Catalytic asymmetric Si-O coupling of simple achiral silanes and chiral donor-functionalized alcohols

Article abstract of DOI:10.1002/anie.200905561

"Chemical Equation Presented" Biomimetic and efficient: Mixed calcium manganese(III) oxides (see structure; Ca green, Mn red, O white) with elemental compositions and structures mimicking the active site of photosystem II were found to be highly active catalysts for the oxidation of water to molecular oxygen. As for PSII, the presence of Ca²⁺ greatly enhances the catalyst performance in comparison to the related manganeseonly system Mn₂O₃.

Full text of DOI:10.1002/anie.200905561

Angewandte
Chemie
DOI: 10.1002/anie.200905561
Kinetic Resolution
ꢀ
Catalytic Asymmetric Si O Coupling of Simple Achiral Silanes and
Chiral Donor-Functionalized Alcohols**
Andreas Weickgenannt, Marius Mewald, Thomas W. T. Muesmann, and Martin Oestreich*
Kinetic resolution[1] of alcohols is usually based on acylation
although the indispensable role of silicon-based protective
groups[2] in synthetic organic chemistry might actually call for
the related silylation to render a conventional alcohol
protection step asymmetric.[3] An innovative report by
Ishikawa et al. had remained unnoticed[4] until Hoveyda
et al. perfected asymmetric silylation through desymmetriza-
tion[5] and kinetic resolution.[6] Analogous to the acylation of
alcohols,[7] these protocols rely on a nucleophilic organo-
catalyst and a chlorosilane as the electrophilic silicon source;
stoichiometric amounts of a base are necessary to absorb the
hydrochloric acid produced in the course of the reaction (I;
Scheme 1).
the direct coupling of an alcohol and a silane is catalyzed by a
[11,12]
ꢀ
copper(I) hydride complex (“Cu H”),
and enantiomer
discrimination originates in the stereochemical information at
the asymmetrically substituted silicon atom (transition state
TS1; Figure 1).
Figure 1. Origin of stereoinduction in reagent- and catalyst-controlled,
ꢀ
ꢀ
Cu H-catalyzed dehydrogenative Si O couplings. Si*=asymmetrically
substituted silicon atom, L=monodentate ligand, L*=chiral mono-
dentate ligand, N=sp2-hybridized nitrogen donor, R=aryl or alkyl
group.
Naturally, our next goal was to develop a catalyst-
ꢀ
controlled asymmetric dehydrogenative Si O coupling with
achiral silanes and chiral ligands (III; Scheme 1).[13,14] We had,
however, learned in our previous work that achiral mono-
dentate phosphine ligands are generally far superior to
related bidentate ligands.[8,9] A quantum-chemical investiga-
tion[9] indicated that asymmetric induction in the planned
ꢀ
Scheme 1. Kinetic resolution by formation of an Si O bond.
R1 ¼R2 =aryl or alkyl, Si=triorganosilyl group.
ꢀ
enantioselective Cu H catalysis will have to arise from a
single monodentate chiral ligand (transition state TS2;
Figure 1).[15] While such a stereochemical situation is not
totally unprecedented in transition-metal catalysis,[16–19] it still
is a demanding task, for which prominent ligand classes are
available:[20] MOP-type phosphine ligands[21] and ligands
Parallel to this significant progress, we had devised a
conceptually distinct approach to stereoselective Si O bond
ꢀ
formation employing silicon-stereogenic silanes (II;
Scheme 1).[8–10] In this reagent-controlled kinetic resolution,
having the general formula O2P X in which a chiral backbone
ꢀ
is connected to the oxygen atom[22] [phosphoramidites (O2P
ꢀ
N),[23] phosphites (O2P O), and phosphonites (O2P C)].
Herein, we introduce a novel method for kinetic resolution
ꢀ
ꢀ
[*] A. Weickgenannt, M. Mewald, T. W. T. Muesmann,
Prof. Dr. M. Oestreich
ꢀ
based on an enantioselective dehydrogenative Si O coupling
Organisch-Chemisches Institut
ꢀ
catalyzed by a chiral Cu H complex. All data strongly
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
support a mechanism in which only one monodentate
enantiopure ligand is responsible for the chiral discrimina-
tion.
