Monodentate non-C2-symmetric chiral N-heterocyclic carbene complexes for enantioselective synthesis. Cu-catalyzed conjugate additions of aryl- and alkenylsilylfluorides to cyclic enones

Article abstract of DOI:10.1021/jo900589x

(Chemical Equation Presented) A new class of enantioselective conjugate addition (ECA) reactions that involve aryl- or alkenylsilyl fluoride reagents and are catalyzed by chiral non-C₂-symmetric Cu-based N-heterocyclic carbene (NHC) complexes a

Full text of DOI:10.1021/jo900589x

Monodentate Non-C2-symmetric Chiral N-Heterocyclic Carbene
Complexes for Enantioselective Synthesis. Cu-Catalyzed Conjugate
Additions of Aryl- and Alkenylsilylfluorides to Cyclic Enones
Kang-sang Lee and Amir H. Hoveyda*
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467
amir.hoVeyda@bc.edu
ReceiVed March 20, 2009
A new class of enantioselective conjugate addition (ECA) reactions that involve aryl- or alkenylsilyl
fluoride reagents and are catalyzed by chiral non-C2-symmetric Cu-based N-heterocyclic carbene (NHC)
complexes are disclosed. Transformations have been designed based on the principle that a catalytically
active chiral NHC-Cu-aryl or NHC-Cu-alkenyl complex can be accessed from reaction of a Cu-halide
precursor with in situ-generated aryl- or alkenyltetrafluorosilicate. Reactions proceed in the presence of
1.5 equiv of the aryl- or alkenylsilane reagents and 1.5 equiv of tris(dimethylamino)sulfonium
difluorotrimethylsilicate (TASF). Desired products are isolated in 63-97% yield and 73.5:26.5-98.5:
1.5 enantiomeric ratio (47%-97% ee). A major focus of the present studies is the design, evaluation,
and development of new chiral imidazolinium salts and their derived NHC-Cu complexes as catalysts
that promote reactions of various carbosilanes to a range of electrophilic substrates. Toward this end,
nearly 20 new chiral monodentate imidazolinium salts, most of which are non-C2-symmetric, have been
prepared and fully characterized and their ability to serve as catalysts in the ECA reactions has been
investigated.
Introduction
development of chiral NHC-Cu complexes that catalyze C-C
bond-forming reactions with the more functional group tolerant
and less moisture- and oxygen-sensitive organosilanes (vs the
aforementioned alkylmetal reagents).
The emergence of N-heterocyclic carbenes (NHCs) has had
a notable impact on the development of a variety of catalytic
transformations.1,2 Research in these laboratories has focused
on the design and development of a number of chiral bidentate
NHC-based Ru,3 Cu,4 and Mg5 complexes. The derived Cu-
based systems promote conjugate addition and allylic alkylation
reactions in high enantioselectivity; in all such processes, metal-
based nucleophiles, such as Grignard, dialkyl- or diarylzinc, or
trialkyl- or dialkylarylaluminum reagents are used. We have
more recently turned our attention toward identification and
Herein, we detail the development of a Cu-catalyzed enan-
tioselective conjugate addition (ECA) process6 that involves
easily accessible aryl- or vinyltrifluorosilanes (eq 1). Transfor-
mations can be performed with five-, six-, seven-, and eight-
membered ring cyclic enones (n ) 1-4, eq 1), furnishing the
desired ꢀ-aryl- and ꢀ-alkenyl cyclic ketones in up to 98.5:1.5
and 96:4 enantiomeric ratio (er), respectively. The present
(1) For recent reviews on N-heterocyclic carbenes as catalysts in organic
synthesis, see: (a) Enders, D.; Niemeier, O.; Henseler, A. Chem. ReV. 2007,
107, 5606–5655. (b) Marion, N.; D´ıez-Gonza´lez, S.; Nolan, S. P. Angew. Chem.,
Int. Ed. 2007, 46, 2988–3000.
(2) For representative reviews on N-heterocyclic carbenes as ligands in metal-
catalyzed processes, see: (a) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G.
Angew. Chem., Int. Ed. 2007, 46, 2768–2813. (b) Gade, L. H.; Bellemin-
Laponnaz, S. Top. Organomet. Chem. 2007, 21, 117–157. (c) Tekavec, T. N.;
Louie, J. Top. Organomet. Chem. 2007, 21, 159–192.
(3) (a) Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda, A. H.
J. Am. Chem. Soc. 2002, 124, 4954–4955. (b) Van Veldhuizen, J. J.; Gillingham,
D. G.; Garber, S. B.; Kataoka, O.; Hoveyda, A. H. J. Am. Chem. Soc. 2003,
125, 12502–12508. (c) Gillingham, D. G.; Kataoka, O.; Garber, S. B.; Hoveyda,
A. H. J. Am. Chem. Soc. 2004, 126, 12288–12290. (d) Van Veldhuizen, J. J.;
Campbell, J. E.; Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127,
6877–6882. For an overview, see: (e) Hoveyda, A. H.; Gillingham, D. G.; Van
Veldhuizen, J. J.; Kataoka, O.; Garber, S. B.; Kingsbury, J. S.; Harrity, J. P. A.
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10.1021/jo900589x CCC: $40.75
Published on Web 05/15/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 4455–4462 4455

Lee and Hoveyda
SCHEME 1. Plausible Pathway for Conjugate Addition of
ArSiF3 Catalyzed by an NHC-Cu Complex
investigations have led us to design, prepare, and examine
approximately 20 new non-C2-symmetric chiral imidazolinium
salts, utilized to access the derived monodentate NHC-Cu
complexes. It should be noted that although Pd-7,8 and
Rh-catalyzed9,10 conjugate additions of organosilanes, including
the related enantioselective protocols, have been reported
previously, this disclosure puts forward the first examples of
Cu-catalyzed variants of this class of transformations.11
Design, synthesis, and examination of catalytic activity of
easily accessible and readily modifiable chiral NHC complexes
that can be used in enantioselective synthesis is a principal
impetus for carrying out the investigations described in this
report. Identification of an efficient set of protocols that allows
for efficient activation of aryl- as well as alkenylsilanes by NHC-
based catalysts serves as another main objective. We surmised
that once the appropriate class of chiral catalysts and methods
for use of the Si-based reagents are identified and established,
a number of C-C bond-forming protocols involving several
types of electrophiles (e.g., carbonyls or imines) would follow.
