Stereocontrolled synthesis and functionalization of cyclobutanes and cyclobutanones.

In the last decade a certain number of new cyclobutane and cyclobutanone synthesis and functionalization protocols have been published. Organo- and biocatalyzed eco-friendly approaches to cyclobutane-containing molecules have been developed with interesting results. Also, successful new total synthesis of bioactive compounds and drugs have been recently reported where a four membered ring represented the key intermediate. Therefore, the rising interest in this field represents a great point of discussion for the scientific community, disclosing the synthetic potential of strained four membered ring carbocyclic compounds. Herein we report a critical survey on the literature concerning the enantiocontrolled synthesis and functionalization of cyclobutane derivatives, with particular attention to metal-free, low impact methodologies, published during the period 2000-2013.

Catalytic enantioselective Amadori-Heyns rearrangement of racemic α-hydroxy ketones with arylamines: synthesis of optically active α-arylamino ketones.

A novel synthesis of optically active α-arylamino ketones through an organocatalytic enantioselective Amadori-Heyns rearrangement is described.

Very high stereoselectivity in organocatalyzed desymmetrizing aldol reactions of 3-substituted cyclobutanones.

N-Phenylsulfonyl (S)-proline catalyzes the direct aldol reaction of 3-substituted cyclobutanones and aryl aldehydes in good yield and with excellent diastereoselectivity and enantioselectivity. This desymmetrization process provides highly functionalized cyclobutanones with control over three contiguous stereogenic centers.

Organocatalytic asymmetric tandem condensation-intramolecular rearrangement-protonation: an approach to optically active α-amino thioester derivatives.

An unprecedented and conceptually novel chiral Brønsted base/Brønsted acid catalytic method for the enantioselective synthesis of α-amino thioesters through a tandem condensation-intramolecular rearrangement-protonation has been developed which provides a number of important synthetic building blocks in good yield and with moderate to good enantioselectivities.