Our investigation commenced with an extensive survey of
chiral monodentate ligands (Table 1) and achiral triorgano-
silanes (Table 2). For this, we selected proven donor-func-
tionalized alcohol rac-1 from our preceding work,[8–10] but the
copper/base/solvent combination (CuCl/NaOtBu/toluene)
previously used[8,9] failed to secure adequate turnover. Con-
siderable experimentation then led to the CuCl/Cs2CO3/THF
system, in which the use of Cs2CO3 is essential to suppress the
[**] This research was supported by the Deutsche Forschungsgemein-
schaft (Oe 249/4-1), the Fonds der Chemischen Industrie (predoc-
toral fellowship to A.W., 2008–2010), and the Aventis Foundation
(Karl-Winnacker-Stipendium to M.O., 2006–2008). We thank Hen-
drik F. T. Klare for full characterization of the donor-functionalized
alcohols.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200905561.
Angew. Chem. Int. Ed. 2010, 49, 2223 –2226
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2223

Communications
ꢀ
undesired base-catalyzed Si O coupling otherwise observed
in THF.[24] As the initial results obtained with a MeO-MOP
ligand[25] were disappointing, we mainly focussed on phos-
phoramidites and phosphonites. We included different binol-
L1 and taddol-based[26] ligands L2 in our systematic screening,
Scheme 2. Interplay of two-point binding of ligand and substrate.
metathesis. Moreover, the selectivity factor emerged as
independent of the copper-to-ligand ratio; both 1:2 and 1:1
were equally effective, yet turnover was lower with the latter,
likely owing to insufficient stabilization of the copper(I)
hydride complex.[15] Excess ligand inhibits the reaction.
The screening of literally dozens of acyclic and cyclic
and selected data are summarized in Table 1. To our surprise,
phosphoramidites[23] derived from both binol and taddol were
largely unproductive. In contrast, taddol-derived phosphon-
ites L2[22a] were particularly promising (Table 1, entries 1–6),
and L2g (s = 14) emerged as the ideal ligand thus far (Table 1,
entry 7). We note that all test reactions were optimized for the
selectivity factor s[27] rather than for conversion and enantio-
meric excess.[28]
ꢀ
silanes showed that the dehydrogenative Si O coupling is
very sensitive towards the substitution pattern at the silicon
atom (Table 2 and the Supporting Information). Silanes
bearing a tert-butyl group were
completely inert; trialkylsilanes
were also not acceptable. Reactiv-
Table 1: Ligand identification and screening of taddol-based phosphonites.
ity increased with the number of
aryl groups (Ph3SiH > MePh2SiH >
Me2PhSiH) likely because of higher
Lewis acidity[24] in that order.
MePh2SiH combined good reactiv-
ity with good selectivity. We there-
Entry.
Ligand
X
Ar
Conv. [%][a]
ee [%][b]
s[c]
fore explored the steric and elec-
tronic possibilities of MeAr2SiH
and designated 3a as a reference
point (Table 2, entry 1). We derived
a few general trends: Any steric
1
2
3
4
5
6
7
L2a
L2b
L2c
L2d
L2e
L2f
L2g
C6H5
2,4,6-Me3C6H2
C6H5
C6H5
C6H5
C6H5
3,5-Me2C6H3
4-tBuC6H4
2-C10H7
47
33
51
30
32
51
55
41
6
4.0
1.4
3.0
9.4
9.5
5.9
14
nBu
tBu
tBu
tBu
tBu
38
32
35
57
84
ꢀ
bulk in proximity to the Si H bond
thwarted turnover (3b and 3i,
Table 2, entries 2 and 9). Con-
versely, only little influence on
selectivity was seen with 3c and 3j
(Table 2, entries 3 and 10). Elec-
tronic and presumably steric fine-
tuning of the arene through meta
1
[a] Conversion monitored and determined by H NMR spectroscopy as well as GLC analysis using an
internal standard. [b] Enantiomeric excess determined by HPLC analysis on chiral Daicel Chiralpak
columns. [c] Selectivity factor calculated from s=ln[(1ꢀC)(1ꢀee)]/ln[(1ꢀC)(1+ee)] where ee=ee/100
and C=conversion/100.[27]
Control experiments with novel bidentate phosphonite L3
and rac-1 as well as its nonfunctionalized counterpart rac-4
gave further indication of the single-point binding of the
ligand (Scheme 2): In reactions with rac-1 and L3, discrim-
ination of enantiomers (s = 2.0) is in the range of that
obtained with monodentate L2c (s = 3.0), indicating that L3
is not chelating in the stereochemistry-determining step to
make room for silane coordination (rac-1!(S)-2a). Con-
versely, no conversion is evident in the absence of a donor
tethered to the alcohol (rac-4!(S)-5a), which in turn
suggests that the donor in rac-1 is crucial in the s-bond
(both positions) and para substitution showed that + I
substituents (3d, 3e, and 3 f) and ꢀI substituents (3g) are
tolerated while + M substitution (3h) is not (Table 2,
entries 4–7 and 8). With silane 3d, an excellent selectivity
factor of > 20 was obtained.
