Dynamic Kinetic Resolution Processes Based on the Switchable Configurational Instability of Allenyl Copper Reagents.

The configurational instability of allenyl copper reagents is unveiled. An experimental study highlights the crucial role of Li+ and of the reaction temperature in the control of the configurational stability of allenyl copper reagents. A judicious choice of the reaction conditions allows efficient dynamic kinetic resolution processes and gives a one-pot access to homopropargylic alcohols or amines bearing up to four contiguous defined stereogenic centers.

Diastereodivergent behavior of alkyl versus cyano allenylcuprates toward aldehydes: a key role for lithium.

The stereodivergent behavior of allenyl(cyano)- and allenyl(alkyl)cuprates toward aldehydes, providing a selective preparation of both syn- and anti-homopropargylic alcohols, is described. This study, which combines both experimental and theoretical support, shows that the copper nontransferred "dummy ligand" controls the localization of the lithium cation with respect to the allenylcuprate moiety. As a consequence, Li(+) acts as a Lewis acid activator but also controls the diastereoselectivity during the addition of allenylcuprates onto aldehydes. The combined high selectivity, efficiency, and versatility of these cuprate compounds opens the way to new one-pot synthetic procedures, as illustrated by the combined Klein rearrangement/transmetalation methodology described herein.

Palladium-catalyzed cyclization of unsaturated beta-amino alcohols: a new access to enantiopure bicyclic oxazolidines.

Chiral unsaturated beta-amino alcohols possessing a dialkylamino function cyclize in the presence of Pd(II) catalysts and reoxidants to afford enantiopure bicyclic oxazolidines with total regio- and stereocontrol. The scope and limitations of this transformation have been studied.

Short enantioselective syntheses of trans-5-alkylprolines from new functionalized amino alcohols.

Amino alcohols, having an enol ether function, cyclized in acidic medium to give quantitatively diastereosomerically pure bicyclic compounds that were transformed in five steps in enantiopure trans-5-alkylproline derivatives.

Addition of hetero allenyl copper reagents to aldehydes: scope and behavior.

Cyanocuprates derived from propargylic amines or ethers react with aldehydes to give regioselectively the corresponding anti-homopropargylic alcohols with a high level of diastereoselectivity. Such selectivity could be obtained independently of the nature of the heteroatom (amine or ethers) or the acetylenic substituents. Excellent selectivities can be reached regardless of the aldehydes used, remarkably also with vinylic or acetylenic ones. A reactivity scale for the cuprates bearing different acetylenic substituents was established to be: SiMe3 >Ph> Et. The rate of the addition reaction to aldehydes was also found to be slowed down in the presence of HMPA underlining the crucial role of the Li counterion. DFT calculations have shown that the relationship between the rate and the acetylenic substituent is not connected to a possible metallotropic equilibrium but to the stability of the reactive allenic species compared to the less-stable propargylic isomer.

Addition of a chiral copper reagent derived from propargylic oxazolidininone to aldehydes.

[reaction: see text] The copper reagent arising from an optically pure propargylic oxazolidinone was found to react regio- and diastereoselectively with aldehydes, leading, in a one-pot procedure, to the anti homopropargylic amino alcohols derivatives in good yields.

Copper reagents: a new and efficient solution for the selective addition of metallated propargylic amines to aldehydes.

[reaction: see text] Anti alpha-amino-homopropargylic alcohols are prepared by addition of metallated propargylic amines to aldehydes. Among the four organometallic (LI, Zn, Ti, Cu) derivatives used, the most effective are the copper reagents.

Diastereoselective aldolization of alpha-aminonitriles. Diastereoselective synthesis of beta-amino alcohols and beta,gamma-diamino alcohols.

Aldolization performed by addition of lithiated N-benzyl-N-tert-butylaminoacetonitrile to aldehydes provides diastereomerically pure anti-beta-hydroxy-alpha-aminonitriles. They are transformed into syn,anti-protected beta,gamma-diamino alcohols by a two-step procedure, involving addition of a Grignard reagent and reduction. The cleavage of the N-tert-butyl group is achieved by a simple acidic treatment. The application of this methodology to chiral, nonracemic aldehydes is studied. Starting from D-isopropylideneglyceraldehyde, an anti, anti, syn, anti-(2R,3S,4S,5R,6R)-diaminotriol is prepared in acceptable yield and with a good level of diastereoselectivity.