Stereogenic-at-metal Zn- and Al-based N-Heterocyclic Carbene (NHC) complexes as bifunctional catalysts in Cu-free enantioselective allylic alkylations

Article abstract of DOI:10.1021/ja904654j

Investigations detailed herein demonstrate the ability of chiral bidentate N-heterocyclic carbenes to promote directly - without the need for a Cu salt - site- and enantioselective C-C bond forming reactions. Within this context, catalytic allylic alkylat

Full text of DOI:10.1021/ja904654j

Published on Web 07/24/2009
Stereogenic-at-Metal Zn- and Al-Based N-Heterocyclic
Carbene (NHC) Complexes as Bifunctional Catalysts in
Cu-Free Enantioselective Allylic Alkylations
Yunmi Lee, Bo Li, and Amir H. Hoveyda*
Department of Chemistry, Merkert Chemistry Center, Boston College Chestnut Hill,
Massachusetts 02467
Received June 8, 2009; E-mail: amir.hoveyda@bc.edu
Abstract: Investigations detailed herein demonstrate the ability of chiral bidentate N-heterocyclic carbenes
to promote directlyswithout the need for a Cu saltssite- and enantioselective C-C bond forming reactions.
Within this context, catalytic allylic alkylations of various allylic phosphates with dialkylzinc and trialkyla-
luminum reagents, performed with chiral bidentate imidazolinium salts and in the absence of a Cu salt, are
described. The Cu-free transformations deliver products bearing tertiary or (all-carbon) quaternary
stereogenic centers with exceptional site- (>98:<2 SN2′:SN2) and high enantioselectivity [up to 97.5:2.5
enantiomer ratio (er)]. A chiral Zn-based N-heterocyclic carbene (NHC) complex, which serves as the catalyst
for the enantioselective allylic alkylation reactions, is isolated and fully characterized. Spectroscopic and
X-ray crystallographic studies indicate that the sulfonate group within the stereogenic-at-Zn bidentate
complexes coordinates syn to the proximal phenyl substituent of the NHC backbone (vs the initially expected
anti). Investigations regarding a related NHC-Al complex reveal similar structural attributes. The studies
outlined provide a plausible rationale regarding the mechanism of Cu-free allylic alkylation reactions that
involve dialkylzinc or trialkylaluminum reagents as well as the previously reported alkylmagnesium halides.
On the basis of the research disclosed, it is proposed that bidentate metal-carbene complexes can serve
as effective bifunctional catalysts, a critical attribute that differentiates such NHC-based complexes from
the corresponding monodentate variants.
complexes,5 allowing us to identify a critical, and somewhat
unexpected, stereochemical feature of these entities. We dem-
onstrate that the high reactivity and selectivity levels observed
in C-C bond forming processes promoted through the use of
bidentate NHC ligands6,7 might be largely due to the ability of
the corresponding metal-based complexes to serve as bifunc-
tional catalysts.8
Introduction
The research described herein sheds light on mechanistic
details of C-C bond forming reactions which are promoted by
chiral bidentate N-heterocyclic carbene (NHC) complexes and
involve alkylmetal reagents (Grignard, dialkylzinc and trialky-
laluminum reagents).1 Significant insight has been obtained
through detailed examination of Cu-free2-4 catalytic allylic
alkylations, transformations which give rise to tertiary or (all-
carbon) quaternary stereogenic centers with high site- (>98:<2
SN2′:SN2) and enantioselectivities [up to 97.5:2.5 enantiomer
ratio (er)]. The present studies have led to the synthesis, isolation
and characterization of stereogenic-at-Zn and Al-based NHC
Discovery and development of chiral catalysts for enantiose-
lective addition of readily available nucleophiles to easily
accessible electrophilic substrates remains an important objective
in modern chemical synthesis.9 One area of interest relates to
catalytic enantioselective allylic alkylations of allylic halides
or phosphates with organometallic nucleophiles, such as Mg-,
(1) For 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. (d) N-Heterocyclic Carbenes in Transition Metal Catalysis;
Glorius, F., Ed.; Springer-Verlag: Berlin, Heidelberg, 2007.
(2) For Cu-free (non-enantioselective) conjugate addition and/or intramo-
lecular allylic alkylation processes involving organozinc reagents, see:
(a) Komanduri, V.; Pedraza, F.; Krische, M. J. AdV. Synth. Catal. 2008,
350, 1569–1576. (b) Kobayashi, K.; Ueno, M.; Naka, H.; Kondo, Y.
Chem. Commun. 2008, 3780–3782.
(5) For overviews regarding stereogenic-at-metal complexes, see: (a)
Brunner, H. Angew. Chem., Int. Ed. 1999, 38, 1194–1208. (b)
Fontecave, M.; Hamelin, O.; Me´nage, S. Top. Organomet. Chem. 2005,
15, 271–288. For a recent example, see: (c) Malcolmson, S. J.; Meek,
S. J.; Sattely, E. S.; Schrock, R. R.; Hoveyda, A. H. Nature 2008,
456, 933–937.
(6) For applications of chiral bidentate NHC-Cu complexes to enanti-
oselective allylic alkylation reactions, 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) Van Veldhuizen, J. J.; Campbell,
J. E.; Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127,
6877–6882. (c) Kacprzynski, M. A.; May, T. L.; Kazane, S. A.;
Hoveyda, A. H. Angew. Chem., Int. Ed. 2007, 46, 4554–4558. (d)
Gillingham, D. G.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2007, 46,
3860–3864. (e) Lee, Y.; Akiyama, K.; Gillingham, D. G.; Brown,
M. K.; Hoveyda, A. H. J. Am. Chem. Soc. 2008, 130, 446–447.
(3) For a report regarding Cu-free enantioselective allylic alkylation
reactions promoted by Mg-based chiral bidentate NHC complexes and
involving alkylmagnesium halides, see: Lee, Y.; Hoveyda, A. H. J. Am.
Chem. Soc. 2006, 128, 15604–15605.
(4) For Cu-free catalytic enantioselective conjugate addition reactions
involving dialkylzinc reagents, see: Bra¨se, S.; Ho¨fener, S. Angew.
Chem., Int. Ed. 2005, 44, 7879–7881.
9
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J. AM. CHEM. SOC. 2009, 131, 11625–11633 11625

A R T I C L E S
Lee et al.
