Yulia A. Khomutova

Six-Membered Cyclic Nitronates as 1,3-Dipoles in Formal [3 + 3]-Cycloaddition with Donor–Acceptor Cyclopropanes. Synthesis of New Type of Bicyclic Nitrosoacetals

The first formal [3 + 3]-cycloaddition of nitronates with donor-acceptor cyclopropanes is reported. The reaction is catalyzed by ytterbium trifluoromethanesulfonate and leads to hitherto unknown bicyclic nitrosoacetals, possessing two annelated six-membered rings.

Synthesis of PDE IVb Inhibitors. 1. Asymmetric Synthesis and Stereochemical Assignment of (+)- and (−)-7-[3-(Cyclopentyloxy)-4-methoxyphenyl]hexahydro-3H-pyrrolizin-3-one

Asymmetric synthesis of GlaxoSmithKlines highly potent phosphodiesterase inhibitor 1 has been accomplished in nine steps and 16% overall yield. The original strategy suggested involves as a key step the silylation of enantiopure six-membered cyclic nitronates 4 obtained by a highly stereoselective [4 + 2]-cycloaddition of an appropriate nitroalkene 5 to trans-1-phenyl-2-(vinyloxy)cyclohexane. Functionalization of the resulting 5,6-dihydro-4H-1,2-oxazine and subsequent stereoselective reduction of 1,2-oxazine ring in intermediate 2 furnished the pyrrolizidinone framework with the recovery of chiral auxiliary alcohol.

Synthesis of B,O,N-Doped Adamantanes and Diamantanes by Condensation of Oximes with Boronic Acids.

Condensation of oximes with boronic acids RB(OH)2 or B(OH)3 affords remarkably stable 2,4,10-trioxa-1,5,7-triaza-3-boroadamantanes via an unprecedented multicomponent process. The mechanism involves the reversible generation of unstable oxime cyclotrimers, which are readily intercepted by boronic acids.

Stereoselective Synthesis ofUnnatural β-Amino Acids from Nitroethane via 5,6-Dihydro-4H-1,2-oxazin-3-ylacetates

The reduction of easily available methyl 5,6-dihydro-4H-1,2-oxazin-3-ylacetates provides an efficient route to different diastereomerically pure unnatural β-amino acids. A two-step protocol including reduction of the C=N bond of the initial oxazine with sodium cyanoborohydride during the first step and hydrogenation of the N-O bond during the second step produced the target β-amino acid esters with higher stereoselectivity than obtained with conventional catalytic hydrogenation.

Synthesis of Substituted 5-(3-Hydroxypropyl)pyrrolidin-2-onesand Pyrrolizidinones from Nitroethane via C3 Functionalized 5,6-Dihydro-4H-1,2-oxazines: A Novel Approach to SomeAnalogues of the Antidepressant Rolipram

Easily accessible [(5,6-dihydro-4H-1,2-oxazin-3-yl)methyl]malonates 1 were converted into substituted 5-(3-hydroxypropyl)pyrrolidin-2-ones 2 and pyrrolizidinones 3, which are versatile products and intermediates for organic and bioorganic chemistry. The synthetic sequence suggested includes stereoselective two-step reduction of an oximino fragment, followed by intramolecular cyclization involving one of the CO 2 Me groups and decarboxylation in the last stage. The efficiency of this strategy was demonstrated by the stereoselective synthesis of pyrrolizidinone rac-4, a highly efficient analogue of antidepressant Rolipram, from nitroethane.