Highly Efficient Darzens Reactions Mediated by Phosphazene Bases under Mild Conditions

Abstract

The highly basic and poorly nucleophilic phosphazene base P 1t-Bu promotes the Darzens condensation of α-halo esters with aromatic aldehydes affording α,β-epoxy esters in nearly quantitative yields under mild conditions and in short reaction times. The more basic P 4 -t-Bu phosphazene was found useful with low reactivity aldehydes. These reactions can be performed in aprotic organic solvents of low polarity, thus minimizing the hydrolysis of α,β-epoxy esters which often accompanies the base-promoted Darzens condensations.

CuII-Catalyzed cis-Selective Synthesis of Ketoepoxides from Phenacyl Bromides and Water

“…The source of epoxy oxygen was confirmed through the incorporation of O 18 into the product ( O 18 -4a ) on performing the reaction in CH 3 CN–H 2 O 18 (v/v 9:1, eq (iii)). Formation of aldehyde intermediate can’t be concluded during the reaction course because phenacyl bromide ( 1a ) and benzaldehyde ( 3 ) yields trans -epoxide , ( 10 , eq (iv)) to the reaction conditions, which is contrary to our observation, i.e., formation of cis -diastereoisomers. Benzaldehyde is obtained, if only benzyl bromide ( 2a ) is subjected under the reaction conditions for a prolonged time (eq (v)).…”

“…Typical methods of epoxide synthesis include the treatment of alkene with peracids, peroxides, oxone, hypohalides, and others. Like Sharpless and co-workers, other several modifications for face-selective oxygen transfer were developed toward asymmetric epoxidation with chiral catalysts and/or auxiliaries. , Further, base-induced dehydrohalogenation of 1,2-halohydrins, Darzens condensation of aldehydes and α-halocarbonyl/sulfonyl/ester compounds, and insertion of carbine into CO bonds are useful for this purpose. The diastereoselective syntheses of α,β-ketoepoxides are executed using N -heterocyclic carbene (NHC), or organocatalyst and/or base promoted oxidative coupling of styrenes and aldehydes.…”