Asymmetric synthesis of α-chiral allylic silanes by enantioconvergent γ-selective copper(I)-catalyzed Allylic Silylation

Article abstract of DOI:10.1002/anie.201300648

Gamma way: Regio- and enantioselective allylic substitution with a silicon nucleophile generated by copper(I)-catalyzed Si-B bond activation provides direct access to α-chiral allylic silanes from linear acceptors. The enantioconvergent catalysis employing McQuade's six-membered N-heterocyclic-carbene-copper(I) catalyst is applicable to aryl- and alkyl-substituted allylic phosphates (see scheme). Copyright

Full text of DOI:10.1002/anie.201300648

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DOI: 10.1002/anie.201300648
Allylic Substitution
Asymmetric Synthesis of a-Chiral Allylic Silanes by Enantioconvergent
g-Selective Copper(I)-Catalyzed Allylic Silylation**
Lukas B. Delvos, Devendra J. Vyas, and Martin Oestreich*
Dedicated to Professor Larry E. Overman on the occasion of his 70th birthday
ꢀ
Transmetalation of the Si B linkage with selected transition
metal–oxygen bonds releases silicon nucleophiles that are
transferred to various acceptors under carbon–silicon bond
formation.[1,2] An impressive number of monofunctionaliza-
tions based on this activation mode has been developed in the
past few years,[1] but catalytic asymmetric variants are
available for just a handful of those.[3] These are essentially
limited to conjugate additions[4] using either chiral diphos-
phine–{RhI-O}[5] or NHC–{CuI-O}[6] complexes.[7] Just
recently, an enantioselective 1,2-addition using a preformed
chiral diphosphine–{CuI-F} complex was reported.[8,9] The
copper(I)-catalyzed transmetalation approach is remarkably
general,[1,2,6–8,10,11] and we had elaborated a branched-selective
allylic substitution of linear allylic chlorides, yielding a-chiral
allylic silanes in racemic form (E-1!g-2, Scheme 1).[10] An
des[13,14a] and phosphates[14b,c] catalyzed by a copper(I) com-
plex containing a chiral N-heterocyclic carbene (NHC)
ligand.[15,16]
When we presented the racemic procedure for the above
g-selective allylic displacement,[10a] we had already tested
achiral and chiral phosphine ligands, but these merely slowed
down the reaction rate (minutes at ꢀ788C versus hours at
08C). No or little asymmetric induction had been obtained
with commercially available diphosphine ligands.[18,19] We
then decided to use chiral NHCs as ligands because these
have emerged as effective in g-selective allylic substitution
ꢀ
involving the related copper(I)-catalyzed B B bond activa-
tion.[20] Also, enantioselective 1,4-addition of either silicon or
[6]
[21]
ꢀ
ꢀ
boron nucleophiles released from Si B and B B com-
pounds, respectively, were shown to be catalyzed by NHC–
{CuI-O} complexes.
We selected C2-symmetric L1 and C1-symmetric L2 as
representative chiral NHCs, and we also included Bodeꢀs
triazolium ion-derived NHC L3[22] into our survey
(Scheme 2). L1 (allylic substitution with carbon nucleo-
philes)[23] and L2 (allylic substitution and conjugate addition
Scheme 1. Branched-selective allylic substitution of allylic chlorides
ꢀ
involving copper(I)-catalyzed activation of the Si B bond in Sugi-
nome’s Me2PhSiBpin[17] (3).[10a]
enantioselective procedure for this highly regioselective
transformation is particularly attractive as it provides direct
access to these prevalent chiral reagents[12] from non-silicon-
containing precursors. We present herein an enantio- and
regioselective allylic substitution of linear allylic chlori-
[*] L. B. Delvos, Prof. Dr. M. Oestreich
Institut fꢀr Chemie, Technische Universitꢁt Berlin
Strasse des 17. Juni 115, 10623 Berlin (Germany)
E-mail: martin.oestreich@tu-berlin.de
Homepage: http://www.organometallics.tu-berlin.de
Dr. D. J. Vyas
NRW Graduate School of Chemistry
Organisch-Chemisches Institut
Westfꢁlische Wilhelms-Universitꢁt Mꢀnster
Corrensstrasse 40, 48149 Mꢀnster (Germany)
[**] D.J.V. thanks the NRW Graduate School of Chemistry for a predoc-
toral fellowship (2008–2011). M.O. is indebted to the Einstein
Foundation (Berlin) for an endowed professorship.
Scheme 2. Chiral NHCs as ligands in the copper(I)-catalyzed, regio-
and enantioselective allylic silyl transfer to an allylic chloride (NHCs
were generated with KOtBu prior to the addition of the reactants).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201300648.
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with boron nucleophile)[20a,21a] were used before as ligands in
copper(I) catalysis, whereas L3 is a rather unusual choice for
a transition-metal-catalyzed reaction. The racemic procedure
(Scheme 1) was slightly modified: CH2Cl2 as solvent secured
better azolium salt solubility and 08C as reaction temperature
allowed for reasonable reaction rate (E-1a!g-(R)-2a,
Scheme 2). While both regio- and enantioselectivity were
poor with L1, the g/a ratios were, however, excellent with L2
and L3. NHC L3 induced a promising 65% ee. In situ
formation of these NHC complexes might be an issue, and
we had already known from our previous work that the
ligand-free catalysis is fast.[10a] To avoid a racemic background
reaction, we turned to preformed NHC complexes and
selected six-membered NHC-copper(I) complex L4·CuCl
that was introduced by McQuade.[24] Its successful application
to conjugate addition[21d] and allylic substitution[20b] involving
Table 1: Enantio- and regioselective copper(I)-catalyzed SN2’ allylic
silylation of allylic phosphates.
