Carbohydrate-derived amino-alcohol ligands for asymmetric alkynylation of aldehydes

Article abstract of DOI:10.1021/ol052503l

Conformationally restricted amino alcohols based on carbohydrate scaffolds provide flexible and fine-tuneable libraries that greatly expand the range of ligands available in the Zn(OTf)₂-mediated addition of alkynes to aldehydes, in some cases with very high stereoselectivities.

Full text of DOI:10.1021/ol052503l

ORGANIC
LETTERS
2
006
Vol. 8, No. 2
07-210
Carbohydrate-Derived Amino-Alcohol
Ligands for Asymmetric Alkynylation of
Aldehydes
2
†
‡
,†
Daniel P. G. Emmerson, William P. Hems, and Benjamin G. Davis*
Department of Chemistry, UniVersity of Oxford, Chemistry Research Laboratory,
Mansfield Road, Oxford OX1 3TA, U.K., and Johnson Matthey Catalysis and Chiral
Technologies, 28, Cambridge Science Park, Milton Road, Cambridge CB4 0FP, U.K.
ben.daVis@chem.ox.ac.uk
Received October 16, 2005
ABSTRACT
Conformationally restricted amino alcohols based on carbohydrate scaffolds provide flexible and fine-tuneable libraries that greatly expand
the range of ligands available in the Zn(OTf) -mediated addition of alkynes to aldehydes, in some cases with very high stereoselectivities.
2
Enantioenriched, secondary propargyl alcohols are important
synthetic building blocks, but there are few methods for
preparing them in consistently high yield and ee. Corey’s
by a straightforward procedure that does not require inert
atmosphere techniques or high-grade dry solvent. There is
still some room for improvement in terms of substrate
1
9
chiral oxazaborolidine promoted alkynylation and Carreira’s
generality for this reaction, but relatively little investigation
zinc triflate catalyzed2 method in which N-methylephedrine
A is the chiral promoter are the two leading examples, giving
highly enantiopure, secondary propargyl alcohols (>90% ee).
,3
into the effect of ligand structure has been undertaken.
Indeed, for the zinc triflate catalyzed reaction, to date only
1
0,11
one ligand B
has improved upon N-methylephedrine.
Chan4 and Pu have both reported methods involving Ti-
BINOL catalysts and alkynylzinc reagents prepared with
dialkylzincs and terminal acetylenes, which give high yields
and enantioselectivity, especially for aromatic aldehydes.
Reduction of prochiral alkynones also provides an alternative
,5
6,7
Notably the use of B improved yields for reactions of
aliphatic aldehydes without R-branching, which had been
problematic for the N-methylephedrine promoted reaction.
No ligand has shown broad reactivity with aromatic alde-
hydes in this reaction.
8
means of entry.
Carbohydrates have recently received much attention as
1
2-16
sources of chiral ligands for asymmetric catalysis.
part of our ongoing studies
As
2
The Zn(OTf) -catalyzed method offers operational advan-
1
7,18
into the application of
tages over other methods: the alkynylzinc may be prepared
glucosamine-derived, amino alcohol ligands 4 to promote
asymmetric transformations, we report here the first thorough
investigation into the influence that ligand structure has on
asymmetric, zinc triflate catalyzed alkynylation. In particular,
the trans-decalin-like framework of such ligands provides a
†
‡
University of Oxford.
Johnson Matthey Catalysis and Chiral Technologies.
1) Corey, E. J.; Cimprich, K. A. J. Am. Chem. Soc. 1994, 116, 3151-
(
3
152.
(2) Frantz, D. E.; F a¨ ssler, R.; Carreira, E. M. J. Am. Chem. Soc. 2000,
1
22, 1806-1807.
(3) Frantz, D. E.; F a¨ ssler, R.; Tomooka, C. S.; Carreira, E. M. Acc. Chem.
(8) Noyori R.; Tomino, I.; Tanimoto; Y. J. Am. Chem. Soc. 1979, 101,
3129; Matsumura, K.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem.
Soc. 1997, 119, 8738.
Res. 2000, 33, 373-381.
(4) Lu, G.; Li, X.; Chan, W. L.; Chan, A. S. C. Chem. Commun. 2002,
1
72-173.
(9) For a recent example of difficulties, see: Marshall, J. A.; Bourbeam,
M. P. Org. Lett. 2003, 5, 3197.
(
5) Li, X.; Lu, G.; Kwok, W. H.; Chan, A. S. C. J. Am. Chem. Soc.
