We describe a tandem Mitsunobu/3,3-sigmatropic rearrangement of allylic azides on a chiral auxiliary system that favors one regioisomer thanks to its exceptional steric bias. The sequence may be completed by the oxidative cleavage of the auxiliary or by a ring-closing metathesis reaction that produces a carbo- or heterocycle directly and a recyclable form of the chiral auxiliary. Applications of the methodology to the total synthesis of (+)-coniine, (+)-lentiginosin, and (+)-pumiliotoxin C are reported.
[reaction: see text] The challenging structural features and important biological activity of (+)-compactin (1) explain the substantial synthetic interest that it has generated. We report a novel enantioselective approach to the advanced intermediate 2a, which constitutes a formal synthesis of (+)-1. The sequence utilizes MacMillan's organocatalytic Mukaiyama-Michael reaction, which stereoselectively adds the silyloxyfuran 6 to alpha,beta-unsaturated aldehyde 7. The chirality generated in this reaction guides the formation of the other three consecutive stereocenters found in 2a.
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Azides P 0095Sterically Biased 3,3-Sigmatropic Rearrangement of Chiral Allylic Azides: Application to the Total Syntheses of Alkaloids. -Treatment of allylic alcohols of type (I) with HN3 under Mitsunobu conditions leads to allylic azides which can undergo sigmatropic rearrangement to afford chiral azides of type (II). The configuration of hydroxyl group, geometry of C=C double bond, and nature of substituent R 1 play an important role on the reaction outcome. The allylic azides are versatile building blocks which can smoothly be converted into amino acids [cf. (III)] and alkaloids. -(LAUZON, S.; TREMBLAY, F.; GAGNON, D.; GODBOUT, C.; CHABOT, C.; MERCIER-SHANKS, C.; PERREAULT, S.; DESEVE, H.; SPINO*, C.; J. Org. Chem. 73 (2008) 16, 6239-6250; Dep. Chim., Fac. Sci., Univ. Sherbrooke, Sherbrooke, Que. J1K 2R1, Can.; Eng.) -Jannicke 52-060
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