Conclusive evidence for an SN2-Si mechanism in the B(C 6F5)3-catalyzed hydrosilylation of carbonyl compounds: Implications for the related hydrogenation

Article abstract of DOI:10.1002/anie.200801675

Just ask silicon: An experimentally straightforward yet effective Walden-type analysis showcases the usefulness of silanes with a stereogenic silicon center as stereochemical probes. The B(C₆F₅) ₃-catalyzed hydrosilylation and likely the related hydrogenation proceed through linear B-H-Si-O transition states, as verified by flawless inversion of the absolute configuration at silicon (see scheme). (Chemical Equation Presented).

Full text of DOI:10.1002/anie.200801675

Angewandte
Chemie
DOI: 10.1002/anie.200801675
Reaction Mechanisms
Conclusive Evidence for an SN2-Si Mechanism in the B(C6F5)3-
Catalyzed Hydrosilylation of Carbonyl Compounds: Implications for
the Related Hydrogenation**
Sebastian Rendler and Martin Oestreich*
The precise mechanistic understanding of chemical trans-
formations is an urgent challenge in synthetic chemistry as it
guides the targeted design of improved or even novel
processes. For example, transition-metal-free reduction of
=
C X bonds (X = O and NR) catalyzed by boron-based Lewis
acids is currently attracting considerable attention.[1] Illumi-
nating its mechanism(s) of action might open the door for the
development of yet unknown enantioselective variants. In this
context, commercially available tris(pentafluorophenyl)bor-
ane (1)[2] is a particularly effective catalyst for both hydro-
silylation and hydrogenation.[3] In a series of seminal papers,
Piers et al. had reported a protocol that is based on
triorganosilanes as stoichiometric reducing reagents.[4] More-
over, Stephan et al. reported that dihydrogen—clearly the
Scheme 1. The Piers mechanism of the B(C6F5)3-catalyzed hydrosilyla-
tion of carbonyl compounds.
most desirable reducing agent—also facilitates smooth turn-
[5,6]
=
ꢀ
over in C NRand C N reductions.
In this scenario, an
unconventional B(C6F5)3-catalyzed activation of dihydrogen
is operative.[5] The direct investigation of this dihydrogen
activation[8] by experimentally straightforward techniques is
certainly demanding, though.[9,10] In turn, examination of the
closely related silane activation[11,12] might provide a solid
foundation for the delineation of the basic mechanistic
principles of both processes.[13] We report herein a simple
yet conclusive investigation of the transition state operative in
the B(C6F5)3-catalyzed hydrosilylation of prochiral acetophe-
none using a silane with a stereogenic silicon center[14] as a
stereochemical probe.[15,16] We then discuss implications for
the related hydrogenation.
resonance structures 3a and 3b of the thus-formed inter-
mediate rationalize the capability of 1 to abstract a hydride
from silicon in the subsequent step. Silyl transfer to the Lewis
basic carbonyl oxygen of 4 thereby produces ion pair 5 (3!5).
As implied by the complete absence of any crossover
when two different mass-labeled silanes are used,[4b] the ion
pair is apparently not solvent-separated and undergoes rapid
hydride transfer from the borohydride to the electrophilic
carbon of the silylcarboxonium ion to give 6 along with
regenerated catalyst 1 (5!1). The fate of intermediate 3 has
remained vague: Concerted SN2-type displacement at silicon
(SN2-Si[18,19]) of a boron-coordinated hydride by the carbonyl
oxygen of 4 has been postulated. Another intriguing piece of
information emerges from rapid H/D exchange when 2 and its
deuterated congener are used in the absence of Lewis
bases.[4b]
Based on comprehensive experimental data, Piers et al.
