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The Synthesis of Long‐Chain α‐Alkyl‐β‐Hydroxy Esters Using Allylic Halides in a Fráter–Seebach Alkylation
Author(s) -
Khan Ashna A.,
Chee Stephanie H.,
Stocker Bridget L.,
Timmer Mattie S. M.
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201101472
Subject(s) - chemistry , alkylation , halide , alkyl , allylic rearrangement , tsuji–trost reaction , reactivity (psychology) , organic chemistry , yield (engineering) , medicinal chemistry , catalysis , medicine , materials science , alternative medicine , pathology , metallurgy
The Fráter–Seebach alkylation is a highly efficient means to diastereoselectively introduce α‐substituents to chiral β‐hydroxy esters, however, the yields of reactions in which longer chain alkyl halides are used can be disappointing. To provide a more robust protocol for the alkylation of β‐hydroxy esters, we prepared a variety of long‐chain allylic iodides with the view that the greater reactivity of the allylic system would lead to enhanced efficiency. Indeed, for all substrates studied, the yield of the α‐alkylation was greatly improved for the unsaturated allylic halides compared to their analogous saturated counterparts. Our methodology thus provides an improved means by which to access a variety of important lipophilic compounds such as mycolic acids, which are found on the cell wall of M. tuberculosis .