We finally applied the protocol deemed most successful to
this point to several substrates with different donor groups
(Table 3, entries 1–4) and varied substituents R at the
carbinol carbon atom (Table 3, entries 5–10). As expected,
the selectivity factors were dependent on the steric and
electronic effects imparted by the substitution pattern of the
2224 www.angewandte.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 2223 –2226

Angewandte
Chemie
Table 2: Identification of suitable silanes and screening of MeAr2SiH.[d,e]
In summary, we have accomplished an enantioselective,
ꢀ
dehydrogenative Si O coupling for the first time. Extensive
screening of ligands and silanes led to the discovery of a
copper(I)/phosphonite/silane combination that affords
remarkably high selectivity factors in several cases. A note-
worthy aspect is the fact that only a single chiral monodentate
ligand is involved in the stereochemistry-determining s-bond
metathesis (cf. TS2; Figure 1). We think that this new
approach to kinetic resolution through the asymmetric
coupling of alcohols and silanes will stimulate further
research in this area.
Entry
Silane
Ar
Conv. [%][a]
ee [%][b]
s[c]
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3 f
3g
3h
3i
C6H5
55
0
84
–
14
–
10
35
9.5
18
7.2
Received: October 5, 2009
Published online: December 3, 2009
2-MeC6H4
3-MeC6H4
3,5-Me2C6H3
4-MeC6H4
4-tBuC6H4
4-CF3C6H4
4-MeOC6H4
1-C10H7
48
51
42
49
60
5
63
88
51
75
78
–
Keywords: asymmetric catalysis · dehydrogenative coupling ·
.
kinetic resolution · monodentate ligands · silicon
–
–
0
–
10
3j
2-C10H7
43
54
10
[1] E. Vedejs, M. Jure, Angew. Chem. 2005, 117, 4040 – 4069; Angew.
Chem. Int. Ed. 2005, 44, 3974 – 4001.
[2] a) P. G. M. Wuts, T. W. Greene, Greeneꢀs Protective Groups in
For footnotes [a]–[c], see Table 1. [d] For data on the other silanes tested,
see the Supporting Information. [e] All reactions were conducted using
CuCl (5 mol%), L2g (12.5 mol%), and Cs2CO3 (5 mol%) with a
substrate concentration of 0.8m in THF at room temperature for 48 h.
Organic Synthesis, 4th ed., Wiley, New York, 2007, pp. 165 – 221;
´
b) P. J. Kociensky, Protecting Groups, 3rd ed., Thieme, Stuttgart,
2004, pp. 188 – 230.
[3] For a Highlight, see: S. Rendler, M. Oestreich, Angew. Chem.
2008, 120, 254 – 257; Angew. Chem. Int. Ed. 2008, 47, 248 – 250.
[4] T. Isobe, K. Fukuda, Y. Araki, T. Ishikawa, Chem. Commun.
2001, 243 – 244.
[5] a) Y. Zhao, J. Rodrigo, A. H. Hoveyda, M. L. Snapper, Nature
2006, 443, 67 – 70; b) Z. You, A. H. Hoveyda, M. L. Snapper,
Angew. Chem. 2009, 121, 555 – 558; Angew. Chem. Int. Ed. 2009,
48, 547 – 550.
[6] a) Y. Zhao, A. W. Mitra, A. H. Hoveyda, M. L. Snapper, Angew.
Chem. 2007, 119, 8623 – 8626; Angew. Chem. Int. Ed. 2007, 46,
8471 – 8474; b) Wiskur and Patel recently reported a related
kinetic resolution: S. G. Patel, S. L. Wiskur, Tetrahedron Lett.
