b
6b
8b
9
9
9
9
8b
9
4g; Ph
4h; oMeC6H4
4i; oFC6H4
4j; oF3CC6H4
4k; oMeOC6H4
4l; mFC6H4
4m; pFC6H4
4n; 3-thienyl
borosilane
predominantly
(Table 2, entries 13 and 14: 90–
92% 11g). Another distinction
is that, unlike monodentate
NHC–Cu complexes derived
from 5 and 6a,b or phenol-con-
taining 7, which deliver prod-
ucts that are nearly racemic
(44:56–63:37 e.r., entries 8–11,
22
22
22
2:98
16:84
11:89
95:5
98:2
98.5:1.5
91
[a] Reactions were performed under N2 atmosphere. [b] Determined through analysis of 400 MHz 1H NMR
spectra of unpurified mixtures. [c] Yields of isolated and purified products (Æ5%); values correspond to total
yield for both borosilane isomers. [d] Enantiomeric ratio (e.r.) determined by HPLC analysis; see the Support-
ing Information for details.
Table 2),
those
prepared
through sulfonates 8a,b and 9
yield 11g in 86.5:13.5, 98:2 and 95:5 e.r., respectively (en-
tries 12–14).
NHC–Cu-catalyzed enantioselective protoborations of alkyl-
and aryl-substituted vinylsilanes: Reactions with alkyl-sub-
stituted vinylsilanes (Table 3, entries 1–6), performed at
À158C to achieve the highest enantioselectivity (84:16–
96.5:3.5 e.r.), are completely site-selective (>98% vicinal
borosilanes). The cases of silyl ether (4d; entry 4) and cyclo-
hexyl-containing substrates (4 f; entry 6) indicate that reac-
tion efficiency can be sensitive to steric repulsion caused by
the sizeable BACHTUNGTRENNUNG(pin) and the relatively large substituents that
reside at the site of C–B bond formation.
Compared to vinylsilanes that carry an alkyl group, enan-
tioselective copper–boron additions with aryl- and heteroar-
yl-substituted vinylsilanes deliver high e.r. values when per-
formed at 228C (Table 3, entries 7–14; 93:7–98.5:1.5 e.r.);
unlike the reactions in entries 1–7 of Table 3, lowering of re-
action temperature does not alter enantioselectivities. Site
selectivities with aryl-containing substrates, although not as
exceptionally high as with alkyl-substituted variants, gener-
ate geminal borosilanes preferentially (84% to >98%).
Consistent with the previously proposed rationale regarding
the hyperconjugative stabilization of the incipient Cu–C
bond,[1,2] reactions of substrates with aryl units that carry an
electron-withdrawing group lead to higher degrees of site se-
lectivity (e.g., compare entries 10 and 11, Table 3).
Scheme 2. NHC–Cu-catalyzed site- and enantioselective protoboration of
a vinyl-substituted vinylsilane.
Cu-catalyzed copper–boron addition/protonation of vinyl-
substituted olefin 12 (Scheme 2) and subsequent treatment
with benzaldehyde leads to the formation of a 7:1 mixture
of trisubstituted allylsilanes 14 and 15 (85% combined over-
all yield); each isomer is formed in 95:5 e.r. and with com-
plete control of relative stereochemistry [>98:2 diastereo-
meric ratio (d.r.)]. These observations indicate that, contrary
to reactions with aryl-substituted vinylsilanes, where the
Cu–C bond is generated at the benzylic site (to give geminal
silylborons), an alkene substituent does not compete with a
silyl unit, and the aforementioned carbon–metal bond is
formed exclusively at the Si-bearing carbon (>98%; afford-
ing an allyl- and not a homoallylboron). Furthermore, the
NHC–Cu-catalyzed enantioselective protoboration of an al-
kenyl-substituted vinylsilane: Catalytic protoboration of
diene 12, presented in Scheme 2, sheds additional light re-
garding the mechanism of the Cu-catalyzed process. NHC–
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A. H. Hoveyda et al.
site selectivity shown in Scheme 2 is in direct contrast to for-
merly disclosed Cu–B additions of non-silyl-containing acy-
clic 1,3-dienes promoted by Cu–phosphine complexes;[31]
such transformations afford homoallylic (pinacolato)boron
species predominantly, albeit with low enantioselectivity
(71:29 e.r. for the one reported example). The observed site
selectivity in the latter study indicates that generation of the
Cu–C bond is favored to occur at the allylic site, implying
that the presence of the silyl unit in 12 is capable of over-
ruling such a preference. Additional mechanistic implica-
tions of the above findings will be described below.
Scheme 3. Antibacterial natural products bruguierols A–C.