2
002, 124, 12636-12637.
(10) Jiang, B.; Chen, Z.; Xiong, W. Chem. Commun. 2002, 1524.
(11) See also: Yamashita, M.; Yamada, K.; Tomioka, K. AdV. Synth.
Catal. 2005, 347, 1649.
(
6) Moore, D.; Pu, L. Org. Lett. 2002, 4, 1855-1857.
7) Xu, M.-H.; Pu, L. Org. Lett. 2002, 4, 4555-4557.
(
1
0.1021/ol052503l CCC: $33.50
© 2006 American Chemical Society
Published on Web 12/21/2005

rigidity that would allow us to investigate the effects of
conformational restriction that contrasts the two ligands A
and B used to date. On the basis of preliminary screening of
primary and secondary amines, we selected tertiary amines
for this study. We chose to use a ligand family that exhibited
both functional and stereochemical diversity and conse-
quently chose R-gluco ligands 4a-f (Scheme 1) with
Table 1. Addition of Phenylacetylene 2 to 1a
d
ligand
ligand stereochemistry
yield ee (%)
c e
b
R
R′
(%)
(config)
f
1
2
3
4
5
6
7
8
9
1
4a
4a
4b
4c
4d
4e
4f
5
R-G
-(CH
-(CH
2
)
)
2
O(CH
O(CH
2
)
)
2
2
-
-
3
95
58
73
38
37
96
94
92
8
71 (R)
97 (R)
99 (R)
81 (R)
79 (R)
54 (R)
39 (R)
99 (R)
22 (R)
35 (R)
R-G
R-G
R-G
R-G
R-G
R-G
â-G
R-M
R-A
2
2
2
-(CH
-(CH
2
)
)
4
-
-
2
5
Et
Et
Pr
Pr
Bn
-(CH
-(CH
-(CH
Bn
2
2
2
)
)
)
2
2
2
O(CH
O(CH
O(CH
2
2
2
)
)
)
2
2
2
-
-
-
Scheme 1. Stereochemically and Functionally Diverse Family
6
0
7
2
of Ligands Tested in Zn(OTf) -Promoted Alkynylation
a
Ratio Zn(OTf)2/ligand/Et3N/PhCtCH/c-C6H11CHO ) 1.1:1.2:1.2:1.2:
b
1
.0. Temperature ) 40 °C. Ligand stereochemistry: R/â refers to anomeric
c
stereochemistry, G ) glucose, A ) allose, M ) mannose. Isolated yield,
d
after column chromatography. Determined by chiral GC using a 25 m
e
CDex-â chiral column. Absolute stereochemistry determined by polarim-
23
1
23
etry on product from entry 2, [R] D ) -9.9 (c 1.22, CHCl3) [lit. [R]
D
f
-
2
10.8 (c 1.0, CHCl3)], and thereafter by order of elution. Temperature )
3 °C.
reaction. The results of this screening process improved
enantioselectivity yet further: ligands 4b and 5 both pro-
moted the reaction with almost complete enantioselectivity
(
entries 3 and 8); 5 also gave an excellent yield. These levels
q
of enantioselectivity represent an improvement in ∆∆G for
diastereomeric transition states that lead to 3R vs 3S (∆∆∆G
q
1
0
(
R-S)), compared to the best prior ligand, of ∼3800 J
mol .
General trends could also be discerned from the results.
different C-2 amine substituents, as well as three diastereo-
mers of 4a, 5-7. In particular, the latter enabled us to
precisely investigate the effect of inverting the C-1, C-2, and
C-3 stereogenic centers of the ligand in turn (4a f 5 or f
-
1
2
0
First, cyclic amine substituents at C-2 gave enantioselec-
tivities and yields higher than those of noncyclic ones (Table
7
or f 6, respectively). The synthesis of these ligands has
1
, entries 2-4 vs 5-7). Second, â-gluco ligands gave
17,18
been described in previous work.
be derived on a gram scale from N-acetyl glucosamine in
overall yields of 28-34% for 4a-e, 19% for 4f, 14% for 5,
In brief they may all
selectivity higher than that of their R-anomers (Table 1,
entries 8 vs 2), whereas R-manno ligands gave good yields
but low enantioselectivity and R-allo ligands gave only poor
yields and low enantioselectivity. The diastereomeric fine-
tuning shown, in particular, by â-gluco vs R-gluco ligands
highlights the importance of second-sphere/chiral relay
effects, which may be readily exploited in carbohydrate
ligands as a result of their abundance of stereogenic centers.17
Encouraged by these excellent results for ligands 4a and
18% for 6, and 4% for 7.
