Stereoselectivity and generality of the palladium-catalysed cyclopropanation of α,β-unsaturated carboxylic acids derivatized with Oppolzer's sultam

Abstract

A series of a,P-unsaturated carboxylic acids derivatized with camphorsultam 1 as a chiral auxiliary has been stereoselectively cyclopropanated. The selectivity of the reaction produces cyclopropanated products with the 1R.2R absolute configuration as indicated by the optical rotations as well as b y an X-ray structure determination. The temperature dependence of the reaction was studied with three substrates. The highest stereoselectivity was obtained at temperatures above 25 "C. Branching at the a-or P-carbons disfavours complete conversion, and electron-withdrawing substituents at these positions seem to prevent the reaction. The auxiliary was removed b y using titanium(tv) isopropoxide in benzyl alcohol followed b y alkaline hydrolysis of the intermediate ester. The potent 5-HT,, receptor agonist (1 R,2S)-2-(2-hydroxypheny1)-N,N-dipropylcyclopropylamine 13 was synthesized b y this method.Paper 3/0450 1 C

Multigram Synthesis of Heterabicyclo[n.1.0]alkan‐1‐yl Trifluoroborates

“…It should be noted that high reactivity of vinyl boronates 5 bearing a trisubstituted double bond towards diazomethane is not usual since, in our experience, trisubstituted alkenes typically do not react under such conditions [35, 49, 50] . A more detailed study of this phenomenon will be reported in another publication.…”

Tranylcypromine Substituted cis-Hydroxycyclobutylnaphthamides as Potent and Selective Dopamine D3 Receptor Antagonists

“…The optically pure key intermediate (1 S ,2 S )-2-(4-chlorophenyl)cyclopropane-carboxylic acid 24 was prepared according to a reported method. 32 Treatment of the acid chloride 20 with sodium (1 R )-(+)-2,10-camphorsultam afforded the enoyl sultams 21 in excellent yield (>93%). Reaction of 21 with diazomethane in the presence of a catalytic amount of palladium acetate gave a cyclopropanated diastereomeric mixture of (1 R )-(+)-2,10-camphorsultam-(1 S ,2 S )-2-phenylcyclopropane-carboxamide 22 and (1 R )-(+)-2,10-camphorsultam-(1 R ,2 R )-2-phenyl-cyclopropane-carboxamide 23 in a ratio of 7:1.…”

Diastereoselective Cyclopropanation by Using Camphorpyrazolidinone Derived α,β-Unsaturated Amides and Ylide

“…For simple olefin substituent, the Diastereoselectivity is decreased from toluene to acetonitrile. In contrast to the reported method for simple cyclopropanation 26 respectively. The sultam -dimethyl (2o) substrates do not give any product at all.…”