Catalytic enantioselective allenylation reactions of aldehydes with tethered bis(8-quinolinolato) (TBOx) chromium complex

Article abstract of DOI:10.1021/ja0679578

The utility of the new class of chiral ligand, tethered bis(8-quinolinol) (TBOxH), is further explored. Its chromium complex, TBOxCr(III)Cl, effectively catalyzes the asymmetric allenylation reactions of various aldehydes at room temperature with high yie

Full text of DOI:10.1021/ja0679578

Published on Web 12/21/2006
Catalytic Enantioselective Allenylation Reactions of Aldehydes with Tethered
Bis(8-quinolinolato) (TBOx) Chromium Complex
Guoyao Xia and Hisashi Yamamoto*
Department of Chemistry, The UniVersity of Chicago, 5735 South Ellis AVenue, Chicago, Illinois 60637
Received November 12, 2006; E-mail: yamamoto@uchicago.edu
Table 1. Asymmetric Allenylation Reactions of Benzaldehyde
Allenes have proven to be versatile and useful intermediates in
organic synthesis due to the existence of the two orthogonal
π-bonds.1 Recently, R-allenic alcohols have drawn much attention
because of their unique reactivities and the ease of further conver-
sion into compounds with other functional groups.1,2 Practical
methods for the synthesis of R-allenic alcohols by coupling
propargylic reagents with carbonyl groups have often been limited
by lack of chemoselectivity as well as enantioselectivity. This is
due to the ambient nature of propargylic carbanions, which generally
exist as an equilibrium mixture of allenic and propargylic organo-
metallic derivatives.1a,d,3 Despite these complications, several meth-
ods have been developed for the regiospecific construction of
R-allenic alcohols in recent years.1d,4 Among these enantioselective
synthetic methods,1f,5 only a very limited number of catalytic asym-
metric allenylation have been reported.6,7 The nucleophilic addition
of organochromium reagents to aldehydes is a powerful C-C bond-
forming method.8 The allenylation reactions between aldehydes and
propargylic halides catalyzed by chromium complexes are known
to be very useful due to excellent chemoselectivity, broad compat-
ibility with different functional groups, and environmentally benign
process.7 However, there are still some difficulties in terms of (1)
the enantioselectivities of R-allenic alcohols, (2) scope of substrates,
and (3) the ease of operation with commercially available reagents.
We earlier developed and synthesized a tethered bis(8-quinoli-
nolato) (TBOx) chromium catalyst and applied it to asymmetric
pinacol coupling reactions9 of aldehydes and asymmetric Nozaki-
Hiyama allylation reactions.10 This successful catalytic redox system
was further applied to the asymmetric allenylation reaction between
benzaldehyde and commercially available 1-trimethylsilyl-3-bro-
mopropyne.
First, TBOxCr(III)Cl (5 mol %) and Mn powder were mixed in
THF under an atmosphere of Ar at room temperature. After 10
min, to the reaction mixture was added 1-trimethylsilyl-3-bro-
mopropyne,11 and the mixture was stirred for 30 min. Then,
benzaldehyde and the silyl chloride were added successively and
slowly. After 48 h, the isolated crude product was treated with
TBAF in THF at room temperature to afford 1-phenylbuta-2,3-
dien-1-ol as the only product. If the crude product was treated with
0.5 N HCl in THF, TMS-substituted R-allenic alcohol could be
obtained in lower yield.12 As shown in Table 1, by using TMSCl
(1 equiv), the R-allenic alcohol was obtained in 77% yield with
only 17% ee (entry 1). When TESCl (1 equiv) was used, the
enantioselectivity of the product was increased dramatically ac-
companied by good yield (entry 4). The different reaction rates
between TMSCl (entry 2) and TESCl (entry 5) were observed when
no catalyst was applied. If more than 1 equiv of silyl chloride was
used, the desired product was generated in higher yield but lower
ee (entries 3 and 6). Finally, when 1-trimethylsilyl-3-bromopropyne
(1.5 equiv) and TESCl (1 equiv) were applied, the desired R-allenic
alcohol was produced with 91% yield and 96% ee (entry 8).
Under the optimized reaction conditions, a very wide scope of
aldehydes was successfully allenylated in moderate to high yields
eeb
(%) (config)c
entry
SiCl
yielda (%)
1
1 equiv
1 equiv
1 equiv
1 equiv
1 equiv
1 equiv
1.25 equiv
1.5 equiv
1 equiv
1 equiv of TMSCl
1 equiv TMSCl
77
37
83
71
<5
74
82
91
89
17 (R)
2d
3
1.2 equiv of TMSCl
1 equiv of TESCl
1 equiv of TESCl
1.2 equiv of TESCl
1 equiv of TESCl
1 equiv of TESCl
1 equiv of TESCl
