Abstract
Given its synthetic relevance, the catalytic enantioselective reduction of β,β-disubstituted nitroalkenes has received a great deal of attention. Several bio-, metal-, and organo-catalytic methods have been developed, which however are usually applicable to single classes of nitroalkene substrates. In this paper, we present an account of our previous work on this transformation, which implemented with new disclosures and mechanistic insights results in a very general protocol for nitroalkene reductions. The proposed methodology is characterized by (i) a remarkably broad scope encompassing various nitroalkene classes; (ii) Hantzsch esters as convenient (on a preparative scale) hydrogen surrogates; (iii) a simple and commercially available thiourea as catalyst; (iv) user-friendly procedures. Overall, the proposed protocol gives a practical dimension to the catalytic enantioselective reduction of β,β-disubstituted nitroalkenes, offering a useful and general platform for the preparation of nitroalkanes bearing a stereogenic center at the β-position in a highly enantioenriched form. A transition state model derived from control kinetic experiments combined with literature data is proposed and discussed. This model accounts and justifies the observed experimental results.
Highlights
The enantioselective reduction of pro-chiral β,β-disubstituted nitroalkenes is a powerful synthetic transformation
By slightly varying reaction conditions, we show its application to nitroalkenes 2 [40], 1 and 3, providing a very general and broadly useful protocol for enantioselective transfer hydrogenation reactions of β,β-disubstituted nitroalkenes based on a readily available catalyst
We have presented a very general methodology for organocatalytic enantioselective transfer hydrogenation reactions of β,β-disubstituted nitroalkenes, making use of a simple thiourea catalyst, and Hantzsch esters as convenient hydrogen donors
Summary
The enantioselective reduction of pro-chiral β,β-disubstituted nitroalkenes is a powerful synthetic transformation. It provides a straightforward access to optically active nitroalkanes carrying a configurationally stable stereogenic center at the β-position of the nitro group. These compounds can be converted to broadly useful chiral building blocks (e.g., enantioenriched β-chiral amines) exploiting the renowned synthetic versatility of the nitro moiety [1,2,3]. This reaction has received considerable attention from the synthetic chemistry community, leading to several efficient protocols based on different catalytic approaches and encompassing various nitroalkene substrates. Variations in the aryl and alkyl moieties of substrates 1 have only been partially addressed
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