2009, 50, 1164 – 1166.
alcohol. For example, when the nitrogen donor was flanked
by an additional methyl group, this resulted in less efficient
enantiomer discrimination (Table 3, entry 2). Both aryl and
alkyl residues were accepted as R groups. We had expected
the latter to be problematic based on our previous experi-
ence.[8–10] Turnover was poor with cyclohexyl-substituted
alcohols, while methyl- and trifluoromethyl-bearing carbinols
were resolved with excellent selectivities (Table 3, entries 8–
10).
Table 3: Survey of different donors and substituents.
Entry Alcohol Donor
R
Silyl ether of fast-reacting enantiomer
Slow-reacting enantiomer
s[c]
yield [%][d]
ee [%][b]
yield [%][d]
ee [%][b] conv. [%][a]
1[e]
2
3
4
5
6
7
8
9
rac-1
rac-6
rac-7
rac-8
2-pyridyl
Ph
Ph
Ph
Ph
(S)-2d
49
59
54
44
49
59
54
25
43
46
84
60
72
56
70
47
71
(R)-1
(R)-6
(R)-7
(R)-8
(R)-9
(R)-10 27
(R)-11 40
(R)-12 62
(R)-13 38
39
38
43
43
39
88
87
95
76
80
87
92
30
86
97
51
59
57
57
53
65
56
25
53
58
35
11
22
8.2
14
7.3
19
25
20
23
2-(6-picolyl)
2-quinolyl
1-isoquinolyl
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
(S)-15d
(S)-16d
(S)-17d
(S)-18d
(S)-19d
(S)-20d
(S)-21d
(S)-22d
(R)-23d
rac-9
1-C10H7
2-C10H7
4-MeOC6H4
Cy
CF3
Me
rac-10
rac-11
rac-12
rac-13
rac-14
n.d.[f]
n.d.[f]
70
10
(S)-14
40
For footnotes [a]–[c], see Tables 1 and 2. [d] Yield of analytically pure product isolated by flash chromatography on silica gel. [e] This kinetic resolution
could also be performed on a larger scale (5.0 mmol). [f] n.d. =not determined.
Angew. Chem. Int. Ed. 2010, 49, 2223 –2226
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
2225

Communications
[7] G. Hꢀfle, W. Steglich, H. Vorbrꢁggen, Angew. Chem. 1978, 90,
Ohmura, H. Taniguchi, M. Suginome, Org. Lett. 2009, 11, 2880 –
602 – 615; Angew. Chem. Int. Ed. Engl. 1978, 17, 569 – 583.
[8] a) S. Rendler, G. Auer, M. Oestreich, Angew. Chem. 2005, 117,
7793 – 7797; Angew. Chem. Int. Ed. 2005, 44, 7620 – 7624; b) B.
Karatas, S. Rendler, R. Frꢀhlich, M. Oestreich, Org. Biomol.
Chem. 2008, 6, 1435 – 1440; c) A. Steves, M. Oestreich, Org.
Biomol. Chem. 2009, 7, 4464 – 4469.
2883.
0
ꢀ
[18] a) For a Pt -catalyzed B B bond activation using a phosphonite,
see: H. E. Burks, L. T. Kliman, J. P. Morken, J. Am. Chem. Soc.
2009, 131, 9134 – 9135; b) For a Ni0-catalyzed allylation using a
phosphonite, see: P. Zhang, J. P. Morken, J. Am. Chem. Soc.
2009, 131, 12550 – 12551.
[9] S. Rendler, O. Plefka, B. Karatas, G. Auer, R. Frꢀhlich, C. Mꢁck-
Lichtenfeld, S. Grimme, M. Oestreich, Chem. Eur. J. 2008, 14,
11512 – 11528.
[19] For an example in ring-closing metathesis, see: S. J. Malcolmson,
S. J. Meek, E. S. Sattely, R. R. Schrock, A. H. Hoveyda, Nature
2008, 456, 933 – 937.
[10] H. F. T. Klare, M. Oestreich, Angew. Chem. 2007, 119, 9496 –
9499; Angew. Chem. Int. Ed. 2007, 46, 9335 – 9338.
[20] B. D. Chapsal, I. Ojima in New Methodologies and Techniques
for a Sustainable Organic Chemistry, NATO Science Series
Vol. 246 (Eds.: A. Mordini, F. Faigl), Springer, Heidelberg, 2008,
pp. 29 – 54.