Representative functionalization and utility in chemical syn-
thesis: The Cu-catalyzed protocol detailed above provides
access to borosilyl entities that cannot be prepared efficient-
ly or selectively through the use of common methods involv-
ing various boron hydride reagents. For example, when n-
butyl-substituted 4a is treated with three equivalents of
BH3·thf (3.0 h, 228C) or 9-borabicyclononane (9-BBN) after
two hours at 608C, a 1:1 and 2:1 mixture of geminal:vicinal
borosilanes are generated. Furthermore, under the same
conditions, none of the organoboron products are obtained
upon treatment of phenyl-substituted vinylsilane 4g with 9-
BBN (<2% conv.). Subjection of the same substrate with
BH3·thf results a 4:1 mixture of the vicinal and geminal
products (>98% conv.).
Previous research in other laboratories has demonstrated
that C–B bonds in enantiomerically enriched borosilanes
can be selectively functionalized (vs. C–Si bonds).[32] For ex-
ample, as illustrated in Equation (1), geminal products can
be converted to the derived enantiomerically enriched allyl-
silanes,[33] representative of an important class of reagents in
chemical synthesis,[34] based on an efficient procedure re-
cently introduced by Aggarwal and co-workers.[35] The abili-
ty to prepare silyl-substituted olefins of high enantiomeric
purity is noteworthy, since there are only a small number of
catalytic enantioselective approaches that furnish access to
this valuable class of organosilicon reagents, and none of the
existing protocols offer an attractive approach for synthesis
of entities such as 16 [Eq. (1)].[36] Adoption of the reported
procedures would be less attractive, as they would require
bacteria, and were isolated in 2005 from the stem of the
Bruguiera gymmorrhiza tree.[38]
The route for enantioselective synthesis of bruguierol A[39]
is illustrated in Scheme 4. Sequential NHC–Cu-catalyzed
protosilylation and protoboration of commercially available
aryl alkyne 2o leads to the formation of geminal borosilane
17 in 77% overall yield, 97% site selectivity and 97.5:2.5
e.r. Conversion to allylsilane 18, proceeds in the same
manner as described above in 85% yield [cf. Eq. (1)]. Site-
selective Rh-catalyzed hydroformylation[40] of the terminal
alkene (7:1 linear:branched) involving in situ reduction of
the aldehyde formed delivers enantiomerically enriched silyl
carbinol 19 in 80% yield. Subsequent oxidation of the C–Si
bond[41] in the presence of NaHCO3, based on a procedure
developed by Krohn and Khanbabaee,[42] affords diol 20 in
84% overall yield. Catalytic oxidative conversion to lactone
21 (79% yield),[43] followed by methyl addition/Lewis acid-
catalyzed cyclization generates tricyclic 22 (65% overall
yield for the two steps), conversion of which to the natural
product has been previously reported.[44]
Several attributes of the sequence presented in Scheme 4,
underlining the utility of the Cu-catalyzed catalytic proto-
cols developed in this study, are noteworthy:
1) The enantiomerically enriched secondary carbinol 20, a
representative of a class of alcohols that can be obtained
through the present set of NHC–Cu-catalyzed protocols,
cannot be prepared efficiently by the use of NHC–Cu-cata-
lyzed protoboration protocol developed recently in these
laboratories.[1a] As exhibited in the transformation in Equa-
tion (2), in spite of higher loading (7.5 vs. 5.0 mol%) catalyt-
ic Cu–B addition to the disubstituted aryl alkene that lacks
an allylic heteroatom unit is significantly less efficient.[45]
the use of di
preparation of which is less than straightforward; if di-
ACHTUNGTRENNUNG
(alkyl)benzylaluminum species are employed,[37] a mixture
ACHTUNGTRENNUNG(benzyl)zinc or triACHUTNGTREN(NGUN benzyl)aluminum reagents,
of benzyl and alkyl addition products would likely be ob-
tained.
To explore and demonstrate further the utility of the Cu-
catalyzed method, we have ex-
amined the possibility of apply-
ing the NHC–Cu-catalyzed pro-
tosilylation/protoboration
se-
quence towards synthesis of
bruguierol A. Bruguierols A–C,
shown in Scheme 3, are mem-
bers of a family of natural prod-
ucts active against Gram-posi-
tive as well as Gram-negative
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Enantiomerically Enriched Vicinal and Geminal Borosilanes
FULL PAPER
Scheme 4. Application of the Cu-catalyzed method towards enantioselective synthesis of bruguierol A.
2) To the best of our knowledge, catalytic enantioselective
reduction of ketones that carry a linear and a b-branched
unit is scarce and likely proceed with low preference due to
the similarity in the size of the two substituents.[46]
formations that involve alkyl-substituted substrates (cf. en-
tries 1–7, Table 2); therefore, Cu–B must be aligned with the
C–C double bond in such a way that leads to the generation
of a Si-substituted Cu–C bond. In the case of silyl-containing
aryl olefins, on the other hand, where either the silyl or the
aryl group is capable of influencing site selectivity, only cer-
tain sulfonate-bridged bidentate NHC–Cu complexes fur-
nish a relatively strong preference for the geminal borosi-
lanes (cf. entries 8–14, Table 2); the reason for such site se-
lectivities will be discussed in the next section.
