C O M M U N I C A T I O N S
Table 3. AHF of 1,2-Disubstituted Olefins with Ligand 1a
ligand preparation and Prof. Tehshik Yoon and co-workers for
access to SFC instrumentation. Funding was provided by the
National Science Foundation (CHE-0715491, graduate fellowship
for G.W.W.), the NIH (R01 GM67163), and Abbott Laboratories
(graduate fellowship for R.I.M.). The NMR facilities at UW-
Madison are funded by the NSF (CHE-9208463, CHE-9629688)
and NIH (RR08389-01).
Supporting Information Available: Experimental details, charac-
terization data, and conditions for the determination of enantiomeric
excess. This material is available free of charge via the Internet at http://
pubs.acs.org.
References
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(6) For additional important reports of the AHF of related substrates, see: (a)
Becker, Y.; Eisenstadt, A.; Stille, J. K. J. Org. Chem. 1980, 45, 2145–
2151. (b) Parrinello, G.; Deschenaux, R.; Stille, J. K. J. Org. Chem. 1986,
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a Conditions: 70 °C, 140 psig syn gas (CO/H2 ) 1:1), [alkene] )
0.75
M in toluene, substrate/Rh ) 200:1, Ligand/Rh ) 1.1:1.
b Determined via 1H NMR spectroscopy. c See Supporting Information
for methods used to determine enantiomeric excess. d A small amount
(6%) of 3-phenyl propanal was observed, presumably arising from
isomerization followed by tautomerization to the aldehyde.
(7) Only one aldehyde was observed via 1H NMR spectroscopy.
(8) Brice, J. L.; Meerdink, J. E.; Stahl, S. S. Org. Lett. 2004, 6, 1845–1848.
(9) For selected recent examples, see: (a) Smith, A. B., III; Beauchamp, T. J.;
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Figure 2. Synthesis of ꢀ3-aminoaldehydes via oxidative amination of
unfunctionalized olefins followed by AHF.
carboxamides, this initial example represents a promising future
direction for the synthesis of ꢀ3-aminoaldehydes.
(10) Reaction conditions: allyloxy-tert-butyldimethylsilane (30 mmol, 4.5 M),
Rh(acac)(CO)2 (3 µmol), 1 (3 µmol), 80 °C, 5 h. The reaction proceeded
with 99% conversion to aldehydes, R:ꢀ ) 1.8:1, 92% ee. The linear
aldehyde can be separated from the branched by flash chromatography to
provide the pure chiral aldehyde with no degradation of enantioenrichment.
(11) For example, see: (a) ref 5c. (b) Sakai, N.; Nozaki, K.; Takaya, H. J. Chem.
Soc., Chem. Commun. 1994, 395–396.
In summary, enantioselective hydroformylation with diazaphos-
pholane ligands enables atom-efficient synthesis of chiral amino-
and alkoxyaldehydes from simple substrates under mild conditions.
These results, together with previously published examples,2,4-6
significantly extend the range of chiral aldeydes that can be
practically and effectively produced by asymmetric hydroformy-
lation and used in the synthesis of more complex organic molecules.
(12) Brice, J. L.; Harang, J. E.; Timokhin, V. I.; Anastasi, N. R.; Stahl, S. S.
J. Am. Chem. Soc. 2005, 127, 2868–2869.
(13) AHF of methyl N-acetamidoacrylate has been demonstrated but was shown
to provide exclusively the internal regioisomer: see ref 6d,e.
(14) Refer to the Supporting Information for the investigation of additional
substrates.
Acknowledgment. We are grateful to Dow Chemical for their
generous donation of Rh(acac)(CO)2 and assistance with large scale
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