[21] For an account of chiral monodentate phosphine ligands (MOP
ligands), see: T. Hayashi, Acc. Chem. Res. 2000, 33, 354 – 362.
[22] For seminal papers on Y2P–X-type ligands (Y= O, N and X = N,
O, C), see: a) J.-i. Sakaki, W. B. Schweizer, D. Seebach, Helv.
Chim. Acta 1993, 76, 2654 – 2665; b) A. Alexakis, J. Frutos, P.
Mangeney, Tetrahedron: Asymmetry 1993, 4, 2427 – 2430;
c) A. H. M. de Vries, A. Meetsma, B. L. Feringa, Angew.
Chem. 1996, 108, 2526 – 2528; Angew. Chem. Int. Ed. Engl.
1996, 35, 2374 – 2376.
[23] For authoritative accounts, see: a) A. J. Minnaard, B. L. Feringa,
L. Lefort, J. G. de Vries, Acc. Chem. Res. 2007, 40, 1267 – 1277;
b) B. L. Feringa, Acc. Chem. Res. 2000, 33, 346 – 353.
[24] A. Weickgenannt, M. Oestreich, Chem. Asian J. 2009, 4, 406 –
410.
[25] 2-Diphenylphosphino-2’-methoxy-1,1’-binaphthyl: Y. Uozumi,
A. Tanahashi, S.-Y. Lee, T. Hayashi, J. Org. Chem. 1993, 58,
1945 – 1948.
[11] C. Lorenz, U. Schubert, Chem. Ber. 1995, 128, 1267 – 1269.
[12] For reviews of “Cu–H” chemistry, see: a) S. Rendler, M.
Oestreich, Angew. Chem. 2007, 119, 504 – 510; Angew. Chem.
Int. Ed. 2007, 46, 498 – 504; b) C. Deutsch, N. Krause, B. H.
Lipshutz, Chem. Rev. 2008, 108, 2916 – 2927; c) B. H. Lipshutz,
Synlett 2009, 509 – 524.
[13] D. R. Schmidt, S. J. OꢂMalley, J. L. Leighton, J. Am. Chem. Soc.
2003, 125, 1190 – 1191.
[14] J. T. Issenhuth, S. Dagorne, S. Bellemin-Laponnaz, J. Mol. Catal.
A 2008, 286, 6 – 10.
[15] The copper-to-ligand ratio might nevertheless deviate from 1:1
because more than one ligand might be necessary to stabilize
Cu–H intermediates: a) H. Zhang, R. M. Gschwind, Angew.
Chem. 2006, 118, 6540 – 6544; Angew. Chem. Int. Ed. 2006, 45,
6391 – 6394; b) H. Zhang, R. M. Gschwind, Chem. Eur. J. 2007,
13, 6691 – 6700.
0
ꢀ
[16] a) For MOP-type ligands in Pd -catalyzed Si B bond activation,
see: T. Ohmura, H. Taniguchi, M. Suginome, J. Am. Chem. Soc.
2006, 128, 13682 – 13683; b) For a remarkable example in a Ni0-
catalyzed reductive coupling using a menthol-derived mono-
phosphine, see: K. M. Miller, W.-S. Huang, T. F. Jamison, J. Am.
Chem. Soc. 2003, 125, 3442 – 3443.
[26] D. Seebach, A. K. Beck, A. Heckel, Angew. Chem. 2001, 113,
96 – 142; Angew. Chem. Int. Ed. 2001, 40, 92 – 138.
[27] H. B. Kagan, J. C. Fiaud in Topics in Stereochemistry, Vol. 18
(Eds.: E. L. Eliel, S. H. Wilen), Wiley, New York, 1988, pp. 249 –
330.
[17] a) For an IrI-catalyzed hydrogenation using a phosphoramidite,
see: F. Giacomina, A. Meetsma, L. Panella, L. Lefort, A. H. M.
de Vries, J. G. de Vries, Angew. Chem. 2007, 119, 1519 – 1522;
Angew. Chem. Int. Ed. 2007, 46, 1497 – 1500; b) For a Pd0-
[28] As reaction rates were surprisingly slow even with 5.00 mol%
CuCl, lower loadings were not tested.
ꢀ
catalyzed Si B bond activation using a phosphoramidite, see: T.
2226 www.angewandte.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 2223 –2226