Scheme 1. Lewis Base Activation in Cu-Based and Cu-Free
Pathways to Catalytic Allylic Alkylation
resulting in alkylation of the substrate via Wi (Scheme 1) and
precluding the need for a Cu salt or a Cu-based complex.
Association of the leaving group (LG), typically a Lewis basic
entity, with the Lewis acidic metal center should might facilitate
the alkylation process (see Wi).
We recently demonstrated the validity of the latter approach
through development of a class of reactions that involves
γ-chloro-R,ꢀ-unsaturated esters as substrates, a chiral NHC as
the catalyst and alkylmagnesium halide reagents.3 We have
illustrated that, in the absence of a Cu salt, NHC-Mg-catalyzed
reactions proceed to afford products bearing an all-carbon
quaternary stereogenic center12 with moderate to high site- (78:
22-93:7 SN2′:SN2) and enantioselectivity (81.5:18.5-99:1 er);
an example is illustrated in eq 1. In comparison, as depicted in
eq 2, in the presence of a Cu salt (CuCl2•2H2O), catalyst
turnover frequency is higher (0.5 mol % catalyst in 0.5 h vs 5
mol % in 24 h) and the transformation proceeds with similar
enantioselectivity. The desired chiral products, however, are
usually obtained in lower yields, partly due to inferior site-
selectivity, as demonstrated by the representative processes
shown (eq 1-2). Cu-free catalytic enantioselective allylic
Zn- or Al-based reagents.10 Such transformations often require
the presence of an additional Cu-based salt. Thus, it is often a
chiral Cu catalyst, generated in situ, which promotes C-C bond
formation (see top pathway in Scheme 1). The higher activity
of chiral Cu-based complexes, versus when only metal salts are
used or in reactions where only an organometallic reagent is
present (C-M in Scheme 1), is due to the activation provided
by one or more Lewis basic ligands11 that are bound to the
transition metal (i and ii, Scheme 1). The donor ligands (LB in
Scheme 1) raise the nucleophilicity of the Cu-bound carbon (ii),
while enhancing the π-Lewis acidicity of the transition metal
(Lewis base activation of a Lewis acid). The above factors
collectively translate into a highly effective alkylating agent (cf.
conversion of iii to iW and the alkylation product in Scheme 1).
An alternative strategy, also illustrated in Scheme 1 (bottom
pathway), involves direct actiVation of the organometallic
reagent by a nucleophilic Lewis base (W, Scheme 1). That is,
association of the Lewis basic catalyst (LB) with the Mg-, Zn-
or Al-based alkylating agent (C-M) might lead to its activation
in the same manner as described above for the Cu-based system,
(7) For applications of chiral bidentate NHC-Cu complexes to enanti-
oselective conjugate addition reactions, see: (a) Arnold, P. L.; Rodden,
M.; Davis, K. M.; Scarisbrick, A. C.; Blake, A. J.; Wilson, C. Chem.
Commun. 2004, 1612–1613. (b) Lee, K.-S.; Brown, M. K.; Hird,
A. W.; Hoveyda, A. H. J. Am. Chem. Soc. 2006, 128, 7182–7184. (c)
Clavier, H.; Coutable, L.; Toupet, L.; Guillemin, J.-C.; Mauduit, M.
J. Organomet. Chem. 2005, 690, 5237–5254. (d) Brown, M. K.; May,
T. L.; Baxter, C. A.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2007,
46, 1097–1100. (e) Martin, D.; Kehrli, S.; d’Augustin, M.; Clavier,
H.; Mauduit, M.; Alexakis, A. J. Am. Chem. Soc. 2006, 128, 8416–
8417. (f) May, T. L.; Brown, M. K.; Hoveyda, A. H. Angew. Chem.,
Int. Ed. 2008, 47, 7358–7362. (g) Brown, M. K.; Hoveyda, A. H.
J. Am. Chem. Soc. 2008, 130, 12904–12906.
(8) For a recent review on bifunctional enantioselective catalysis, see:
(a) Ma, J.-A.; Cahard, D. Angew. Chem., Int. Ed. 2004, 43, 4566–
4583. (b) Na´jera, C.; Sansano, J. M.; Saa´, J. M. Eur. J. Org. Chem.
2009, 2385–2400. For additional examples of bifunctional enantiose-
lective catalysis, see: (c) Kacprzynski, M. A.; Hoveyda, A. H. J. Am.
Chem. Soc. 2004, 126, 10676–10681. (d) Kanai, M.; Kato, N.;
Ichikawa, E.; Shibasaki, M. Synlett 2005, 1491–1508. (e) Carswell,
E. L.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2006,
45, 7230–7233. (f) Paull, D. H.; Abraham, C. J.; Scerba, M. T.; Alden-
Danforth, E.; Lectka, T. Acc. Chem. Res. 2008, 41, 655–663. (g) Friel,
D. K.; Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2008, 130,
9942–9951.
alkylation (EAA) reactions, unlike those performed in the
presence of a Cu salt,6 are inefficient and proceed with little or
no site- or enantioselectivity with substrates that lack a
carboxylic ester group; the example depicted in eq 3 is
representative.
On the basis of the above findings, we designed experiments
that offer insight regarding the structural attributes of non-Cu-
based chiral NHC-metal complexes and their ability to promote
(9) ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds; Springer: Berlin, Germany, 1999.
(10) For reviews on catalytic allylic alkylation reactions that involve “hard”
alkyl- or arylmetal-based reagents, see: (a) Hoveyda, A. H.; Hird,
A. W.; Kacprzynski, M. A. Chem. Commun. 2004, 1779–1785. (b)
Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed. 2005, 44, 4435–
4439. (c) Falciola, C. A.; Alexakis, A. Eur. J. Org. Chem. 2008, 3765–
3780.
(11) For a review on Lewis base catalysis, see: Denmark, S. E.; Beutner,
G. L. Angew. Chem., Int. Ed. 2008, 47, 1560–1638.
(12) Quaternary Stereocenters: Challenges and Solutions for Organic
Synthesis; Christophers, J., Baro, A., Eds; Wiley-VCH: Wenheim,
2006.