We began by using ligand 4a, phenylacetylene 2, and
cyclohexanecarboxaldehyde 1 following the method of
Carreira and co-workers using their optimized conditions
2
19
2
1
(
(
Table 1). The reaction essentially failed at room temperature
entry 1), and only a trace of the desired secondary alcohol
was recovered. However, at 40 °C product was isolated in
5
, we wished to investigate the possibility of developing a
95% yield and 97% ee (entry 2), a marginally higher ee than
catalytic version of this reaction. For this purpose we chose
ligand 4a and varied temperature, solvent, and reagent
stoichiometry as shown in Table 2. We tested DCM and THF
as alternative solvents for the reaction and found that THF
severely hindered the reaction (Table 2, entry 4), whereas
DCM caused only a slight deterioration of both yield and ee
compared to toluene (Table 2, entry 3). Upon initial use of
both sub-stoichiometric Zn(OTf)
reduced (entries 5 and 6). However, experiments using 1
equiv of Zn(OTf) and sub-stoichiometric 4a led to a
successful system using 0.55 equiv of ligand (entry 7) in
which the yield (86%) and ee (93%) were only slightly
reduced compared to the reaction with 1.2 equiv of ligand.
A ∼2:1 ratio of Zn(II) to ligand appeared to be the maximum
2,10
for any of the previously reported methods.
applied our other ligands 4b-f, 5, 6, and 7 to this model
We then
(
12) For reviews, see: Kunz, H.; R u¨ ck, K. Angew. Chem., Int. Ed. Engl.
993, 32, 336. Hale, K. J. In 2nd Supplements to the 2nd Edition of Rodd’s
Chemistry of Carbon Compounds; Sainsbury, M., Ed.; Elsevier: New York,
1
1
993; Vol. 1E-G, pp 217-313. Inch, T. D. AdV. Carbohydr. Chem.
Biochem. 1972, 27, 191. For related organocatalysis, see: Shi, Y. Acc. Chem.
Res. 2004, 37, 488.
2
and ligand, yields were
(13) Bauer, T.; Tarasiuk, J.; Pasniczek, K. Tetrahedron: Asymmetry 2002,
1
3, 77.
(
(
14) Selke, R.; Ohff, M.; Riepe, A. Tetrahedron 1996, 52, 15079.
15) Masumoto, S.; Usuda, H.; Suzuki, M.; Kanai, M.; Shibasaki, M. J.
2
Am. Chem. Soc. 2003, 125, 5634.
(
16) Di e´ guez, M.; Ruiz, A.; Claver, C. Dalton Trans. 2003, 15, 2957.
(17) Emmerson, D. P. G.; Villard, R.; Mugnaini, C.; Batsanov, A.;
Howard, J. A. K.; Hems, W. P.; Tooze, R. P.; Davis, B. G. Org. Biomol.
Chem. 2003, 1, 3826.
18) Emmerson, D. P. G.; Hems, W. P.; Davis, B. G. Tetrahedron:
Asymmetry 2005, 16, 213.
19) Ligand (1.2 equiv) and Zn(OTf)2 (1.1 equiv) were disolved in
(
(20) For another example of a chiral morpholino alcohol, see: Nugent,
W. A. Chem. Commun. 1999, 1369.
(
toluene, followed by addition of Et3N and then, after 2 h, acetylene followed
by aldehyde.
(21) Bull, S. D.; Davies, S. G.; Fox, D. J.; Garner, A. C.; Sellers, T. G.
