Structural optimization of enantiopure 2-cyclialkylamino-2-aryl-1,1-diphenylethanols as catalytic ligands for enantioselective additions to aldehydes.

The structural optimization of a family of modular, enantiopure beta-amino alcohol ligands with a common 2-amino-2-aryl-1,1-diphenylethanol skeleton, whose stereogenicity was introduced through the Jacobsen epoxidation of 1,1-diphenyl-2-arylethylenes, has led to the identification of a small set of optimal catalysts with enhanced activity and enantioselectivity in the addition of alkylzinc and arylzinc reagents to aldehydes. Criteria for the discrimination between apparently analogous, highly enantioselective ligands are proposed.

Mechanistic studies on the conversion of dicobalt octacarbonyl into colloidal cobalt nanoparticles.

In situ ATR-FTIR monitoring has allowed the direct study of the effect of additives (trioctylphosphine oxide [TOPO] and oleic acid) on the kinetics and rate of the thermal decomposition of dicobalt octacarbonyl leading to the formation of colloidal cobalt nanoparticles (CoCNPs). The study has shown that additives usually considered as simple surfactants influence the rate and kinetics of the decomposition of dicobalt octacarbonyl. Several of the initial intermediates connecting Co2(CO)8 with CoCNPs have been identified, and a tentative mechanism for the formation of the colloidal nanoparticles has been proposed.

Synthesis of heavily substituted 1,2-amino alcohols in enantiomerically pure form.

[reaction: see text] A simple and convenient methodology for the preparation of optically pure 2-amino-2-aryl-1,1-diphenylethanols is presented. Allylamine was found to produce the ring-opening of triaryloxiranes in a regioselective and a stereospecific fashion. Removal of the allyl protecting group provided the free 1,2-amino alcohols in enantiomerically pure form.

Polystyrene-supported (R)-2-piperazino-1,1,2-triphenylethanol: a readily available supported ligand with unparalleled catalytic activity and enantioselectivity.

A very active and highly enantioselective catalytic resin, designed for minimal perturbation of the catalytic center by the polymer matrix, has been assembled in two steps from (S)-triphenylethylene oxide, piperazine, and Merrifield resin and tested in the enantioselective ethylation of aldehydes. 1-Arylpropanols of 94-95% ee are obtained in high yield by the use of only 2 mol % of catalytic resin at 0 degrees C for 4 h.

2-Piperidino-1,1,2-triphenylethanol: a highly effective catalyst for the enantioselective arylation of aldehydes.

Here we report the use of 2-piperidino-1,2,2-triphenylethanol (5) as an outstanding catalyst for the ligand-catalyzed arylation of aldehydes. The use of 5 and a 2/1 mixture of Et(2)Zn/Ph(2)Zn provided the corresponding chiral diarylcarbinols with enantiomeric excess of up to 99% ee. The effect of temperature on the reaction enantioselectivity was studied and the inversion temperature (T(inv)) was determined to be 10 degrees C for reaction with p-tolylaldehyde. Most remarkably, lowering the amount of catalyst (5) to 0.5 mol % still afforded excellent levels of enantiocontrol (93.7% ee). Kinetics of the catalyzed and uncatalyzed arylation of aldehydes was studied by means of in situ FT-IR. The background uncatalyzed addition rates to p-tolylaldehyde when using pure Ph(2)Zn and Et(2)Zn/Ph(2)Zn (2/1) suggest that in the latter case a mixed zinc species forms (EtPhZn) minimizing the undesired nonselective addition. Formation of EtPhZn was modeled at the DFT calculation level. A four-center TS (TS-V) corresponding to the Et/Ph scrambling was localized along with two dimers (D-IV and D-VI). The model supports the hypothesis that Et/Ph exchange is a kinetically facile process. Gas evolution experiments during the formation of the active catalyst showed that the formation of an active site with a ONZn-Et (10) moiety is kinetically favored over ONZn-Ph (11). Finally, the phenyl transfer to benzaldehyde was modeled at the PM3(tm) level through anti and syn 5/4/4 tricyclic TS structures for both 10 and 11. The model could correctly predict the sense and selectivity of the overall process and predicted that 11 should be more selective than 10.

New silica-immobilized chiral amino alcohol for the enantioselective addition of diethylzinc to benzaldehyde.

[reaction: see text] A readily available chiral amino alcohol has been immobilized on silica by sol-gel synthesis and grafting. The solid prepared according to the latter method led to the best enantioselectivity (77% ee) described for the asymmetric addition of diethylzinc to benzaldehyde using inorganic solids.

Addition of diethylzinc to dicobalt hexacarbonyl complexes of alpha,beta-acetylenic aldehydes with virtually complete enantioselectivity. A formal synthesis of (+)-incrustoporin.

[reaction: see text] The addition of diethylzinc to dicobalt hexacarbonyl complexes of acetylenes mediated by (R)-2-piperidino-1,1,2-triphenylethanol takes place with very high enantioselectivity (96-99% ee) to afford the S enantiomers of dicobalt hexacarbonyl complexes of 1-alkynyl-1-propanols. The utility of this process is exemplified by the development of a short, highly enantioselective (99% ee) synthesis of unnatural incrustoporin.

A Superior, Readily Available Enantiopure Ligand for the Catalytic Enantioselective Addition of Diethylzinc to alpha-Substituted Aldehydes.

The lithium perchlorate-induced ring opening of (S)-triphenylethylene oxide (3) with secondary amines (piperidine (a), N-methylpiperazine (b), N-phenylpiperazine (c) and morpholine (d)) takes place in a stereospecific and completely regioselective manner to afford (R)-2-(dialkylamino)-1,1,2-triphenylethanols (4a-d). These amino alcohols catalytically induce the addition of diethylzinc to benzaldehyde with high enantioselectivity at 0 degrees C and at room temperature. Ligand 4a, which provides the highest enantioselectivity at 0 degrees C, has been studied in the addition of Et(2)Zn to a family of 20 representative aliphatic and aromatic aldehydes 5a-t. For a 17-membered set of alpha-substituted substrates (5a-m,q-t), including ortho-, meta-, and para-substituted benzaldehydes, the naphthaldehydes, alpha,beta-unsaturated and aliphatic (cyclic and acyclic) aldehydes, the mean enantiomeric excess of the resulting alcohols 6a-m,q-t is 97%, whereas for three alpha-unsubstituted specimens (5n-p) the addition takes place with an enantioselectivity of 92-93%.