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Efficient Solvent‐Free Robinson Annulation Protocols for the Highly Enantioselective Synthesis of the Wieland–Miescher Ketone and Analogues
Author(s) -
Bradshaw Ben,
EtxebarríaJardi Gorka,
Bonjoch Josep,
Viózquez Santiago F.,
Guillena Gabriela,
Nájera Carmen
Publication year - 2009
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200900321
Subject(s) - chemistry , annulation , enantioselective synthesis , ketone , aldol reaction , intramolecular force , organocatalysis , yield (engineering) , organic chemistry , combinatorial chemistry , catalysis , materials science , metallurgy
A highly efficient (93% overall yield) and enantioselective (94% ee ) synthesis of the Wieland–Miescher ketone (10‐g scale) through a solvent‐free Robinson annulation procedure is reported. The process involves only 1 mol% triethylamine as the base in the initial Michael process and the organocatalyst N ‐tosyl‐( S a )‐binam‐ L ‐prolinamide (2 mol%) and benzoic acid (0.5 mol%) for the intramolecular aldol process. This green protocol is applied to a wide range of valuable building block analogues of the Wieland–Miescher ketone (10 examples). Among these, a noteworthy compound for terpene synthesis is the 8a‐allyl derivative, which is prepared in 93% yield and 97% ee in a process allowing the recovery and reutilization of the organocatalyst. Furthermore, a one‐pot, two‐step process has also been developed.