For alkyl-substituted vinylsilanes, examination of molecu-
lar models indicates that similar unfavorable steric interac-
tions are present in the modes of addition represented by I
and II (Scheme 5); the low reactivity with the sterically
more congested 8b (entry 6, Table 2; 53% conv.) supports
this contention. The manner in which the vinylsilane is pro-
posed to associate with the chiral cuprate in I and II under-
lines the significance of one of the more distinctive structur-
al attributes of sulfonate-containing family of bidentate cup-
rates; the syn stereochemistry of the bridging ligand and the
phenyl group of the chiral carbene[47] leads to the availability
of a relatively spacious binding pocket to allow the Cu com-
plex to make room for the large vinylsilane as shown in I
and II (as well as V and VI, Scheme 5).[49] When the reaction
involves the monodentate NHC–Cu complex, Cu–B addition
occurs more readily (98% conv., entry 3, Table 2) and pref-
erentially through III; the steric repulsion between the large
dimethylphenylsilyl group and the phenyl unit of the chiral
NHC moiety, as highlighted in IV (Scheme 5), appears to
3) Although the strategy in Scheme 4 involves a slightly
longer sequence than a previously reported approach,[39c] it
is the first to utilize a catalytic enantioselective process (vs.
the use of chiral pool as the substrate source) and requires
lower loadings of a precious metal (0.5 mol% Rh vs.
5.0 mol% Pt salt). Additionally, diol 20 has been prepared
through enantioselective allyl addition to the corresponding
aldehyde,[39b] followed by hydroboration of the resulting ho-
moallylic alcohol; such an approach, however, is less concise
than that illustrated in Scheme 4 (two additional steps from
a commercially available starting material).
Stereochemical models to account for levels and trends in
enantioselectivity: The enantioselectivity outcomes in Cu-
catalyzed protoborations of alkyl- and aryl-substituted vinyl-
silanes can be rationalized through the models presented in
Scheme 5. The stereochemical isomers represented for the
chiral NHC–Cu complexes are based on the strong structur-
al preferences indicated by spectroscopic as well as crystal-
lographic data available for sulfonate-bridged bidentate[47]
and monodentate complexes and/or ligands.[48]
The variations in the identity of the most effective catalyst
for reactions of alkyl- versus aryl-substituted vinylsilanes
partly arise from differences in the preferred modes of site
selectivity. Vicinal isomers are formed exclusively in trans-
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3209

A. H. Hoveyda et al.
Scheme 5. Proposed models for the observed levels and trends in enantioselectivity.
lead to significant destabilization of IV, thus leading to the
observed levels of enantioselectvity with monodentate cata-
lysts.
products (92% and 90%, respectively; entries 13 and 14,
Table 2). In reactions with bidentate complexes derived
from 8b or 9, among the four possible modes of addition, V
and VI in Scheme 5 and IX and X in Scheme 6, only one
(V) seems to be devoid of destabilizing steric repulsion that
is engendered upon substrate binding. Similar to factors that
determine enantioselectivity (see above), when mesityl-con-
taining 8a is used, the smaller ortho methyl unit does not
present the same degree of steric hindrance as is observed
with 8b (shown in Scheme 5 and 6) or 9 and site selectivity
suffers. In support of the proposed model, site selectivity is
In catalytic protoborations of aryl-substituted vinylsilanes,
copper–boron addition can occur via modes V or VI
(Scheme 5); the steric interaction with the protruding ortho
substituent of the NHCꢁs N–Ar moiety (iPr in 8b, Ph in 9)
is more costly in VI, when it involves the larger dimethyl-
phenylsilyl unit (vs. an H in V). The lower e.r. obtained with
8a, which carries a smaller N–Mes (Table 2, entries 12 and
13; 86.5:13.5 vs. 98:2 e.r.) as well as the similarly high enan-
tioselectivity delivered by 9 (Table 2, entries 13 and 14; 98:2
vs. 95:5 e.r.) are congruent with the suggested scenario.
Unlike the significant energetic difference between III and
IV that arises from the sizeable silyl unit, the degree of dis-
crimination between VII and VIII is too small to furnish
products of high enantiomeric purity.[50]
Origin of high site selectivity in reactions of aryl-substituted
vinylsilanes catalyzed by sulfonate-bridged bidentate NHC–
Cu complexes: The findings presented in Tables 2 and 3 in-
dicate that the differences in the electronic attributes of an
alkyl and a silyl group lead to uniformly high site selectivity
in the copper–boron addition process, leading to the forma-
tion of a silyl-substituted Cu–C bond. When aryl-substituted
vinylsilanes serve as the substrates, where either the aryl or
the silyl group[51] can serve to stabilize the incipient Cu–C
bond (see below for further discussion), NHC–Cu com-
plexes derived from monodentate imidazolinium salts such
as 5 or 6a, b, as well as that derived from phenolic 7, deliver
moderate selectivities in favor of the geminal borosilanes.
