C O M M U N I C A T I O N S
Scheme 2. Effects of Olefin Structure on Regioselectivitya
hydroacylation.26 In this study, we have developed a regio- and
enantioselective hydroacylation of unstrained terminal and disub-
stituted olefins under mild conditions based on the high directing
potential of coordinating sulfur atoms and by identifying a highly
enantioselective spiro-phosphoramidite ligand, (R)-SIPHOS-PE. Fu-
ture studies will focus on expanding the concepts outlined in this
report to other heteroatom-based and removable directing groups.
Acknowledgment. We thank the University of Toronto, the
Canada Foundation for Innovation, the Ontario Research Fund, the
National Science and Engineering Council of Canada (NSERC),
and Boehringer Ingelheim (Canada) Ltd. for funding. V.M.D. is
grateful for an Alfred P. Sloan Fellowship. M.M.C. is grateful for
an Ontario Graduate Scholarship (OGS). K.G.M.K. is grateful for
an Edwin Walter and Margery Warren Ontario Graduate Scholar-
ship in Science and Technology (OGSST). B.G. is thankful for an
NSERC Undergraduate Student Research Award (USRA).
a Conditions: salicylaldehyde 1a (1.0 equiv), olefin (1.5 equiv),
[Rh(COD)Cl]2 (5 mol %), ligand (10 mol %), K3PO4 (0.2 equiv), CH2Cl2,
40 °C; isolated yields.
Supporting Information Available: Experimental procedures,
characterization data for new compounds, and chiral analyses. This
information is available free of charge via the Internet at http://
pubs.acs.org.
investigated, the resulting hydride intermediates preferentially
undergo hydroacylation via five-membered rhodacycles, rather than
four- or six-membered rings. Thus, 10, which contains chelating
homoallylic sulfide 2a, reacts via five-membered 11 to yield the
branched ketone product. In comparison, 13, which contains allylic
sulfide 8, undergoes hydroacylation via 15, rather than the four-
membered rhodacycle 14, to give the linear product.24,25 The
monodentate phosphoramidite ligands used in this study likely aid
in accommodating the high degree of coordination at Rh from the
double-chelating substrates.
References
(1) Willis, M. C. Chem. ReV. 2010, 110, 725.
(2) (a) Barnhart, R. W.; Wang, X.; Noheda, P.; Bergens, S. H.; Whelan, J.;
Bosnich, B. J. Am. Chem. Soc. 1994, 116, 1821. (b) Kundu, K.; McCullagh,
J. V.; Morehead, A. T., Jr. J. Am. Chem. Soc. 2005, 127, 16042. (c) Coulter,
M. M.; Dornan, P. K.; Dong, V. M. J. Am. Chem. Soc. 2009, 131, 6932,
and references therein.
(3) Stemmler, R. T.; Bolm, C. AdV. Synth. Catal. 2007, 349, 1185.
(4) Phan, D. H. T.; Kou, K. G. M.; Dong, V. M. J. Am. Chem. Soc. 2010, doi:
10.1021/ja107738a.
(5) Osborne, J. D.; Randell-Sly, H. E.; Currie, G. S.; Cowley, A. R.; Willis,
M. C. J. Am. Chem. Soc. 2008, 130, 17232.
Scheme 3. Rationale for Observed Regioselectivitiesa
(6) Shibata, Y.; Tanaka, K. J. Am. Chem. Soc. 2009, 131, 12552.
(7) For a definition of simple olefins as those not belonging to strained or
conjugated systems, see: Tsui, G. C.; Menard, F.; Lautens, M. Org. Lett.
2010, 12, 2456.
(8) Inui, Y.; Tanaka, M.; Imai, M.; Tanaka, K.; Suemune, H. Chem. Pharm.
Bull. 2009, 57, 1158.
(9) (a) Jun, C.-H.; Lee, D.-Y.; Lee, H.; Hong, J.-B. Angew. Chem., Int. Ed.
2000, 39, 3070. (b) Willis, M. C.; McNally, S. J.; Beswick, P. J. Angew.