suggested a seemingly counterintuitive three-step mechanism
for
the
hydrosilylation
of
carbonyl
compounds
(Scheme 1).[4a,b] The catalysis commences with the activation
of silane 2 by the strong Lewis acid 1 through reversible
ꢁ
coordination to the hydridic Si H bond (1!3). The two
Inspired by remarkable achievements utilizing stereo-
genicity at silicon as a chiral probe,[15,20] we decided to
examine the nature and consecutive reaction of intermediate
3 by applying our previously developed family of asymmetri-
cally substituted silanes.[14] We first assessed silanes rac-2a–d
in the hydrosilylation of acetophenone (4) in the presence of
catalytic amounts of catalyst 1 (5.0 mol%) in order to identify
[*] Dr. S. Rendler, Prof. Dr. M. Oestreich
Organisch-Chemisches Institut
Westfälische Wilhelms-Universität Münster
Corrensstrasse 40, 48149 Münster (Germany)
Fax: (+49)251-83-36501
E-mail: martin.oestreich@uni-muenster.de
Homepage: http://www.uni-muenster.de/Chemie.oc/research/
oestreich/oe_welcome.html
a
sufficiently reactive stereogenic silane (4!rac-6,
Scheme 2). It is interesting to note that, without exception,
all silanes decorated with a tBu group—cyclic rac-2a,[21a]
cyclic and strained rac-2c,[21b] and acyclic rac-2d[21c]—were
to completely unreactive. In contrast, cyclic rac-2b[15b] equip-
ped with an iPr group readily delivered the desired product
rac-6b in good yield and with notable diastereoinduction
(vide infra). The difference in steric hindrance between iPr-
[**] The authors thank Marion Emmert (group of Prof. Dr. Gerhard
Erker, Münster)for a sample of B(C 6F5)3. This research was
supported by the Fonds der Chemischen Industrie and the Aventis
Foundation (Karl-Winnacker-Stipendium to M.O., 2006–2008).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200801675.
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uration of (SiR,R)-6b was deduced from the configuration of
the isolated alcohol (R)-8 (38% ee).
This result clearly supports a concerted SN2-Si mechanism
for the reduction step. Spontaneous heterolytic dissociation of
intermediate 3 (Scheme 1) would liberate a free (or toluene-
stabilized[26]) achiral silylium ion, thereby producing racemic
material. Nucleophilic attack at silicon by the Lewis basic
carbonyl oxygen of 4 must occur anti to the quasi-linear B-H-
Si array[4b,27] via transition state 7 (Scheme 3). Moreover, we
emphasize that 7 should be regarded as a transition state
because any lifetime on the reaction timescale would likely
result in racemization by pseudorotational processes like
those observed with hypervalent cyclic silicon intermedi-
ates.[28]
Scheme 2. Screening of suitable chiral probes.
The origin of diastereoinduction is noteworthy as it is
induced by the single-point-bound stereogenic silicon atom
coordinated to the Lewis basic carbonyl oxygen (5,
Scheme 1). Piers et al. had already presented solid data that
it is the borohydride and not another molecule of the silane
that functions as the reducing agent.[4b] Overall, the reaction
studied here represents an example of chirality transfer from
silicon to carbon,[29] which follows a “one-silicon” as opposed
to a “two-silicon” cycle.[15]
To further exclude involvement of free silylium ions, we
performed another rigorous control experiment. An equimo-
lar mixture of enantioenriched silane (SiR)-2b (90% ee) and
deuterium-labeled achiral silane [2H]-9 was exposed to the
substituted rac-2b and tBu-substituted rac-2a might account
for this dramatic reactivity difference in an assumed SN2-Si
displacement. However, this argument is inconclusive since
Reed et al. had demonstrated that iPr-substituted silanes
display a higher tendency to form silylium-ion-type inter-
mediates as a result of a-C-H hyperconjugative stabiliza-
tion;[22] these silanes would thus show superior reactivity in an
SN1-Si-type mechanism.
Strong evidence against a free silylium ion intermediate[23]
would come from the classical reaction setup for a Walden
inversion at silicon,[18] which required repeating the reduction
with enantioenriched silane (SiR)-2b [4!(SiR,R)-6b,
Scheme 3].[24] Prochiral ketone 4 was treated with (SiR)-2b
(90% ee) in the presence of catalytic amounts of B(C6F5)3 to
borane catalyst
1 in the absence of a Lewis base
(Scheme 4).[30] Mass spectrometric analysis of the isotopic
Scheme 4. Racemization-free scrambling in the absence of a Lewis
base: No support for free silylium ions [B=B(C6F5)3 and Si or
Si’=R3Si].
Scheme 3. Two-step stereochemical analysis: An inversion–retention
pathway.
distribution after 2 h at room temperature showed complete
scrambling: (SiR)-[1H/2H]-2b (89% ee, H/D 54:46) and [2H]-9
(H/D 50:50). The preservation of the stereochemical integrity
in isolated (SiR)-[1H/2H]-2b excludes: 1) a mechanism
through (achiral) silylium ion intermediates and 2) an SN2-Si
displacement at activated 3 with a silane as the attacking
nucleophile as both of these would bring about racemization.
