Effect of multinuclear copper/aluminum complexes in highly asymmetric conjugate addition of trimethylaluminum to acyclic enones

Article abstract of DOI:10.1002/anie.201206297

Al and friends: Asymmetric conjugate addition of Me₃Al to β,β-disubstituted α,β-unsaturated ketones in the presence copper and L1 leads to a highly efficient construction of an all-carbon-substituted chiral quaternary center. This result is the first example of an asymmetric conjugate addition of Me₃Al to acyclic enones to give a chiral quaternary carbon center with excellent yield and enantioselectivity under mild reaction conditions. Copyright

Full text of DOI:10.1002/anie.201206297

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Angewandte
Communications
DOI: 10.1002/anie.201206297
Synthetic Methods
Effect of Multinuclear Copper/Aluminum Complexes in Highly
Asymmetric Conjugate Addition of Trimethylaluminum to Acyclic
Enones**
Kohei Endo,* Daisuke Hamada, Sayuri Yakeishi, and Takanori Shibata*
Over the past few decades, the asymmetric conjugate addition
of organometallic reagents to activated olefins has become
one of the most powerful approaches to chiral molecules,
especially for installation of a small alkyl group on a chiral
carbon atom.[1] Although there have been various reports on
the asymmetric conjugate addition of organometallic reagents
to cyclic enones for the creation of an all-carbon substituted
chiral quaternary stereogenic center,[2] the use of acyclic
enones still presents a formidable challenge. The steric
congestion around a b,b-disubstituted olefin prevents 1,4-
addition, but favors 1,2-addition, and the chiral catalyst hardly
recognizes the enantioface because of the similarity of
substituents on an olefinic carbon atom (Figure 1).[3]
organometallic reagents to acyclic activated olefins. Hayashi
and co-workers reported the rhodium-catalyzed asymmetric
conjugate addition of organoboron compounds to a,b-unsa-
turated esters and enones with an excess amount of Ar4BNa
or organoboroxine under thermal conditions, with enones
typically providing lower enantioselectivity.[4] Alexakis,
Woodward, and co-workers reported the rhodium-catalyzed
asymmetric addition of PhAlMe2 to b,b-disubstituted enones
and the yields were moderate.[5] Asymmetric addition reac-
tions for the construction of a chiral quaternary carbon center
have been developed extensively, but the alkylation remains
a challenging transformation. There are various alternate
approaches involving the installation of an aryl, vinyl, or
alkynyl group to starting materials bearing an alkyl group.
Fillion and co-workers reported the copper-catalyzed asym-
metric conjugate addition of dialkylzinc reagents to Mel-
drumꢀs acid derivatives at temperatures ranging fromÀ408C
to room temperature.[6] They reported that the functional
groups present on the aromatic moiety affected the enantio-
selectivities, and sterically hindered substrates did not give
the desired products. Hoveyda and co-workers developed the
copper-catalyzed asymmetric conjugate addition of dialkyl-
zinc reagents to nitro alkenes at À788C, and methylation gave
less than 90% ee.[7] These previous results indicate that
additional manipulation may be required to establish excel-
lent yields and enantioselectivities for the construction of an
all-carbon substituted chiral quaternary center, including
a methyl-substituted carbon atom. A facile approach to the
installation of a small methyl group on a chiral quaternary
carbon atom has generally been difficult to achieve.[8]
Although there are alternate approaches to the creation of
a methyl-substituted chiral quaternary carbon center using
starting materials containing a methyl group, a new entry for
the direct methylation to give an all-carbon-substituted chiral
quaternary center would contribute to the synthesis of useful
chiral building blocks. We describe herein a novel multi-
nuclear copper/aluminum-catalyzed asymmetric conjugate
addition of Me3Al for the construction of a chiral tertiary
carbon center and chiral quaternary carbon center in high to
excellent yields with high to excellent eevalues.
Figure 1. Regioselective addition to b,b-disubstituted a,b-unsaturated
ketones.
