Copper-catalyzed Si-B bond activation in branched-selective allylic substitution of linear allylic chlorides

Article abstract of DOI:10.1002/anie.201004658

The harder they come, the better they leave! Chloride is superior to all common leaving groups in the γ-selective allylic substitution of linear precursors. This approach involves a novel copper-catalyzed Si-B bond activation (see scheme; γ/α≥98:2, 7-examples; Si=SiMe₂Ph and B=Bpin with pin=pinacolato).

Full text of DOI:10.1002/anie.201004658

Angewandte
Chemie
DOI: 10.1002/anie.201004658
Allylic Substitution
ꢀ
Copper-Catalyzed Si B Bond Activation in Branched-Selective Allylic
Substitution of Linear Allylic Chlorides**
Devendra J. Vyas and Martin Oestreich*
I
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The transmetalation of interelement linkages with Cu
Oalkyl complexes provides a facile entry into nucleophilic
main group element/copper(I) compounds. An intriguing s-
bond metathesis is believed to be the activating step, thus
building a conceptual bridge between the emerging areas of
Cu H, Cu B, and Cu Si[1c] chemistry (I–III; Figure 1).
Both conjugate addition[2–4] and allylic or propargylic sub-
stitutions[5–7] with these reagents are currently attracting
tremendous attention.
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[1a]
I
[1b]
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Scheme 1. Branched-selective allylic substitution of allylic chlorides.
THF=tetrahydrofuran.
reagent.[8] The lithium chloride is an issue in asymmetric
variants, and we verified experimentally the detrimental
effect of lithium cations on enantioselective conjugate
additions.[13] The role of chloride anions still remains to be
elucidated. It is therefore desirable to devise a method for the
I
[14]
ꢀ
generation of Cu Si reagents not burdened with excess
lithium chloride. Herein, we report an unprecedented allylic
substitution of linear allylic chlorides to produce branched
allylic silanes by utilizing the copper-catalyzed activation of a
Figure 1. Transmetalation of interelement linkages through s-bond
metathesis as the common denominator (Si=SiMe2Ph and B=Bpin
with pin=pinacolato).
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Si B bond (a-1!g-2; Scheme 1, right).
ꢀ
As part of our continuing focus on selective C Si bond-
Our previous studies on the g-selective allylic transposi-
tion of linear allylic precursors by using the (Me2PhSi)2Zn-
derived copper(I) reagent had shown that allylic chlorides a-1
were superior (rs > 93:7; see Scheme 1).[10] We therefore
started to survey Me2PhSiBpin–CuCN combinations with and
without additives in that reaction (a-1a!g-2a and a-2a;
Table 1). CuCN alone was unable to promote this allylic
displacement (Table 1, entry 1). Unexpectedly, no conversion
was seen despite the addition of NaOtBu to form air- and
moisture-sensitive CuOtBu (Table 1, entry 2). NaOtBu is a
common base in such copper(I) catalyses,[2–6] and our result
stands in contrast to the report by Lee and Hoveyda (see
Scheme 2).[4] The use of NaOMe instead of bulkier NaOtBu
was, however, successful (Table 1, entry 3), thus agreeing with
findings by Chatani and co-workers (CuOAc/MeOH).[11]
The moderate level of regiocontrol (g/a = 90:10) was
improved to excellent regioselectivity (g/a = 98:2) by low-
ering the reaction temperature from 08C to ꢀ788C (Table 1,
forming reactions, we have developed a broadly applicable
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method for the catalytic generation of Cu Si reagents from
(Me2PhSi)2Zn and CuX (X = I or CN).[8] The thus-generated
silicon-based cuprate reagents were particularly useful for the
preparation of branched allylic silanes, either by enantiospe-
cific allylic substitution of a-chiral allylic precursors with an
oxygen leaving group (carboxylate or carbamate)[9] or by
regioselective allylic transposition of linear allylic halides (a-
1!g-2; Scheme 1, left).[10] An alternative way of accessing a
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ꢀ
Cu Si reagent is the above-mentioned activation of a Si B
bond with a copper(I) alkoxide (III; Figure 1).[4,11] Treatment
of readily prepared Me2PhSiBpin[12] with CuX (X = OtBu[4] or
OAc[11]) is expected to yield Me2PhSiCu, the same copper(I)
complex as generated from (Me2PhSi)2Zn and CuX (X = I or
CN). These Cu Si reagents only seem to be identical
(neglecting different counteranions), as the latter is contami-
nated with excess lithium chloride introduced with the zinc
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[*] D. J. Vyas, Prof. Dr. M. Oestreich
Organisch-Chemisches Institut
Westfꢀlische Wilhelms-Universitꢀt Mꢁnster
Corrensstrasse 40, 48149 Mꢁnster (Germany)
Fax: (+49)251-83-36501
E-mail: martin.oestreich@uni-muenster.de
Homepage: http://www.uni-muenster.de/Chemie.oc/oestreich
[**] D.J.V. thanks the NRW Graduate School of Chemistry for a
predoctoral fellowship (2008–2011).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201004658.
Scheme 2. Proposed catalytic cycle.
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Table 1: Optimization of the reaction conditions.[a]
Table 2: Survey of leaving groups.[a]
Entry
Base
Ligand
T
[8C]
t
[h]
g/a[b]
Yield
[%][c]
Entry
Allylic
precursor
Leaving
group
g/a[b]
Yield
[%][c]
[d]
1
2
3
4
5
6
7
8
–
–
–
–
–
0!RT
0
0
48
1
1
–
–
–
–
1
2
3
4
5
6
7
a-1a
a-3a
a-4a
a-5a
a-6a
a-7a
a-8a
Cl
Br
98:2
72:28
91:9
16:84
18:82
18:82
19:81
88
89
85
79
70
83
74
[e]
NaOtBu
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
NaOMe
90:10
98:2
96:4
95:5
98:2
98:2
71
88
71
56
71
57
OP(O)(OEt)2
OC(O)OEt
OC(O)NHPh
OC(O)Ph
OC(O)Me
ꢀ78
6
Ph3P[f]
dppp
dppf
DPEphos
0!RT
0!RT
0!RT
0!RT
24
72
24
48
[a] All reactions were conducted according to the general procedure,
using the indicated allylic precursors a-3a–a-8a. [b] Ratio of regioisom-
ers determined by GLC analysis prior to purification. [c] Combined yield
of analytically pure regioisomers after purification by flash chromatog-
raphy on silica gel. LG=leaving group.
[a] All reactions were conducted according to the general procedure with
addition of the indicated ligand (entries 5–8). [b] Ratio of regioisomers
determined by GLC analysis prior to purification. [c] Combined yield of
analytically pure regioisomers after purification by flash chromatography
on silica gel. [d] No reaction. [e] No conversion of allylic chloride and
decomposition of Me2PhSiBpin observed. [f] 10 mol%. dppp=1,3-
bis(diphenylphosphanyl)propane, dppf=1,1’-bis(diphenylphosphanyl)-
ferrocene, DPEphos=bis(2-diphenylphosphanylphenyl) ether.
Table 3: Copper-catalyzed, g-selective allylic substitution of allylic
chlorides.
entries 3 and 4). Both g/a ratios are perfectly in accord with
those obtained with the (Me2PhSi)2Zn–CuCN reagent,[10]
again corroborating the assumption that Me2PhSiCu is the
nucleophile in these catalyses.[8d,10] We then tested Ph3P and a
series of bidentate phosphines (Table 1, entries 5–8) to see
whether a prospective asymmetric variant would be poten-
tially fruitful. Added ligands had a dramatic effect on the
reaction rate, and the reactions had to be performed at 08C. It
is remarkable though that the regioselectivities were as high
as those obtained under the “ligand-free” reaction conditions
at ꢀ788C. A control experiment without CuCN but with
NaOMe gave no conversion.
With the phosphine-free protocol in hand, we next probed
the effect of the leaving group on the regioselectivity (a-3a–
a-8a ! g-2a and a-2a; Table 2). We were anticipating the
same trend as in our previous study,[10] that is, g selectivity for
halides and phosphates (Table 2, entries 1–3) and a selectivity
for carbonates, carbamates, and carboxylates (Table 2,
entries 4–7). We found this to be also true for the novel
catalytic system with a noteworthy deviation: a-5a–a-8a with
oxygen leaving groups react with substantially eroded a se-
lectivities of g/a ꢁ 18:82 (Table 2, entries 4–7) as opposed to
flawless g/a < 1:99 in the cuprate series.[8c,10] From this data, it
appears that the Me2PhSiBpin–CuCN–NaOMe system tends
to prefer the branched isomer.
Entry
Allylic
precursor
Substituent
R
Allylic
silane
g/a[a]
Yield
[%][b]
1
2
3
4
5
6
7
8
a-1a
a-1b
a-1c
a-1d
a-1e
a-1 f
a-1g
a-1h
Ph
g/a-2a
g/a-2b
g/a-2c
g/a-2d
g/a-2e
g/a-2 f
g/a-2g
g/a-2h
98:2
98:2
99:1
98:2
88
77[c]
94
83
95
81
84
72
4-MeOC6H4
3-MeOC6H4
4-F3CC6H4
4-BrC6H4
Cy
98:2
>99:1
>99:1
76:24
iPr
Me3Si
[a] Ratio of regioisomers determined by GLC analysis or by 1H NMR
spectroscopy prior to purification. [b] Combined yield of analytically pure
regioisomers after purification by flash chromatography on silica gel.
[c] Yield of isolated product over two steps based on the corresponding
allylic alcohol. Cy=cyclohexyl.
silyl-substituted a-1h was comparable to that seen with the
known method[10] (Table 3, entry 8). We explain this modest
g selectivity (g/a = 76:24) by a steric rather than an electronic
effect because the tBu-substituted allylic chloride (not shown)
reacted with even worse selectivity (g/a = 62:38), whereas iPr-
substituted a-1g produced the g regioisomer with g/a > 99:1
(Table 3, entry 7).
Encouraged by the superb regioselectivity obtained with
a-1a, we set out to extend the scope of the new method (a-
1b–a-1h ! g-2b–g-2h and a-2b–a-2h; Table 3). We were
also able to use less Me2PhSiBpin and NaOMe, now
1.5 equivalents each. To our delight, both aryl- and alkyl-
substituted precursors a-1a–a-1e and a-1 f–a-1g, respec-
tively, yielded the corresponding allylic silanes with excellent
regioselectivities (Table 3, entries 1–5 as well as entries 6 and
7), exceeding previously reported ones.[10] The g/a ratio for
The tentative mechanism (Scheme 2) is based on the
ꢀ
quantumchemical analysis of the related activation of the B
B linkage by Marder and co-workers (II and III; Figure 1).[1b]
We emphasize the role of added or generated alkoxide:
OtBu[4] (in CuOtBu) is likely to be too sterically hindered to
allow for the s-bond metathesis to occur, whereas OMe (in
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Angewandte
Chemie
CuOMe[11]) secures smooth Si B bond activation, which
agrees with our experiments (Table 1, entries 2 and 3).
ꢀ
402 – 412; conjugate addition: b) M. Oestreich, B. Weiner,
Synlett 2004, 2139 – 2142; allylic substitution: c) M. Oestreich,
G. Auer, Adv. Synth. Catal. 2005, 347, 637 – 640; alkyne, diene,
and styrene addition: d) G. Auer, M. Oestreich, Chem.
Commun. 2006, 311 – 313.
ꢀ
This copper-catalyzed Si B bond activation through
transmetalation and its application to allylic substitution
closes an important gap.[18] It is a competitive alternative to
the established cuprate chemistry.[8a,10] Branched allylic
silanes are now accessible with synthetically useful levels of
regiocontrol. We also showed that phosphine ligands are
tolerated in this catalysis, finally opening the door to
asymmetric variants.[9,19–21]
[9] E. S. Schmidtmann, M. Oestreich, Chem. Commun. 2006, 3643 –
3645.
[10] D. J. Vyas, M. Oestreich, Chem. Commun. 2010, 46, 568 – 570,
and references therein.
[11] To date, the only reports of Me2PhSiBpin activation are:
a) Ref. [4]; b) M. Tobisu, H. Fujihara, K. Koh, N. Chatani, J.
Org. Chem. 2010, 75, 4841 – 4847.
[12] For the preparation of Me2PhSiBpin from Me2PhSiLi and
HBpin, see a) M. Suginome, T. Matsuda, Y. Ito, Organometallics
2000, 19, 4647 – 4649; for a recent summary of Me2PhSiBpin
chemistry, see b) T. Ohmura, M. Suginome, Bull. Chem. Soc.
Jpn. 2009, 82, 29 – 49.
Received: July 28, 2010
Published online: September 10, 2010
Keywords: allylic substitution · copper · regioselectivity · silicon ·
.
[13] G. Auer, B. Weiner, M. Oestreich, Synthesis 2006, 2113 – 2116.
transmetalation
ꢀ
[14] Our research group introduced the rhodium-catalyzed Si B
activation,[15] which is likely to follow a similar transmetalation
I
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mechanism (see III; Figure 1). The resultant nucleophilic Rh Si
ꢀ
[1] For investigations into the mechanisms, see a) Cu H: S.
Rendler, O. Plefka, B. Karatas, G. Auer, R. Frꢀhlich, C. Mꢁck-
reagent participates in conjugate addition[15] and propargylic
substitution[16] but, in our hands, not in allylic substitution.[17] We,
therefore, decided to study the related copper(I) catalysis.
[15] a) C. Walter, G. Auer, M. Oestreich, Angew. Chem. 2006, 118,
5803 – 5805; Angew. Chem. Int. Ed. 2006, 45, 5675 – 5677; b) C.