Sulfonate-bridged Cu complex generated through the use of
8a gives a nearly equal mixture of the two isomers (52% vi-
cinal product; entry 12, Table 2). It is the unique attribute of
bidentate cuprates originating from salts 8b and 9 that cul-
minates in a strong preference for the formation of geminal
Scheme 6. Rationale for high site selectivity in reactions of aryl-substitut-
ed vinylsilanes.
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Enantiomerically Enriched Vicinal and Geminal Borosilanes
FULL PAPER
affected more severely than enantioselectivity when Mes-
containing 8a is used (vs. 8b or 9; see entries 12–14,
Table 2); it is the competition between modes of reaction
represented by X and VI that determine site selectivity (low
preference in the case of 8a), whereas enantioselectivity is
dictated by whether the pathway represented by V is prefer-
red over that which proceeds through VI (the latter being
more energetically demanding). With regard to reactions of
aryl-substituted vinylsilanes and monodentate NHC–Cu
complexes, in addition to transformations that would pro-
ceed via VII–VIII (Scheme 5), the alternative pathway that
involves XI (Scheme 6) would be equally favorable; molecu-
lar models indicate that the tilt of the symmetric 2,6-diethyl-
phenyl moiety of the chiral ligand allows the large silyl
group to be readily accommodated, leading to low site selec-
tivity.
copper–boron addition to an aryl-substituted vinylsilane can
be made to proceed in high site selectivity with the aromatic
ring substituent serving as the overriding group (e,
Scheme 7), even though a silyl group is capable of exerting
strong control of site selectivity (>98% vicinal borosilanes
with alkyl-substituted vinylsilanes; Tables 2 and 3). In com-
petition with an alkenyl unit, however, a silyl group exerts
the stronger influence, causing exclusive formation of a vici-
nal borosilane (Scheme 2 and f, Scheme 7).
Thus, in cases where an alkene with only one strong di-
recting group (a substituent that can effectively stabilize the
incipient Cu–C bond), such as vinylborons that are alkyl-
substituted, vinylsilanes, and aryl olefins (a–c, Scheme 7) as
well as an alkenyl-substituted vinylsilane (f), site selectivity
is under substrate-control; in such instances, all NHC–Cu
catalysts, regardless of whether they are mono- or bidentate,
afford high site selectivity. In contrast, with vinylboron and
vinylsilane entities that are aryl-substituted (d and e,
Scheme 7), it is only sulfonate-bridged bidentate NHC–Cu
complexes that deliver high site selectivity (cf. Table 2);
other catalyst systems deliver minimal discrimination. As an
example, when the NHC–Cu complex derived from imidazo-
linium salt 3 and CuCl is used to effect protoboration of
phenyl-substituted vinyl(pinacolato)boron, a nearly equal
mixture of vicinal and geminal diboron products are ob-
tained [55:45; 1.0 mol% NHC–Cu–Cl from 3, 1.0 mol%
Site selectivity of Cu–B addition as a function of substrate
versus catalyst control: The variations in site selectivity as a
function of the electronic attributes of the vinylsilane sub-
stituent, as summarized in Scheme 7, provide additional in-
sight regarding the mechanism of Cu-catalyzed C–B bond
NaOtBu, 1.1 equiv B2ACTHNUTRGNEUNG(pin)2, 2.0 equiv MeOH, toluene, 228C,
1.0 h]. Thus, in cases where a substrate alkene carries two
able directing units, high selectivity must be, and has been,
achieved through catalyst control.
Conclusion
The investigations described here put forth a cost effective,
general, efficient and selective catalytic protocol for synthe-
sis of a wide assortment of (E)-b-vinylsilanes, which can be
converted by another Cu-catalyzed method, to two different
classes of borosilanes. The investigations described above
further illustrate utility of chiral C1-symmetric monodentate
and—in particular—the bidentate sulfonate-containing
NHC–Cu catalysts in facilitating site- and stereoselective
synthesis of organoboron entities. The C–B and C–Si bonds
within the resulting products might be differentiated by a
variety of well-established procedures that convert the
former to C–C, C–O or C–N bonds;[52] as a result, the Cu-
catalyzed site- and enantioselective protocol should prove to
be of utility. Factors that control the site selectivity with
which copper–boron addition occurs (e.g., substrate vs. cata-
lyst control), as elucidated in the investigations presented
herein, should prove critical in further development of this
class of catalytic transformations.