It is therefore plausible to suggest a s-bond metathesis
involving a four-centered cyclic transition state. Related
transition-metal-catalyzed processes are known to proceed
with stereoretention at silicon.[14,15,31] Transition-state 10
(Scheme 4) consisting of two borane-activated silanes fulfills
the stereochemical requirements; alternatively, a complex of
yield optically active (SiR,R)-6b as a mixture of diastereomers
(d.r. 74:26). After racemization-free reductive cleavage of
(SiR,R)-6b with diisobutylaluminum hydride (DIBAL-H)
under standard reaction conditions,[21a,25] silane (SiS)-2b was
recovered in high chemical yield and with inverted absolute
configuration [(SiR,R)-6b!(SiS)-2b]. With 90% ee for (SiR)-
2b and 84% ee for (SiS)-2b, inversion at the silicon atom is
virtually immaculate (97% inversion and marginal 3%
racemization). Absolute configurations were unambiguously
assigned by HPLC analysis on a chiral stationary phase as well
as by analysis of the optical rotation. The relative config-
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[8] a) G. J. Kubas, Proc. Natl. Acad. Sci. USA 2007, 104, 6901 – 6907;
type 3 (Scheme 1) might be sufficiently reactive to directly
undergo s-bond metathesis with a free silane.
b) J. W. Tye, M. B. Hall in Activation of Small Molecules (Ed.:
W. B. Tolman), Wiley-VCH, Weinheim, 2006, pp. 126 – 158.
[9] Attempts to spectroscopically observe B(C6F5)3–dihydrogen
adducts have been unfruitful so far: G. C. Welch, D. W. Stephan,
J. Am. Chem. Soc. 2007, 129, 1880 – 1881.
[10] For an excellent quantum-chemical investigation including a
plausible mechanism, see: T. A. Rokob, A. Hamza, A. Stirling,
T. Soós, I. Pµpai, Angew. Chem. 2008, 120, 2469 – 2472; Angew.
Chem. Int. Ed. 2008, 47, 2435 – 2438.
[11] M. S. Eisen in The Chemistry of Organic Silicon Compounds,
Vol. 3 (Eds.: Z. Rappoport, Y. Apeloig), Wiley, New York, 2001,
pp. 2037 – 2128.
[12] S. Rendler, M. Oestreich in Modern Reduction Methods (Eds.:
P. G. Andersson, I. J. Munslow), Wiley-VCH, Weinheim, 2008,
pp. 183 – 207.
[13] A relationship of that is also observed in Cu-H-catalyzed
reductions: a) S. Rendler, M. Oestreich, Angew. Chem. 2007,
119, 504 – 510; Angew. Chem. Int. Ed. 2007, 46, 498 – 504;
b) B. H. Lipshutz in Modern Organocopper Chemistry (Ed.: N.
Krause), Wiley-VCH, Weinheim, 2002, pp. 167 – 187; c) J. M.
Stryker, W. S. Mahoney, J. F. Daeuble, D. M. Bestrensky in
Catalysis of Organic Reactions (Ed.: W. E. Pascoe), Marcel
Dekker, New York, 1992, pp. 29 – 44.
Based on these insights into the B(C6F5)3-catalyzed
hydrosilylation, conclusions might be drawn, to a certain
extent, for the closely related hydrogenation.[10] A compar-
ꢁ1 [32]
ꢁ
ꢁ
ison of the bond energies of R3Si H (90 kcalmol
) and H
H (108 kcalmolꢁ1[8]) corroborates that B(C6F5)3-catalyzed
heterolytic dissociation of H2 into the contact ion pair
“H [HB(C6F5)3] ” is, as is the case for R3Si H, an unfavor-
able event in the absence of a Lewis base. However, an SN2-
type process at hydrogen similar to that at silicon is
implicated:[10] h1 (end-on) coordination[27] of B(C6F5)3 to
+
ꢁ
ꢁ
ꢁ
dihydrogen could activate the H H bond for nucleophilic
attack by the Lewis basic substrate. Again, a tight contact ion
pair consisting of an iminium ion (with imines as substrates[5])
and the borohydride is formed. Liberation of the amine after
subsequent hydride transfer then completes the catalytic
cycle.