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Stereogenic-at-Metal Zn- and Al-Based NHC Complexes
A R T I C L E S
Table 1. Allylic Alkylation Reactions with Et2Zn in the Presence of
EAA; we aimed to elucidate on the mechanism by which such
C-C bond forming processes are promoted. Our decision to
focus initially on organozinc reagents (vs the originally exam-
ined alkylmagnesium halides) was partly due to higher stability
of NHC-Zn complexes. Our efforts to secure and analyze
rigorously an NHC-Mg complex,13 such as that derived from
a chiral bidentate imidazolinium salt, proved unsuccessful. We
therefore turned our attention to the corresponding Zn-based
chiral carbenes, since we surmised that an NHC derived from
a late transition metal would be less elusive. In addition,
investigation of Cu-free EAA reactions with organozinc and
organoaluminum reagents would allow us to determine whether
such protocols are effective with a wider range of substrates
(vs alkylmagnesium halides mentioned above).
Various Nucleophilic Catalystsa
Results and Discussion
1. Cu-Free, NHC-Catalyzed Enantioselective Allylic Alkyla-
tion (EAA) Reactions with Dialkylzinc Reagents. i. Evaluation of
NHCs and Other (Non-Carbene) Lewis Bases. We began by
examining the ability of an in situ-generated NHC-Zn complex
to catalyze allylic alkylations. We probed the effectiveness of
carbenes derived from achiral and chiral imidazolinium salts
1-6 as well as Ag-based NHC complex 7 to promote the
reaction with allylic phosphate 8a and Et2Zn (Table 1; see below
for reactions with the corresponding chlorides). Transformations
were carried out at 0 °C in THF and were allowed to proceed
for 24 h. As indicated in entry 1 of Table 1, there is no reaction
between 8a and Et2Zn under such conditions in the absence of
a catalyst. In the presence of 5.0 mol % achiral imidazolinium
salt 1, which is likely deprotonated by the dialkylzinc reagent
to afford the NHC-Zn complex, there is 20% conversion to 9,
which is generated with complete site-selectivity (>98:<2 SN2′:
SN2). When chiral bidentate NHC 2 is used, the amount of the
desired product is nearly doubled (38% conv), a strong
preference for SN2′ mode of addition persists, and 9 is formed
in 86:14 er (entry 3, Table 1). Alkylation promoted by the
carbene derived from 3a (entry 4) proceeds with high site-
selectivity (>98:<2) and improved enantioselectivity (94:6 er),
yet less efficiently than that catalyzed by 2 (18% conv vs 38%
conv). Use of the methyl ether derived from imidazolinium salt
3 leads to complete erosion of catalytic activity, as shown in
entry 5 of Table 1. Chiral NHC-Zn complexes from valinol-
derived imidazolinium salt 4 as well as 5 are entirely ineffective
(entries 6-7); this is either because deprotonation by the
organometallic reagent and generation of the chiral Zn-based
complex is inefficient, or, more likely, due to inability of the
corresponding NHCs to provide the proper nucleophilic activation.
The most active catalyst is the Zn-carbene derived from chiral
imidazolinium sulfonate 6a: >98% conversion is observed and
the desired product 9 is isolated in 64% yield with >98% site-
selectivity and in 82:18 er (entry 8). As was the case with 3b
in contrast to 3a (entries 4-5,Table 1), catalytic activity is lost
with alkylsulfonate 6b (entry 9, Table 1). In spite of high site-
selectivity and appreciable enantioselectivity, EAA with the
derived Ag-complex 7 is inefficient (7% conv; entry 10).
Spectroscopic studies (400 MHz 1H NMR) indicate a particularly
sluggish Ag-Zn exchange as the likely source of the minimal
catalytic activity. When reaction of a 10:1 mixture of Et2Zn
entry
Lewis base
conv (%)b
SN2′:SN2b
erc
1
2
3
4
5
6
7
8
none
<2
20
38
18
<2
<2
<2
>98d
<5
7
-
>98:<2
>98:<2
>98:<2
-
-
-
>98:<2
-
>98:<2
-
-
-
86:14
94:6
-
-
-
82:18
-
81:19
-
-
-
1
2
3a
3b
4
5
6a
9
6b
10
11
12
13
7e
PPh3
(O)PPh3
Ph2P(CH2)2PPh2
<2
<2
<2
-
-
a Reactions were performed under N2 atmosphere. b Conversion and
site-selectivity were determined by analysis of 400 MHz 1H NMR
spectra of product mixtures prior to purification. c Enantiomer ratios
were determined by GLC analysis; see the Supporting Information for
details. d Product isolated in 64% yield after purification. e 2.5 mol % of
dimer used.
and Ag-based carbene 7 (d8-THF, 22 °C) is monitored, only
45-50% conversion to a new NHC complex is observed after
48 h (the bidentate Zn complex; see below). When the process
in entry 10 (Table 1) is allowed to proceed for 48 h, conversion
is increased to 38%, furnishing 9 with high site-selectivity
(>98% SN2′) and in 78:22 er. It should be noted that the
alkylation process in entry 10 of Table 1 is performed at 0 °C
(vs 22 °C used for the spectroscopic analysis mentioned before).
The findings in entries 11-13 of Table 1 underline the unique
ability of NHC-based complexes to serve as effective catalysts
for EAA reactions with a dialkylzinc reagent. Attempts to
promote alkylation through the use of triphenylphosphine (entry
11), the derived phosphine oxide (entry 12),8a,d,f or dppe (entry
13), resulted in quantitative recovery of the starting material (8a).
ii. NHC-Zn-Catalyzed Reactions of Allylic Phosphates Bear-
ing Disubstituted Olefins. Cu-free EAA reactions, catalyzed by
the NHC-Zn complex obtained from imidazolinium sulfonate
6a, can be performed with a range of dialkylzinc reagents and
allylic phosphates (Table 2). The achiral product, derived from
(13) For X-ray structures of monodentate NHC-Mg complexes, see: (a)
Schumann, H.; Gottfriedsen, J.; Glanz, M.; Dechert, S.; Demtschuk,
J. J. Organomet. Chem. 2001, 617-618, 588–600. (b) Arduengo, A. J.,
III.; Rasika Dias, H. V. R.; Davidson, F.; Harlow, R. L. J. Organomet.
Chem. 1993, 462, 13–18.
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J. AM. CHEM. SOC. VOL. 131, NO. 32, 2009 11627

A R T I C L E S
Lee et al.
