Journal of the American Chemical Society
Communication
(2) (a) Mao, B.; Geurts, K.; Fananas-Mastral, M.; van Zijl, A. W.;
Fletcher, S. P.; Minnaard, A. J.; Feringa, B. L. Org. Lett. 2011, 13, 948.
For reviews, see: (b) Bandichhor, R.; Nosse, B.; Reiser, O. Top. Curr.
Chem. 2005, 243, 43. (c) Kitson, R. R. A.; Millemaggi, A.; Taylor, R. J.
K. Angew. Chem., Int. Ed. 2009, 48, 9426.
(3) (a) Shen, Z.; Khan, H. A.; Dong, V. M. J. Am. Chem. Soc. 2008,
130, 2916. (b) Shen, Z.; Dornan, P. K.; Khan, H. A.; Woo, T. K.;
Dong, V. M. J. Am. Chem. Soc. 2009, 131, 1077. (c) Phan, D. H. T.;
Kim, B.; Dong, V. M. J. Am. Chem. Soc. 2009, 131, 15608. (d) Khan,
H. A.; Kou, K. G. M.; Dong, V. M. Chem. Sci 2011, 2, 407.
(4) Applying [Rh((S,S,R,R)-Duanphos)NO3] (the catalyst in ref 3c)
for hydroacylation of 4-oxobutyrophenone yielded only the decarbon-
ylation product (unpublished result).
(5) Hydroacylation of 4-oxobutyrophenone with [Rh(dppe)(ace-
tone)2][ClO4] gave a 60% yield of the ketone hydroacylation product
along with a 35% yield of the decarbonylation product. See: Bergens,
S. H.; Fairlie, D. P.; Bosnich, B. Organometallics 1990, 9, 566.
(6) (a) For the use of an NHC to cyclize 2-keto benzaldehydes, see:
Chan, A.; Scheidt, K. A. J. Am. Chem. Soc. 2006, 128, 4558. (b) The
NHC catalyst from ref 6a was not applicable to the cyclization of 4-
oxobutyrophenone. See: Chan, A. Ph.D. Thesis, Northwestern
University, Evanston, IL, 2008. (c) Hydroacylation of 4-oxo-1-
pentanal with RuHCl(CO)(PPh3)3 gave a 32% yield of the ketone
hydroacylation product along with a 55% yield of the aldehyde
dimerization product. See: Omura, S.; Fukuyama, T.; Murakami, H.
O.; Ryu, I. Chem. Commun. 2009, 6741. (d) For the use of iridium
hydrides in the hydroacylation of 2-(2-oxopropyl)benzaldehydes, see:
Suzuki, T.; Yamada, T.; Watanabe, K.; Katoh, T. Bioorg. Med. Chem.
Lett. 2005, 15, 2583. (e) Hsu, J.-L.; Fang, J. J. Org. Chem. 2001, 66,
8573.
were obtained for both electron-rich and -deficient substrates
(96 and 95% ee, respectively; entries 2 and 3). While a
benzofuryl-substituted ketone was cyclized in good yield (entry
5), furyl and alkynyl substrates (entries 6−8) were transformed
with poor efficiency.24 However, introducing a gem-dimethyl
group on the backbone (entries 9−11) promoted cyclization of
these otherwise challenging substrates (55−98% yield, 90% ee).
Finally, we wondered how the ruthenium catalysts would
compare to the cationic rhodium catalysts that our laboratory
previously used to cyclize seven-membered-ring precursors 1
and 2-keto benzaldehydes 2.3a,c For this study, A was chosen as
the catalyst to avoid base-induced aldol reactions, and acetone
was not added because 1 and 2 were already in the aldehyde
oxidation state. While derivatives of 1 and other seven- or eight-
membered-ring precursors were resistant to hydroacylation,25 a
2-keto benzaldehyde derivative underwent efficient hydro-
acylation to generate the corresponding phthalide in 85% yield
with 90% ee (Scheme 2). Thus, the rhodium and ruthenium
catalysts provide complementary scope and mechanistic
pathways for asymmetric ketone hydroacylation.