Scheme 7. The influence of different substituents on the sense of site se-
lectivity in NHC–Cu-catalyzed Cu–B additions.
forming reactions. It can be readily predicted that with a
boron-,[2] aryl-,[1] or silyl-substituted alkene (cf. Tables 2 and
3), the Cu–C bond is favored to be generated at the carbon
that bears the aforementioned substituent with >98% selec-
tivity (a–c, Scheme 7). It is more difficult to forecast, a
priori, whether any site selectivity should be expected—and
in favor of which isomer—when an olefin substrate carries
two of the three units (boryl, silyl, and aryl groups) that can
give rise to high site selectivity (e.g., d–f, Scheme 7). Previ-
ous investigations indicate that, in spite of the fact that an
aryl and a (pinacolato)boron group are strong directing
units (cf. a and b), in a Cu–B addition to an aryl-substituted
vinylboron substrate, in the presence of the appropriate Cu
catalyst (see below),[2a] the (pinacolato)boron moiety can
play a dominant role in determining the site of Cu–C bond
formation (d, Scheme 7). As demonstrated in this study,
Studies in connection with the design of additional chiral
NHC ligands for other metal-catalyzed copper–boron addi-
tions are underway. Development of efficient and stereose-
lective functionalization of such boron-containing organo-
copper entities other than protonation of the Cu–C bonds,
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3211

A. H. Hoveyda et al.
(0.5 mL). The vessel was sealed with a cap and the mixture allowed to
stir at 228C for 2.0 h. Bis(pinacolato)diboron (1; 27.9 mg, 0.110 mmol)
was added to the above solution, causing it to turn immediately dark
brown. The vial was re-sealed and removed from the glovebox, and the
solution was allowed to stir at 228C for 30 min under an atmosphere of
demonstration of their utility in chemical synthesis and ap-
plications to preparation of complex molecules are in prog-
ress.
N2. After this time, (E)-dimethylACTHNUGTRENNUG(phenyl)ACHTUGNTREN(NUGN styryl)silane (4g, 23.8 mg,
0.100 mmol) and MeOH (8.2 mL, 0.200 mmol) were added, and the re-
sulting mixture was allowed to stir at 228C for 24 h. The reaction was
quenched by passing the mixture through a short plug of celite and silica
gel and eluted with Et2O (3ꢂ2 mL). The filtrate was concentrated in
vacuo to provide a brown oil, which was purified by silica gel chromatog-
raphy (hexanes:Et2O=80:1) to afford 11g (along with 8% 10g) as a col-
orless oil (33.0 mg, 0.0901 mmol, 90% yield).
Experimental Section
Representative procedure for alkyne protosilylation: In a N2-filled glove-
box, an oven-dried vial (4 mL, 17ꢂ38 mm) with a magnetic stir bar was
charged with imidazolinium salt 3 (30.8 mg, 0.0900 mmol, 1.0 mol%),
CuCl (9.0 mg, 0.090 mmol, 1.0 mol%), NaOtBu (34.6 mg, 0.360 mmol),
and tetrahydrofuran (thf, 10 mL). The reaction vessel was sealed and the
solution was allowed to stir at 228C for 2.0 h. The borosilane reagent
Compound 11g: IR (neat): n˜ =3067 (w), 3025 (w), 2977 (m), 1494 (m),
1351 (s), 1248 (m), 1143 (s), 1113 (m), 837 (m), 814 (m), 774 (m), 730 (s)
(Me2PhSi–BACHTUNGTRENNUNG(pin); 2.478 g, 9.450 mmol) was added to the solution, caus-
1
cmÀ1; H NMR (400 MHz, CDCl3): d=7.60–7.58 (2H, m), 7.38–7.36 (3H,
ing the solution to turn immediately dark brown. The vial was re-sealed
and removed from the glovebox; the solution was allowed to stir at 228C
for 30 min under an atmosphere of N2. Phenylacetylene (988 mL,
9.00 mmol) and MeOH (547 mL, 12.5 mmol, 1.5 equiv) were added. The
resulting mixture was allowed to stir at 228C for 12 h before the reaction
was quenched by passing the mixture through a short plug of celite and
silica gel and eluted with Et2O (3ꢂ2 mL). The filtrate was concentrated
in vacuo to provide a brown oil, which was purified by silica gel chroma-
tography (hexanes:Et2O=80:1) to afford the desired product 4g as a col-
orless oil (1.988 g, 0.927 mmol, 93% yield).
m), 7.21–7.16 (4H, m), 7.11–7.09 (1H, m), 2.78 (1H, dd, J=14.0,
12.0 Hz), 2.68 (1H, dd, J=14.0, 3.2 Hz), 1.09–1.05 (7H, m), 1.02 (6H, s),
0.39 (3H, s), 0.37 ppm (3H, s); 13C NMR (100 MHz, CDCl3): d=144.9,
138.7, 134.0, 129.1, 128.3, 128.1, 127.8, 125.5, 83.0, 31.7, 25.0, 24.8, 16.2,
À2.2, À3.3 ppm; HRMS (ESI+): calcd for C22H35B1N1O2Si1 [M+NH4]+:
20
384.2530; found: 384.2523; specific rotation: [a]D +14.8 (c=1.73,
CHCl3) for an enantiomerically enriched sample of 98:2 e.r.