Catalytic ECA reactions with cyclic enones were, therefore,
selected to serve as a platform for exploring the utility of NHC-
based catalysts to promote enantioselective C-C bond-forming
reactions with organosilanes.
promote conjugate addition of an organosilane to an enone. We
surmised that reaction of an NHC-Cu complex (I, Scheme 1),
wherein the transition metal is bound to an effective leaving
group (e.g., a halide), with an in situ-generated hypervalent12
tetrafluoroaryl silicate, can give rise to the derived NHC-Cu-aryl
complex II (Scheme 1).13 As shown in Scheme 1, the requisite
pentavalent aryl silicate would be obtained through reaction of
a trifluoroaryl silane and an appropriate fluorinating agent.
Association of the Lewis acidic NHC-Cu with the R,ꢀ-
Results and Discussion
1. Mechanistic Considerations. We began by envisioning
a plausible pathway through which an NHC-Cu complex might
(4) For application of bidentate NHC-Cu complexes, developed in these
laboratories, to catalytic enantioselective allylic alkylations and conjugate
additions, see: (a) Larsen, A. O.; Leu, W.; Nieto-Oberhuber, C.; Campbell, J. E.;
Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 11130–11131. (b) Lee, K-s.;
Brown, M. K.; Hird, A. W.; Hoveyda, A. H. J. Am. Chem. Soc. 2006, 128,
7182–7184. (c) Reference 3d. (d) Brown, M. K.; May, T. L.; Baxter, C. A.;
Hoveyda, A. H. Angew. Chem., Int. Ed. 2007, 46, 1097–1100. (e) Kacprzynski,
M. A.; May, T. L.; Kazane, S. A.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2007,
46, 4554–4558. (f) Lee, Y.; Akiyama, K.; Gillingham, D. G.; Brown, M. K.;
Hoveyda, A. H. J. Am. Chem. Soc. 2008, 130, 446–447. (g) May, T. L.; Brown,
M. K.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2008, 47, 7468–7472. (h) Brown,
M. K.; Hoveyda, A. H. J. Am. Chem. Soc. 2008, 130, 12904–12906. For related
developments from other laboratories, see: (i) Arnold, P.; Rodden, M.; Davis,
K. M.; Scarisbrick, A. C.; Blake, A. J.; Wilson, C. Chem. Commun. 2004, 1612–
1613. (j) Clavier, H.; Coutable, L.; Toupet, L.; Guillemin, J.-C.; Mauduit, M. J.
Organomet. Chem. 2005, 690, 5237–5254. (k) Martin, D.; Kehrli, S.; d’Augustin,
M.; Clavier, H.; Mauduit, M.; Alexakis, A. J. Am. Chem. Soc. 2006, 128, 8416–
8417. For application of the same class of chiral bidentate NHC complexes to
enantioselective hydroboration, see: (l) Lee, Y.; Hoveyda, A. H. J. Am. Chem.
Soc. 2009, 131, 3160–3161.
(5) Lee, Y.; Hoveyda, A. H. J. Am. Chem. Soc. 2006, 128, 15604–15605.
(6) For recent reviews on enantioselective conjugate addition reactions
involving organometallic nucleophilic reagents, see: (a) Krause, N.; Hoffmann-
Ro¨der, A. Synthesis 2001, 171–196. (b) Feringa, B. L., Naaz, R.; Imbos, R.;
Arnold, N. A, In Modern Organocopper Chemistry; Krause, N., Ed.; Wiley-
VCH: Weinheim, 2002; pp 224-258. (c) Lo´pez, F.; Minnaard, A. J.; Feringa,
B. L. Acc. Chem. Res. 2007, 40, 179–188. (d) Harutyunyan, S. R.; den Hartog,
T.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem. ReV. 2008, 108, 2824–
2852. (e) Alexakis, A.; Ba¨ckvall, J. E.; Krause, N.; Pa`mies, O.; Die´guez, M.
Chem. ReV. 2008, 108, 2796–2823. (f) von Zezschwitz, P. Synthesis 2008, 1809–
1831. (g) Gutnov, A. Eur. J. Org. Chem. 2008, 4547–4554. (h) Yamamoto, Y.;
Nishikata, T.; Miyaura, N. Pure Appl. Chem. 2008, 80, 807–817.
(9) For non-enantioselective Rh-catalyzed conjugate addition reactions with
arylsiloxanes, see: (a) Mori, A.; Danda, Y.; Fujii, T.; Hirabayashi, K.; Osakada,
K. J. Am. Chem. Soc. 2001, 123, 10774–10775. (b) Huang, T.-S.; Li, C.-J. Chem.
Commun. 2001, 2348–2349. (c) Oi, S.; Honma, Y.; Inoue, Y. Org. Lett. 2002,
4, 667–669. (d) Koike, T.; Du, X.; Mori, A.; Osakada, K. Synlett 2002, 301–
303. (e) Murata, M.; Shimazaki, R.; Ishikura, M.; Watanabe, S.; Masuda, Y.
Synthesis 2002, 717–719. For a review of Rh-catalyzed conjugate addition
reactions, see: (f) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829–2844.
(10) For Rh-catalyzed ECA reactions involving aryl- or alkenylsilanes, see:
(a) Oi, S.; Taira, A.; Honma, Y.; Inoue, Y. Org. Lett. 2003, 5, 97–99. (b)
Otomaru, Y.; Hayashi, T. Tetrahedron: Asymmetry 2004, 15, 2647–2651. (c)
Oi, S.; Taira, A.; Honma, Y.; Sato, T.; Inoue, Y. Tetrahedron: Asymmetry 2006,
17, 598–602. (d) Hargrave, J. D.; Herbert, J.; Bish, G.; Frost, C. G. Org. Biomol.
Chem. 2006, 4, 3235–3241. (e) Nakao, Y.; Chen, J.; Imanaka, H.; Hiyama, T.;
Ichikawa, Y.; Duan, W.-L.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2007,
129, 9137–9143.
(11) For conjugate additions of alkylcopperpentafluorosilicates to R,ꢀ-
unsaturated ketones promoted by stoichiometric amounts of Cu(OAc)2, see: (a)
Yoshida, J.; Tamao, K.; Kakui, T.; Kurita, A.; Murata, M.; Yamada, K.; Kumada,
M. Organometallics 1982, 1, 369–380. For Cu-catalyzed cross-coupling reactions
of alkynyl- and alkenylsilanes, respectively, see: (b) Nishihara, Y.; Ikegashira,
K.; Mori, A.; Hiyama, T. Tetrahedron Lett. 1998, 39, 4075–4078. (c) Nishihara,
Y.; Ikegashira, K.; Toriyama, F.; Mori, A.; Hiyama, T. Bull. Chem. Soc. Jpn.