R. Pure Appl. Chem. 1998, 70, 1501.
208
Org. Lett., Vol. 8, No. 2, 2006

Table 2. Catalytic Asymmetric Alkynylation of 2 with 1
Table 3. Alkynylation of Aldehydes with Phenylacetylene
no. of equiv
temp time
yield
ee
b
Zn(OTf)
2
Et
3
N
4a
(°C)
(h)
solvent (%)a (%)
1
2
3
4
5
6
7
8
9
1
1
1
1.1
1.1
1.1
1.1
0.2
0.5
1.1
1.1
0.5
0.2
0.2
0.5
1.2
1.2
1.2
1.2
0.5
1.2
1.2
1.2
1.2
0.22
23
40
40
40
40
40
40
40
40
60
60
60
21
21
21
48
21
21
21
21
21
21
21
44
PhMe
PhMe
DCM
THF
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
3
95
86
8
14
39
86
55
65
64
20
56
71
97
89
51
67
91
93
54
37
84
39
33
temp
(°C)
time
(h)
yield
ee
a
b
ligand
R
(%)
(%)
0.55 0.55
1
4a
5
i-Pr
i-Pr
c-Pr
c-Pr
t-Bu
t-Bu
23
23
23
23
40
40
40
40
60
23
23
40
23
50
23
23
23
50
23
50
40
40
40
40
40
40
40
20
21
21
10
40
40
24
44
44
44
44
44
44
44
44
72
44
80
70
64
71
51
62
55
46
68
4
15
50
38
19
43
18
11
12
36
62
17
14
95
97
65
94
81
97
92
73
26
74
98
91
97
64
23
0
1.2
1.2
1.2
0.5
1.2
1.2
0.55
0.22
0.22
0.22
0.22
0.22
2
3
4a
5
4
0
1
2
5
4a
5
6
7
4a
4c
4a
4a
5
n-C
n-C
n-C
6
6
6
H
H
H
13
13
13
8
a
Isolated yield after column chromatography. b Determined by chiral
9
GC using 25 m CDex-â column. Absolute configuration (R) for all.
10
Ph(CH
Ph(CH
Ph
2
)
)
2
2
1
1
1
1
1
1
2
3
4
5
2
c
4a
5
p-CH
p-CH
p-CH
p-CH
p-CH
p-CH
3
3
3
3
3
3
C
C
C
C
6
H
H
H
H
4
4
4
5
7
6
6
6
that was tolerated (entries 7 vs 8). We then investigated the
reaction at 60 °C and found that a good ee (84%) and
moderate yield (64%) could be achieved under these condi-
tions with a catalytic (20 mol %) amount of Zn(OTf)
base (entry 10).22 Interestingly, at 60 °C, a larger excess of
16
4f
5
4
1
1
7
8
OC
6
H
H
4
nd
nd
98
81
nd
nd
5
OC
6
4
19
5
p-ClC
p-ClC
6
H
H
4
4
2
and
2
2
0
1
5
6
4a
5
PhCHdCH
PhCHdCH
base with respect to Zn(OTf)
lectivity (entries 10 and 11).
2
was detrimental to enantiose-
22
a
As for Table 2. b Determined by chiral HPLC (chiracel OD column).
Determined by chiral GC (25 m CDex-â column). nd ) not determined.
c
We then turned our attention to substrate generality using
the noncatalytic conditions optimized in Table 1. Using the
two most successful ligands 4a and 5 we first tested addition
of phenylacetylene 1 to a range of straight chain and R-
branched aliphatic aldehydes and para-substituted aromatic
aldehydes (Table 3). Cyclopropanecarboxaldehyde, isobu-
tyraldehyde, and pivalaldehyde were chosen as examples of
branched chain aldehydes, and in all cases excellent enan-
tioselectivities were obtained in additions of phenylacetylene
reacted aldehyde was isolated as a 0.8:1 mixture of diaster-
eomers (∼50% yield for both ligands 4a and 5). An
analogous product was observed by NMR and MS from the
addition to heptaldehyde. The potential of this tandem aldol-
2
4-30
Tishchenko reaction
is being explored.
Benzaldehyde, p-chlorobenzaldehyde, p-tolualdehyde, p-
anisaldehyde, and the conjugated aldehyde cinnamaldehyde
were chosen as representative examples of aromatic alde-
hydes (entries 12-22). Additions to benzaldehyde using
ligand A have been reported to give reduced yields due to
Canizzaro side-reaction and alkynyl zinc reagents prepared
in situ by the reaction of terminal alkynes with dialkyl zincs
have usually been employed for aromatic aldehydes.5 The
only high yield for addition to benzaldehyde using the amino-
(entries 1-6, Table 3). Indeed when the ligand 5 was used
our results mostly improved upon the best enantioselectivities
previously reported for these reactions,2 although in some
cases yields using ligand 5 were lower.