Compound 4g: IR (neat): n˜ =3067 (w), 2995 (w), 2955(w), 1947 (w), 1604
(m), 1427 (m), 1301 (m), 1112 (m), 1027 (w), 989 (m), 827 (s), 726 (s),
688 (s) cmÀ1 1H NMR (400 MHz, CDCl3): d=7.59–7.56 (2H, m), 7.46–
;
Acknowledgements
7.40 (2H, m), 7.38–7.36 (3H, m), 7.35–7.31 (3H, m), 6.94 (1H, d, J=
19.2 Hz), 6.59 (1H, d, J=19.2 Hz), 0.44 ppm (6H, s); 13C NMR
(100 MHz, CDCl3): d=145.5, 138.7, 138.3, 134.1, 129.2, 128.7, 128.3,
128.0, 127.2, 126.6, À2.4 ppm; HRMS (ESI+): calcd for C16H22N1Si1 [M+
NH4]+: 256.1521; found: 256.1519.
Financial support was provided by the NSF (CHE-1111074). We thank F.
Gao and Dr. Y. Lee for helpful discussions and Frontier Scientific, Inc.
for gifts of boron-based reagents used in the study.
Representative procedure for site- and enantioselective NHC–Cu-cata-
lyzed protoboration of alkyl-substituted vinylsilanes: In a N2-filled glove-
box, an oven-dried vial (4 mL, 17ꢂ38 mm) with a magnetic stir bar was
charged with imidazolinium salt 6b (3.2 mg, 0.0050 mmol), CuCl (0.5 mg,
0.0050 mmol), NaOtBu (7.7 mg, 0.0800 mmol), and thf (0.5 mL). The
vessel was capped and the solution was allowed to stir at 228C for 2.0 h.
Bis(pinacolato)diboron (1; 27.9 mg, 0.110 mmol) was added, causing the
mixture to turn immediately dark brown. The vial was re-sealed and re-
moved from the glovebox; the resulting mixture was allowed to stir at
228C for 30 min under an atmosphere of N2. At this time, the mixture
was allowed to cool to À788C (dry ice/acetone bath) and a solution of
[1] a) Y. Lee, A. H. Hoveyda, J. Am. Chem. Soc. 2009, 131, 3160–3161;
b) R. Corberꢃn, N. W. Mszar, A. H. Hoveyda, Angew. Chem. 2011,
123, 7217–7220; Angew. Chem. Int. Ed. 2011, 50, 7079–7082.
[2] a) Y. Lee, H. Jang, A. H. Hoveyda, J. Am. Chem. Soc. 2009, 131,
18234–18235; for an application of NHC–Cu-catalyzed enantiose-
lective protoboration of a vinylboron species in the preparation of a
biologically active molecule, see:b) S. J. Meek, R. V. OꢁBrien, J. Lla-
veria, R. R. Schrock, A. H. Hoveyda, Nature 2011, 471, 461–466.
[3] We have adopted the term “protoboration” (as opposed to “hydro-
boration”) to underline the distinct mechanism through which the
transformation occurs: an initial Cu–B addition followed by Cu–C
protonation (vs. the involvement of a hydride addition process). The
label “protosilylation” is used in the same vein. A general scheme is
provided below.
(E)-hex-1-en-1-yldimethylACTHNUTRGNE(NUG phenyl)silane (4a; 21.8 mg, 0.100 mmol) in thf
(0.2 mL) followed by MeOH (8.2 mL, 0.200 mmol) were added. The vial
was placed in a À158C cryocool; after 24 h, the solution was allowed to
cool to À788C and the reaction was quenched by passing the mixture
through a short plug of celite and silica gel and eluted with Et2O (3ꢂ
2 mL). The filtrate was concentrated in vacuo to provide a brown oil,
which was purified by silica gel chromatography (hexanes:Et2O=50:1) to
afford the desired product
84% yield).
ACHTUNGTRENUN(NG 10a) as a colorless oil (29.1 mg, 0.0840 mmol,
Compound 10a: IR (neat): n˜ =2977 (w), 2956 (w), 2925 (w), 2857 (w),
1377 (m), 1315 (m), 1247 (m), 1143 (s), 1112 (m), 968 (w), 829 (s), 727
(s), 699 (s), 468 (w) cmÀ1 1H NMR (CDCl3, 400 MHz): d=7.55–7.52
;
(2H, m), 7.35–7.32 (3H, m), 1.43–1.33 (1H, m), 1.29–1.22 (5H, m), 1.21
(12H, s), 1.08–1.06 (1H, m), 1.05–0.97 (1H, m), 0.85 (3H, t, J=6.8 Hz),
0.76 (1H, dd, J=14.4, 5.2 Hz), 0.28 ppm (6H, s); 13C NMR (CDCl3,
100 MHz): d=140.3, 133.8, 128.7, 127.7, 82.9, 34.7, 31.3, 25.0, 24.9, 23.0,
16.7, 14.2, À2.1, À2.3 ppm; HRMS (ESI+): calcd for C20H39B1N1O2Si1
20
[M+NH4]+: 364.2843; found: 364.2860; specific rotation: [a]D À7.61
[4] For recent reviews on Rh-catalyzed enantioselective hydroboration,
see: a) C. M. Crudden, D. Edwards, Eur. J. Org. Chem. 2012, 4695–
4712; b) A-M. Carroll, T. P. OꢁSullivan, P. J. Guiry, Adv. Synth.