There have been only a few reports on the construction of
a chiral quaternary carbon center by the conjugate addition of
[*] Prof. Dr. K. Endo
Department of Chemistry, Graduate School of Natural Science and
Technology, Kanazawa University
Kakuma, Kanazawa, Ishikawa, 920-1192 (Japan)
and
PRESTO (Japan) Science and Technology Agency (JST)
4-1-8 Honcho Kawaguchi, Saitama, 332-0012 (Japan)
E-mail: kendo@se.kanazawa-u.ac.jp
D. Hamada, S. Yakeishi, Prof. Dr. T. Shibata
Department of Chemistry and Biochemistry, School of Advanced
Science and Engineering, Waseda University
Ohkubo, Shinjuku, Tokyo 169-8555 (Japan)
E-mail: tshibata@waseda.jp
Our current interests in the development of multinuclear
complexes showed that our original multinuclear complexes
based on BP1, BP2, SP1, and SP2 gave unprecedented
catalytic performances in asymmetric alkylation reactions
using organozinc reagents (Figure 2).[9] Thus, we examined
the asymmetric conjugate addition of Et2Zn to the b,b-
disubstituted enone (E)-1, bearing a methyl substituent, in the
presence of CuCl2·2H2O (5 mol%) and either BP1 or SP2
[**] This work was supported by the JST PRESTO program, Grant-in-Aid
for Young Scientists (B) from the Japan Society for the Promotion of
Science, the Kurata Memorial Hitachi Science and Technology
Foundation, and Hokuriku Bank. We thank Ryotaro Takayama
(Waseda University) for his experimental assistance.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201206297.
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Table 1: Screening of catalysts for addition of Me3Al to chalcone.
No.
x
Ligand (y)
t [h]
Yield [%][a]
ee [%][b]
1
2
3
4
5
6
7
8
5
5
5
5
1
1
1
1
5
5
5
5
5
2
5
BP1 (5)
BP1 (10)
BP2 (5)
BP2 (10)
SP1 (1)
SP1 (2)
3
5
3
1
24
24
1
8
1
4
3
2
1
98
97
98
98
25
23
98
52
91
78
93
92
91
85
91 (52)
49 (S)
55 (S)
63 (S)
71 (S)
<1
Figure 2. Representative ligands.
<1
SP2 (1)
SP2 (2)
98 (R)
98 (R)
88 (S)
89 (S)
84 (S)
82 (S)
95 (S)
94 (S)
23 (6) (S)
(5 mol%) as a ligand [Eq. (1); THF = tetrahydrofuran].
However, the reaction did not proceed at all.[10] We therefore
focused on the use of organoaluminum reagents for the
9[c]
10[c]
11[c]
12[c]
13[c]
14[c]
15[d]
BP2 (10)
BP2A (10)
BP2B (10)
BP2C (10)
BP2D (10)
BP2D (4)
BP2-MOM (10)
2
2 (6)
1
[a] Yields determined by H NMR spectroscopy. [b] The ee value was
determined by HPLC analysis using a chiral stationary phase.
[c] Cu(OTf)2 was used. [d] Results using Cu(OTf)2 are given within
parentheses.
construction of copper/aluminum multinuclear complexes
with the chiral catalysts.[11,12] Organoaluminum reagents are
some of the most useful organometallic reagents, and recently
have been shown to broaden the utility of conjugate addition
reactions, especially to cyclic enones.[13,14] Although the
conjugate addition of organoaluminum reagents to cyclic
enones makes it possible to construct a chiral quaternary
carbon atom, there have been no previous reports of the
reaction with acyclic b,b-disubstituted a,b-unsaturated
ketones. Furthermore, organoaluminum reagents typically
promote 1,2-addition without a catalyst because of their hard
Lewis-acidic character.[3]
We initially examined the construction of a chiral tertiary
carbon atom through the copper-catalyzed asymmetric con-
jugate addition of Me3Al to chalcone (2a), since there are
only a few successful reports of the highly asymmetric
conjugate addition of Me3Al to acyclic enones (Table 1).[14]
The use of BP1 with CuCl2·2H2O gave moderate ee values,
and the use of a 2:1 ratio of BP1 to CuCl2·2H2O improved the
ee value (entries 1 and 2). Thus, the use of BP2 increased the
ee value (entries 3 and 4). Although the use of SP1 gave
almost racemic mixtures, the use of SP2 achieved excellent
yield with excellent enantioselectivity (entries 5–8). The
reaction in the presence of SP2 gave the opposite major
enantiomer compared to BP2. We further examined the use
of a modified BP1, but the ee value was not improved. Thus,
the functionalized BP2 derivatives were examined for the
further improvement of the enantioselectivity. The screening
of copper salts and ligands revealed that the use of Cu(OTf)2
and electron-withdrawing groups in a phosphorous moiety
achieved the higher catalytic activity and ee values (entry 13).