2000, 73, 985–990. For Cu-catalyzed reactions of allyltrimethoxysilane to
carbonyl-containing compounds and imines, see: (d) Yamasaki, S.; Fujii, K.;
Wada, R.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2002, 124, 6536–6537.
For Rh-catalyzed enantioselective conjugate addition reactions that involve
vinylsilanes, see: (e) Shintani, R.; Ichikawa, Y.; Hayashi, T.; Chen, J.; Nakao,
Y.; Hiyama, T. Org. Lett. 2007, 9, 4643–4645.
(7) For non-enantioselective Pd-catalyzed conjugate additions with arylsi-
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752–753. (b) Denmark, S. E.; Amishiro, N. J. Org. Chem. 2003, 68, 6997–
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2007, 710–712. (d) Lerebours, R.; Wolf, C. Org. Lett. 2007, 9, 2737–2740.
(8) For Pd-catalyzed ECA reactions involving aryl- or alkenylsilanes, see:
Nishikata, T.; Yamamoto, Y.; Gridnev, I. D.; Miyuara, N. Organometallics 2005,
24, 5025–5032.
(12) For reviews regarding the chemistry of hypervalent silanes, see: (a)
Kumada, M.; Tamao, K.; Yoshida, J.-i. J. Organomet. Chem. 1982, 239, 115–
132. (b) Chuit, C.; Corriu, R. J. P.; Reye, C.; Young, J. C. Chem. ReV. 1993, 93,
1371–1448. (c) Rendler, S.; Oestreich, M. Synthesis 2005, 1727–1747. (d) Orito,
Y.; Nakajima, M. Synthesis 2006, 1391–1401.
(13) For a recent study regarding transmetalation of an NHC-Cu-F complex
with triethoxyarylsilanes, see: Herron, J. R.; Ball, Z. T. J. Am. Chem. Soc. 2008,
130, 16486–16487.
4456 J. Org. Chem. Vol. 74, No. 12, 2009

Carbene Complexes for EnantioselectiVe Synthesis
TABLE 1. Activity of NHC ·Ag(I) Complexes for Enantioselective
a
CA Reaction of Cyclohexenone with PhSiF3
FIGURE 1. X-ray structure of NHC · Ag(I) complex 3 (two views
shown).
(X-ray shown in Figure 1) or 4 in the presence of CuCl proceeds
to 52% and 17% conversion, delivering enantiomerically
enriched ꢀ-phenylcyclohexanone 5 in 85.5:14.5 and 67:33 er,
respectively (entries 3 and 4, Table 1). The ECA in the presence
of non-C2-symmetric 3 is more efficient (52% vs 17% conver-
sion) as well as more enantioselective (85.5:14.5 vs 67:33 er)
than the C2-symmetric complex 4.15,16
entry
NHC·Ag; mol %
conv (%)b
erc
1
2
3
4
1; 2.5
2; 2.5
3; 5.0
4; 5.0
<2
<2
52
17
85.5:14.5
67:33
a Reactions performed under N2 atmosphere. b Conversion levels were
determined by analysis of 400 MHz 1H NMR spectra of unpurified
products. c Enantiomeric ratio (er) values were determined by GLC
We have demonstrated that bidentate NHC complexes such
as 1 and 2 can be used to promote a number of enantioselective
Cu-catalyzed processes involving Zn-, Mg-, or Al-based
nucleophiles.4,5 In all such cases, initial reaction of the nucleo-
philic organometallic reagent with the derived well-characterized
dimeric NHC-Cu complex3d,4a likely results in the generation
of monomeric bidentate Cu-carbenes, which are likely the
catalytically active entities. It is plausible that the inactivity of
the bidentate chiral NHCs, which exist in the dimeric form, is
because the less nucleophilic phenyltetrafluorosilicate (vs the
aforementioned metal-based reagents) is unable to promote
effective dissociation of the corresponding dimeric Cu complexes.
Two different views of the X-ray structure of 3 and several
noteworthy values are depicted (Figure 1). The dihedral angles
listed in Figure 1 indicate that the dissymmetric aryl unit of 3
is significantly more tilted than the symmetric mesityl unit; such
a conformational preference is likely to minimize unfavorable
steric interaction with the phenyl group of the NHC backbone.
As will be discussed below, the above structural attributes are
relevant to the design of effective monodentate NHC-based
catalysts.
3. Identification of an Optimal Cu Salt and Reaction
with Isolated Chiral NHC-Cu Complexes. Before initiating
our studies regarding determination of the optimal chiral
monodentate complex, we determined the identity of the most
effective Cu salt. As the findings in Table 2 illustrate, in the
presence of complex 3 nearly all salts examined deliver
cyclohexanone 5 with similar enantioselectivity (84:16-86.5:
13.5 er), with the highest conversion being observed when
reaction is performed in the presence of CuBr (entry 2, Table
2). The lack of activity of the complex derived from CuCN
analysis; see the Supporting Information for details. TASF
(Me2N)3SSi(Me3)F2.
)
unsaturated ketone furnishes complex III; subsequent conjugate
addition would generate the desired C-aryl bond. Reaction of
the resulting NHC-Cu-enolate IV with another equivalent of
the hypervalent arylsilicate is expected to deliver the conjugate
addition product V along with tetrafluorosilane (Scheme 1).
2. Identification of an Effective Class of Chiral NHC-Cu
Complexes. Our next objective became to identify which class
of NHC-Cu complexes most efficiently promotes conjugate
addition according to the general pathway depicted in Scheme
1. Key observations from this segment of our investigations are
shown in Table 1; commercially available cyclohexenone and
trifluorophenylsilane served as the representative substrate and
organosilane, respectively, and tris(dimethylamino)sulfonium
difluorotrimethylsilicate (TASF) was used for in situ formation
of the hypervalent silicate.14
Bidentate NHC-Cu complexes (2.5 mol %) derived from
the reaction of Ag-based carbenes 1 and 2 (entries 1-2, Table
1) are ineffective in promoting conjugate addition. In contrast,
reaction with 5 mol % of monodentate Ag-based complexes 3
(14) For details regarding examination of various silylating agents in different
solvents, leading to selection of TASF as the optimal choice, see the Supporting
Information.