Entry Phosphate Allylic silane
g/a ratio[a] Yield ee
[%][b] [%][c]
1
2
E-4a
E-4b
97:3
96:4
82
92
96[d]
ꢀ
B B bond activation had also attracted our attention.
95
Gratifyingly, g/a = 96:4 and 71% ee at a high yield of isolated
product were obtained with L4·CuCl, whereas its in situ
formation resulted in irreproducible enantiomeric excess
values.
3
E-4c
97:3
93
93
The procedure applied to the other alkene isomer resulted
in significantly lower enantiomeric excess yet same absolute
configuration (E-1a and Z-1a!g-(R)-2a, Scheme 3).
4
5
E-4d
E-4e
97:3
98:2
97:3
81
88
88[d]
95[e]
6
7
8
E-4 f
E-4g
E-4h
91
35
25
97[d]
6:94
–
Scheme 3. Enantioconvergent allylic substitution of allylic chlorides
and phosphates. Reaction conditions: L4·CuCl (5.0 mol%), 3
(1.5 equiv), NaOMe (1.5 equiv), CH2Cl2, 08C.
65:35
78
1
McQuade and co-workers had discovered this peculiar
enantioconvergence in their enantioselective preparation of
branched allylic boronates from linear allylic aryl ethers, but
enantiomeric excesses were on a similar order of magnitu-
de.[20b] We also tested phosphate as leaving group (g/a = 91:9
in the racemic series[10a]), and were delighted to see that
McQuadeꢀs observations were confirmed in our allylic
silylation (E-4a and Z-4a!g-(R)-2a, Scheme 3). The level
of enantiocontrol was excellent, and both alkene geometries
transformed into R configuration with more than 90% ee.
We then continued with representative allylic phosphates
having E alkene configuration (Table 1). Aryl-substituted E-
4a–E-4c reacted cleanly with excellent enantiomeric excesses
that are independent of the electronic nature of the sub-
stituent at the aryl group (entries 1–3). Likewise, yields and
asymmetric induction were superb with primary and secon-
[a] Determined by GLC and H NMR analysis. [b] Combined yield of
analytically pure regioisomers after purification by flash chromatography
on silica gel. [c] Determined by HPLC analysis using chiral stationary
phases. [d] Absolute configuration assigned by comparison with the
optical rotation of reported allylic silanes.[14b,25] [e] Value likely to be
higher but full baseline separation of the enantiomers was not achieved.
dary alkyl-substituted E-4d–E-4 f (entries 4–6). The g/a ratios
were all synthetically useful, except for a tertiary alkyl group
at the alkene, where the ratio was essentially reversed
(entry 7). It is worthy of note that conversion and yield was
poor with the tert-butyl-substituted acceptor, affording a-2g
in 35% yield. That result might be viewed as support for the
notion that L4·CuCl strongly favors the g carbon atom, and if
that is not accessible, a attack is not a competing alternative.
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Likewise, a substituent at C2 as in E-4h eroded both the g/
a ratio and the enantiomeric excess, and the yield of isolated
product was again poor (entry 8).
stitution with a silicon nucleophile. This was achieved by using
McQuadeꢀs NHC–copper(I) complex L4·CuCl as catalyst.
Aside from Hayashiꢀs seminal work,[13] the present method
finally provides a reliable way to directly make a-chiral allylic
silanes in high enantiomeric excesses from simple linear
acceptors derived from allylic alcohols.
Allylic silanes g-(R)-2a with an aryl as well as g-(S)-2d
and g-(S)-2 f with an alkyl group were prepared and fully
characterized before,[14b,25] and we assigned the absolute
configuration as R and S, respectively by comparison of the
optical rotations. These configurations are in accordance with
the model proposed by McQuade for his copper(I)-catalyzed,
enantioconvergent allylic substitution with a boron nucleo-
phile,[20b] and the same analysis might apply to our catalysis
with the silicon nucleophile (IE and IZ, Figure 1, upper).
Received: January 24, 2013
Published online: March 19, 2013
Keywords: allylic substitution · asymmetric catalysis ·
.
carbene ligands · copper · silicon
ꢀ
[1] For a general review of Si B bond activation, see: M. Oestreich,
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ꢀ
[2] For a brief review of Si B bond activation through trans-
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[3] Enantioselective difunctionalization, that is, carbon–boron and
carbon–silicon bond formation in a single synthetic operation, of
ꢀ
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Figure 1. McQuade’s model[20b] (upper) or h3 p-allyl copper(III) inter-
mediate (lower) to rationalize enantioconvergence (LG=leaving
group).
However, enantioconvergence is also an indication of the
catalysis passing through a common intermediate starting
from diastereomeric allylic acceptors; that is, the h3 p-allyl
copper(III) complex II (Figure 1, lower). Neither McQuade
nor we are presently able to rule out either pathway.
The allylic substitution of d-hydroxy allylic phosphate is
a particularly interesting transformation (E-4i!g-(R)-2i,
Scheme 4). It produces a protected b-hydroxy a-chiral allylic
silane that cannot be easily made by allylation of formalde-
hyde with Roushꢀs g-silicon-substituted allylic boronates.[26]
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standing challenge of accessing a-chiral allylic silanes from
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Scheme 4. Selective transformation of a d-hydroxy allylic phosphate
into an b-hydroxy a-chiral allylic silane.
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ꢀ
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