3
In summary, the preparation of a potentially versatile -
substituted ,-unsaturated lactam is described. The chirality at
the -position of the lactam was established by using a tert-
butanesulfinamide auxiliary. The ,-unsaturated lactam was
efficiently provided by ring-closing methathesis. Ultimately, a
Baylis-Hillman reaction was used to deliver the substitution at
the -position of the ,-unsaturated lactam but had to be
incorporated prior to ring-closing metathesis. We believe that
this method can be applied to synthesize various -substituted
,-unsaturated lactams, which could be valuable precursors
toward natural products and pharmaceutical compounds.
7.
Although the Ellman group reported that allylmagnesium bromide
was added from the Si-face of (S)-tert-butylsulfinyl imine 17 to
deliver 18 (ref 3a), the opposite configuration was later confirmed
by the Nelson group (ref 3b). The Nelson group prepared (R)-
benzamide 19 from both the commercially available (R)-2-amino-
4-pentenoic acid (20) and using Ellman’s method with (S)-tert-
butanesulfinamide. Then, they discovered that the retention time
of both benzamides (19) was identical on chiral HPLC.
Acknowledgments
The authors wish to thank the NIH-NIGMS (R01GM080269-01),
Amgen, and Caltech for financial support. S.-J.H thanks
Fulbright (Foreign Student Program, No. 15111120) and the Ilju
Foundation of Education & Culture (Pre-doctoral Research
Fellowship) for financial support. Dr. Mona Shahgholi (Caltech)
and Naseem Torian (Caltech) are acknowledged for high-
resolution mass spectrometry assistance.
8.
9.
(a) Donohoe, T. J.; Fishlock, L. P.; Procopiou, P. A. Org. Lett.
2008, 10, 285–288. (b) Hoffmann, T.; Lanig, H.; Waibel, R.;
Gmeiner, P. Angew. Chem., Int. Ed. 2001, 40, 3361–3364.
Acidic removal of the silyl and tert-butanesulfinyl groups of 8
followed by carbamate formation with CDI afforded 21. Although
acylation of 21 generated metathesis precursor 22, attempted ring-
closing metathesis with Hoveyda-Grubbs 2nd generation catalyst
to form bicycle 23 led only to double bond isomerization,
generating 24.
Supplementary Material
Supplementary data associated with this article can be found,
in the online version, at XXXXXXXXXXXX.
References and notes
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obtained with Hoveyda-Grubbs 2nd generation catalyst.