(15) For examples of C2-symmetric chiral NHC-metal complexes used in
enantioselective catalysis, see: (a) Herrmann, W. A.; Goossen, L. J.; Ko¨cher,
C.; Artus, G. R. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 2805–2807. (b) Seiders,
T. J.; Ward, D. W.; Grubbs, R. H. Org. Lett. 2001, 3, 3225–3228. (c) Guillen,
F.; Winn, C. L.; Alexakis, A. Tetrahedron: Asymmetry 2001, 12, 2083–2086.
(d) Pytkowicz, J.; Roland, S.; Mangeney, P. Tetrahedron: Asymmetry 2001, 12,
2087–2089. (e) Ma, Y.; Song, C.; Ma, C.; Sun, Z.; Chai, Q.; Andrus, M. B.
Angew. Chem., Int. Ed. 2003, 42, 5871–5874. (f) Jensen, D. R.; Sigman, M. S.
Org. Lett. 2003, 5, 63–65. (g) Tominaga, S.; Oi, Y.; Kato, T.; An, D. K.;
Okamoto, S. Tetrahedron Lett. 2004, 45, 5585–5588. (h) Reference 4k. (i)
Chaulagain, M. R.; Sormunen, G. J.; Montgomery, J. J. Am. Chem. Soc. 2007,
129, 9568–9569. (j) Sato, Y.; Hinata, Y.; Seki, R.; Oonishi, Y.; Saito, N. Org.
Lett. 2007, 9, 5597–5599. (k) Baxter, R. D.; Montgomery, J. J. Am. Chem. Soc.
2008, 130, 9662–9663. (l) Xu, L.; Shi, Y. J. Org. Chem. 2008, 73, 749–751.
(m) Matsumoto, Y.; Yamada, K.; Tomioka, K.-i. J. Org. Chem. 2008, 73, 4578–
4581. (n) Lillo, V.; Prieto, A.; Bonet, A.; D´ıaz-Requejo, M. M.; Ram´ırez, J.;
Pe´rez, P. J.; Ferna´ndez, E. Organometallics 2009, 28, 659–662. (o) Reference
4l.
(16) Although non-C2-symmetric chiral monodentate NHCs are commonly
employed as catalysts (see ref 1), application of the corresponding metal-based
complexes is relatively uncommon in enantioselective catalysis. See: (a) Enders,
D.; Gielen, H.; Runsink, J.; Breuer, K.; Brode, S.; Boehn, K. Eur. J. Inorg.
Chem. 1998, 913–919. (b) Duan, W.-L.; Shi, M.; Rong, G.-B. Chem. Commun.
2003, 2916–2917. (c) Focken, T.; Rudolph, J.; Bolm, C. Synthesis 2005, 429–
436. (d) Li, S.-J.; Zhong, J.-H.; Wang, Y.-G. Tetrahedron: Asymmetry 2006,
17, 1650–1654. (e) Fournier, P.-A.; Collins, S. K. Organometallics 2007, 26,
2945–2949. (f) Vehlow, K.; Wang, D.; Buchmeiser, M. R.; Blechert, S. Angew.
Chem., Int. Ed. 2008, 47, 2615–2618. (g) Reference 15n.
J. Org. Chem. Vol. 74, No. 12, 2009 4457

Lee and Hoveyda
TABLE 2. Screening of Cu Salts for ECA Reaction of
SCHEME 3. Models for Chiral NHC-Cu-Substrate
Association
Cyclohexenone with PhSiF3 with NHC ·Ag Complex 3a
entry
Cu salt
CuCl
CuBr
CuBr2 ·Me2S
CuI
CuOAc
CuCN
(CuOTf)2 ·C6H6
(MeCN)4CuPF6
conv (%)b
erc
1
2
3
4
5
6
7
8
52
79
30
26
38
<2
53
35
85.5:14.5
86.5:13.5
85:15
84.5:15.5
84:16
d
84:16
84:16
a-c See Table 1. d 5.0 mol % of 3 and 2.5 mol % of Cu salt used.
SCHEME 2. Synthesis and Examination of Catalytic
Activity of NHC-Cu Complexes 7 and 8a
philic alkene. Accordingly, the substrate can approach the chiral
catalyst through four quadrants, represented by A-D (Scheme
3); the orientation of the N-Ar substituents of the NHC are based
on X-ray crystal structures such as those shown in Figure 1.
The quadrant labeled as A represents the most accessible
mode of association for a substrate molecule (Scheme 3). In
contrast, complex B, expected to deliver the opposite product
enantiomer, should be less favored as a result of steric
interactions with the dissymmetrically substituted N-Ar unit.
Examination of molecular models indicates that the presence
of a meta substituent, such as d in B, might lead to enhancement
of enantioselectivity by discouraging B versus A. Positioning
of a group ortho to d would be detrimental to A as well as B;
it is such interactions that we expect to render reaction through
C and D as energetically unfavorable. In a C2-symmetric chiral
NHC, one that lacks substituents b and d, similar arguments
hold except that A and D would represent equally favorable
pathways. In light of the above considerations, our initial finding
regarding the higher effectiveness of the non-C2-symmetric
complex 3 derived from imidazolinium salt 6 versus that
obtained from the C2-symmetric 4 (Table 1) emerged as
noteworthy. We continued to focus on the development of non-
C2-symmetric variants; this decision was not only based on our
preliminary findings but also because dissymmetric NHC-metal
complexessparticularly the monodentate variantsshave not
been widely developed and utilized in enantioselective cataly-
sis.16
5. Preparation and Examination of Catalytic Activity
of Various Chiral Monodentate Non-C2-symmetric NHC
Complexes. We investigated the ability of a number of chiral
monodentate non-C2-symmetric NHC-Cu complexes to pro-
mote the ECA to cyclohexenone with PhSiF3. The chiral
imidazolinium salts used to synthesize the derived Cu complexes
and the results obtained from each corresponding ECA process
are summarized in Scheme 4.
a. Variations at the Symmetric N-Aryl Moiety. We began
by investigating the effect of the alteration of the size of
the substituents of the symmetrically substituted N-Ar unit of
the carbene on efficiency and enantioselectivity. Examination
of the models presented in Scheme 3 suggests that the
substituents represented by b and c might influence selectivity
by discouraging substrate approach proximal to the sym-
metrically substituted N-aryl group. Such variations can change
the orientation of the phenyl units of the carbene backbone, in
a See the Supporting Information for detailed procedures.
(entry 6, Table 2) likely reflects the strong Cu-CN bond [i.e.,
the derived NHC-Cu-Ar (II in Scheme 1) is not generated].
