Iterative deoxypropionate synthesis based on a copper-mediated directed allylic substitution: formal total synthesis of borrelidin (C3-C11 fragment).
A new iterative strategy for the flexible preparation of any oligodeoxypropionate stereoisomer is presented which relies on an o-DPPB-directed copper mediated allylic substitution employing enantiomerically pure Grignard reagents; the reaction is working with perfect control over all aspects of the reaction selectivity. This key C--C bond-forming step features reversed polarity compared with established enolate alkylation methodology. It thus avoids existing problems of enolate alkylation strategies such as enolate reactivity as well as costs and problems associated with the chiral auxiliary. Practicability of this new method is demonstrated through application in natural product syntheses. Thus, an efficient synthesis of the northern part of the angiogenesis inhibitor borrelidin (28), the deoxypropionate building block 27, could be devised, representing a formal total synthesis.
Herber
Christian
C
Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104 Freiburg, Germany.
Breit
Bernhard
B
D000498:Allyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D005233:Fatty Alcohols / Q000138:chemical synthesis; D011422:Propionates / Q000138:chemical synthesis*
D000498:Allyl Compounds; D005233:Fatty Alcohols; D011422:Propionates; C005066:borrelidin; D003300:Copper