Catal. 2005, 347, 609–631.
(c=1.96, CHCl3) for an enantiomerically enriched sample of 91:9 e.r.
Representative procedure for site- and enantioselective NHC–Cu-cata-
lyzed protoboration of aryl-substituted vinylsilanes: In a N2-filled glove-
box, an oven-dried vial (4 mL, 17ꢂ38 mm) with a magnetic stir bar was
charged with imidazolinium salt 8b (2.9 mg, 0.0050 mmol, 5.0 mol%),
CuCl (0.5 mg, 0.0050 mmol), NaOtBu (7.7 mg, 0.080 mmol) and thf
[5] For initial disclosures regarding site-selective addition of an NHC–
Cu–B
ACHTUNGTREN(NUNG pin)to an alkene (styrene), see: D. S. Laitar, E. Y. Tsui, J. P.
Sadighi, Organometallics 2006, 25, 2405–2408.
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Enantiomerically Enriched Vicinal and Geminal Borosilanes
FULL PAPER
[6] M. Suginome, H. Nakamura, Y. Ito, Angew. Chem. 1997, 109, 2626–
2628; Angew. Chem. Int. Ed. Engl. 1997, 36, 2516–2518.
[7] T. Ohmura, H. Furukawa, M. Suginome, J. Am. Chem. Soc. 2006,
128, 13366–13367.
[8] H. Ito, T. Toyoda, M. Sawamura, J. Am. Chem. Soc. 2010, 132,
5990–5992.
[24] For examples of site selective aluminum–hydride additions to termi-
nal alkynes, see: F. Gao, A. H. Hoveyda, J. Am. Chem. Soc. 2010,
132, 10961–10963 and references cited therein.
[25] For addition reactions of cuprate reagents to various alkyne sub-
strates, see reference [13].
[26] For a procedure for preparation of Me2PhSiBACTHNUGRTENUNG(pin), see: M. Sugi-
nome, T. Matsuda, Y. Ito, Organometallics 2000, 19, 4647–4649. The
details of the modified protocol used by us to access multi-gram
quantities of these materials is included in the Supporting Informa-
tion.
[9] H. Ito, Y. Horita, E. Yamamoto, Chem. Commun. 2012, 48, 8006–
8008.
[10] For other catalytic (non-enantioselective) methods for synthesis of
borosilanes, see: H.-Y. Jung, J. Yun, Org. Lett. 2012, 14, 2606–2609.
[11] a) T. Ohmura, H. Taniguchi, M. Suginome, J. Am. Chem. Soc. 2006,
128, 13682–13683; b) T. Ohmura, M. Suginome, Org. Lett. 2006, 8,
2503–2506; c) H. Ito, Y. Kosaka, K. Nonoyama, Y. Sasaki, M. Sawa-
mura, Angew. Chem. 2008, 120, 7534–7537; Angew. Chem. Int. Ed.
2008, 47, 7424–7427; d) J. K. Park, D. T. McQuade, Synthesis 2012,
44, 1485–1490; for an efficient (non-catalytic) method for enantiose-
lective synthesis of geminal borosilanes, see: e) V. K. Aggarwal, M.
Binanzer, M. C. de Ceglie, M. Gallanti, B. W. Glasspoole, S. J. F.
Kendrick, R. P. Sonawane, A. Vꢃzquez-Romero, M. P. Webster, Org.
Lett. 2011, 13, 1490–1493.
[12] For an example of a strong influence exerted by a catalystꢁs struc-
ture on the outcome of NHC–Cu-catalyzed protoborations of termi-
nal alkynes, see: H. Jang, A. R. Zhugralin, Y. Lee, A. H. Hoveyda,
J. Am. Chem. Soc. 2011, 133, 7859–7871.
[13] For studies regarding silyl–copper additions to alkynes, see: a) I.
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[27] For the initial observation that in situ reaction of a copper–alkyl
complex with MeOH can lead to re-generation of the corresponding
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[28] The proposed rationale is consistent with reactivity variations as a
function of substrate structure in the related reactions of aryl olefins.