Chem., Int. Ed. 2004, 43, 340. (c) Roy, A. H.; Lenges, C. P.; Brookhart,
M. J. Am. Chem. Soc. 2007, 129, 2082.
(10) For examples of Rh-catalyzed, branch-selective intermolecular hydroacyl-
ation with dienes, see: (a) Imai, M.; Tanaka, M.; Tanaka, K.; Yamamoto,
Y.; Imai-Ogata, N.; Shimowatari, M.; Nagumo, S.; Kawahara, N.; Suemune,
H. J. Org. Chem. 2004, 69, 1144. With anhydrides and styrene derivatives,
see: (b) Hong, Y.-T.; Barchuk, A.; Krische, M. J. Angew. Chem., Int. Ed.
2006, 45, 6885.
(11) Miura developed the use of salicylaldehyde in intermolecular alkyne
hydroacylation; see: (a) Kokubo, K.; Matsumasa, K.; Miura, M.; Nomura,
M. J. Org. Chem. 1997, 62, 4564. (b) Kokubo, K.; Matsumasa, K.;
Nishinaka, Y.; Miura, M.; Nomura, M. Bull. Chem. Soc. Jpn. 1999, 72,
303.
(12) For pioneering studies on the use of sulfur-containing, chelating hydroa-
cylation substrates, see: (a) Bendorf, H. D.; Colella, C. M.; Dixon, E. C.;
Marchetti, M.; Matukonis, A. N.; Musselman, J. D.; Tiley, T. A.
Tetrahedron Lett. 2002, 43, 7031. (b) Reference 9b.
(13) For other uses of chiral mono- and diphosphine spiro ligands in asymmetric
catalysis, see: Xie, J.-H.; Zhou, Q.-L. Acc. Chem. Res. 2008, 41, 581.
(14) See the Supporting Information for complete details on ligand screening.
(15) Olefin 2a and related substrates were tested in Rh-catalyzed hydroformyl-
ation reactions in an attempt to generate branched regioisomers, but
regioselectivities were moderate; see: Campi, E. M.; Jackson, W. R.;
Perlmutter, P.; Tasdelen, E. E. Aust. J. Chem. 1993, 46, 995.
(16) In a reaction between 1a and 2a, using the conditions of Table 2, but
without any added base, trace conversion to 3aa (∼2%) was observed
after 48 h.
(17) For a recent application of alkyl aryl sulfides in Ni-catalyzed alkenylative
cross-coupling reactions with Grignard reagents, see: Ishizuka, K.; Seike,
H.; Hatakeyama, T.; Nakamura, M. J. Am. Chem. Soc. 2010, 132, 13117.
(18) For a recent report that demonstrates the effects of silver salts in
enantioselective intramolecular ketone hydroacylation, see: Phan, D. H. T.;
Kim, B.; Dong, V. M. J. Am. Chem. Soc. 2009, 131, 15608.
(19) Willis has used ꢀ-thioacetal-substituted aldehydes as chelating substrates
in intermolecular hydroacylation; see: (a) Willis, M. C.; Randell-Sly, H. E.;
Woodward, R. L.; Currie, G. S. Org. Lett. 2005, 7, 2249. (b) Willis, M. C.;
Randell-Sly, H. E.; Woodward, R. L.; McNally, S. J.; Currie, G. S. J. Org.
Chem. 2006, 71, 5291.
a The aromatic backbone of salicylaldehyde 1a has been omitted.
This regio- and enantioselective intermolecular hydroacylation
reaction does not require high temperatures, which can increase
unwanted decarbonylation pathways. Hydrogenating a precatalyst
or preparing cationic Rh complexes is also not required, thus
rendering the protocol simple to perform. Our study features the
first intermolecular hydroacylation system that concomitantly
addresses all of the aspects of reactivity, regioselectivity, and
enantioselectivity of unstrained, nonconjugated olefins.3-6,8
Heteroatom-based directing groups have been used with great
success to control regioselectivities in many other intermolecular
olefin functionalizations, including the related hydroformylation
reaction, but had yet to be applied in this capacity to intermolecular
9
16332 J. AM. CHEM. SOC. VOL. 132, NO. 46, 2010