In summary, the refined mechanistic picture of the
B(C6F5)3-catalyzed hydrosilylation bodes well for the devel-
opment of catalytic asymmetric approaches. It seems that
their efficiency will highly depend on asymmetric induction of
a chiral nonracemic borane.[3,33] A proof of principle was
included in a very recent report, which might also stimulate
further research in this area.[5b]
Our mechanistic investigation and proof of an SN2-Si
transition state in the Si!B hydride-transfer step is predi-
cated on a simple Walden-type analysis employing a silane
having a silicon stereocenter as a stereochemical probe. It
might well be worth applying this technique to systems relying
on other Lewis bases, e.g., phosphines,[9] and to the recent
dihydrogen-splitting molecules introduced by Stephan
et al.[6,7,34]
[14] M. Oestreich, Synlett 2007, 1629 – 1643.
[15] a) M. Oestreich, S. Rendler, Angew. Chem. 2005, 117, 1688 –
1691; Angew. Chem. Int. Ed. 2005, 44, 1661 – 1664; b) S. Rendler,
M. Oestreich, C. P. Butts, G. C. Lloyd-Jones, J. Am. Chem. Soc.
2007, 129, 502 – 503.
[16] We explicitly note that a recent report on the supposably
mechanistically related dehydrogenative silylation of alcohols[17]
also included an inconclusive observation—substantial racemi-
zation at silicon—for the hydrosilylation of carbonyl compounds
with a silicon-stereogenic silane: S. Shinke, T. Tsuchimoto, Y.
Kawakami, Silicon Chem. 2007, 3, 243 – 249.
[17] J. M. Blackwell, K. L. Foster, V. H. Beck, W. E. Piers, J. Org.
Chem. 1999, 64, 4887 – 4892.
[18] a) L. H. Sommer, Stereochemistry, Mechanism, and Silicon,
McGraw-Hill, New York, 1965; b) L. H. Sommer, Intra-Sci.
Chem. Rep. 1973, 7, 1 – 44; c) R. J. P. Corriu, C. Guerin, J. J. E.
Moreau in Topics in Stereochemistry, Vol. 15 (Ed.: E. L. Eliel),
Wiley, New York, 1984, pp. 355 – 374.
Received: April 9, 2008
Published online: July 9, 2008
Keywords: hydrosilylation · Lewis acids ·
[19] A. P. Bento, F. M. Bickelhaupt, J. Org. Chem. 2007, 72, 2201 –
2207.
.
nucleophilic substitution · reaction mechanisms · silicon
[20] Selected examples: a) A. G. Brook, Acc. Chem. Res. 1974, 7, 77 –
84; b) V. Bagheri, M. P. Doyle, J. Taunton, E. E. Claxton, J. Org.
Chem. 1988, 53, 6158 – 6150; c) M. P. Doyle, K. G. High, V.
Bagheri, R. J. Pieters, P. J. Lewis, M. M. Pearson, J. Org. Chem.
1990, 55, 6082 – 6086; d) K. Tomooka, A. Nakazaki, T. Nakai, J.
Am. Chem. Soc. 2000, 122, 408 – 409; e) A. Nakazaki, T. Nakai,
K. Tomooka, Angew. Chem. 2006, 118, 2293 – 2296; Angew.
Chem. Int. Ed. 2006, 45, 2235 – 2238.
[21] a) S. Rendler, G. Auer, M. Keller, M. Oestreich, Adv. Synth.
Catal. 2006, 348, 1171 – 1182; b) S. Rendler, O. Plefka, B.
Karatas, G. Auer, R. Frꢀhlich, C. Mꢁck-Lichtenfeld, S.
Grimme, M. Oestreich, unpublished results; c) G. L. Larson, E.
Torres, J. Organomet. Chem. 1985, 293, 19 – 27.
[1] A. L. Kenward, W. E. Piers, Angew. Chem. 2008, 120, 38 – 42;
Angew. Chem. Int. Ed. 2008, 47, 38 – 41.
[2] A. G. Massey, A. J. Park, J. Organomet. Chem. 1964, 2, 245 – 250.
[3] a) G. Erker, Dalton Trans. 2005, 1883 – 1890; b) W. E. Piers, Adv.
Organomet. Chem. 2005, 52, 1 – 76; c) W. E. Piers, T. Chivers,
Chem. Soc. Rev. 1997, 26, 345 – 354.
[4] a) D. J. Parks, W. E. Piers, J. Am. Chem. Soc. 1996, 118, 9440 –
9441; b) D. J. Parks, J. M. Blackwell, W. E. Piers, J. Org. Chem.
2000, 65, 3090 – 3098; c) J. M. Blackwell, E. R. Sonmor, T.
Scoccitti, W. E. Piers, Org. Lett. 2000, 2, 3921 – 3923.