Scheme 2. Hydroacylation of a 2-Keto Benzaldehyde
(7) A dynamic kinetic resolution reduction/lactonization sequence to
cyclize 1,4-keto esters using Noyori’s ATH catalysts has been
developed. See: Steward, K. M.; Gentry, E. C.; Johnson, J. S. J. Am.
Chem. Soc. 2012, 134, 7329.
(8) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97.
(9) For a review of borrowing hydrogen, see: Dobereiner, G. E.;
Crabtree, R. H. Chem. Rev. 2010, 110, 681.
(10) For in situ oxidation of alcohols to aldehydes in diene and
alkyne hydroacylation protocols under transfer hydrogenation
conditions, see: (a) Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am.
Chem. Soc. 2008, 130, 14120. (b) Williams, V. M.; Leung, J. C.;
Patman, R. L.; Krische, M. J. Tetrahedron 2009, 65, 5024. For a review
of this topic and other C−C bond-forming reactions under transfer
hydrogenation conditions, see: (c) Moran, J.; Krische, M. J. Pure Appl.
Chem. 2012, 84, 1729.
In summary, we have reported a novel strategy for the
asymmetric hydroacylation of 1,4- and 1,5-keto alcohols. The
use of a bifunctional ATH catalyst was crucial to obtain
reactivity at room temperature, chemoselectivity for ketone
hydroacylation over aldehyde dimerization, and high enantio-
selectivity. Although this transformation is oxidative overall, the
reaction was found to be autocatalytic in a reductant (iPrOH)
and inhibited by excess oxidant (acetone). γ-Butyrolactones, δ-
valerolactones, and phthalides are accessible by this method.
ASSOCIATED CONTENT
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(11) An alternative mechanism in which oxidation of the primary
alcohol precedes ketone reduction is possible.
(12) For selected examples of diol oxidation to lactones using metal
hydride catalysts, see: (a) Ito, M.; Osaku, A.; Siibashi, A.; Ikariya, T.
Org. Lett. 2007, 9, 1821. (b) Suzuki, T.; Morita, K.; Tsuchida, M.;
Hiroi, K. Org. Lett. 2002, 4, 2361. (c) Suzuki, T.; Morita, K.; Matsuo,
S
* Supporting Information
Experimental procedures, characterization data for new
compounds, and chiral analyses. This material is available free
Y.; Hiroi, K. Tetrahedron Lett. 2003, 44, 2003. (d) Endo, Y.; Backvall,
̈
AUTHOR INFORMATION
Corresponding Author
Notes
■
J.-E. Chem.Eur. J. 2011, 17, 12596. (e) Maytum, H. C.; Tavassoli, B.;
Williams, J. M. J. Org. Lett. 2007, 9, 4387.
(13) For a review of Ru(PNN) complexes for acylation of secondary
alcohols by esters with dihydrogen liberation and related trans-
formations, see: Gunanathan, C.; Milstein, D. Acc. Chem. Res. 2011, 44,
588.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(14) For a review of olefin hydroacylation catalysts with a focus on
those that do not involve aldehyde C−H oxidative addition, see:
Leung, J. C.; Krische, M. J. Chem. Sci. 2012, 3, 2202.
■
We thank the University of California at Irvine, the Natural
Sciences and Engineering Research Council of Canada
(NSERC), and the University of Toronto for support. S.K.M.
is grateful for a Canada Graduate Scholarship (CGS), and
V.M.D. is grateful for an Eli Lilly Grantee Award.
(15) EtOAc gave the highest enantioselectivity among the various
solvents that were examined. Benzene, toluene, 1,2-dichloroethane,
and acetonitrile gave good reactivity but slightly lower enantiose-
lectivity. Tetrahydrofuran, 1,4-dioxane, and dichloromethane showed
lower reactivity. See the Supporting Information (SI) for details.
(16) The absolute configuration of the lactone was determined by
correlation of the optical rotation with literature data and was the same
as that expected for ATH of the same ketone. See the SI for details.
REFERENCES
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(accessed April 3, 2013).
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dx.doi.org/10.1021/ja4021974 | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX