Ruthenium-catalysed synthesis of fluorinated bicyclic amino esters through tandem carbene addition/cyclopropanation of enynes

Abstract

The reaction of fluorinated 1,6- and 1,7-enynes, containing the moiety N(PG)C(CF 3)(CO 2R), with diazo compounds in the presence of [RuCl(cod)(Cp*)] (cod=cycloocta-1,5-diene, Cp*=C 5Me 5, PG=protecting group) as the catalyst precursor leads to the formation of fluorinated 3-azabicyclo[3.1.0]hexane-2-carboxylates and 4-azabicyclo-[4.1.0]heptane-3-carboxylates. This catalytic transformation was applied to various protecting groups and has proved to be a selective and a general synthetic tool to form constrained proline or homoproline derivatives in good yields. Z stereoselectivity of the created alkenyl group is obtained with N 2CHSiMe 3, whereas N 2CHCO 2Et favours selectively the E configuration for the same double bond. The diastereoselectivity exo/endo depends on the size of the created ring. The X-ray structures of two products have been determined, showing the stereochemistry of the compounds. The reaction can be understood by initial [2+2] addition of the Ru=CHY bond, generated from diazoalkane, with the C≡CH bond of the enyne leading to a key bicyclic ruthenacyclobutane, which promotes the cyclopropanation, rather than metathesis. This selective formation of bicyclic [n.1.0] compounds results from the ruthenium-catalysed creation of three carbon-carbon bonds in a single step under mild conditions. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.