The additions of 1 to heptaldehyde and 3-phenylpropi-
onaldehyde were investigated as examples of additions to
aliphatic aldehydes without R-branching using ligands 4a,
,10
2
3
,6,31
4c, and 5 (entries 7-11). High yielding additions of
10
acetylenes to such aliphatic aldehydes remain a particular
challenge using existing ligands.23 We found that only
moderate yields (55%) were possible with heptaldehyde and
poor yields (15%) were obtained with 3-phenylpropional-
dehyde, although enantioselectivity was high in both cases
2
alcohol/ Zn(OTf) system employed ligand B and gave 85%
yield and 97% ee. We too found reaction with aromatic
aldehydes to be problematic, especially for cinnamaldehyde
and the aromatic aldehydes with para electron-donating
groups for which low yields were recorded. In some cases
(92% and 98% ee, entries 7 and 11, Table 3, respectively).
Warming to 60 °C for the addition to heptaldehyde improved
yield (68%) but drastically reduced ee (26%, entry 9). Aldol
self-condensation of straight chain aliphatic aldehydes has
been suggested23 as a reason for reduced yields. We found
no such byproducts; rather, in the addition to 3-phenylpro-
pionaldehyde, a product due to aldol reaction followed by
crossed-Tishchenko reaction between aldol adduct and un-
(24) Bodnar, P. M.; Shaw, J. T.; Woerpel, K. A. J. Org. Chem. 1997,
2, 5674.
6
(
(
25) Evans, D. A.; Hoveyda, A. H. J. Am. Chem. Soc. 1990, 112, 6447.
26) Curran, D. P.; Wolin, R. L. Synlett 1991, 317.
(27) Berkhardt, E. R.; Bergman, R. G.; Heathcock, C. H. Organometallics
990, 9, 30.
1
(
28) Mahrwald, R.; Costisella, B. Synthesis 1996, 1087. Rohr, K.; Herre,
R.; Mahrwald, R. Org. Lett. 2005, 7, 4499.
29) Horiuchi, Y.; Taniguchi, M.; Oshima, K.; Utimoto, K. Tetrahedron
Lett. 1995, 36, 5353.
30) For catalytic variants, see: Mascarenhas, C. M.; Miller, S. P.; White,
(
(
(
22) This compares with selectivities of 86% ee in, e.g., ref 23.
P. S.; James P. Morken, J. P. Angew. Chem., Int. Ed. 2001, 40, 601.
Gnanadesikan, V.; Horiuchi, Y.; Ohshima, T.; Shibasaki, M. J. Am. Chem.
Soc. 2004, 126, 7783.
(31) Xu, Z.; Wang, R.; Xu, J.; Da, C.-S.; Yan, W.-J.; Chen, C. Angew.
Chem., Int. Ed. 2003, 42, 5747.
(23) Anand, N. K.; Carreira, E. M. J. Am. Chem. Soc. 2001, 123, 9687.
For another catalytic system developed during the course of this work, see
also: Takita, R.; Yakura, K.; Ohshima, T.; Shibasaki, M. J. Am. Chem.
Soc. 2005, 127, 13760.
Org. Lett., Vol. 8, No. 2, 2006
209

Canizzaro products were isolated, but interestingly ketones
probably resulting from crossed Canizzaro reaction between
aldehyde and product alcohol were also formed. Nonetheless,
high enantioselectivity (97% ee) was still achieved in these
examples when 5 was used as the ligand despite low yields
In conclusion, we have found a ligand, 5, that gives very
high enantioselectivities for the addition of terminal acetyl-
enes to aldehydes, generally improving upon results obtained
with A. For more challenging substrates, such as unbranched
aliphatic and aromatic aldehydes, we have recorded excellent
enantioselectivities but more disappointing yields. Isolated,
characterized byproducts suggest previously unobserved
aldol/crossed-Tishchenko or crossed-Cannizaro reactions
compete. Moreover, ligand stereochemical diversification
revealed that â-gluco 5 gave enhanced enantioselectivity over
R-gluco 4a. Thus, variation of anomeric configuration tunes
enantioselectivity (∆∆∆G (R-S) of 2800-5000 J mol )
and demonstrates that chiral information may be “relayed”
to the metal binding site. Variation of stereogenic centers
directly adjacent to the N,O-binding site to create R-allo 6
or R-manno 7 ligands has an even larger effect.
