Development of Asymmetric Cyclopentane Annulation Utilizing the Characteristics of Heteroatoms

1995 Fiscal Year Final Research Report Summary

• Project/Area Number: 06672091
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Chemical pharmacy
• Research Institution: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• Principal Investigator: TAKEDA Kei Toyama Med. & Pharm. Univ., Fac. of Pharm. Sci., Lecturer, 薬学部, 講師 (30135032)
• Project Period (FY): 1994 – 1995
• Keywords: Cyclopentane annulation / [3+2] Annulation / Asymmetric synthesis / Catalytic asymmetric synthesis / 0rostanoids / Clavulones

Research Abstract

An extension of the [3+2] annulation using beta-heteroatom-substituted acryloylsilanes developed by our group to an asymmetric version was investigated. Reaction of acryloylsilanes, bearing an optically active oxazolinylmethylthio group at their beta-position, with lithium enolate of alkyl methyl ketones afforded separable diastereomeric cyclopentenols in acceptable diasteroselectivities. The cyclopentenol could be transformed into enantiomerically pure 4-hydroxycyclopentenone, a basic structure in biologically active prostanoids. Catalytic asymmetric [3+2] annulation using commercially available chiral ligands such as sparteine and bisoxazoline derivatives proved possible although the observed enantiomeric excess was not high yet.
This annulation has been successfully applied to the syntheses of clavulone II and clavulone III which is antitumor marine prostanoids.
In the course of the study on the cyclopentane annulation, we discovered an efficient and stereospecific [3+4] annulation, which has been achieved by using (E)-(beta-(trimethylsilyl) acryloyl)-silane in combination with alkenyl methyl ketone enolate, affording novel, highly functionalized cycloheptenones in a straightforward manner.