It might be for a similar reason that dimeric Cu complexes
derived from 1 and 2 do not promote reaction: the Si-based
nucleophile may not readily react with, and displace, the
corresponding Cu-O bond.
We prepared chiral complexes 7 and 8, as illustrated in
Scheme 2, and investigated their ability to initiate the model
ECA process versus the related transformations promoted by
in situ-prepared catalysts. Although similar enantioselectivities
are observed, use of carbenes 7 and 8 gives rise to more efficient
conjugate additions. Thus, with 7, reaction proceeds to 82%
conversion (vs 52% when prepared in situ); when bromide 8 is
utilized, >98% conversion is achieved under identical conditions
(Scheme 2; see below for a discussion regarding the higher
activity with NHC-CuBr complexes).
4. Theoretical Basis for Catalyst Development; Structural
Features of an Effective Chiral NHC-Cu Catalyst. To base
the design and development of chiral NHC catalysts on a
mechanistic framework, we made the assumption that catalyst-
substrate association is the critical stereochemistry-determining
step of the catalytic cycle (see Scheme 1) and evaluated various
modes of interaction, some of which are depicted in Scheme 3.
We reasoned that the unsaturated carbonyl coordinates to the
chiral NHC-CuAr complex in a manner that permits maximum
overlap between the Cu-aryl bond and the π* of the electro-
4458 J. Org. Chem. Vol. 74, No. 12, 2009

Carbene Complexes for EnantioselectiVe Synthesis
SCHEME 4. Screening of Non-C2-symmetric Imidazolinium Salts Used To Prepare Monodentate NHC-CuBr Complexes for
a
ECA Reaction of Cyclohexenone with PhSiF3
a Reactions performed under N2 atmosphere; see the Supporting Information for detailed experimental procedures. b CuCl used and reaction performed
at 60 °C. c The derived Cu-based complexes are formed as 2:1 (14), 1:1 (15), 17:1 (20), 9:1 (22), and 19:1 (23) mixtures of atropisomers; all other complexes,
including that derived from 21, are formed as a single isomer (>98:<2). The major diastereomer and/or that used, after separation and purification, in the
ECA process is illustrated. All stereoisomer ratios were determined by analysis of the 400 MHz H NMR spectra of the unpurified mixtures. d Reaction
1
performed at 60 °C.
turn altering the conformational preferences of the dissymmetri-
cally substituted N-Ar moiety. The observed differences in the
activity and selectivity of chiral complex 3 and the C2-symmetric
4 (see Table 1) might, therefore, be partly due to conformational
preferences of one N-Ar group, which depends on whether the
other N-aryl unit is symmetrically (as in 4) or nonsymmetrically
(e.g., 3) substituted. As will be discussed below in more detail,
the larger steric presence provided by the 2,6-disubstituted
N-aryl unit, an attribute that may not be available in a
C2-symmetric complex, gives rise to higher reactivity.
We first prepared and examined the activity of the CuBr
complexes derived from imidazolinium salts 9-11 (Scheme 4).
We established that changing the Me groups of the mesityl unit
in 6 to the larger Et units results in higher enantioselectivity
(90:10 er vs 85:15 er for 6) without a significant diminution in
efficiency. When alterations of this type are extended to the
i-Pr substituents (cf. 10, Scheme 4), however, ECA efficiency
suffers (49% conversion vs 95% conversion with 9 or >98%
conversion with 6), but 5 is still generated with similar
enantiomeric purity (89:11 er vs 90:10 er with 9; see Scheme
4). The significance of the NHC’s N-Ar substituents to enan-
tioselectivity is exhibited by the low er values obtained in the
reactions performed with the CuBr complex derived from
imidazolinium salts 11-13 (66.5:33.5 er, 60:40 er and 57:43
er, respectively). These findings illustrate that with NHC-Cu
complexes that bear sterically demanding substituents (e.g.,
Cu-carbenes derived from 10 and 13), the rate of formation of
the requisite NHC-Cu-aryl (i.e., I f II, Scheme 1) as well
as coordination with the enone substrate (i.e., II f III, Scheme
1) is adversely affected.
b. Variations at the Dissymmetric N-Aryl Moiety. Next,
we examined the effect of the substituents represented by a in
the models shown in Scheme 3. We hypothesized that in
complexes derived from 14-16, association of the Lewis basic
heteroatom-containing substituent, as represented by complex
E, might further discourage substrate chelation through mode
J. Org. Chem. Vol. 74, No. 12, 2009 4459

Lee and Hoveyda
SCHEME 5. Cu-Catalyzed Enantioselective CA Reactions
of Cyclohexenone and PhSiF3 with Minor NHC Rotamers
and the C2-Symmetric Variant of 23
C (Scheme 3). As the data in Scheme 4 illustrate, however,
ECA with Cu salts derived from 14-16 deliver 5 with slightly
lower or similar enantioselectivity [78.5:21.5 er, 84.5:15.5 er,
and 70.5:29.5 er, respectively, vs NHC derived from 6, affording
98% conversion and 85:15 er]. The data obtained for reactions
promoted by chiral carbenes corresponding to 14-16 thus
illustrate that, although association of the substituent a with the
Cu center, as depicted in E, might disfavor C (Scheme 3), the
resulting conformational tilt of the N-aryl moiety can reduce
selectivity by rendering the front left quadrant of the complex
accessible and coordination through mode B more favorable.
from C2-symmetric 26 (Scheme 5), corresponding to optimal
imidazolinium salt 23 (Scheme 4), although equally discriminat-
ing (95:5 er), is a less active catalyst (68% vs 98% conversion).
Such a difference in reactivity might be the result of stronger
tendency of the relatively less hindered C2-symmetric Cu-based
complex to transform into less active bridged structures. This
proposal is supported by the stronger tendency of Cl-based
complexes (vs Br-based) to form structures with interconnecting
halogen ligands,18 and the larger difference in the efficiency of
ECA reactions performed in the presence of NHC-Cu-chlorides
derived from 3 and 4 (Table 1, 52% vs 17% conversion). It
might be suggested that for similar reasons, when C2-symmetric
26 is utilized in the presence of CuCl, there is only 16%
conversion under identical conditions (vs 68% conversion with
CuBr; see Scheme 5). Thus, by discouraging the formation of
less active Cu-based systems, the larger size of the substituents
of the symmetric N-aryl moiety promotes higher activity without
engendering diminution of enantioselectivity.
