Premium
Cyclopropanation of Enantiopure Metal Alkenyl Carbenes with 2‐Methoxyfuran: A Practical Route to Carboxycyclopropylglycine Precursors
Author(s) -
Barluenga José,
de Prado Ana,
Santamaría Javier,
Tomás Miguel
Publication year - 2007
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.200601332
Subject(s) - enantiopure drug , cyclopropanation , cyclopropane , carbene , enantioselective synthesis , chemistry , nucleophile , combinatorial chemistry , reactivity (psychology) , organic chemistry , medicinal chemistry , ring (chemistry) , stereochemistry , catalysis , medicine , alternative medicine , pathology
We have examined the reactivity of enantiopure alkenyl Fischer carbene complexes 1 , readily available from the chiral pool, with 2‐methoxyfuran 4 . In this reaction, polyfunctionalised cyclopropylcarbenes 5 are obtained under very mild conditions and with high selectivity, the major stereoisomer being isolated in an enantiopure form. The reaction involves the conjugate nucleophilic addition of 2‐methoxyfuran 4 to the carbene complexes 1 followed by ring closure of the resulting zwitterionic intermediate species. The oxidation of the carbene 5 a results in the formation of the enantiopure cyclopropane diester 6 . Further elaboration of the cyclopropane 6 allows for an efficient enantioselective access to alcohols or diols 7 – 9 as well as to cyclopropanecarbaldehydes 10 – 12 . The protocol described herein provides a very simple entry to interesting enantiopure precursors of carboxycyclopropylglycine derivatives from readily available starting materials. In order to test this potential as carboxycyclopropylglycine precursors, the aminocyanation of the cyclopropanecarbaldehyde 10 was undertaken and the α‐aminocyano derivative 13 was isolated as a single diastereosiomer.