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Enantioselective Synthesis of cis ‐1,2‐Disubstituted Cyclopentanes and Cyclohexanes by Suzuki–Miyaura Cross‐Coupling and Iridium‐Catalyzed Asymmetric Hydrogenation
Author(s) -
Schumacher Andreas,
Schrems Marcus G.,
Pfaltz Andreas
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.201102650
Subject(s) - asymmetric hydrogenation , cyclopentanes , enantioselective synthesis , chemistry , trifluoromethanesulfonate , iridium , cyclopentene , cyclohexanes , catalysis , yield (engineering) , metathesis , organic chemistry , medicinal chemistry , combinatorial chemistry , polymerization , materials science , polymer , metallurgy
Abstract A series of 1,2‐disubstituted cyclohexene derivatives was prepared through Suzuki–Miyaura cross‐coupling of 2‐bromo‐1‐cyclohexenecarbaldehyde or 2‐carbomethoxy‐1‐cyclohexen‐1‐yl triflate with arylboronates. These tetra‐substituted cyclic alkenes were subjected to Ir‐catalyzed asymmetric hydrogenation. In this way cis ‐1‐methoxymethyl‐2‐arylcyclohexanes were obtained in high yield with excellent enantio‐ and diastereoselectivities (up to >99 % ee , >99 % cis ) by using phosphinomethyloxazolines as ligands. Asymmetric hydrogenation of analogous cyclopentene derivatives, prepared by Suzuki–Miyaura cross‐coupling, proved to be more difficult and proceeded with lower enantioselectivities of up to 88 % ee . The synthetic potential of this cross‐coupling/asymmetric‐hydrogenation strategy was demonstrated by an enantioselective route to chiral hexahydrofluorenones.