Premium
Regioselective Annulation of 1,5‐Diketones: Access to Functionalized Hagemann’s Esters
Author(s) -
Gassama Abdoulaye,
d’Angelo Jean,
Cavé Christian,
Mahuteau Jacqueline,
Riche Claude
Publication year - 2000
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 - 10.1002/1099-0690(200009)2000:18<3165::aid-ejoc3165>3.0.co;2-7
Subject(s) - annulation , chemistry , regioselectivity , methyl vinyl ketone , michael reaction , cyclohexenone , aldol condensation , adduct , ketone , bicyclic molecule , reagent , enone , organic chemistry , medicinal chemistry , catalysis
The synthesis of the “functionalized” Hagemann’s ester ( S )‐ 18 was investigated. The common starting material in these approaches was enamino ester ( S , Z )‐ 5 , which was prepared through the condensation of keto diester 4 with ( S )‐1‐phenylethylamine. The Michael addition reaction of 5 with methyl vinyl ketone gave the expected adduct ( S )‐ 6 with an ee ⩾ 95%. However, all attempts at annulation of 6 invariably afforded the unwanted cyclohexenone derivatives 7 or 8 . The addition of 5 to Nazarov reagent 9 furnished adduct ( S )‐ 10 with an ee ⩾ 95%. The Triton B‐induced annulation of 10 unexpectedly gave aldol 11 . Depending on the reaction conditions, annulation of 11 afforded either the bicyclic lactone 12 , or cyclohexenones 13 or 15 . An efficient way of reversing the sense of the regiochemistry of the previous annulation was found, based on the use of diethyl 2‐oxo‐3‐vinylphosphonate ( 16 ) as a Michael acceptor. Thus, the condensation of 5 with 16 gave ( S )‐ 17 with an ee ⩾ 95%, and cyclization of ( S )‐ 17 under Horner−Wadsworth−Emmons conditions gave the desired Hagemann’s ester ( S )‐ 18 . The structural assignments for 18 were ascertained by chemical correlation with the known hydrindenedione ( S )‐ 21 .