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Selectivity in the Intermolecular Diels–Alder Reaction of Conjugated Trienes: Experimental and Theoretical Approaches
Author(s) -
Remeur Camille,
Desrat Sandy,
Gandon Vincent,
Roussi Fanny
Publication year - 2018
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.201800472
Subject(s) - chemistry , regioselectivity , intermolecular force , conjugated system , selectivity , organic chemistry , computational chemistry , catalysis , combinatorial chemistry , molecule , polymer
Eleven analogs of the natural product meiogynin A, an inhibitor of proteins of the Bcl‐2 family, have been elaborated by an intermolecular Diels–Alder (DA) reaction of various conjugated chloro‐trienes, in order to determine the influence of the modification of the south part of meiogynin A on its biological activity. The chloro‐trienes were obtained in two to five steps from commercial compounds through a selective hydrochlorination of bromoalkyne intermediates to ( Z )‐1,2‐dihalogenated alkenes followed by a chemoselective Suzuki–Miyaura cross‐coupling. The intermolecular DA reaction of these trienes with two α,β‐unsaturated carboxylic acids as dienophiles occurred with a perfect regioselectivity and good to excellent diastereoselectivities. These selectivities could be rationalized by DFT calculations.