C O M M U N I C A T I O N S
Table 2. Stereoselective Insertion of (-)-Phenylmenthyl
Aryldiazoacetates to Aldehydesa
Figure 2. Possible explanation of the observed stereochemistry.
aldehyde by the inversion of the configuration at the diazonium
carbon followed by denitrogenation.
entry
R1
Ar
yieldb (%)
dec (%)
1
3-tolyl
2-tolyl
4-MeOC6H4
4-ClC6H4
Ph
Ph
Ph
Ph
Ph
67
65
42
62f
89
>95
>95
89
>95
87
In summary, we have realized the triflic acid-catalyzed formal
C-C bond insertion of aryldiazoacetates to aldehydes as a means
of constructing an all-carbon quaternary center. Introduction of the
phenylmenthyl moiety as chiral auxiliary allowed the facile access
to a variety of optically active R,R-disubstituted-R-formyl esters.
2
3d
4
5e
6e
7e
Ph
Ph
85
89
94
94
Acknowledgment. This work was partially supported by a
Grant-in-Aid for Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
Supporting Information Available: Experimental details and
characterization data for new compounds. This material is available
8d
9
10
11
4-MeOC6H4
Ph
4-ClC6H4
Ph
4-tolyl
56
85
>95
>95
>95
3-MeOC6H4
3-MeOC6H4
4-ClC6H4
72f
53f
73f
References
a Reactions were performed with aldehyde (1.0 mmol) and phenylmenthyl
aryldiazoacetate (0.2 mmol) in the presence of 20 mol % TfOH (0.040
mmol). b Isolated yield. c Determined by 1H NMR of the crude reaction
mixture. d Performed at -40 °C. e Performed with 1.2 equiv of aldehyde.
f Yield determined after the reduction of the aldehyde.
(1) For selected examples, see: (a) Murakami, M.; Ashida, S. Chem. Commun.
2006, 4599. (b) Murakami, M.; Ashida, S.; Matsuda, T. J. Am. Chem.
Soc. 2005, 127, 6932. (c) Nakao, Y.; Yada, A.; Ebata, S.; Hiyama, T. J.
Am. Chem. Soc. 2007, 129, 2428. (d) Nakao, Y.; Yukawa, T.; Hirata, Y.;
Oda, S.; Satoh, J.; Hiyama, T. J. Am. Chem. Soc. 2006, 128, 7116. (e)
Kondo, T.; Niimi, M.; Nomura, M.; Wada, K.; Mitsudo, T. Tetrahedron
Lett. 2007, 48, 2837.
(2) For a recent example of the formal C-C bond insertion and its application
to the synthesis of natural product, see: (a) Tambar, U. K.; Stoltz, B. M.
J. Am. Chem. Soc. 2005, 127, 5340. (b) Tambar, U. K.; Ebner, D. C.;
Stoltz, B. M. J. Am. Chem. Soc. 2006, 128, 11752.
(3) (a) Kano, T.; Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2006, 128,
2174. (b) Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2007, 129,
10054. (c) Hashimoto, T.; Naganawa, Y.; Kano, T.; Maruoka, K. Chem.
Commun. 2007, 5143.
(4) (a) Mahmood, S. J.; Hossain, M. M. J. Org. Chem. 1998, 63, 3333. (b)
Dudley, M. E.; Morshed, Md. M.; Brennan, C. L.; Islam, M. S.; Ahmad,
M. S.; Atuu, M.-R.; Branstetter, B.; Hossain, M. M. J. Org. Chem. 2004,
69, 7599. (c) Kanemasa, S.; Kanai, T.; Araki, T.; Wada, E. Tetrahedron
Lett. 1999, 40, 5055.
(5) (a) Holmquist, C. R.; Roskamp, E. J. J. Org. Chem. 1989, 54, 3258. (b)
Holmquist, C. R.; Roskamp, E. J. Tetrahedron Lett. 1992, 33, 1131. (c)
Padwa, A.; Hornbuckle, S. F.; Zhang, Z.; Zhi, Li. J. Org. Chem. 1990,
55, 5297.
(6) Isolated examples using 6-diazopenicillanate and aldehydes, see: (a)
Sheehan, J. C; Chacko, E.; Lo, Y. S.; Ponzi, D. R., Sato, E. J. Org. Chem.
1978, 43, 4856. (b) Sheehan, J. C.; Nakajima, K.; Chacko, E. Heterocycles
1979, 13, 227. (c) Karady, S.; Amanto, J. S.; Reamer, R. A.; Weinstock,
L. M. J. Am. Chem. Soc. 1981, 103, 6765. (d) Jephcote, V. J.; Jowett, I.
C.; John, D. I.; Edwards, P. D.; Luk, K.; Slawin, A. M.; Williams, D. J.
J. Chem. Soc., Perkin Trans. 1 1986, 2187. (e) Jephcote, V. J.; John, D.
I. J. Chem. Soc., Perkin Trans. 1 1986, 2203.
Figure 1. Ortep representation of (-)-phenylmenthyl R-phenyl-R-(2-tolyl)-
R-formyl ester with elipsoids shown at 50% probability level. Hydrogen
atoms are omitted for clarity.
of the substituent and substitution pattern, the desired product could
be obtained in moderate yields with high stereoinduction. The major
limitation we found during this study was the inapplicability of
o-substituted aryldiazoacetate.
The absolute configuration of the newly generated all-carbon
quaternary stereocenter was unambiguously confirmed by X-ray
crystallographic analysis of R-phenyl-R-(2-tolyl)-R-formyl ester
(Table 2, entry 2) as shown in Figure 1.
The possible pathway that accounts for this observed stereo-
chemistry is shown in Figure 2. The key asymmetric induction step
is thought to be the first addition of the electronegative R-carbon
of aryldiazoacetate to aldehyde. Effective shielding of one diaste-
reotopic face of aryldiazoacetate might be realized by the phenyl
group of the chiral auxiliary. The intermediate diazonium salt would
then rearrange into the product via migration of R1 group of
(7) For reviews on the asymmetric synthesis of quaternary carbon centers,
see: (a) Trost, B. M.; Jiang, C. Synthesis 2006, 369. (b) Christoffers, J.;
Baro, A. AdV. Synth. Catal. 2005, 347, 1473. (c) Christoffers, J., Baro,
A., Eds. Quaternary Stereocenters: Challenges and Solutions for Organic
Synthesis; Wiley-VCH: Weinheim, Germany, 2005. (d) Douglas, C. J.;
Overman, L. E. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5363.
(8) For the recent examples of asymmetric insertion of X-H bond to
diazoacetates, see: (a) Lee, E. C.; Fu, G. C. J. Am. Chem. Soc. 2007,
129, 12066. (b) Maier, T. C.; Fu, G. C. J. Am. Chem. Soc. 2006, 128,
4594. (c) Chen, C.; Zhu, S.-F.; Liu, B.; Wang, L.-X.; Zhou, Q.-L. J. Am.
Chem. Soc. 2007, 129, 12616. (d) Liu, B.; Zhu, S.-F.; Zhang, W.; Chen,
C.; Zhou, Q.-L. J. Am. Chem. Soc. 2007, 129, 5834. (e) Davies, H. M.
L.; Hansen, T.; Churchill, M. R. J. Am. Chem. Soc. 2000, 122, 3063.
(9) Whitesell, J. K. Chem. ReV. 1992, 92, 953.
(10) Corey, E. J.; Ensley, H. E. J. Am. Chem. Soc. 1975, 97, 6908.
JA710532J
9
J. AM. CHEM. SOC. VOL. 130, NO. 8, 2008 2435