(entry 13). Increasing the temperature was not greatly
successful in improving the yield and often resulted in a
reduced ee (entry 14). In the case of benzaldehyde and
electron-deficient p-chlorobenzaldehyde, better yields (50-
62%) were achieved, and once again enantioselectivity was
excellent (91-98% ee, entries 12 and 19, Table 3). Increasing
the temperature to 50 °C from 23 °C resulted in increased
yield but lower (81%) ee (entry 20, Table 3). Encouraged
by these results, stereochemical and functional changes in
ligand were tested in the addition of 2 to p-tolualdehyde.
Trends were as for addition to 1, a slight increase in yield
but reduction in ee for R-manno 7 (entry 15, Table 3) and a
dramatic loss of activity and enantioselectivity for dibenzyl-
amine 4f (entry 16).
q
-1
It is interesting that the two most successful ligands bear
2
-(4-morpholinyl) moieties; corresponding deoxo, 2-pip-
eridinyl, ligand 4c showed significantly reduced enantiose-
lectivities. Although, in the absence of investigations into
nonlinear effects, we cannot rule out a bimetallic intermediate
such as that operating in DIAB-catalyzed addition of
Finally, we investigated the applicability of our ligands
to additions to 1 of a range of terminal acetylenes with
different functionalities: silyl ethers, a primary alcohol, and
a secondary alcohol under noncatalytic conditions (Table 4).
3
2
dialkylzincs to aldehydes, it seems reasonable to speculate
that the morpholinyl oxygen plays an important role in
coordinating zinc in a tentative tridentate transition state such
as C (Figure 1). Basic molecular models, low reactivity in
Table 4. Alkynylation of Aldehydes by Terminal Acetylenes
temp
(°C)
time
(h)
yield
ee
(%)
a
ligand
R′
R
(%)
d
b
b
c
1
2
3
4
5
6
7
8
9
5
Ph(CH
Ph(CH
2
)
)
2
2
Cx
t-Bu
Cx
Cx
Cx
Cx
Cx
Cx
Cx
23
23
23
50
23
50
50
23
50
24
24
44
44
44
20
12
44
20
89
77
39
71
8
68
90
11
42
95
5
2
>99
4a
5
Me
Me
Me
Me
2
2
2
2
COH
94
99
c
c
c
c
c
c
COH
5
COTMS
COTMS
98
5
97
Figure 1. Proposed transition states.
5
HO(CH
2
)
2
98
>99
98
5
Et
Et
3
Si
Si
5
3
a-c
As for Table 3. d Cx ) cyclohexyl.
THF (Table 2), and similar suggested coordination in
3
3
dialkylzinc-aldehyde additions support this possibility.
Alternatively, in line with a proposed bifunctional mechanism
3
4
for dialkynylzinc-aldehyde reaction, this oxygen may act
as a Lewis base activating zinc acetylide in a transition state
such as D.
Ligand 5 was selected since it had given the highest
enantioselectivities. 4-Phenylbut-1-yne gave good yields
(
77-89%, entries 1 and 2) and excellent enantioselectivity,
especially for the addition to pivalaldehyde (>99% ee, entry
). Using 2-methylbut-3-yn-2-ol and its TMS protected
analogue, moderate to good yields were achieved at an
elevated temperature also in excellent enantioselectivity
Acknowledgment. We thank Johnson Matthey Catalysis
and Chiral Technologies (D.P.G.E.) for funding.
2
Supporting Information Available: Experimental pro-
cedures and characterization. This material is available free
of charge via the Internet at http://pubs.acs.org.
(
entry 4, 99% ee). These results demonstrated the tolerance
of the reaction to a secondary alcohol, but silyl ether
protection was not severely detrimental to either yield or ee.
A high yield (90%) and excellent ee (98%) was also observed
for but-3-yn-1-ol (entry 7). Excellent enantioselectivity
OL052503L
(
32) Kitamura, M.; Okada, S.; Suga, S.; Noyori, R. J. Am. Chem. Soc.
(
>99% ee, entry 8) was observed in the reaction with
1
989, 111, 4028.
triethylsilylacetylene but the yield was low (11%); increasing
reaction temperature improved yield (42%, entry 9) without
severely diminishing ee (98%).
(33) Hanyu, N.; Aoki, T.; Mino, T.; Sakamoto, M.; Fujita, T. Tetrahe-
dron: Asymmetry 2000, 11, 4127.
34) Kang, Y.-F.; Liu, L.; Wang, R.; Yan, W.-J.; Zhou, Y.-F. Tetrahe-
dron: Asymmetry 2004, 15, 3155.
(
210
Org. Lett., Vol. 8, No. 2, 2006