6. Catalytic ECA Reactions of Cyclic Enones and
Arylsilyltrifluorides Catalyzed by Chiral Monodentate
Non-C2-symmetric NHC-Cu Complexes. The generality of
the Cu-catalyzed protocol to promote the enantioselective CA
reactions of various cycloalkenones with a range of arylsilyl-
trifluorides19 has been evaluated; the results of these studies
are illustrated in Table 3. With cyclohexenone (entries 1-5),
reactions are efficient, affording products in 90-93% yield. Silyl
reagents bearing a sterically hindered (entry 2, Table 3), an
electron-donating (entry 3), or an electron-withdrawing (entry
4) aryl group undergo reaction efficiently (90-93% yield after
purification) and in high enantioselectivity (94:6-96.5:3.5 er).
As illustrated in entry 5 of Table 3, with diphenylsilyldif-
luoride, use of 0.75 equiv of the reagent leads to >98%
conversion; the desired product is isolated in 92% yield and
94:6 er. The latter finding indicates that both aryl units of
Ph2SiF2 are transferred in the course of the catalytic process.
The transformations shown in entries 6-11 of Table 3 involve
medium ring substrates cycloheptenone and cyclooctenone;
products are obtained in 63-92% yield and 92.5:7.5 to 98.5:
1.5 er. Reactions with the seven-membered ring enone proceed
slightly less efficiently than those of cyclohexenone: with the
sterically hindered o-MeC6H4SiF3 (entry 7, Table 3), ECA
Synthesis and examination of the catalytic activity of
complexes derived from chiral salts 17-19 (Scheme 4) dem-
onstrates that increasing the size of substituent a engenders
diminution of enantioselectivity as well. As illustrated in F,
conformational adjustment to minimize steric repulsion between
the ortho N-aryl substituent and the NHC backbone likely leads
to a similar conformational preference.
The above studies led us to probe the catalytic activity of
chiral NHCs that would disfavor mode of complexation B
(Scheme 3). Accordingly, imidazolinium salts 20 and 21
(Scheme 4) were synthesized and examined. Positioning of a
methyl substituent at the ortho (20, Scheme 4) or meta (21)
site of the dissymmetric N-aryl group of the NHC gives rise to
a reaction that proceeds with slightly lower selectivity compared
to the parent 9 (87:13 and 88.5:11.5 er, respectively, vs 90:10
er; see Scheme 4). We hypothesized that the positive effect of
the o-methyl of 20 in discouraging reaction through B is likely
offset by also disfavoring complex A, and the m-methyl of 21
is not sufficiently sizable to make its presence felt by the
approaching substrate. That the NHC derived from 22, bearing
an i-Pr unit at the meta site of the N-aryl group delivers an
improved 93.5:6.5 er and that enantioselectivity is further
improved when tert-butyl-bearing 23 is used (95:5 er) lends
credence to the proposed model.
c. Reaction Promoted by Minor Atropisomers and a
C2-Symmetric NHC. Synthesis of chiral imidazolinium salts
20-23, wherein the dissymmetric N-aryl groups contain an
ortho as well as a meta substituent, also yields some of the
alternative atropisomer as the minor diastereomer (see Scheme
4 for isomer ratios); two examples (24 and 25) are depicted in
Scheme 5. As the representative data indicate (Scheme 5), these
minor diastereomers, separated from the major isomers by silica
gel chromatography,17 serve to generate substantially less
effective chiral catalysts. The diminished reactivity and enan-
tioselectivity observed with 24 and 25 are likely because mode
of association A is rendered less energetically preferred due to
unfavorable interaction between the protruding o-phenyl sub-
stituent and the bound enone substrate.
(18) (a) Carvajal, A.; Liu, X.-Y.; Alemany, P.; Novoa, J. J.; Alvarez, S. Int.
J. Quantum Chem. 2002, 86, 100–105. (b) Samant, R. A.; Ijeri, V. S.; Srivastava,
A. K. J. Electroanal. Chem. 2002, 534, 115–121.
(19) The arylsilyltrifluoride reagents used in this study are based on previously
reported procedures: (a) Brook, M. A.; Neuy, A. J. Org. Chem. 1990, 55, 3609–
3616. (b) Powell, D. A.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 7788–7789.
The aryl-based reagents are typically obtained in 40-65% yield after distillation.
d. Rationale for Lower Efficiency of the C2-Symmetric
NHC Complexes. It is noteworthy that the Cu complex derived
(17) See the Supporting Information for experimental details.
4460 J. Org. Chem. Vol. 74, No. 12, 2009

Carbene Complexes for EnantioselectiVe Synthesis
TABLE 3. Catalytic Enantioselective CA Reactions of Cyclic
Enones and Aryltrifluorosilanes with NHC-Cu Complexes Derived
from Imidazolinium Salt 23a
TABLE 4. Catalytic ECA Reactions of Cyclic Enones and
Alkenyltrifluorosilanes with NHC-Cu Complexes Derived from 23a
entry
n
(aryl)SiF3
C6H5SiF3
o-MeC6H4SiF3
p-OMeC6H4SiF3
p-FC6H4SiF3
Ph2SiF2
conv (%)b
yield (%)c
erd
95:5
96.5:3.5
94:6
94:6
94:6
1
2
3
4
5
6
7
8
2
2
2
2
2
3
3
3
3
3
4
1
1
98
>98e
>98
95e,f
>98g
97
91
90
93
92
92
92
63
68
65
85
80
85
92
C6H5SiF3
95:5
o-MeC6H4SiF3
p-OMeC6H4SiF3
p-FC6H4SiF3
Ph2SiF2
C6H5SiF3
C6H5SiF3
68e,h
77e
98.5:1.5
92.5:7.5
93:7
9
76f
10
11
12
13
90g
86e
94:6
92.5:7.5
81.5:18.5
90:10
92
o-MeC6H4SiF3
>98i
a Reactions performed under N2 atmosphere. b Conversion values
1
(consumption of substrate) determined by analysis of 400 MHz H NMR
spectra of the unpurified mixtures. c Yields of isolated products after
purification. d Enantiomer ratio values determined by GLC or HPLC
analysis; see the Supporting Information for complete details. e Reaction
time ) 40 h. f 3 equiv of TASF used. g 0.75 equiv of Ph2SiF2 used. h 20
mol % catalyst loading utilized. i Reaction temperature ) 60 °C.
a-d See Table 1.