Table 2. NHC-Zn-Catalyzed Enantioselective Allylic Alkylation Reactions of Disubstituted Olefins with Dialkylzinc Reagentsa
entry
substrate (R)
(alkyl)2Zn
product
mol (%) 6a
temp (°C)
time (h)
conv (%);b yield (%)c
SN2′:SN2b
erd
1
2
3
4
5
6
7
8a (Ph)
8b (o-MeC6H4)
8c (Cy)
8c (Cy)
8c (Cy)
8d (PhMe2Si)
8d (PhMe2Si)
i-Pr2Zn
Et2Zn
Me2Zn
Et2Zn
i-Pr2Zn
Et2Zn
n-Bu2Zn
10
11
12
13
14
15
16
5
5
5
5
10
5
-15
-15
-15
-15
0
60
24
30
48
24
48
48
67; 60
>98; 62
75; 54
96; 79
81; 64
86; 59
77; 59
>98:<2
>98:<2
>98:<2
>98:<2
>98:<2
>98:<2
>98:<2
90.5:9.5
91.5:8.5
89.5:10.5
92.5:7.5
96:4
94.5:4.5
93:7
-15
22
5
a Reactions were performed under N2 atmosphere. b Conversion and site selectivity were determined by analysis of 400 MHz 1H NMR spectra of
product mixtures prior to purification. c Yields of purified products. d Enantiomer ratios were determined by GLC analysis; see the Supporting
Information for details.
Table 3. NHC-Zn-Catalyzed Enantioselective Allylic Alkylation Reactions of Trisubstituted Olefins with Dialkylzinc Reagentsa
entry
substrate (R)
(alkyl)2Zn
product
mol (%) 6a
temp (°C)
time (h)
conv (%);b yield (%)c
SN2′:SN2b
er
1
2
3
4
5
6
7
17a (Ph)
17a (Ph)
17a (Ph)
17b (p-CF3C6H4)
17c (p-NO2C6H4)
17d (Cy)
Et2Zn
18
19
20
21
22
23
24
10
10
5
5
10
5
-30
-30
0
-30
-30
-15
-15
48
72
24
48
48
48
48
95; 91
72; 71
64; 52
>98; 68
>98; 82
72; 58
>98; 85
>98:<2
>98:<2
>98:<2
>98:<2
>98:<2
>98:<2
>98:<2
95.5:4.5
95.5:4.5
95.5:4.5
94.5:5.5
94.5:5.5
97.5:2.5
94:6
n-Bu2Zn
i-Pr2Zn
Et2Zn
Et2Zn
Et2Zn
17e (CO2t-Bu)
n-Bu2Zn
5
a-c See Table 2.
SN2 mode of addition is not detected in any of the transforma-
tions depicted in Table 2. Effective substrates include those
bearing a sterically demanding aryl unit (entry 2), an alkyl
(entries 3-5) or a silyl (entries 6-7) substituent. The outcome
of transformations represented in entry 8 of Table 1 and entries
1-7 in Table 2 demonstrate that Zn-catalyzed processes,
although less efficient, proceed with similar enantioselectivity
as the corresponding Cu-catalyzed variants. For example, EAA
with (i-Pr)2Zn and 8c in the presence of 1.0 mol % of the Cu-
based catalyst derived from treatment of Ag-based dimeric
complex of imidazolinium salt 3a and CuCl2•2H2O proceeds
to >98% conversion in 24 h (-15 °C), delivering 14 (entry 5,
Table 2) in 68% yield, >98:<2 SN2′:SN2 and 98.5:1.5 er6b (vs
81% conv, 64% yield, >98:<2 SN2′:SN2 and 96:4 er with 10
mol % NHC-Zn complex derived from 6a at 0 °C for 24 h).
The Zn complex derived from 6a can be used to obtain the
desired products in useful degrees of enantiomeric purity
(89.5:10.5-96:4 er). Even in instances where use of a less
reactive organozinc reagent and a sizable alkene substituent
requires EAA to be performed at ambient temperature to achieve
complete conversion, transformations proceed with appreciable
enantioselectivity (e.g., 93:7 er for alkylations of (PhMe2Si)-
substituted alkene with n-Bu2Zn in entry 7, Table 2).
detectable amount of achiral SN2 product. Thus, Zn-catalyzed
reactions of the more substituted olefins (Table 3) generally
proceed with higher enantioselectivities than those of the
corresponding disubstituted alkenes. It should also be noted that
for alkylation with the sterically demanding (i-Pr)2Zn, reaction
temperature must be raised to 0 °C; regardless, C-C bond
formation proceeds without significant diminution in enanti-
oselectivity.
2. Elucidation of the Structure of a Chiral Bidentate NHC-
Zn(II) Complex. To establish the identity of the purported chiral
NHC-Zn complex, we first set out to gain insight through
spectroscopic studies. Thus, as illustrated in Scheme 2, subjec-
tion of 6a to 3.0 equivalents of Et2Zn at 22 °C for 24 h leads
to clean formation of a new entity with distinct signals indicative
of a monomeric bidentate Zn-carbene (25). Representative key
1
values are shown in Scheme 2. In the H NMR spectrum (400
MHz), the protons of the Et unit are represented by signals at
δ +0.63 (methyl) and -0.63 ppm (methylene); the upfield shift
of the signals of the Et group, particularly that of the methylene
group of the EtZn(NHC) (from δ +0.02 ppm to -0.63 ppm),
is congruent with the σ-donating effect of the N-heterocyclic
carbene, causing an increase in the electron density of the bound
carbon. The chemical shift value in the 100 MHz 13C NMR
spectrum for the transition metal-bound carbene carbon (δ 204.0
ppm) is consistent with previously reported chemical shifts for
monodentate NHC-Zn complexes.14
iii. NHC-Zn-Catalyzed Reactions of Allylic Phosphates Bear-
ing Trisubstituted Olefins. Next, we sought to challenge the
catalytic activity of the NHC-Zn complex in the context of
reactions that involve trisubstituted olefins, and which generate
all-carbon quaternary stereogenic centers.12 As the data il-
lustrated in Table 3 show, the Cu-free catalytic conditions for
EAA of dialkylzinc reagents to trisubstituted olefins of allylic
phosphates give rise to formation of the desired products
(18-24) in 52-91% yield and 94:6-97.5:2.5 er without any
The NOE studies resulted in an unexpected observation; as
illustrated in Scheme 2, spectroscopic investigations led us to
(14) For reports regarding X-ray structures of monodentate NHC-Zn(II)
complexes, see: (a) Reference 13b. (b) Wang, D.; Wurst, K.;
Buchmeiser, M. R. J. Organomet. Chem. 2004, 689, 2123–2130.