The use of a 2 mol% catalyst loading was enough to give the
corresponding product 3a in 85% yield with 94% ee
(entry 14). The presence of free hydroxy groups was required
for high yield and ee values (entry 15).
A wide variety of enones was examined (Table 2). The
reaction using BP2D gave the opposite major enantiomer
compared to the one obtained with SP2. The reaction of the
chalcone derivatives 2a–j bearing functional groups gave the
desired products 3a–j in high to excellent yields and ee values
(entries 1–10). In contrast, the reaction of the aliphatic enones
2k–n typically gave decreased yields. Although the yields
were low to moderate in the presence of Cu(OTf)2 and BP2D,
the use of CuCl2·2H2O and SP2 achieved moderate to high
yields with high ee values (entries 11–14).
The achievement of the efficient copper-catalyzed con-
jugate addition of Me3Al for the construction of a chiral
tertiary carbon center prompted us to examine the formidable
challenge of constructing a chiral quaternary carbon center.
The reaction of (E)-1a and Me3Al (2 equiv) was carried out in
the presence of CuCl2·2H2O (5 mol%) and our originally
developed ligands (5 or 10 mol%) in THF at temperatures
ranging from 08C to room temperature (Table 3). The copper
catalyst derived from BP1 gave the desired product 4a in
almost quantitative yield with 50% ee. The 1,4-addition
reaction proceeded exclusively without any by-products, not
even the 1,2-adduct (entry 1). Surprisingly, we discovered that
the use of a 2:1 ratio of BP2 to CuCl2·2H2O gave the product
in almost quantitative yield with more than 98% ee (entry 2).
The free hydroxy groups were required for high yield
(entry 3). Further screening of the ligands revealed the
specific character of the spinol architecture. The reaction in
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Table 2: Enones for methyl-substituted tertiary chiral carbon centers.
Table 3: Screening of catalysts for chiral quaternary carbon center.
No. 2 (R1, R2)
3[c]
3[d]
No.
Ligand (mol%)
t [h]
Yield [%][a]
ee [%][b]
t
Yield
ee
t
Yield
ee
1
2
3
4
5
BP1 (5)
3
1
24
24
3
>98
>98
trace
53
50 (+)
>98 (+)
n.d.
[h] [%][a]
[%][b]
[h] [%][a]
[%][b]
BP2 (10)
BP2-MOM (10)
SP1 (5)
1
2
3
4
5
6
7
2a (Ph, Ph)
1
1
1
5
3
4
3
85 (3a) 95 (S)
75 (3b) 92 (+)
81 (3c) 93 (À)
85 (3d) 89 (À)
81 (3e) 95 (+)
81 (3 f) 91 (+)
86 (3g) 96 (À)
1
1
1
1
1
1
1
91 (3a) 98 (R)
82 (3b) 98 (À)
98 (3c) 95 (+)
46 (3d) 81 (+)
91 (3e) 98 (À)
81 (3 f) 98 (À)
97 (3g) 98 (+)
2b (4-FC6H4, Ph)
2c (4-ClC6H4, Ph)
2d (4-F3CC6H4, Ph)
2e (4-MeC6H4, Ph)
2 f (4-biphenyl, Ph)
2g (4-MeOC6H4,
Ph)
2 (À)
SP2 (5)
>98
95 (À)
1
[a] Yields determined by H NMR analysis. [b] The ee value was was
determined by HPLC analysis using a chiral stationary phase. n.d.=not
determined
8
9
2h (2-Np, Ph)
2i (2-furanyl, Ph)
2
1
2
80 (3h) 94 (+)
48 (3i) 96 (À)
91 (3j) 97 (+)
1
1
1
82 (3h) 97 (À)
86 (3i) 98 (+)
79 (3j) 98 (À)
tively, in high to excellent yields with excellent ee values
(entries 3 and 4). Unexpectedly, the reaction of (E)-1d
bearing an isopropyl group at the b position did not give
reproducible results, and the isomerization of (E)-1d to (Z)-
1d was observed by TLC analysis during the reaction
(entry 5). In contrast, the reaction of (Z)-1d gave the product
4d in 28% yield with 97% ee (À) using BP2 and 73% yield
with more than 98% ee (+) using SP2, and unreacted (Z)-1d
was recovered in each case (entry 6). The same reaction
conditions in the absence of CuCl2·2H2O and a ligand
significantly promoted the isomerization of (E)-1d. The
10 2j (2-thiophenyl,
Ph)
11 2k, cyclohexyl, Ph
12 2l (n-pentyl, Ph)
13 2m (Ph, Me)
1
1
7
98 (3k) 71 (À)
2
94 (3k) 98 (+)
4 (3l)
32
65 (+) 24 88 (3l) 83 (À)
76 (S)
4
4
76
98 (R)
(3m)
49 (3n) 33 (R)
(3m)
40 (3n) 94 (S)
14 2n (n-butyl, Me)
1
[a] Yield of isolated product. [b] The ee value was determined by either
HPLC or GC analysis using a chiral stationary phase. [c] Cu(OTf)2
(2 mol%) and BP2D (4 mol%). [d] CuCl2·2H2O (1 mol%) and SP2
(1 mol%) were used.
