1,2- vs 1,4-Addition of Acylbenzotriazoles to α,β-Unsaturated Aldehydes and Ketones. A Novel Route to 3-Alkyl-4,6-diaryl-3,4-dihydropyran-2-ones

Abstract

Lithiation of aliphatic 1-acylbenzotriazoles with subsequent reaction with alpha,beta-unsaturated ketones and aldehydes affords either 3,4,6-trisubstituted 3,4-dihydropyran-2-ones or 1,3-dienes depending on the carbonyl reagent used. Substituent effects on product yield and isomer ratio are discussed.

1,2,3-Triazoles

“…A similar addition of anions derived from acylbenzotriazoles 949 to cinnamaldehydes provide unstable β-lactones that undergo spontaneous ring opening and decarboxylation to dienes 952 (a mixture of ( E,E ) and ( E,Z ) isomers). However, in the case of chalcones, the nucleophilic attack goes on the β-carbon atom to yield 3,4-dihydropyran-2-ones 953 , via intramolecular acylation of the oxygen atom in anionic intermediates 950 <2002JOC3104> .

Scheme 157

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N‐Heterocyclic Carbene Catalysis as a Tool for Gaining Access to the 3,4‐Dihydropyran‐2‐one Skeleton

“…In 1997, Kobayashi12 reported the first example, followed by Katritzky 13. Mukayama utilized chiral quaternary ammonium phenoxides derived from chinchona alkaloids in a new organocatalysed Michael process under phase‐transfer conditions 14.…”

N-TFA-Gly-Bt-Based Stereoselective Synthesis of Substituted 3-Amino Tetrahydro-2H-pyran-2-ones via an Organocatalyzed Cascade Process

“…N -Acyl derivatives of benzotriazole (COBt) are known as powerful acylating agents and have found widespread application in organic synthesis . Although the strong electron-withdrawing properties of the Bt group can significantly increase the acidity of hydrogen atom at the α-position, only a few studies focused on the α-functionalization of COBts. , Katritzky et al reported a fascinating formation of polysubstituted 3,4-dihydropyran-2-ones or 1,3-dienes by intramolecular cyclization of lithium enolates of N -acylbenzotriazoles to α,β-unsaturated carbonyl compounds in good yields and up to 20:1 dr . Barbas et al found the first organocatalyzed asymmetric α-functionalization of 4-nitrobenzyl COBt to yield the product with low chiral induction (20% ee).…”

“…33 Although the strong electron-withdrawing properties of the Bt group can significantly increase the acidity of hydrogen atom at the αposition, only a few studies focused on the α-functionalization of COBts. 34,35 yields and up to 20:1 dr. 36 Barbas et al found the first organocatalyzed asymmetric α-functionalization of 4-nitrobenzyl COBt to yield the product with low chiral induction (20% ee). We report herein an efficient organocatalyzed asymmetric cascade reaction with N-TFA glycine Bt and α,βunsaturated aldehydes as the substrates affording chiral 3,4,6-trisubstituted tetrahydro-2H-pyran-2-ones in up to 65% overall yield and 99% ee (Scheme 1E).…”