A convenient synthesis of functionalized isoxazolines and related 5-hydroxyisoxazolidine-4-carboxylates

The effectiveness of Sc(OTf)₃ as a Lewis acid catalyst for the 1,4-addition reaction of carbamates to appropriate 2-acetyl-2-pentenoic esters is herein reported. In particular, N-benzyl-(tert-butyldimethylsilyloxy)carbamate added efficiently to the title substrates to afford a new class of polyfunctionalized isoxazolidines and isoxazolines.     

Me2Zn mediated, tert-butylhydroperoxide promoted, catalytic enantioselective Reformatsky reaction with aldehydes

A practical and highly enantioselective catalytic Reformatsky reaction with aldehydes using a cheap, commercially available aminoalcohol as ligand is described.     

Synthesis and biological evaluation of azido- and aziridino-hydroxyl-beta-lactams through stereo- and regioselective epoxide ring opening

Two new classes of azido- and aziridino-hydroxyl-beta-lactam containing structures have been prepared by means of a stereo- and regioselective epoxide ring opening. The straightforwardness of the procedure makes this strategy useful for the synthesis of potentially bioactive compounds. Some selected examples showed promising activity in acyl CoA-cholesterol acyltransferase inhibition assays.     

Iron-catalyzed [3 + 2] annulation of aminocyclopropanes with aldehydes: stereoselective synthesis of aminotetrahydrofurans

The first method for the [3 + 2] annulation of donor-acceptor aminocyclopropanes with aldehydes is reported. The reaction is catalyzed by iron trichloride on alumina in yields up to 99% and with excellent cis selectivities (up to >20:1) and represents a stereoselective and atom economic access to valuable 2-aminotetrahydrofurans, which constitute the core of DNA and RNA.     

Formal homo-Nazarov and other cyclization reactions of activated cyclopropanes

The Nazarov cyclization of divinyl ketones gives access to cyclopentenones. Replacing one of the vinyl groups by a cyclopropane leads to a formal homo‐Nazarov process for the synthesis of cyclohexenones. In contrast to the Nazarov reaction, the cyclization of vinyl‐cyclopropyl ketones is a stepwise process, often requiring harsh conditions. Herein, we describe two different approaches for further polarization of the three‐membered ring of vinyl‐cyclopropyl ketones to allow the formal homo‐Nazarov reaction under mild catalytic conditions. In the first approach, the introduction of an ester group α to the carbonyl on the cyclopropane gave a more than tenfold increase in reaction rate, allowing us to extend the scope of the reaction to non‐electron‐rich aryl donor substituents in the β position to the carbonyl on the cyclopropane. In this case, a proof of principle for asymmetric induction could be achieved using chiral Lewis acid catalysts. In the second approach, heteroatoms, especially nitrogen, were introduced β to the carbonyl on the cyclopropane. In this case, the reaction was especially successful when the vinyl group was replaced by an indole heterocycle. With a free indole, the formal homo‐Nazarov cyclization on the C3 position of indole was observed using a copper catalyst. In contrast, a new cyclization reaction on the N1 position was observed with Brønsted acid catalysts. Both reactions were applied to the synthesis of natural alkaloids. Preliminary investigations on the rationalization of the observed regioselectivity are also reported.     

Organocatalytic Stereoselective α‐Alkylation of Aldehydes with Stable Carbocations

The organocatalytic stereoselective alkylation of aldehydes is carried out with the four stable carbocations 1 , 2 , 3 , 4 in the presence of a catalytic amount (20 mol%) of MacMillan imidazolidinones 5 , 6 . In all reactions, lutidine was used as a base. The alkylation reactions are investigated at different temperatures with linear and branched aldehydes. In the case of carbocation tropylium fluoroborate, an interesting reversal of alkylation product configuration was observed, which is driven by entropic effects in the reaction. The absolute configuration of the products obtained is determined by chemical correlation and found to be in general agreement with the model proposed by MacMillan to justify the stereoselectivity obtained in the reactions promoted by catalysts of type 5 , 6 .     

Copper-promoted enantioselective Reformatsky-type reaction with ketones

Controlled living polymerization of a broad range of monomers is a radical process known as ATRP (atom transfer radical polymerization) and is mediated by a variety of metals. A complex of copper has been found to be the most efficient catalyst, with a copper(I)/copper(II) catalytic cycle. The radical, enantioselective catalytic Reformatsky reaction mediated by Me₂Zn can be efficiently promoted by copper(I) complexes avoiding the use of other promoters such as air and oxidant, giving more reproducible and affordable conditions. The CuCN-mediated enantioselective addition of ethyliodoacetate to functionalized ketones is described in this paper.