9
11628 J. AM. CHEM. SOC. VOL. 131, NO. 32, 2009

Stereogenic-at-Metal Zn- and Al-Based NHC Complexes
A R T I C L E S
Scheme 2. Synthesis and Structure of NHC-Zn(II) Complex 25a
Scheme 3. Catalytic EAA with NHC-Zn Complex 25 and a
Proposed Mechanism
a All NMR data were measured in THF-d8. Mes ) 2,4,6-Me3-C6H2.
establish that the arylsulfonate coordinates to the Zn metal such
that it is situated syn to the adjacent Ph moiety of the NHC.
The results of the spectroscopic studies, as depicted in Scheme
2, are supported by X-ray crystallographic studies. The unex-
pected stereochemical mode of sulfonate coordination, involving
a Zn-O bond that is not longer than expected,15 is in contrast
to that observed in the dimeric Ag-based 7 (Table 1).7d It appears
that chelation of the sulfonate with the Zn center causes tilting
of the N-aryl unit (Ccarbene-N-C-C dihedral angle ) 49.5°)
such that the ortho unit of the same substituent (H1 in 25,
Scheme 2) and the backbone of the N-heterocyclic carbene (H2
in 25) are brought into close proximity. Such propinquity would
be destabilizing if the coordinating group and the neighboring
phenyl of the NHC were to adopt an anti orientation (i.e.,
transpose H2 and Ph in 25). The previously observed anti
relationship (established by X-ray)7d between the phenyl unit
of the NHC and the sulfonate in dimeric Ag complex 7 is likely
because chelation involves a metal that is bound to the other
sulfonate of the dimeric complex. Thus, the smaller
Ccarbene-N-C-C dihedral angle in the dimeric structure (∼2°
vs a more significant tilt of ∼50° in 25) causes the steric
repulsion between the sulfonate and the phenyl group to be the
dominant factor, leading the two moieties to be oriented anti to
one another.16 It is for similar reasons that the sulfonate is anti
to the NHC’s phenyl substituent in imidazolinium salt 6a (X-
ray).7d
to examining the ability of 25 to serve as a catalyst for EAA
reactions. Subjection of allylic phosphate 8a to one equivalent
of 25 under conditions used for transformations in Table 1 (THF,
22 °C, 24 h), results in complete recovery of the starting material
(Scheme 3). When 30.0 equivalents of Et2Zn are introduced,
establishing a catalyst:dialkylzinc ratio congruous with the
catalytic transformation (1:30-60), the allylic phosphate is
completely consumed, affording 9 in 82:18 er and with >98%
SN2′ selectivity.
The above findings indicate that the ability of the chiral NHC-
Zn complex (25) to serve as an alkylation catalyst requires the
presence of a dialkylzinc. It appears that, unlike the initially
suggested scenario in Scheme 1 (see Wi), the chiral complex
does not directly alkylate the allylic phosphate; that is, the alkyl
group of 25 is likely not transferred to the substrate. Alterna-
tively, we put forward the hypothesis presented in Scheme 3,
involving the intermediacy of I. The alkylation process might
therefore commence with replacement of the bound THF in 25
by a substrate molecule; the Lewis basic phosphate serves as
the point of association with the Lewis acidic Zn center.
Generation of the catalyst•substrate complex results in activation
of the allylic phosphate toward reaction with the dialkylzinc
reagent, which, in turn, is delivered by the protruding Lewis
basic oxygen of sulfonate unit. The intermediacy of I provides
an explanation for the high SN2′ selectivities observed in all
alkylation reactions.
The Lewis basicity of the sulfonate is likely enhanced due
to strong electron donation from the NHC via the transition
metal. The significance of a sulfonate oxygen that is properly
situated to cause delivery of the dialkylzinc reagent, an attribute
directly linked to the conformationally rigid structure of the
bidentate NHC, is underlined by the ineffectiveness of the
corresponding alkyl-sulfonate 6b (see Table 1). The inactivity
of 6b is in agreement with the contention that it is likely the
bidentate NHC complex that promotes alkylation (vs the
dissociated zwitterionic variant). The above scenario is further
supported by the fact that the corresponding allylic chlorides
(vs phosphates) are ineffective as substrates in this class of Zn-
catalyzed EAA reactions;17 the less Lewis basic halide likely
does not chelate as effectively with the Zn center and the bound
substrate is not properly situated for directed alkylation. In cases
3. Catalytic Cycle for NHC-Zn-Catalyzed EAA Reactions.
With a well-characterized enantiomerically and stereoisomeri-
cally pure chiral bidentate NHC-Zn complex in hand, we turned
(15) A Zn-O bond length of 2.078 Å has been observed for Zn-
(OSO2CF3)4•THF complex. (X-ray analysis; see: Amel’chenkova,
E. V.; Denisova, T. O.; Nefedov, S. E. Zh. Neorg. Khim. 2006, 51,
1218–1263.)
(16) The Zn-C bond in Et2Zn has been calculated to be 1.950 Å; the
corresponding values are increased to 1.982 Å in 25. However, due
to large number of steric and electronic differences caused by NHC
and its sulfonate tether, caution should be exercised as to whether
comparison of these data shed any meaningful light on the effect of
the bidentate carbene association with the alkylzinc reagent. For DFT
calculations on lengths of bonds in dialkylzinc reagents, see: (a)
Markies, P. R.; Schat, G.; Akkerman, O. S.; Bickelhaupt, F.; Smeets,
W. J. J.; Spek, A. L. Organometallics 1990, 9, 2243–2247. (b) Haaland,
A.; Green, J. C.; McGrady, G. S.; Downs, A. J.; Gullo, E.; Lyall,
M. J.; Timberlake, J.; Tutukin, A. V.; Volden, H. V.; Østby, K.-A.
Dalton Trans. 2003, 4356–4366.
9
J. AM. CHEM. SOC. VOL. 131, NO. 32, 2009 11629

A R T I C L E S
Lee et al.
Scheme 4. Synthesis and Catalytic Activity of NHC-Zn(II) Complex
where R1 (Scheme 3) is smaller in size than R2, such as the
catalytic alkylations in Tables 2-3, high efficiency and enan-
tioselectivity is observed. If R1 is more sterically demanding
than R2, however, delivery of the dialkylzinc reagent becomes
energetically unfavorable (steric repulsion with the coordinated
alkylmetal reagent). Consistent with this proposal, when the Z
olefin isomer corresponding to 17a is subjected to the same
conditions as used in Table 3 (THF, -15 °C, 24 h), only 11%
conversion is attained and rac-18 is isolated. The suggested
mechanistic scheme also offers a plausible rationale regarding
the unique efficiency of the sulfonate-containing NHC com-
plexes in promoting EAA of allylic phosphates with dialkylzinc
reagents: the sulfonate oxygen is properly oriented to coordinate
and deliver the alkylzinc reagent to react with the alkene of the
Lewis acid-activated substrate. In addition, the aforementioned
chelation elevates the nucleophilicity of the bound dialkylzinc
reagent. In brief, the bidentate chiral NHC complex likely serves
as a bifunctional catalyst.8,18
27a
a All NMR data were measured in THF-d8.
