Gin, Eckelbarger and Wilmot. JACS, 2006, ASAP. DOI: 10.1021/ja063304f.
Ring expansion-action in this latest paper from David Gin, regarding the total synthesis of (-)-deoxyharringtonine, an anti-leukemia alkaloid. Starting from simple starting materials, they created the complex 7,5,5 system very quickly, using the ring-strain inherant in aziridines to open to a 7-member ring via a cyclisation.
This was then N-alkylated with Me3SiCH2I, which permited O-acylation with PivCl. The silyl group was then removed, generating a short-lived nonstabilized azomethine ylide. A stereo- and regioselective 1,3-dipolar cyclisation onto the PhSO2CH=CH2 led to the spiro-pyrrolidine. Phew! An impressive set of steps, creating two rings and completing the carbocyclic core of the target.
Other cool steps include a Yb(OTf)3 mediated mono-acylation of the free diol, and use of SmI2 to remove the sulfonate group. The side-chain (a non-trivial component, which produced in an impressive sequence) was then attached using Yamaguchi conditions, resulting in the desired product. The work is full of interesting reactions, and is a great read.