Cyrille Kouklovsky

Regio‐ and Stereochemical Studies on the Nitroso‐Diels–Alder Reaction with 1,2‐Disubstituted Dienes

The regioselectivity of the nitroso-Diels-Alder reaction between unsymmetrical acyclic dienes and Boc-nitroso (Boc=tert-butoxycarbonyl) reagent or the Wightman chiral chloronitroso reagents has been studied. With the Boc-nitroso reagent, the selectivity is a consequence of steric effects at the C1-position in the diene and electronic effects at the C2-position in the diene. The combination of an unprotected hydroxyethyl side chain at C1 and an electron-withdrawing group at C2 allows complete regioselectivity in favour of the proximal isomer. The same isomer was obtained exclusively with the chiral nitroso reagent with high enantioselectivities. A model based on steric effects is proposed.

Cyanomethylene cyclopropane, a useful dipolarophile and dienophile in [2+3] and [2+4] cycloadditions

Abstract Cyanomethylene cyclopropane, prepared for the first time on large scale, proved to be a reactive dipolarophile and dienophile in several cycloadditions. The reactivity of this compound has been compared with 3-methyl-2-butenenitrile, ethyl 3-methyl-2-butenoate and ethoxycarbonylmethylene cyclopropane.

Oxazoline- N -oxide mediated asymmetric cycloadditions. Recent progress in the stereo-selective syntheses of β -lactones and β -lactams

Camphor-derived oxazoline-N-oxides are versatile dipoles in a new kind of asymmetric [2+3] cycloadditions. Recent applications of this methodology allowed the stereoselective syntheses of several b-lactones natural products such as 1233A and tetrahydrolipstatine. Two formal syntheses of b-lactams antibiotics, b-methyl thienamycin and carpetimycin A, have also been achieved using this type of cycloaddition.

Synthesis of Oxaspirannic Building Blocks by Regioselective Nitroso‐Diels–Alder Reactions

Spirocyclic structures: Nitroso-Diels-Alder reactions of 1,3-disubstituted cyclohexadienes were found to be regiodivergent, depending on the nitroso derivative used. Cycloaddition with Wightmans chloronitroso derivative was totally regio- and stereoselective. This methodology was applied to the synthesis of heterospiranic frameworks after N-O bond cleavage and cyclization (see scheme; Boc=tert-butoxycarbonyl, Tf=trifluoromethanesulfonyl).

Oxazoline N-Oxide Mediated [3+2] Cycloadditions: Application to a Formal Synthesis of a (+)-β-Methylcarbapenem

[3+2] Cycloaddition between a camphor-derived oxazoline N-oxide 9 and the γ,δ-unsaturated enamino ester 11 afforded the single adduct 6. A stereoselective reduction of the enamino ester side chain allowed the control of the absolute configuration of the two additional asymmetric centres. Nitrogen protection and oxidative hydrolysis of the resulting product 13, followed by further functional group manipulations, led to the β-lactam derivative 1, a known precursor of the β-methylthienamycin derivative2a.

CCDC 1575356: Experimental Crystal Structure Determination

Related Article: Dmytro Ryzhakov, Maxime Jarret, Regis Guillot, Cyrille Kouklovsky, and Guillaume Vincent|2017|Org.Lett.|19|6336|doi:10.1021/acs.orglett.7b03155