Walter, M. Oestreich, Angew. Chem. 2008, 120, 3878 – 3880;
Angew. Chem. Int. Ed. 2008, 47, 3818 – 3820; c) C. Walter, R.
Frꢀhlich, M. Oestreich, Tetrahedron 2009, 65, 5513 – 5520; d) E.
Hartmann, M. Oestreich, Angew. Chem. 2010, 122, 6331 – 6334;
Angew. Chem. Int. Ed. 2010, 49, 6195 – 6198.
Lichtenfeld, S. Grimme, M. Oestreich, Chem. Eur. J. 2008, 14,
11512 – 11528; b) Cu B: L. Dang, Z. Lin, T. B. Marder, Organo-
metallics 2008, 27, 4443 – 4454; c) Cu Si: we are not aware of
any reports related to the mechanism of this transmetalation.
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[2] For authoritative reviews of Cu H in conjugate addition, see
a) C. Deutsch, N. Krause, B. H. Lipshutz, Chem. Rev. 2008, 108,
2916 – 2927; b) S. Rendler, M. Oestreich, Angew. Chem. 2007,
119, 504 – 510; Angew. Chem. Int. Ed. 2007, 46, 498 – 504.
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[3] For recent summaries of Cu B in conjugate addition, see
[16] H. Ohmiya, H. Ito, M. Sawamura, Org. Lett. 2009, 11, 5618 –
5620.
a) J. A. Schiffner, K. Mꢁther, M. Oestreich, Angew. Chem. 2010,
122, 1214 – 1216; Angew. Chem. Int. Ed. 2010, 49, 1194 – 1196;
b) L. Dang, Z. Lin, T. B. Marder, Chem. Commun. 2009, 3987 –
[17] K. Mꢁther, M. Oestreich, unpublished results, 2009.
[18] For a palladium-catalyzed allylic silane synthesis involving
oxidative addition of Me2PhSiBpin, see T. Ohmura, H. Tanigu-
chi, M. Suginome, J. Am. Chem. Soc. 2006, 128, 13682 – 13683.
[19] For a review of the chemistry of allylic silanes, see a) L.
Chabaud, P. James, Y. Landais, Eur. J. Org. Chem. 2004, 3173 –
3199; for the preparation of allylic silanes, see b) T. K. Sarkar in
Science of Synthesis, Vol. 4 (Ed.: I. Fleming), Thieme, Stuttgart,
2002, pp. 837 – 925.
[20] For recent (indirect syntheses) of a-chiral allylic silane, see a) D.
Li, T. Tanaka, H. Ohmiya, M. Sawamura, Org. Lett. 2010, 12,
3344 – 3347; b) 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.
3995.
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[4] For Cu Si in conjugate addition, see K.-s. Lee, A. H. Hoveyda,
J. Am. Chem. Soc. 2010, 132, 2898 – 2900.
[5] For Cu H in propargylic substitution, see a) C. Zhong, Y.
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Sasaki, H. Ito, M. Sawamura, Chem. Commun. 2009, 5850 –
5852; b) C. Deutsch, N. Krause, B. H. Lipshutz, Org. Lett.
2009, 11, 5010 – 5012.
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[6] For Cu B in allylic substitution, see a) H. Ito, C. Kawakami, M.
Sawamura, J. Am. Chem. Soc. 2005, 127, 16034 – 16035; b) H. Ito,
S. Ito, Y. Sasaki, K. Matsuura, M. Sawamura, J. Am. Chem. Soc.
2007, 129, 14856 – 14857; c) H. Ito, T. Okura, K. Matsuura, M.
Sawamura, Angew. Chem. 2010, 122, 570 – 573; Angew. Chem.
Int. Ed. 2010, 49, 560 – 563; d) A. Guzman-Martinez, A. H.
[21] A few test runs using binap (rs = 98:2) and josiphos (rs = 90:10)
yielded only racemic g-2a, not even reaching full conversion
after several days at ambient temperature (binap = 2,2’-bis(di-
phenylphosphanyl)-1,1’-binaphthyl and josiphos = 1-[2-(diphe-
nylphosphanyl)ferrocenyl]ethyldicyclohexylphosphine).
Hoveyda, J. Am. Chem. Soc. 2010, 132, 10634 – 10637.
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[7] There are no reports of Cu Si in allylic substitution by
transmetalation of interelement bonds. This is the topic of the
present investigation.
[8] For an account of the versatile (Me2PhSi)2Zn–CuX chemistry,
see a) A. Weickgenannt, M. Oestreich, Chem. Eur. J. 2010, 16,
Angew. Chem. Int. Ed. 2010, 49, 8513 –8515
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