Catalytic enantioselective Nozaki-Hiyama allylation reaction with tethered bis(8-quinolinolato) (TBOx) chromium complex

Article abstract of DOI:10.1021/ja058454p

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 Nozaki-Hiyama allylation reactions of various aldehydes at room temperature with high yield (up to 95%) and high enantioselectivity (up to 99% ee). The scope of the present method is shown to be wide, and this method represents an efficient access to chiral homoallylic alcohols. Copyright

Full text of DOI:10.1021/ja058454p

Published on Web 02/04/2006
Catalytic Enantioselective Nozaki-Hiyama Allylation Reaction 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 December 13, 2005; E-mail: yamamoto@uchicago.edu
Table 1. Nozaki-Hiyama Allylation Reactions of Aldehydes
Catalyzed by TBOxCr(III)Cl
The addition of organochromium compounds to aldehydes,
known as the Nozaki-Hiyama (NH) reaction,1 has proven to be a
powerful C-C bond formation method by virtue of its high chemo-
and stereoselectivity and ease of the reaction under mild conditions.2
Catalytic asymmetric NH methodologies have been recognized as
important and effective methods and environmentally friendly
processes for the synthesis of chiral homoallylic alcohols. Although
there have been a limited number of reports on asymmetric catalysis
of these reactions,3 the enantioselectivities, yields, and the scope
of the substrates were not satisfactory.3,4 Herein, we report this
catalytic, highly enantioselective NH allylation reaction.
We earlier developed and synthesized a new chiral tethered bis-
(8-quinolinolato) (TBOx) chromium catalyst and applied it to the
highly enantio- and diastereoselective pinacol coupling reaction of
aldehydes.5 This successful catalytic redox system was then applied
to the NH allylation reaction between benzaldehyde and allylchlo-
ride. Competitive reactions between the pinacol coupling reaction
and the NH allylation reaction were observed. The desired
homoallylic alcohol was obtained as minor product with 10% yield
and 73% ee. Fortunately, once the more reactive allylbromide was
applied to the reaction with benzaldehyde, the homoallylic alcohol
from the NH allylation reaction turned out to be the major product
with 82% yield and 74% ee (Scheme 1).
Scheme 1
After carefully optimizing the experimental parameters, the fol-
lowing general reaction procedure was established. First, TBOxCr-
(III)Cl (3 mol %) and Mn were mixed in CH3CN:DME (1:3) under
an atmosphere of Ar at room temperature. After 10 min, to the
reaction mixture was added allylbromide, and the mixture was
stirred for 30 min. Then, benzaldehyde and TESCl were added suc-
cessively and slowly.6 After the indicated reaction time, the isolated
crude product was treated with 1 N HCl to afford the homoallylic
alcohol with 93% yield and 98% ee (entry 3, Table 1).
As shown in Table 1, the catalyst loading could be decreased to
1 mol % while maintaining good yields and enantioselectivities
(entries 2 and 15). Even when 0.5 mol % catalyst was used for the
reaction between benzaldehyde and allylbromide, (R)-1-phenylbut-
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 CH3CN:toluene (1:1) was used
as solvent. e Crude products were treated with TBAF in THF. f Enantiomeric
excess was determined by 19F NMR of the corresponding MTPA ester.
3-en-1-ol in 75% yield with 86% ee was afforded (entry 1). By
using 10 mol % catalyst, 99% ee for benzaldehyde (entry 4) and
98% ee for cyclohexanecarboxaldehyde (entry 18) with good yields
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C O M M U N I C A T I O N S
allylation reaction was achieved.10 (3) Crotylation of benzaldehyde
led to a 5.5:1 ratio of anti to syn and >95% ee for both
diastereomers.11 Studies are currently underway to elucidate the
mechanism.12 Furthermore, the applications of TBOx in other
asymmetric catalysis will be reported in due course.
Table 2. TBOxCr(III)Cl-Catalyzed Addition of Other Allylic
Bromides to Aldehydes
Acknowledgment. Dedicated to Prof. H. Nozaki and Prof. T.
Hiyama for their pioneering work in this field. We thank the
National Science Foundation (NSF) for financial support of this
research.
Supporting Information Available: Experimental procedures,
spectral data for all new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