Scheme 5. Effect of Structure on the Ability of Bidentate NHC
Complexes to Serve as Catalysts
The critical role that we put forward for the chiral catalyst’s
sulfonate, in particular the pseudoequatorially disposed sulfonate
oxygen, to alkylation efficiency and enantioselectivity is con-
sistent with the inferior activity of the corresponding carbonyl-
containing 27 (Scheme 4). That is, complex 27, which, based
on spectroscopic studies (Scheme 4), likely bears a structure
closely related to 25, does not contain an appropriately disposed
Lewis basic oxygen to direct the addition of an alkylmetal
reagent. Accordingly, in contrast to allylic alkylations performed
in the presence of the NHC derived from sulfonate 6a, reactions
involving carboxylate 26 are far less efficient and enantiose-
lective; the example depicted in Scheme 4 is illustrative.
The above mechanistic paradigm offers a rationale for the
varied and substantially lower efficiency with which bidentate
NHC-Zn complexes derived from imidazolinium salts 2, 3a,
and 4 promote Cu-free alkylations (see Table 1). In such
complexes, it is likely the oxygen atom of the bridging aryloxy
group that assists the addition of the dialkylzinc reagent. The
attendant ineffectiveness of non-sulfonate complexes as catalysts
might be partly due to the relative position of the Lewis basic
directing group vis-a`-vis the electrophilic π cloud of the bound
substrate. The different degrees of catalyst activity (see Table
1) observed with complexes derived from 2, 3a, and 4 support
the latter contention.
The lower effectiveness of the NHC derived from the
sulfonate-containing imidazolinium salt 6a (vs 3a) in reactions
with alkylmagnesium halides may now be explained as well.3
As shown in Scheme 5 (II and III), the catalyst•substrate
ensemble, containing an γ-chloro-R,ꢀ-unsaturated ester and the
NHC-Mg complex, does not allow for facile delivery of the
alkylmagnesium halide to the electrophilic olefin site due to
undesirable relative orientation of the sulfonate group and the
bound substrate. The electrophilic alkene is less removed from
the metal center (vs alkene of the allylic phosphate in I, Scheme
3) and effective alkylation demands a different positioning of
the Lewis basic directing group. Examination of molecular
models indicates that the sulfonate is posed to promote more
readily the SN2 mode of addition (via II, Scheme 5); such
byproducts are obtained in significant amounts when 6a is used
to promote Cu-free EAA reactions with alkylmagnesium halides.
In contrast, the Lewis basic oxygen in phenoxy-containing IV
(Scheme 5), which is more proximal to the NHC-bound metal
center, is better suited to direct the addition of the Grignard
reagent to a γ-chloro-R,ꢀ-unsaturated ester. The present model
offers a plausible rationale regarding the requirement for the
presence of a substrate that bears an unsaturated carboxylic ester
group for efficient Cu-free EAA reactions involving alkylmag-
nesium halides (see eq 3).
In general, effective bifunctional catalysis hinges on
cooperation between the two reaction-facilitating effects,
which, individually, would not necessarily represent a
sufficient driving force to catalyze a particular transformation.
Such a principle implies that use of a more highly Lewis
acidic complex derived from an NHC bearing an electron
withdrawing sulfonate (6a) must be matched with a less
reactive alkylmetal reagent (i.e., dialkylzinc vs alkylmagne-
sium halide). Otherwise, Lewis base-directed alkylation might
(17) For example, with the allyl chloride corresponding to 8a as the
substrate, with 5 mol % 6a and three equivalents of Et2Zn at 0 °C,
only 27% conversion to 9, which is formed in <55:45 er, is observed
after 24 h. At-15 °C, 20% conversion is achieved and 9 is isolated
in ∼60:40 er.
(18) For studies regarding enantioselective additions of dialkylzinc reagents
promoted by a chiral bifunctional catalyst, see: (a) Yamakawa, M.;
Noyori, R. J. Am. Chem. Soc. 1995, 117, 6327–6335. (b) Kitamura,
M.; Okada, S.; Suga, S.; Noyori, R. J. Am. Chem. Soc. 1989, 111,
4028–4036.
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Stereogenic-at-Metal Zn- and Al-Based NHC Complexes
A R T I C L E S
Scheme 6. Synthesis and Structure of NHC-Al(III) Complex 29
Table 4. Initial Studies on Allylic Alkylations with Me3Al in the
Presence of N-Heterocyclic Lewis Base Catalystsa
entry
Lewis base; (mol %)
conv (%)b
SN2′:SN2b
erc
1
2
3
4
none
6a; 5
6b; 5
7; 2.5
5
10
<2
<2
62:38
80:20
-
-
66.5:33.5
-
-
-
a See Table 1. b See Table 1. c See Table 1. d See Table 1.
not be required for efficient reactivity, causing diminution
in stereoselectivity. Consistent with such a proposal, catalytic
alkylations of allylic phosphates in the presence of 6a and
i-PrMgCl proceed with little or no enantioselectivity. As an
example, reaction of 17a (entry 1, Table 3) with 5 mol % 6a
and i-PrMgCl (2.0 equiv) leads to 54% conversion (-50 °C,
THF, 24 h) and formation of nearly racemic 20 (SN2′:SN2 )
57:43). The higher Lewis acidity of the NHC complex
obtained from the sulfonate-bearing 6a (vs phenol-containing
3a previously used in EAA with Grignard reagents) and the
more Lewis acidic Mg(II) [vs Zn(II) in reactions of Tables
1-2] could be responsible for such low selectivity. That is,
with the strongly Lewis acidic NHC-Mg complex derived
from sulfonate 6a as well as the more nucleophilic Grignard
reagent (vs a dialkylzinc) alkylation can occur without
assistance by the resident Lewis basic sulfonate, leading to
little or no stereochemical induction. Directed catalytic
additions with alkylmagnesium halides thus require the less
Lewis acidic NHC derived from phenol-based (vs sulfonate) 3a,
as shown in the representative case in eq 1 (via IV in Scheme 5).
