Diastereoselective ring-rearrangement metathesis to set the stereochemistry of all-carbon quaternary centres

Jingwei Li,Daesung Lee

doi:10.1039/c2sc20812a

Abstract

A highly diastereoselective ring-rearrangement metathesis of cyclopentene derivatives containing all-carbon quaternary centres is reported. This tandem metathesis process provides cyclohexene derivatives with two contiguous stereogenic centres, one of which is an all-carbon quaternary stereogenic centre, in high yields and excellent diastereoselecitivity. The efficacy of this methodology is showcased in the total synthesis of spiropiperidine alkaloid nitramine. In the meantime, it has been found that metathesis of the corresponding acyclic triene derivatives affords the same products with the same level of efficiency and diastereoselectivity.

Highlights

Construction of all-carbon quaternary carbon centres is a 15 significant challenge in organic chemistry
We envision that the merits of this 30 approach could be readily explored utilizing a metathesis-based rearrangement of symmetric cyclopentene moiety to the corresponding cyclohexene derivatives, whereby setting the allcarbon quaternary stereogenic centre can be realized by the configuration of the secondary hydroxyl group (Eq 2)
To explore the diastereoselective RRM (dRRM) as a means to transform a cyclopentene derivative to the corresponding allyl-containing cyclohexene, phenoxydimethylsilyl protected cyclopentene 1f was chosen as an initial test substrate because this compound 30 could be prepared via gold-catalyzed isomerisation of the corresponding dimethylallylsilyl ether of 2-methyl-1-hexen-5-yn3-ol followed by an intramolecular allyl trapping event.7b When 1f was treated with a catalytic amount (5 mol%) of Grubbs second-generation catalyst in dichloromethane under ethylene 35 gas,8 a smooth transformation of 1f to cyclohexene derivative 2f occurred with a marginal level of diastereocontrol and conversion (Table 1, entry 6)

Summary

Introduction

Construction of all-carbon quaternary carbon centres is a 15 significant challenge in organic chemistry. We envision that the merits of this 30 approach could be readily explored utilizing a metathesis-based rearrangement of symmetric cyclopentene moiety to the corresponding cyclohexene derivatives, whereby setting the allcarbon quaternary stereogenic centre can be realized by the configuration of the secondary hydroxyl group (Eq 2). Ring-rearrangement metathesis–based connectivity change the connectivity change ensued in the ring contraction of 5 cyclohexenyl cation I to the corresponding cyclopentenyl oxonium species II (Scheme 1).7 As such, this RRM process indirectly overrides the kinetically-driven connectivity change of I to II by the counteraction of a thermodynamically-driven metathesis process. 20 The utility and effectiveness of this RRM strategy was illustrated by the conversion of the resultant cyclohexene derivatives containing a stereogenic quaternary carbon centre to spiropiperidine alkaloid nitramine We describe an unprecedented diastereoselective RRM (dRRM) that effectively accomplish desymmetrization of cyclopentene moiety containing a nonstereogenic all-carbon quaternary centre. 20 The utility and effectiveness of this RRM strategy was illustrated by the conversion of the resultant cyclohexene derivatives containing a stereogenic quaternary carbon centre to spiropiperidine alkaloid nitramine

Results and Discussion

Mechanism and diastereoselectivity

Metathesis of acyclic substrates containing three terminal alkenes

Conclusions