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a Isolated yield of a mixture of anti and syn product after chromatographic
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were obtained. Because aliphatic aldehydes are not as reactive as
aromatic aldehydes, the pinacol coupling reactions of aliphatic
aldehydes are slower. Due to this, not only allylbromide (entries
16, 19, 21, 23, and 25) but also allylchloride (entries 17, 20, 22,
24, and 26) could be applied to the NH allylation reaction of
different aliphatic aldehydes to afford homoallylic alcohols in good
yields and good enantioselectivities, albeit with longer reaction time.
The present catalyst system proved to be quite tolerable to changes
in steric effect (entries 8 and 10 in comparison to 3, entries 25 and
26 in comparison to 16) and in electron density effect (entries 5
and 6 for electron-withdrawing groups, entries 7-9 for electron-
donating groups in comparison to 3). We achieved good yields and
over 95% ee with other aryl aldehydes as well (entries 11-13).
Additionally, an R,â-unsaturated aldehyde also proved to be a good
substrate (entry 14).
To further explore the substrate scope, more allylic bromides
were used in the NH allylation of aldehydes. Surprisingly, the
observed diastereoselectivity of the crotylation of benzaldehyde was
high with a 4.4:1 ratio favoring anti-product in 84% yield with
97% ee for both anti and syn forms (entry 1, Table 2). The
crotylation of cyclohexanecarboxaldehyde gave out the homoallylic
alcohols with a 6.3:1 ratio of anti to syn in 73% yield with 96% ee
(anti form) and 97% ee (syn form) (entry 5). When the size of R
was decreased, lower diastereoselectivities were observed with
higher yield and similar enantioselectivities (entry 6 in comparison
to 5). More interestingly, when the size of R′ was increased, higher
diastereoselectivities were observed with only a slight decrease of
yields and enantioselectivities (entries 3 and 4 in comparison to
2). To the best of our knowledge, the observed diastereoselectivities
and the enantiomeric excesses for each diastereomer of those
aldehydes are the highest to date in an asymmetric crotylation using
a Cr(II)-based system.3g,m
(3) (a) Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A. Angew.
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Nakajima, K.; Demeke, D.; Kang, F.; Jun, H.; Wan, Z.; Kishi, Y. Org.
Lett. 2002, 4, 4435-4438. (e) Lombardo, M.; Licciulli, S.; Morganti, S.;
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H.; Nakada, M. Synlett 2003, 570-572. (i) Berkessel, A.; Schro˜der, M.;
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(4) Asymmetric allylations using a Cr(II)-based system not via a catalytic
process: (a) Cazes, B.; Verniere, C.; Gore´, J. Synth. Commun. 1983, 13,
73-79. (b) Chen, C.; Tagami, K.; Kishi, Y. J. Org. Chem. 1995, 60,
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(6) By replacing TESCl with TMSCl or PhMe2SiCl, homoallylic alcohol with
lower yield and lower enantiomeric excesses was obtained.
(7) Wadamoto, M.; Ozasa, N.; Yanagisawa, A.; Yamamoto, H. J. Org. Chem.
2003, 68, 5593-5601.
(8) Nishio, K.; Kobayashi, S. J. Org. Chem. 1994, 59, 6620-6628.
(9) For example, refs 3g and 3m (90 and 94% ee for PhCHO, respectively)
in comparison to entry 4 in Table 1 (99% ee for PhCHO); refs 3g and 3m
(93 and 89% ee for c-C6H11CHO, respectively) in comparison to entry
18 in Table 1 (98% ee for c-C6H11CHO).
(10) For example, ref 3g (10 mol % CrCl3 and 30 mol % chiral ligand) and
ref 3m (5 mol % CrCl3 and 10 mol % chiral ligand) in comparison to
entry 1 in Table 1 (0.5 mol % TBOxCr(III)Cl).
(11) For example, ref 3m (2.3:1 ratio favoring anti-product with 91% ee for
the anti form and 95% ee for the syn form) in comparison to entries 1
and 2 in Table 2.
(12) The reaction proceeds through cis-â chromium complex via the possible
transition structures shown below.
In summary, TBOxCr(III)Cl was shown to efficiently catalyze
the asymmetric NH allylation reaction of both aromatic and aliphatic
aldehydes. (1) Excellent enantioselectivities (up to 99% ee) for the
NH allylation reaction of aldehydes were obtained.9 (2) The lowest
catalyst/substrate ratio (0.5 mol %) for an asymmetric catalytic NH
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