Lewis-Acid-Catalyzed Oxa-Michael Addition to Give α-Diazo-β-alkoxy Carbonyls and Tetrahydro-3H-furo[3,4-c]pyrazoles

Abstract

The conjugate addition of alcohols to vinyl diazonium ions formed via Zn(OTf) 2 -catalysis gives α-diazo-βalkoxy carbonyls. The diazo group is retained in this reaction, and this process is an efficient way to couple a reactive partner to the diazo fragment. As an example, we disclose that addition of allyl alcohols provides tetrahydro-3H-furo [3,4-c]pyrazoles via an addition/cycloaddition sequence. This two-step sequence provides good yields and good diastereoselectivity of these sterically hindered pyrazoline scaffolds with up to three quaternary centers and four stereogenic centers. These products can be elaborated to cyclopropane-fused tetrahydrofurans upon liberation of nitrogen. The reaction conditions are mild, operationally simple, and avoid the use of expensive transition metal catalysts.

Lewis acid mediated allylation of vinyl diazonium ions by allylstannanes

“…We recently reported that vinyl diazonium ions generated by treating α-diazo-β-hydroxy carbonyls with Lewis acids (Scheme 1A) readily serve as activated electrophiles in conjugate addition reactions with enoxysilane, indole and alcohol nucleophiles (Scheme 1, eqn (B) and (C)). [13][14][15][16][17] These bond forming reactions proceed in high yield and the diazo functional group is maintained over the course of these reactions giving access to more complex diazo containing scaffolds that can be taken advantage of in subsequent transformations. For example, allyl alcohols add to vinyl diazonium ions to give tetrahydro-3H-furo [3,4-c]pyrazoles via an addition/cycloaddition sequence.…”

“…For example, allyl alcohols add to vinyl diazonium ions to give tetrahydro-3 H -furo[3,4- c ]pyrazoles via an addition/cycloaddition sequence. 17 In view of the importance of allylation reactions, we sought to develop a reaction that would deliver an allyl nucleophile to the β position of a vinyl diazonium ion to give a more functional group rich α-diazo-β-allyl carbonyl product. In this paper we describe the results of these studies.…”

“…In this case, the diazo alcohol starting material itself acted as a competitive nucleophile giving 16% yield of the bis-diazo ether product ( 7b ), which we have observed before in other systems. 17 A similar alkyl system that has a silyl ether protecting group distal to the reaction center gave allylation product 8 in moderate yield. In this case the lower yield was at least partially due to loss of material during a difficult separation from small amounts of unidentified byproducts.…”

Origins of Diastereoselectivity in the Addition of Enoxysilanes to Vinyl Diazonium Salts

“…We recently showed that vinyl diazonium salts ( 2 , Scheme ) generated from readily available α-diazo-β-hydroxy carbonyls ( 1 ) under mild Lewis acid catalysis are strong electrophiles that will react productively at the β-position with a variety of nucleophiles. − Of these, the addition of silyl enol ethers is notable in that it is similar to a Mukaiyama-Michael addition but provides 2-diazo-1,5-diketone ( 3 ) products in high yields. These diazo products can be used to make a variety of structurally complex substituted furans (e.g., 4 ) …”