4. Synthesis and Characterization of a Chiral Bidentate NHC-
Al (III) Complex and Enantioselective Allylic Alkylation (EAA)
Reactions with Alkylaluminum Reagents. i. Cu-Free NHC-
Catalyzed Reactions with Me3Al. In addition to Cu-catalyzed
EAA reactions involving Mg- and Zn-based alkylating agents,
more recently, we have developed a number of efficient and
highly enantioselective processes that proceed in the presence
of alkyl- or vinylaluminum reagents.6d,e We therefore decided
to establish whether, similar to Zn(II)- based carbenes, the
corresponding chiral bidentate NHC-Al(III) complexes can be
prepared, characterized and used as catalysts.
In the absence of a catalyst, alkylation of allylic phosphate
8a proceeds only to 5% conversion in the presence of Me3Al
(entry 1, Table 4). With imidazolinium salt 6a (entry 2, Table
4), there is only 10% conversion under Cu-free conditions.19
Similar to studies involving the dialkylzinc reagent (Table 1),
use of ethylsulfonate 6b or Ag-based complex 7 does not lead
to product formation (entries 3-4, Table 4).
ii. Synthesis of a Chiral Bidentate NHC-Al(III) Complex
through a Ligand Exchange Process. Spectroscopic studies,
similar to those performed with Et2Zn (see Scheme 2), indicate
that treatment of 6a with five equivalents of Me3Al does not
lead to NHC-Al complex formation after 24 h (THF, 22 °C).
Only when the THF solution is allowed to reflux for 100 h,
∼20% of a new entity is generated [the desired NHC-Al(III)
complex; see below]. Thus, somewhat surprisingly, in contrast
to Et2Zn, Me3Al does not readily deprotonate the imidazolinium
salt, generating the derived Al-carbene; similar observations
have been made with Et3Al.
To access the desired NHC-Al(III) complex, we examined
the possibility of a ligand exchange process between NHC-Zn(II)
25 and a trialkylaluminum reagent. As illustrated in Scheme 6,
subjection of a THF-d8 solution of 25, generated from treatment
of a sample of imidazolinium salt 6a and Et2Zn for 20 h (22
°C), to three equivalents of Me3Al leads to formation of a new
complex (55:45 25:29, same as that mentioned above) after 30
min based on analysis of the corresponding 400 MHz 1H NMR
spectrum. Two new singlets appear at δ -1.40 and -1.74 ppm,
which were assigned to the methyl groups of the Al-based
complex 29; the1H NMR signal for Me3Al appears at δ -0.92
ppm in THF-d8 (Scheme 6).20 When an additional 10 equivalents
of Me3Al is introduced and the mixture is allowed to stir for
another 30 min, Al-based 29 emerges as the major component
(75% of the mixture) and the Zn carbene 25 constitutes 25% of
the mixture (Scheme 6). Subsequent studies allowed us to secure
a suitable crystal of the Al complex 29, the structure of which
is illustrated in Scheme 6.21 Similar to Zn-based 25 (Scheme
2), the sulfonate tether in 29 is syn to the adjacent phenyl group
of the NHC backbone.22
iii. Cu-Free Catalytic Reactions with Me3Al in the Presence
of NHC-Zn Complex 25. In the presence of 1-5 mol % of chiral
(20) The assignments of the chemical shifts for the two Al-bound methyls
is based on the hypothesis that one alkyl unit resides directly below
the π cloud of the mesityl group and should, due to anisotropic factors,
be more effectively shielded (see X-ray of 29 in Scheme 6).
(21) For a report regarding the X-ray structure of a monodentate NHC-
AlMe3 complex, see: (a) Li, X.-W.; Su, J.; Robinson, G. H. Chem.
Commun. 1996, 2683–2684. For an X-ray structure of an NHC-AlH3,
see: (b) Arduengo, A. J., III.; Rasika Dias, H. V.; Calabrese, J. C.;
Davidson, F. J. Am. Chem. Soc. 1992, 114, 9724–9725.
(19) Experiments with trialkylaluminum reagents are performed at -15 °C
(vs 0 °C for dialkylzincs) since at elevated temperatures, alkylation
products are formed through uncatalyzed processes.
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J. AM. CHEM. SOC. VOL. 131, NO. 32, 2009 11631

A R T I C L E S
Lee et al.
Table 5. EAA Reactions of Disubstituted Allylic Phosphates with Me3Al in the Presence of NHC-Zn Complex 25a
entry
substrate (R)
imidazolinium salt; mol %
mol (%) Et2Zn
product
time (h)b
conv (%);b yield (%)c
SN2′:SN2b
erd
1
2
3
4
5
6
8a (Ph)
8a (Ph)
8b (o-MeC6H4)
8e (o-NO2C6H4)
8e (o-NO2C6H4)
8c (Cy)
6a; 5
30; 1
30; 5
6a; 5
30; 5
6a; 5
10
2
10
10
10
10
28
28
31
32
32
12
12
24
24
24
24
24
>98; 88
>98; 90
>98; 88
>98; 79
84; 81e
>98; 83
98:2
98:2
93:7
98:2
98:2
>98:<2
79:21
85.5:14.5
87:13
84.5:15.5
85.5:14.5
87.5:12.5
a-d See Table 2. e After 48 h, >98% conv is observed (95% yield and identical selectivities as shown above).
NHC-Zn complex 25, as illustrated in Table 5, enantioselective
AA reactions with Me3Al proceed with high site- (up to >98:
<2 SN2′:SN2) and appreciable enantioselectivity (79:21-87.5:
12.5 er). The requisite NHC-Zn complex (25) is prepared in
situ through reaction of imidazolinium salt 6a with Et2Zn; <2%
products from addition of the ethyl group is observed in all
cases shown in Table 5. Comparison of the data in Table 5
with those presented in Table 2, regarding reactions with
dialkylzinc reagents, indicates that alkylation involving the more
nucleophilic Me3Al requires shorter reaction time. The extent
to which the transformations summarized in Table 5 involve
catalysis by a Zn-based complex and the Al reagent via a
complex such as I (Scheme 3), or the degree to which such
processes are promoted by Al-based 29 is difficult to establish
(due to rapid ligand exchange). It is likely, however, that the
latter scenario is largely involved based on the Zn-Al exchange
shown in Scheme 6. A final point regarding the AA process in
Table 5 is that, as a comparison of the data in entries 1-2 and
4-5 indicate, in certain cases, the structurally modified NHC
complex derived from 30 delivers higher efficiency and enan-
tioselectivity.23
basic oxygen atoms associated with the second ligation site
can deliver the Lewis acidic alkylmetal reagents to the bound
substrate molecule, activated by coordination to the Lewis
acidic Zn or Al center. Association of the strongly Lewis
basic NHC enhances electron density at the heteroatomic
sites, elevating their ability to associate with Lewis acidic
dialkylzinc or trialkylaluminum reagents.