the presence of SP1 gave a poor result (entry 4). In
sharp contrast, the reaction in the presence of SP2
gave 4a in excellent yield, and showed a dramatic
inversion of the major enantiomer (entry 5). The
present result is the first example of the asymmetric
conjugate addition of Me3Al to acyclic enones to
give a chiral quaternary carbon center in excellent
yield with excellent enantioselectivity under mild
reaction conditions. In sharp contrast, the reaction in
the presence of binap (binap = 2,2’-bis(diphenyl-
phosphanyl)-1,1’-binaphthyl) did not proceed at
all.[14e] The use of 2-(diphenylphosphino)-[1,1’-
binaphthalen]-2-ol bearing phosphorous and hy-
droxy moieties as a ligand gave a trace amount of
product.[15]
A variety of enones were examined for the
construction of a chiral quaternary carbon center
(Table 4). The reaction of (E)-1a in the presence of
BP2 gave 4a in excellent yield upon isolation with an
excellent ee value (entry 1; using BP2). The reaction
in the presence of SP2 gave the opposite major
enantiomer compared to BP2 (entry 1). The olefinic
geometry affected the ee value of the products,[16]
that is, the reaction of (Z)-1a gave 2a in more than
98% yield with 35% ee (À) using BP2 and more
than 98% yield with 75% ee (À) in the presence of
SP2. The major enantiomer was the same using (E)-
1a (entry 2). The reaction of (E)-1b and (E)-1c
bearing either an n-pentyl or benzyl substituent at
Table 4: Scope of enones for chiral quaternary carbon centers.
No. 1 (R1, R2, R3)
4
4
Yield [%][a] ee [%][c]
Yield [%][b] ee [%][c]
1
2
3
4
5
6
7
8
9
(E)-1a (Ph, Et, Ph)
(Z)-1a (Et, Ph, Ph)
>98 (4a)[f] >98 (+) >98 (4a)[g] 95 (À)
>98 (4a)[f] 35 (À)
>98 (4a)[h] 75 (À)
(E)-1b (Ph, n-pent, Ph)
(E)-1c (Ph, Bn, Ph)
(E)-1d (Ph, iPr, Ph)
(Z)-1d (iPr, Ph, Ph)
(E)-1e (4-MeC6H4, Et, Ph)
>98 (4b)[f] >98 (+) >98 (4b)[g] 97 (À)
80 (4c)[i]
97 (+)
72 (4c)[i]
94 (À)
[d]
[d]
–
–
28 (4d)[f]
95 (4e)[f]
97 (À)
73 (4d)[i]
>98 (+)
98 (À)
>98 (+) 97 (4e)[g]
(E)-1 f (4-MeOC6H4, Et, Ph) >98 (4 f)[f] >98 (+) 86 (4 f)[g]
>98 (À)
95 (À)
(E)-1g (3-MeOPh, Et, Ph)
93 (4g)[f]
>98 (+) 60 (4g)[i]
10 (E)-1h (2-MeOC6H4, Et, Ph) 97 (4h)[f]
94 (+)
98 (+)
98 (+)
96 (+)
95 (+)
89 (4h)[g]
90 (4i)[g]
92 (4j)[g]
98 (4k)[g]
98 (À)
11 (E)-1I (4-FC6H4, Et, Ph)
12 (E)-1j (2-FC6H4, Et, Ph)
13 (E)-1k (4-ClC6H4, Et, Ph)
14 (E)-1l (4-CF3C6H4, Et, Ph)
93 (4i)[f]
98 (4j)[f]
93 (4k)[f]
97 (4l)[f]
>98 (À)
>98 (À)
95 (À)
>98 (4l)[g] 95 (À)
97 (4m)[g] 97 (À)
>98 (4n)[g] 97 (À)
15 (E)-1m (2-naphthyl, Et, Ph) 93 (4m)[f] 95 (+)
16 (E)-1n (4-biphenyl, Et, Ph) >98 (4n)[f] 98 (+)
17 (E)-1o (Ph, Et, 4-MeOC6H4) 97 (4o)[f]
>98 (R)[e] >98 (4o)[g] >98 (S)[e]
18 (E)-1p (Ph, Et, 4-ClC6H4)
19 (E)-1q (Ph, Et, Me)
>98 (4p)[f] 98 (+)
96 (4p)[g]
76 (4q)
98 (À)
97 (4q)[f]
93 (À)
>98 (+)
[a] Yield of isolated product obtained using BP2. [b] Yield of isolated product
obtained using SP2. [c] The ee value was determined by HPLC analysis using a chiral
stationary phase. [d] The results were not reproducible. [e] The absolute config-
uration of 4o was determined after the conversion into the known carboxylic acid.