26.5-96:4 er. In contrast to processes with arylsilyltrifluorides
(Table 3), reactions involving medium-ring enones (entries 3-4,
Table 4) proceed with higher enantioselectivity than those with
cyclohexenone (entry 2); the lower selectivity obtained with
cyclopentenone (entry 1) is consistent with catalytic additions
of aryl groups (see above). As indicated by the data summarized
in entries 5-8 of Table 4, similar efficiencies and enantiose-
lectivities are observed in reactions with cyclohexyl-substituted
28 and trisubstituted alkenylsilane 29. Unlike transformations
with arylsilylfluorides, however, increasing the size of the
alkenyl group does not result in higher enantioselectivity
(compare entries 1 and 2 or 6 and 7 in Table 3 with 2 and 8 in
Table 4). The reason for such variations in selectivity, as well
as the rationale for the lower levels of enantiomeric purity of
products from alkenyl addition reactions, requires a better
appreciation of the mechanistic nuances and kinetic differences
between these two classes of ECA reactions.
proceeds to 68% conversion with 20 mol % catalyst and after
an extended reaction time of 40 h. It should be noted, however,
that catalytic ECA with the sterically demanding reagent affords
the highest level of enantioselectivity (98.5:1.5 er in entry 7).
As was the case in reaction with cyclohexenone, substoichio-
metric amounts of Ph2SiF2 are sufficient for achieving 90%
conversion (85% yield, 94:6 er; see entry 10, Table 3).
Cu-catalyzed ECA reactions with cyclopentenone (entries
12-13, Table 3) are equally efficient, compared to the related
transformations with the larger ring enones (85-92% yield);
the desired products are, nonetheless, generated with markedly
lower levels of enantiomeric purity (81.5:18.5 to 90:10 er). It
is possible that mode of catalyst-substrate association B and C
(Scheme 3) become more competitive with the smaller and
sterically less demanding cyclic enones.
7. Cu-Catalyzed ECA Reactions with Alkenylsilyltrifluo-
rides. The corresponding transformations involving alkenylsi-
lyltrifluorides were investigated next. As illustrated by the
example in eq 2, the requisite reagents can be readily accessed
by a two-step procedure starting with a highly efficient and site-
selective Pt-catalyzed hydrosilylation of a terminal alkyne with
trichlorosilyl hydride, followed by treatment with Na2SiF6 to
obtain the derived silyltrifluoride.
Conclusions
We have developed a Cu-catalyzed method for enantiose-
lective conjugate additions of aryl and alkenyl groups to cyclic
enones. Reactions are promoted by chiral monodentate non-
C2-symmetric NHC-Cu complexes and afford the desired
ꢀ-aryl- or ꢀ-vinylcycloalkanones in up to 98.5:1.5 er and 96:4
er, respectively. The present class of catalytic ECA reactions
can be carried out in the presence of easily accessible aryl- or
alkenylsilane reagents and thus do not require use of the
corresponding air and moisture sensitive organometallics (e.g.,
organomagnesium halides, organozinc or organoaluminum
reagents). Synthesis of the NHC complexes is relatively
straightforward: parent imidazolinium salts are accessed in three
simple steps, which are easily amenable to large scale prepara-
tions, in up to 76% overall yield from commercially available
enantiomerically pure diphenylethylenediamine.17
The results of our studies regarding Cu-catalyzed ECA
reactions of alkenylsilyltrifluorides20 are summarized in Table
4. Transformations with phenyl-substituted alkenylsilane 27
efficiently afford the desired products in 80-93% yield and 73.5:
(20) Alkenylsilyltrifluorides were prepared based on the same previously
reported procedures used to access the corresponding aryl-based reagents (see
ref 19), but in somewhat lower yields (27-81%).
J. Org. Chem. Vol. 74, No. 12, 2009 4461

Lee and Hoveyda
2-cyclohexenone (32 mg, 0.33 mmol) and NHC-CuBr complex
derived from imidazolinium salt 23 (11 mg, 0.016 mmol) were
added. The vial was sealed with a cap before removal from the
glovebox. After 20 h at 40 °C, the homogeneous light yellow
solution was diluted with CH2Cl2 (3 mL), and the reaction was
quenched by the addition of a 3.0 M solution of HCl (1 mL). The
organic layer was separated, and the aqueous layer was washed
with CH2Cl2 (2 × 2 mL). The combined organic layers were washed
with a saturated aqueous NaHCO3 solution (2 mL), brine (2 mL),
and water (2 × 2 mL) and dried over MgSO4. The volatiles were
removed in vacuo, and the resulting light yellow oil was purified
by silica gel column chromatography (hexanes/Et2O:10/1) to afford
52 mg (0.30 mmol, 91% yield) of (S)-3-phenylcyclohexanone (5)
The investigations described above illustrate the validity of
the catalytic cycle shown in Scheme 1, demonstrating that with
an appropriate NHC-Cu-halide complex, aryl- and vinylsilanes
can be effectively activated and used in enantioselective C-C
bond-forming processes. These studies pave the way for
development of additional catalytic methods that are of sub-
stantial potential utility and involve chiral NHC catalysts,
organosilanes, and other important classes of electrophiles (e.g.,
carbonyls and imines).
We have outlined the development and evaluation of the
catalytic activity of new NHC-metal complexes that can serve
as catalysts for a range of enantioselective processes. Our
investigations shed light on the differences, at times subtle,
regarding the chiral pockets presented by different NHC
complexes for association with various cyclic enones. The
resulting assortment of chiral monodentate non-C2-symmetric
imidazolinium salts that served as precursors to chiral NHC-Cu
catalysts in the investigations detailed here, should be readily
applicable to future research directed toward additions to other
classes of substrates.
1
as a colorless oil: H NMR (400 MHz, CDCl3) δ 7.35-7.31 (2H,
m), 7.26-7.22 (3H, m), 3.05-2.97 (1H, m), 2.63-2.34 (4H, m),
2.18-2.07 (2H, m), 1.91-1.72 (2H, m); optical rotation [R]20
D
-39.1 (c 0.975, CHCl3) for an 95:5 er sample.22
3-Phenylcyclooctanone: IR (neat) 2925 (s), 2854 (s), 1702 (s),
1
1464 (m) cm-1; H NMR (400 MHz, CDCl3) δ 7.33-7.19 (5H,
m), 3.19 (1H, tt, J ) 12.4, 3.2 Hz), 2.95 (1H, t, J ) 12.4 Hz),
2.58-2.41 (3H, m), 2.18-2.06 (1H, m), 1.96-1.84 (2H, m),
1.79-1.50 (4H, m), 1.46-1.36 (1H, m); 13C NMR (100 MHz,
CDCl3) δ 216.2, 146.5, 128.7, 126.8, 126.5, 48.4, 44.8, 43.2, 35.3,
27.8, 24.6, 24.3; HRMS calcd for C14H19O [M + H] (EI+) 203.1436,
Application of the chiral monodentate NHC catalysts to
development of efficient catalytic enantioselective additions of
trifluoroorganosilanes to additional classes of electrophilic
substrates, exploration of the mechanistic details of such
processes, and applications to the synthesis of biologically active
target molecules21 are the subject of ongoing research in these
laboratories.
found 203.1440; optical rotation [R]20 +3.4 (c 0.50, CHCl3) for
D
an 90:10 er sample.