8 (R)
96 (R)
4
5d
6
95 (R)
96 (R)
96 (R)
96 (R)
7
8
9e
a Isolated yield after chromatographic purification. b Enantiomeric excess
was determined by chiral HPLC analysis. c Assigned by comparison of the
sign of optical rotation with reported value. d No TBOxCr(III)Cl was used.
e The reaction was complete in 30 h by using TBOxCr(III)Cl (10 mol %).
with excellent enantioselectivities. As shown in Table 2, para-
substituted aromatic aldehydes with either electron-donating or
electron-withdrawing groups gave excellent enantioselectivities
(entries 1, 4, 5, and 7). However, a higher catalyst loading, more
TESCl, and 1-trimethylsilyl-3-bromopropyne had to be applied to
achieve higher yields for the benzaldehydes with an electron-
withdrawing group (entries 6 and 8). The ortho- and meta-
substituted benzaldehyde could also be allenylated in good yields
with good ee (entries 2 and 3). Bulky aryl aldehydes (entries 9 and
10), heterocyclic aldehyde (entry 11), R,â-unsaturated aldehyde
(entry12), and aliphatic aldehydes (entries 13-15) proved to be
good substrates for this method.
To further explore the substrate scope, the allenylation reactions
of aldehydes with terminally alkyl-substituted propargylic bromide,
which had never succeeded with high enantioselectivities by Cr-
catalyzed asymmetric allenylation reactions previously,13 were
examined under the optimized reaction conditions. As shown in
Table 3, the allenylation reaction between benzaldehyde and
commercially available 1-bromo-2-butyne provided 2-methyl-1-
phenylbuta-2,3-dien-1-ol in 84% yield with 97% ee as the major
product with <5% yield of homopropargylic alcohol (entry 1). In
the allenylation of other aromatic aldehydes with an electron-
donating or electron-withdrawing group (entries 2 and 3), an
aliphatic aldehyde (entry 4) also gave excellent enantioselectivities
with moderate to good yields when R2 was the methyl group.
Increasing the size of the R2 group caused the enantioselectivities
of the allenylation reactions to go down slightly. When R2 is an
ethyl group, benzaldehyde and hydrocinnamylaldehyde were alle-
nylated in good yield with excellent ee (entry 5 compared to entry
1, and entry 6 compared to entry 4). When R2 is a phenyl group,
benzaldehyde was allenylated in 58% yield with 88% ee (entry 7
compared to entries 1 and 5).
9
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J. AM. CHEM. SOC. 2007, 129, 496-497
10.1021/ja0679578 CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Asymmetric Allenylation Reactions of Aldehydes
the allenylation reaction of versatile aldehydes were obtained. (2)
Easy operation with commercially available terminally substituted
propargylic bromide could be achieved. (3) First success for the
allenylation reactions of aldehydes with terminally alkyl-substituted
propargylic bromides that provided excellent chemoselectivities (R-
allenic alcohol as the major product in up to 84% yield) as well as
unprecedented enantioselectivities (up to 97% ee). Studies are
currently underway to elucidate the mechanism.14 The applications
of TBOxH in other asymmetric catalysis will be reported in due
course.
Acknowledgment. Support of this research was provided by
the National Science Foundation (NSF) and Merck & Co.
Supporting Information Available: Experimental procedures and
spectral data. This material is available free of charge via the Internet
at http://pubs.acs.org.
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a Isolated yield after chromatographic purification. b Enantiomeric excess
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a Isolated yield after chromatographic purification. b Enantiomeric excess
was determined by chiral HPLC analysis. c The absolute configuration of
the product was determined to be S.
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(11) The silyl group of the propargylic bromide affected the yields and
enantioselectivities. See Scheme 1 in Supporting Information.
(12) See Scheme 2 in Supporting Information.
In summary, TBOxCr(III)Cl was shown to efficiently catalyze
the asymmetric allenylation reactions of both aromatic and aliphatic
aldehydes. Utilizing this methodology, most of the difficulties were
overcome: (1) Excellent enantioselectivities (up to 97% ee) for
(13) For example, ref 7 in comparison to entry 1 in Table 3.
(14) See Scheme 3 in Supporting Information for the proposed catalytic cycle
and transition structures.
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