[f] Reaction time of 1–3 h. [g] Reaction time of 3–5 h. [h] Reaction time of 7 h.
the b position gave the products 4b and 4c, respec- [i] Reaction time of 24 h.
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absence of Me3Al also promoted the isomerization at
relatively lower reaction rate, thus, the Lewis acidic character
might induce the isomerization. The enones (E)-1e–l bearing
electron-donating or electron-withdrawing substituents gave
the products 4e–l in high to excellent yields with excellent
ee values (entries 7–14). The enones (E)-1m and (E)-1n
bearing electron-rich aryl substituents, such as naphthyl and
biphenyl, gave the corresponding products 4m and 4n in
excellent yields with excellent ee values (entries 15 and 16).
The enones (E)-1o and (E)-1p bearing an electron-donating
or electron-withdrawing substituent, respectively, attached to
a
benzoyl moiety improved the yields and ee values
(entries 17 and 18). An aliphatic enone, such as that of (E)-
1q participated in the reaction (entry 19). The tentative
examination for the use of various organoaluminum reagents
showed that the reaction of Et3Al instead of Me3Al in the
presence of CuCl2·2H2O and BP2 or SP2 gave moderate to
good yields with high to excellent ee values and the unreacted
(E)-1 was recovered [Eq. (2)].
Scheme 2. Synthesis of turmerone.
reagent, and MnO2-mediated oxidation without purification
gave the desired (S)-(+)-ar-turmerone in 60% yield (5 steps).
Furthermore, the mild esterification of 6b provided the
product 7, which is the key intermediate for the synthesis of 8-
deoxyanisatin, in quantitative yield.[17c] The use of SP2 as
a ligand for opposite stereoselectivity gave the intermediate
for the synthesis of frondosin B (Scheme 3).[17d] The asym-
metric conjugate addition of Me3Al to 5c, and the following
reduction gave the desired product 8 in high to excellent yield,
which can readily be converted into frondosin B by a known
literature procedure. Additional investigations into the prep-
aration of natural products bearing chiral quaternary carbon
centers are currently underway.
The preliminary examination using our original catalysts
for asymmetric methylation are demonstrated for the syn-
thesis of natural products.[17] We achieved the first example of
the asymmetric conjugate addition of Me3Al to N-acylpyrrole
derivatives.[18] The reaction of 5a and Me3Al under the
optimized reaction conditions gave the product 6a in 54%
yield with 96% ee, and BP2 was found to be a superior ligand
(Scheme 1). The subsequent reduction using LiBH4 and
NaBH4, with subsequent Swern oxidation could give (S)-
florhydral in 48% yield (3 steps).[17a] We also succeeded in the
synthesis of (S)-(+)-ar-turmerone (Scheme 2).[17b] The asym-
metric conjugate addition of Me3Al to 5b under the optimum
reaction conditions gave the product 6b in high yield with an
excellent ee value. The reduction of 6b using LiBH4 and
NaBH4 gave the corresponding alcohol, and subsequent
oxidation to the aldehyde, nucleophilic addition of a Grignard
Scheme 3. Synthesis of intermediate for frondosin B.