3-Styrylcyclooctanone: IR (neat) 2926 (s), 2855 (s), 1697 (s),
1
1446 (m) cm-1; H NMR (400 MHz, CDCl3) δ 7.36-7.28 (4H,
m), 7.23-7.19 (1H, m), 6.42 (1H, d, J ) 16.0 Hz), 6.18 (1H, dd,
J ) 16.0, 7.2 Hz), 2.87-2.80 (1H, m), 2.64 (1H, t, J ) 12.0 Hz),
2.53-2.37 (3H, m), 2.08-1.96 (1H, m), 1.93-1.80 (2H, m),
1.74-1.67 (1H, m), 1.58-1.36 (4H, m); 13C NMR (100 MHz,
CDCl3) δ 216.2, 137.5, 134.7, 128.7, 128.5, 127.4, 126.2, 46.8,
43.3, 41.6, 33.4, 27.9, 24.6, 23.8; HRMS calcd for C16H21O [M +
H] (ESI+) 229.1592, found 229.1600.
Experimental Section
General protocols, including chiral ligand and catalyst prepara-
tion, and details of X-ray crystallographic studies are provided in
the Supporting Information.
3-(2-Cyclohexylvinyl)cycloheptanone: IR (neat) 2920 (s), 2849
(s), 1699 (s), 1447 (m) cm-1; 1H NMR (400 MHz, CDCl3) δ 5.36
(1H, dd, J ) 15.6, 5.6 Hz), 5.30 (1H, dd, J ) 15.6, 6.0 Hz),
2.57-2.42 (3H, m), 2.35-2.27 (1H, m), 1.96-1.83 (4H, m),
1.72-1.56 (6H, m), 1.48-1.35 (2H, m), 1.33-0.97 (6H, m); 13C
NMR (100 MHz, CDCl3) δ 214.3, 135.3, 131.8, 50.1, 44.2, 40.7,
39.2, 37.7, 33.3, 33.3, 28.6, 26.3, 26.2, 26.2, 24.2; HRMS calcd
for C15H25O [M + H] (ESI+) 221.1905, found 221.1902; optical
Imidazolinium Salt 23. A mixture of 19:1 atropisomers was
1
obtained. The H NMR spectrum (400 MHz) includes only major
atropisomer, which was separated by silica gel column chroma-
tography from minor atropisomer: IR (neat) 3064 (m), 2966 (s),
2875 (m), 1610 (s), 1585 (s), 1478 (s) cm-1; 1H NMR (400 MHz,
CDCl3) δ 8.80 (1H, s), 7.69-7.63 (4H, m), 7.52-7.49 (2H, m),
7.42-7.32 (6H, m), 7.29-7.19 (4H, m), 7.11 (2H, t, J ) 8.0 Hz),
6.93 (1H, dd, J ) 7.4, 1.4 Hz), 6.46 (2H, d, J ) 7.2 Hz), 5.43 (1H,
d, J ) 9.6 Hz), 5.31 (1H, d, J ) 9.2 Hz), 3.14 (1H, dq, J ) 14.8,
7.6 Hz), 2.79 (1H, dq, J ) 15.2, 7.6 Hz), 2.32 (1H, dq, J ) 15.2,
7.6 Hz), 1.90 (1H, dq, J ) 14.8, 7.6 Hz), 1.46 (3H, t, J ) 7.6 Hz),
1.24 (9H, s), 0.89 (3H, t, J ) 7.6 Hz); 13C NMR (100 MHz, CDCl3)
δ 157.6, 153.5, 141.5, 141.2, 138.9, 135.4, 134.9, 131.9, 131.0,
130.7, 130.6, 130.3, 130.3, 129.8, 129.8, 129.7, 129.5, 129.1, 128.8,
128.6, 128.1, 127.7, 127.2, 127.1, 126.7, 75.5, 73.2, 35.0, 31.0,
24.3, 23.6, 14.7, 14.3; HRMS calcd for C41H43N2 [M - BF4](ES+)
563.3426, found 563.3412; optical rotation [R]20D -337.8 (c 1.00,
CHCl3).
rotation [R]20 -10.3 (c 0.50, CHCl3) for an 89.5:11.5 er sample.
D
Acknowledgment. Financial support was provided by the
NSF (CHE-0715138) and the NIH (GM-47480). K.-s. L. is a
Schering-Plough Graduate Fellow. We are grateful to Dr. Bo
Li (Boston College) and Kyoko Mandai (Boston College) for
assistance in securing various X-ray structures and to Adil R.
Zhugralin (Boston College) for helpful discussions. Mass
spectrometry facilities at Boston College are supported by the
NSF (DBI-0619576).
(S)-3-(Phenyl)cyclohexanone (5). An oven-dried vial equipped
with a stir bar was charged with PhSiF3 (79 mg, 0.49 mmol),
tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF, 135
mg, 0.49 mmol), and CH2Cl2 (1 mL) under a dry N2 atmosphere in
a glovebox. The mixture was allowed to stir for 5 min, after which
Supporting Information Available: Experimental proce-
dures and spectral data for substrates and products. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO900589X
(21) For applications of chiral NHC-Cu and NHC-Ru complexes developed
in these laboratories to target-oriented synthesis, see: (a) Gillingham, D. G.;
Hoveyda, A. H. Angew. Chem., Int. Ed. 2007, 46, 3860–3864. (b) Brown, M. K.;
Hoveyda, A. H. J. Am. Chem. Soc. 2008, 130, 12904–12906.
(22) All spectroscopic data match those reported previously; see: Takaya,
Y.; Ogasawara, M.; Hayashi, T. J. Am. Chem. Soc. 1998, 120, 5579–5580.
4462 J. Org. Chem. Vol. 74, No. 12, 2009