For example, whereas the NHC–Cu-catalyzed Cu–B addition/Cu–C
protonation of b-methylstyrene proceed with a similar rate com-
pared to that of its o-tolyl derivative, increasing the size of the alkyl
substituent (e.g., from Me to an iPr) has a significant effect on the
rate of reaction (cf. reference [1a]).
[29] The higher efficiency observed with excess NaOtBu (80 mol%) is
likely because, in addition to a s-bond metathesis process between
NHC–Cu–alkoxide and B
2ACHTUNGTNER(NUNG pin)2, re-generation of NHC–Cu–B-
AHCTUNGTRENNUNG
the sodium boronate derived from addition of NaOtBu or NaOMe
with the diboron reagent. See: B. Jung, A. H. Hoveyda, J. Am.
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132, 1226–1227. A mechanistic rationale for the observed selectivi-
ties was not provided in this report.
[32] Repeated attempts to effect Pd-catalyzed cross coupling of the
geminal or vicinal borosilanes with phenyl iodide resulted in <2%
conversion; such lack of reactivity is likely due to the presence of
the sizeable silyl substituent. Such findings point to a deficiency in
the state-of-the-art Suzuki-type processes, suggesting that with
future advances in such catalytic C–C bond forming reactions in-
volving organoboron reagents, a wider range of enantiomerically en-
riched organosilicon entities will become accessible through the use
of the products obtained by the present methods. For reviews on
Suzuki–Miyaura cross-coupling reactions, see: a) N. Miyuara, A.
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enantioselective synthesis of allylsilanes through Cu-catalyzed conju-
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Y. Ichikawa, K. Takatsu, F.-X. Chen, T. Hayashi, J. Org. Chem.
2009, 74, 869–873; enantiomerically enriched carbonyl-containing
allylsilanes can be accessed through enzymatic kinetic resolution
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Chem. Eur. J. 2013, 19, 3204 – 3214
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www.chemeurj.org
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A. H. Hoveyda et al.
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[45] The finding shown in Equation (2) underlines the important positive
influence of the allylic heteroatom substituents on the facility of the
reactions provided in the initial disclosure (i. e., >98% conv. and up
to 74% yield for Cu–B additions to aryl-substituted allylic alcohols
and ethers; see reference [1a]).
[36] Pure geminal borosilane 11g was obtained through selective oxida-
tion of the vicinal isomer contaminant (~8%; see entry 7, Table 3).
The C–B bonds in the vicinal isomers are more prone to oxidation.
For example, as shown below, when a 23:77 mixture of 10g and 11g
is treated with three equivalents of NaBO3·4H2O (1:1 thf/H2O,
228C, 3.0 h), the vicinal borosilane (10g) is completely consumed,
whereas there is 81% recovery of the geminal isomer (11g) after
chromatography (62% yield). Such diminution in reactivity may be
attributed to the attenuated Lewis acidity at the boron atom of
geminal borosilanes (cf. i), which can arise from stronger hypercon-
jugation of the C–Si s bond with the adjacent boronꢁs partially
vacant p orbital (vs. C–C bond in the vicinal isomers). In addition,
the interaction of the s C–B with the s* O–O, causing the 1,2-shift
that would generate the C–O bond, could be rendered less favorable
through its hyperconjugation with low-lying Si–C s* orbitals (ii).
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[49] As suggested previously,[1b] in reactions that involve less sterically
demanding substrates, such as aryl alkenes, it is the relatively more
sizeable pinacolatoboron that likely occupies the most accessible li-
gation site (vs. vinylsilanes, as illustrated in complexes I and II as
well as V and VI in Scheme 5 and IX and X in Scheme 6).
[50] In reactions involving phenoxy-containing salt 7, expected to serve
as a precursor to a bidentate complex, the enantioselectivity ob-
served with alkyl-substituted 4a and the site selectivity offered with
aryl alkene 4g are similar to those generated by monodentate cata-
lysts (cf. Table 2). Such a trend, also observed with NHC-Cu-cata-
lyzed processes involving an allenylboron reagent,[29] can be ex-
plained by the possibility that the more Lewis basic Cu–OAr more
readily reacts with bis(pinacolato)diboron by s-bond metathesis to
cause cleavage of the bidentate ligand (vs. the less Lewis basic sulfo-
nate in 8a,b and 9).
[51] Previous studies, involving enantioselective Cu–B additions to vinyl-
silanes catalyzed by chiral Cu–phosphine complexes, propose the
preferential formation of Cu–C bond at the Si-substituted carbon;
a) Ref. [8]; b) Ref. [11c]. For initial discussions regarding the effect
of electronic factors on the site selectivity of Cu–B addition to ole-
fins, see: c) Ref. [1a]; d) Ref. [2a].
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[40] For representative reviews on catalytic hydroformylation reactions,
see: a) I. Ojima, C.-Y. Tsai, M. Tzamarioudaki, D. Bonafoux in Or-
Received: October 24, 2012
Published online: January 16, 2013
3214
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