[5] a) P. A. Chase, T. Jurca, D. W. Stephan, Chem. Commun. 2008,
1701 – 1703; b) D. Chen, J. Klankermayer, Chem. Commun.
2008, 2130 – 2131.
[6] For the metal-free hydrogenation of imines and nitriles using the
Stephan catalyst[7] (R2PC6F4B(C6F5)2 systems, R = 2,4,6-
Me3C6H2 or tBu), see: P. A. Chase, G. C. Welch, T. Jurca, D. W.
Stephan, Angew. Chem. 2007, 119, 8196 – 8199; Angew. Chem.
Int. Ed. 2007, 46, 8050 – 8053.
[22] Z. Xie, R. Bau, A. Benesi, C. A. Reed, Organometallics 1995, 14,
3933 – 3941.
[23] For leading references on this controversial debate, see:
a) R. J. P. Corriu, M. Henner, J. Organomet. Chem. 1974, 74,
1 – 28; b) J. B. Lambert, L. Kania, S. Zhang, Chem. Rev. 1995, 95,
1191 – 1201; c) J. B. Lambert, Y. Zhao, Angew. Chem. 1997, 109,
389 – 391; Angew. Chem. Int. Ed. Engl. 1997, 36, 400 – 401;
d) C. A. Reed, Acc. Chem. Res. 1998, 31, 325 – 332; e) K.-C. Kim,
C. A. Reed, D. W. Elliott, L. J. Mueller, F. Tham, L. Lin, J. B.
Lambert, Science 2002, 297, 825 – 827; f) P. P. Gaspar, Science
[7] For the landmark paper, see: G. C. Welch, R. R. San Juan, J. D.
Masuda, D. W. Stephan, Science 2006, 314, 1124 – 1126.
Angew. Chem. Int. Ed. 2008, 47, 5997 –6000
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 5999

Communications
2002, 297, 785 – 786; g) T. Mꢁller, Adv. Organomet. Chem. 2005,
53, 155 – 216.
[24] For an early debate on silylium intermediates and stereogenic
silicon, see: a) J. D. Austin, C. Eaborn, J. Chem. Soc. 1964, 2279 –
2280; b) L. H. Sommer, D. L. Bauman, J. Am. Chem. Soc. 1969,
91, 7076 – 7078.
3522 – 3524; Angew. Chem. Int. Ed. 2004, 43, 3440 – 3442;
b) E. P. A. Couzijn, A. W. Ehlers, M. Schakel, K. Lammertsma,
J. Am. Chem. Soc. 2006, 128, 13634 – 13639.
[29] M. Oestreich, Chem. Eur. J. 2006, 12, 30 – 37.
[30] Treatment of (SiR)-2b (90% ee) with 1 in toluene resulted in no
racemization as well. See the Supporting Information for details.
[31] S. Rendler, G. Auer, M. Oestreich, Angew. Chem. 2005, 117,
7793 – 7797; Angew. Chem. Int. Ed. 2005, 44, 7620 – 7624.
[25] Stereospecificity of reduction with DIBAL-H is secured: M.
Oestreich, G. Auer, M. Keller, Eur. J. Org. Chem. 2005, 184 – 195.
[26] G. A. Olah, G. Rasul, X.-Y. Li, H. A. Buchholz, G. Sanford,
G. K. S. Prakash, Science 1994, 263, 983 – 984.
[32] J. Y. Corey in The Chemistry of Organic Silicon Compounds
(Eds.: S. Patai, Z. Rappoport), Wiley, New York, 1989, pp. 1 – 56.
[33] K. Ishihara, H. Yamamoto, Eur. J. Org. Chem. 1999, 527 – 538.
[34] a) G. C. Welch, L. Cabrera, P. A. Chase, E. Hollink, J. D.
Masuda, P. Wei, D. W. Stephan, Dalton Trans. 2007, 3407 –
3414; b) P. Spies, G. Erker, G. Kehr, K. Bergander, R. Frꢀhlich,
S. Grimme, D. W. Stephan, Chem. Commun. 2007, 5072 – 5074.
[27] For a transition-metal h1-silane complex, see: J. Yang, P. S.
White, C. K. Schauer, M. Brookhart, Angew. Chem. 2008, 120,
4209 – 4211; Angew. Chem. Int. Ed. 2008, 47, 4141 – 4143.
[28] a) E. P. A. Couzijn, M. Schakel, F. J. J. de Kanter, A. W. Ehlers,
M. Lutz, A. L. Spek, K. Lammertsma, Angew. Chem. 2004, 116,
6000 www.angewandte.org
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