[reaction: see text] Homochiral alpha-amino acids, heterocycles, and carbocycles are efficiently constructed via a short sequence of reactions starting from the chiral auxiliary p-menthane-3-carboxaldehyde. The key feature of the sequence is a highly selective tandem Mitsunobu/3,3-sigmatropic rearrangement of hydrazoic acid that procures enantiomerically enriched allylic azides. The sequence is either terminated by oxidative cleavage to provide amino acids or by ring-closing metathesis to provide heterocycles or carbocycles bearing nitrogen.
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.
We describe the synthesis of (+)-aspidofractinine, the enantiomer of a naturally occurring alkaloid of the kopsane family. Key features of the synthesis include a stereospecific cyanate to isocyanate rearrangement on a chiral scaffold, a ring-closing alkene metathesis to cleave the chiral auxiliary, and a chemoselective cyclopropanation to introduce the quaternary carbon at position 7 of aspidofractinine.
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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