Figure 1. Chiral Bidentate NHC-Metal Complex as a Bifunctional Catalyst.
The mechanistic proposals put forth herein account for the
significant variations in the ability of bidentate chiral NHC
complexes to promote different classes of allylic alkylations.
The relative positioning of the Lewis basic heteroatom unit
vis-a`-vis the Lewis acidic metal is likely a critical determinant
as to whether the alkylating agents can be effectively
delivered to a particular set of electrophilic substrates upon
binding to the chiral complex. Through such arguments, we
provide a rationale regarding the effectiveness of two distinct
classes of NHC-based chiral catalysts in promoting Cu-free
Conclusions
We report a series of catalytic enantioselective allylic
alkylations, including those that afford all-carbon quaternary
stereogenic centers. Reactions are promoted by a chiral bidentate
NHC-Zn complex (25) in the absence of a Cu salt. Synthesis,
isolation and characterization of the NHC-Zn complex reveal
several important structural attributes of this emerging class of
chiral Lewis basic ligands. The X-ray structure of stereogenic-
at-Zn carbene 25 indicates that, unlike previously reported
bidentate complexes containing a phenoxy ligation site, the
sulfonate unit coordinates to the transition metal such that it is
oriented syn to the proximal phenyl group of the N-heterocycle
backbone. Studies regarding a derived Al-based chiral bidentate
NHC complex (29) illustrate structural features similar to the
Zn-based system.
The aforementioned stereochemical feature (sulfonate syn
to the NHC phenyl group) is a unique attribute of the
sulfonate-bearing class of chiral bidentate NHCs and will
allow for a better appreciation of the reactivity modes and
the selectivity levels observed in the reactions promoted by
this emerging class of metal complexes.6d,e,7f,g Within this
context, we propose that a significant difference that accounts
for the substantially higher degree of reactivity, site- and
enantioselectivity exhibited by bidentate chiral NHC com-
plexes might be due to the ability of such complexes to serve
as bifunctional catalysts (Figure 1). Accordingly, the Lewis
(22) One feature of the Al-based complex 29 is the shortening of the C-
Al bonds compared to those reported based on analysis of the X-ray
crystal structure of Me3Al [1.94 Å vs 1.96-1.98 Å for non-bridging
methyl (2.13 Å for the bridging methyl);Vranka, R. G.; Amma, E. L.
J. Am. Chem. Soc. 1967, 89, 3121–3126]. The cautionary note in ref
16 likely applies here as well. Nonetheless, it might be suggested that
the shorter metal-methyl bond in 29 might be partly due to the
strongly electron-withdrawing sulfonate ligand, which induces polar-
ization at the metal center, in turn strengthening the Al-C bond
through a strong electrostatic contribution. Similar Al-C bond
shortening within a complex that bears an N,O-bidentate complex has
been previously observed (by X-ray diffraction: Kai, Y.; Yasuoka, N.;
Kasai, N.; Kakudo, M. J. Organomet. Chem. 1971, 32, 165–179). The
relatively small degree of lengthening of the Zn-C bond in 25
(Scheme 2) is likely due to similar factors, since the aforementioned
polarization effects are expected to be more dominant in the complex
that involves the “harder” metal (Al). Such arguments, based on
theoretical investigations, have been previously put forth to explain
various structural attributes of bidentate methylzinc complexes: Weston,
J. Organometallics 2001, 20, 713–720.
(23) For reports where the NHC-Cu complex derived from 30 and closely
related bidentate chiral carbenes are superior to that obtained through
the use of 6a, see: (a) Reference 6e. (b) Reference 7f,g.
9
11632 J. AM. CHEM. SOC. VOL. 131, NO. 32, 2009

Stereogenic-at-Metal Zn- and Al-Based NHC Complexes
A R T I C L E S
EAA reactions with alkylmagnesium halides and dialkylzinc
or trialkylaluminum reagents. Structural information, there-
fore, has led to elucidation of a plausible mechanism through
which NHCs might activate alkylmetals and promote enan-
tioselective C-C bond forming reactions. It should be noted
that the catalytic pathways proposed herein are entirely
different from those likely involved for the corresponding
Cu-catalyzed processes, where it is likely the NHC-bound
copper-alkyl that serves as the alkylating agent (vs the
alkylzinc or alkylaluminum reagent, as described above).
Nontheless, the observations detailed in this report have
significant implications regarding the mechanism of NHC-
Cu-catalyzed allylic alkylations6 as well as the related
conjugate addition7b,e-g processes.
Acknowledgment. The NSF (CHE-0715138) and the NIH (GM-
47480) provided financial support. Y.L. is grateful for Schering-
Plough (2006-7) and AstraZeneca (2007-8) graduate fellowships.
We thank K-s. Lee for developing a synthesis of imidazolinium
salt 26, and Dr. C. A. Baxter and Dr. K. Akiyama for preliminary
experiments. Mass spectrometry facilities at Boston College are
supported by the NSF (DBI-0619576).
The insights gained through the studies detailed above will
be crucial to future utilization of various types of NHC-based
chiral complexes toward future development of catalytic enan-
tioselective methods. Preliminary evidence regarding the ability
of chiral bidentate NHC-Zn complexes to activate common
alkylmetal reagents directly toward enantioselective addition to
other important classes of electrophilic substrates is provided
in eq 4. Identification of new chiral complexes that readily and
stereoselectively promote challenging C-C bond forming
processes, such as that which affords R-quaternary amino ester
33,24 will be one of the objectives of future investigations in
these laboratories.
Supporting Information Available: Experimental procedures
and spectral data for substrates and products. This material is
available free of charge via the Internet at http://pubs.acs.org.
JA904654J
(24) Fu, P.; Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2008, 130,
5530–5541.
9
J. AM. CHEM. SOC. VOL. 131, NO. 32, 2009 11633