In conclusion, we have described the specific character of
our original ligands for the first example of the copper-
catalyzed asymmetric conjugate addition of Me3Al to acyclic
enones at ambient conditions for the creation of a chiral
quaternary carbon center. Most reactions proceeded in
greater than 95% ee. The ligands based on either a binol or
spinol architecture gave products, albeit with the major
products having opposite enantioselectivity. The practical
advantage of the present reaction is the low cost and stability
Scheme 1. Synthesis of (S)-florhydral.
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[6] For a review: a) A. M. Dumas, E. Fillion, Acc. Chem. Res. 2010,
43, 440; b) A. Wilsily, E. Fillion, J. Org. Chem. 2009, 74, 8583;
c) A. Wilsily, T. Lou, E. Fillion, Synthesis 2009, 2066; d) A.
Wilsily, E. Fillion, Org. Lett. 2008, 10, 2801; e) E. Fillion, A.
Wilsily, J. Am. Chem. Soc. 2006, 128, 2774.
of copper salts compared to the precedented rhodium- and
palladium-catalyzed construction of a chiral quaternary
carbon center. Since a methyl-substituted chiral quaternary
carbon center is found in various natural products, the present
discovery could be a new entry into the preparation of
potentially useful chiral molecules. The application of the
present reaction in the synthesis of natural products, multi-
nuclear catalysts, and their characteristic features are being
studied in our laboratory.
[7] J. Wu, D. M. Mampreian, A. H. Hoveyda, J. Am. Chem. Soc.
2005, 127, 4584.
[8] For a review, see: K. Endo, T. Shibata, Synthesis 2012, 44, 1427.
[9] a) K. Endo, M. Ogawa, T. Shibata, Angew. Chem. 2010, 122,
2460; Angew. Chem. Int. Ed. 2010, 49, 2410; b) K. Endo, K.
Tanaka, M. Ogawa, T. Shibata, Org. Lett. 2011, 13, 868; c) K.
Endo, D. Hamada, S. Yakeishi, M. Ogawa, T. Shibata, Org. Lett.
2012, 14, 2342.
[10] The copper-catalyzed asymmetric conjugate addition of organo-
zinc reagents to b-substituted cyclic enones was reported. See:
a) A. W. Hird, A. H. Hoveyda, J. Am. Chem. Soc. 2005, 127,
14988; b) K. Lee, M. K. Brown, A. W. Hird, A. H. Hoveyda, J.
Am. Chem. Soc. 2006, 128, 7182; c) M. K. Brown, T. L. May,
C. A. Baxter, A. H. Hoveyda, Angew. Chem. 2007, 119, 1115;
Angew. Chem. Int. Ed. 2007, 46, 1097.
Received: August 6, 2012
Revised: October 18, 2012
Published online: November 26, 2012
Keywords: aluminum · copper · homogeneous catalysis ·
.
natural products · synthetic methods
[11] Representative binol/Al complexes: a) T. Arai, Y. M. A.
Yamada, N. Yamamoto, H. Sasai, M. Shibasaki, Chem. Eur. J.
1996, 2, 1368; b) T. Arai, H. Sasai, K. Yamaguchi, M. Shibasaki,
J. Am. Chem. Soc. 1998, 120, 441; c) E. Emori, T. Iida, M.
Shibasaki, J. Org. Chem. 1999, 64, 5318.
[1] For reviews, see: a) T. Hayashi, K. Yamasaki, Chem. Rev. 2003,
103, 2829; b) A. Alexakis, J. E. Bꢁckvall, N. Krause, O. Pꢂmies,
M. Diꢃguez, Chem. Rev. 2008, 108, 2796.
[2] Recent examples; a) T. Thaler, P. Knochel, Angew. Chem. 2009,
121, 655; Angew. Chem. Int. Ed. 2009, 48, 645, and references
therein; b) R. Shintani, M. Takeda, T. Nishimura, T. Hayashi,
Angew. Chem. 2010, 122, 4061; Angew. Chem. Int. Ed. 2010, 49,
3969; c) T. L. May, J. A. Dabrowski, A. H. Hoveyda, J. Am.
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