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Ruthenium‐Catalysed Synthesis of Fluorinated Bicyclic Amino Esters through Tandem Carbene Addition/Cyclopropanation of Enynes
Author(s) -
Eckert Matthieu,
Moulin Solenne,
Monnier Florian,
Titanyuk Igor D.,
Osipov Sergey N.,
Roisnel Thierry,
Dérien Sylvie,
Dixneuf Pierre H.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201101209
Subject(s) - cyclopropanation , chemistry , bicyclic molecule , carbene , diazo , ruthenium , moiety , medicinal chemistry , metathesis , stereochemistry , double bond , catalysis , organic chemistry , polymer , polymerization
The reaction of fluorinated 1,6‐ and 1,7‐enynes, containing the moiety N(PG)C(CF 3 )(CO 2 R), with diazo compounds in the presence of [RuCl(cod)(Cp*)] (cod=cycloocta‐1,5‐diene, Cp*=C 5 Me 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 2 CHSiMe 3 , whereas N 2 CHCO 2 Et 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 RuCHY bond, generated from diazoalkane, with the CCH 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.