Total Synthesis Highlights

The dipolar cycloadddition established the requisite stereochemical relationship between the three
contiguous quaternary stereogenic centers of 1. It remained to adjust the functional groups around
the newly-formed carbocyclic ring. Exposure to BF 3 .OEt 2 led to ring opening, followed by
trapping of the intermediate carbocation with the t-butyl ester to give the lactone 13, with
concommitant loss of isobutylene. Hydrolysis and decarboxylation gave the alcohol 14, the acetate
of which was removed by reduction with SmI 2 . The derived enol triflate 15 was reduced to the
alkene, which was deoxygenated by way of the thiolactam 16.
The intramolecular dipolar cycloaddition exemplified by the conversion of 12 to 2 is a specific
representative of a general and powerful approach to indole alkaloids, based on cycloaddition of
an intermediate indole to a dipole or a diene. For more recent work along these lines by Professor
Padwa, see Org. Lett. 2007, 9, 279, and Tetrahedron 2007, 63, 5962,
45. The Overman Synthesis of (-)-Sarain A
Larry E. Overman of the University of California, Irvine has recently (Angew. Chem. Int. Ed. 2006,
45, 2912. ) described the first total synthesis of the antibiotic and antitumor alkaloid (-)-sarain A
(3). The structure of 3 is particularly challenging, with two tertiary amines, one of them attached
to a quaternary center. Note that although sarain A is drawn as the amino aldehyde, in fact the
aldehyde and the proximal amine interact to form zwitterionic species that are difficult to purify.
A key transformation in the assembly of 3 was the intramolecular Mannich cyclization of 1 to 2.
This C-C bond forming reaction established the single carbocyclic ring of 3, while at the same
time constructing with high diastereocontrol the tetraalkylated quaternary center.
The enantiospecific preparation of 1 began with diethyl tartrate 4. The enolate of the derived
oxazoline 5 added with high diastereocontrol to the Z-α,β-unsaturated ester 6 to give 7. The diester
7 included the three continguous stereogenic centers of 8. The details of the conversion of 7 to the
hemiaminal 8 had previously been reported by Professor Overman (J. Org. Chem. 1998, 63,
8096, ; Tetrahedron Lett. 1999, 40, 1273, ; Org. Lett. 2005, 7, 933, ).