Francesco Secci

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.

Synthesis of P-Stereogenic Phospholene Boranes via Asymmetric Deprotonation and Ring-Closing Metathesis

The first examples of the asymmetric synthesis of P-stereogenic vinylic phospholene boranes are described. The synthetic approach is concise and flexible. The route involves (i) asymmetric deprotonation-allylation of a dimethyl phosphine borane; (ii) telescoped regioselective deprotonation, paraformaldehyde trapping, and hydroxyl group elimination to give a diene; and (iii) ring-closing metathesis.

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.

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.

Disulfide-based metal-free α-sulfanylation of ketones

An eco-friendly methodology for the direct α-sulfanylation of ketones, has been developed. The procedure, based on the use of functionalized diaryldisulfides and catalyzed by D,L-proline, represents a mild and efficient approach for the preparation of α-arylthio-ketones.

Synthesis of functionalized tryptamines by Brønsted acid catalysed cascade reactions

An original synthetic protocol has been developed for the preparation of highly functionalized tryptamines from 2-hydroxycyclobutanone and secondary arylamines via a solvent-free Brønsted acid catalysed two-step reaction sequence.

Tetrazole amides as hydrogen-bonding donor catalysts in the chemoselective oxidation of sulphides and disulphides

The oxidation of organosulphides catalyzed by hydrogen bonding donors deriving from aminotetrazole has been studied. The oxidation reaction was performed in CH2Cl2 solution using TBHP (1.1 eq.) as a versatile and chemoselective new catalyst to sulfoxides. 5 mol.% catalyst loading afforded organosulfoxides with complete conversion and yields around 90–95%. Tetrazole amide derivatives can be easily recovered by simple filtration and reused several times. Reactions were carried out in scales ranging between mg and multigram in order to test the robustness of the process. 1H-NMR studies and DFT calculations were exploited to disclose the role of tetrazole amide–TBHP complexes in the sulphides oxidation reaction as new performing catalysts.

New aminotetrazole derivatives as hydrogen bonding catalysts. A green and selective oxidation of organosulphides with H2O2 in H2O

The oxidation of organosulphides catalysed by hydrogen bonding donors derived from aminotetrazole has been studied. The oxidation reaction was performed in a H2O solution using H2O2 as a versatile, green and chemoselective new approach to sulphoxides. Sulphoxide compounds are obtained in high yields and excellent selectivity through a new and easy to perform oxidation protocol. Aminotetrazole derivatives can be recycled by filtration and reused several times without expensive purification procedures.

Organocatalytic synthesis of optically active aryllactic acid derivatives from β-ketosulfoxides

The organocatalytic synthesis of new α-acyloxy-3-arylpropionic thioesters has been accomplished providing some enantioenriched important aryllactic acid derivatives in good yield and enantioselectivities. GRAPHICAL ABSTRACT

Easy access to trans-2,3-disubstituted cyclobutanones, 2,4,5-trisubstituted 3,6-dihydro-2H-pyrans and cis-substituted phenylcyclopropylsulfones by using the highly versatile 1-phenylsulfenyl- or 1-phenylsulfonyl-cyclopropylketones

The high versatility of 1-phenylsulfenyl- or 1-phenylsulfonyl-cyclopropylketones has been exploited for the regioselective synthesis of trans-2,3-disubstituted cyclobutanones, 2,4,5-trisubstituted 3,6-dihydro-2H-pyrans and cis-2-alkyl- or cis-2-aryl-cyclopropylphenylsulfones.