Premium
The Carbonyl Group as Homoconjugated Electron‐Releasing Substituent. Regioselective electrophilic additions at bicyclo[2.2.1]hept‐5‐en‐2‐one, bicyclo[2.2.2]oct‐5‐en‐2‐one, and derivatives
Author(s) -
Carrupt PierreAlain,
Vogel Pierre
Publication year - 1989
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19890720519
Subject(s) - chemistry , regioselectivity , substituent , bicyclic molecule , bromide , electrophile , medicinal chemistry , moiety , electrophilic addition , acetic acid , adduct , chloride , stereochemistry , organic chemistry , catalysis
In CHCl 3 , CH 3 CN, or AcOH, benzeneselenenyl chloride (PhSeCl), bromide (PhSeBr), and acetate (PhSeOAc), 2‐nitrobenzenesulfenyl chloride (NO 2 C 6 H 4 SCl), and 2,4‐dinitrobenzenesulfenyl chloride ((NO 2 ) 2 C 6 H 3 SCl) added to bicyclo[2.2.1]hept‐5‐en‐2‐one ( 5 ) in an. anti fashion with complete stereo‐ and regioselectivity, giving adducts 20–24 in which the chloride, bromide, or acetoxy substituent (X) occupies the endo position at C(6) and the Se‐ or S‐substituent (E) the exo position at C(5), The addition 5 + (NO 2 ) 2 C 6 H 3 SCl→ 24 was accompanied by the formation of (1 RS , 2 RS )‐2‐(2,4‐dinitrophenylthio)cyclopent‐3‐ene‐l‐acetic acid ( 25 ). The latter was the major product in AcOH containing LiClO 4 . The additions of PhSeCl and PhSeBr to bicyclo[2.2.2]oct‐5‐en‐2‐one ( 6 ) were less stereoselective (proportion of exo vs. endo mode of electrophilic attack was ca. 3:1) but highly regioselective gazing adducts 27/28 and 29/30 , respectively, the regioselectivity being the same as that of the electrophilic additions of 5 . The reaction of PhSeCl with a 4:1 mixture of 2‐ exo ‐chloro‐ and 2‐ endo ‐chlorobicyclo[2.2.1]hept‐5‐ene‐2‐carbonitriles ( 12 ) was slower than addition 5 + PhSeCl; it gave adducts 31/32 (4:1) in which the PhSe moiety occupies the exo position at C(6) and the Cl atom the endo position at C(5). The addition of PhSeCl to 2‐chlorobicyclo[2.2.1]oct‐5‐ene‐2‐carbonitriles ( 13 ) was very slow and gave adducts with the same regioselectivity as 12 + PhSeCl, but opposite with that of reactions of the corresponding enones 5 and 6 . PhSeX (X = Cl, Br, OAc) added to 2‐cyanobicyclo[2.2.1]hept‐5‐en‐2‐yl acetates ( 14 ) with the same regioselectivity as 12 + PhSeCl. The additions of PhSeCl, PhSeBr, NO 2 C 6 H 4 SCl, and (NO 2 ) 2 C 6 H 3 SCl to 2‐(bicyclo[2.2.1]hept‐5‐en‐2‐ylidene)propanedinitrile ( 49 ) were not regioselective, showing that a dicyanomethylidene function is not like a carbonyl function when homoconjugated with a π system. The results are in agreement with predictions based on MO calculations suggesting that a carbonyl group homoconjugated with an electron‐deficient centre can behave as an electron‐donating, remote substituent because of favourable n(CO)↔σC(1), C(2)↔p(C(6) hyperconjugative interaction.