Catalytic asymmetric cyano-ethoxycarbonylation reaction of aldehydes using a YLi3 tris(binaphthoxide) (YLB) complex: mechanism and roles of achiral additives

Full details of a catalytic asymmetric cyano-ethoxycarbonylation reaction promoted by a heterobimetallic YLi3 tris(binaphthoxide) complex (YLB 1), especially mechanistic studies, are described. In the cyanation reaction of aldehydes with ethyl cyanoformate, three achiral additives, H2O, tris(2,6-dimethoxyphenyl)phosphine oxide (3a), and BuLi, were required to achieve high reactivity and enantioselectivity (up to >99% yield and up to 98% ee). The roles of achiral additives and the reaction pathway were investigated in detail. In situ IR analysis revealed that the initiation step to generate LiCN from H2O, BuLi, and ethyl cyanoformate is rather slow. On the basis of mechanistic studies of the initiation step to generate an active nucleophilic species, reaction conditions were optimized by using a catalytic amount of acetone cyanohydrin as an initiator. Under the optimized conditions, the induction period decreased and the reaction completed within 9 min using 5 mol % YLB at -78 degrees C. Catalyst loading was successfully reduced to 1 mol %. Kinetic experiments and evaluation of the substituent effects of phosphine oxide revealed that phosphine oxide had beneficial effects on both the reaction rate and the enantioselectivity. The putative active species as well as the catalytic cycle of the reaction are also discussed.     

Catalytic asymmetric allylation of aldehydes via a chiral indium(III) complex

A chiral indium complex has been discovered to effect high enantioselectivities in the addition of allyltributyl stannanes to aldehydes. The allylation of a variety of aromatic, alpha,beta-unsaturated and aliphatic aldehydes resulted in good yields and high enantioselectivities (90-96% ee).     

Catalytic asymmetric allylation of aldehydes using the chiral (salen)chromium(III) complexes

The enantioselective addition of allylstannanes to glyoxylates and glyoxals, as well as simple aromatic and aliphatic aldehydes, catalyzed by chiral (salen)Cr(III) complexes, has been studied. The reaction proceeded smoothly for the reactive 2-oxoaldehydes and allyltributyltin in the presence of small amounts (1-2 mol %) of (salen)Cr(III)BF₄ (1b) under mild, undemanding conditions. However, in the case of other simple aldehydes, the use of high-pressure conditions is required to obtain good yields. Classic chromium catalyst 1b, easily prepared from the commercially available chloride complex 1a, affords homoallylic alcohols usually in good yield and with enantiomeric purity of 50-79% ee. The stereochemical results are rationalized on the basis of the proposed model.     

Catalytic asymmetric hydrogenation of aldehydes

Racemic alpha-arylaldehydes provide the corresponding primary alcohols via dynamic kinetic resolution in excellent enantioselectivities and yields upon hydrogenation using a Noyori ruthenium catalyst; for example, the biologically active (S)-enantiomer of the non-steroidal anti-inflammatory drug ibuprofen could be synthesized via catalytic enantioselective hydrogenation of aldehyde followed by oxidation with potassium permanganate in 76% isolated yield and 96 : 4 er.     

Catalytic asymmetric intramolecular alpha-alkylation of aldehydes

The development of a general catalytic asymmetric aldehyde alpha-alkylation reaction constitutes a major challenge in organic synthesis. Here, we report the first and successful approach toward its solution: (S)-alpha-methyl proline catalyzes the intramolecular alkylation of various halo aldehydes to the corresponding formyl cyclopentanes, -cyclopropanes, or -pyrrolidines in excellent yields and enantioselectivities. Most remarkably, racemization, aldolization, or catalyst alkylation do not occur to any significant extend, further illustrating the power, mildness, and profound selectivity of enamine catalysis.     

Catalytic asymmetric Michael reactions using a chiral rhodium complex

Catalytic asymmetric Michael reaction of β-keto esters and methyl vinyl ketone was achieved using a chiral diamine-based Rh complex to give the Michael adducts in up to 75% e.e.     

Catalytic asymmetric hydrogenation of cyclic anhydrides using ruthenium (II) chiral phosphine complex

Optically active γ- and δ-lactones are obtained by the hydrogenation of five- and six-membered cyclic anhydrides using a Ru(II) complex with chiral phosphine ligand, DIOP, as a catalyst.     

Catalytic enantioselective allylation of aldehydes via a moisture-tolerant chiral BINOL-In(III) complex

A moisture-tolerant chiral indium complex has been developed to effect good enantioselectivities in the addition of allyltributylstannanes to aldehydes. The allylation of a variety of aromatic, α,β-unsaturated and aliphatic aldehydes resulted in both moderate to good yields and high enantioselectivities (up to 86% ee).     

A novel bifunctional Ti(IV) complex catalyzed asymmetric silylcyanation of aldehydes

A novel Lewis acid and Lewis base bifunctional Ti(IV) complex was formed in situ upon the treatment of ligand (R)‐3,3′‐bis(diphenylphosphinoyl)‐BINOL with Ti(PrO‐i)₄, which is proven to be an efficient catalyst in the asymmetric trimethylsilylcyanation of aldehydes. The corresponding cyanohydrins were obtained in high to excellent chemical yield (83–93%) albeit with moderate enantioselectivities (up to 51% enantiomeric excess). © 2010 Wiley Periodicals, Inc. Heteroatom Chem 22:31–35, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20652     

Catalytic asymmetric Henry reactions of silyl nitronates with aldehydes

A catalytic enantioselective Henry reaction of silyl nitronates with aldehydes has been developed. Different chiral Lewis acids have been tested for the reaction and it has been found that a variety of chiral copper-ligand complexes can catalyze the Henry reaction. The best yield, diastereo- and enantioselectivity of the nitroalcohols formed are obtained by the application of a copper(II)-diphenyl-bisoxazoline complex as the catalyst in the presence of tetrabutylammonium triphenylsilyldifluorosilicate (TBAT). In order to minimize the epimerization of the nitroaldol products they were converted into the corresponding Mosher esters. The reaction proceeds well for different aromatic aldehydes reacting with alkyl nitronates.     

Catalytic, asymmetric trans-selective hetero Diels-Alder reactions using a chiral zirconium complex

[reaction: see text] The first catalytic, asymmetric 2,3-trans-selective hetero Diels-Alder reaction has been developed. The reactions of aldehydes with Danishefsky's dienes proceeded smoothly to afford the pyranone derivatives in high yields with high trans-selectivities and enantioselectivities in the presence of a chiral zirconium complex, which was prepared from zirconium tert-butoxide and (R)-3,3'-diiodobinaphthol or its derivatives, primary alcohol, and a small amount of water. This reaction was applied to the concise synthesis of (+)-prelactone C.     

Catalytic enantioselective allylation of aldehydes via a chiral indium(III) complex in ionic liquids

The ionic liquid [hmim][PF₆] has been demonstrated as an efficient and environmentally-friendly reaction medium for the enantioselective allylation of aldehydes via a chiral indium(III) complex. The allylation of a variety of aromatic, α,β-unsaturated and aliphatic aldehydes resulted in moderate to good yields and enantioselectivities (upto 92% ee).     

Catalytic asymmetric oxidative lactonizations of meso-diols using a chiral iridium complex

A chiral amino alcohol/Ir complex catalyzes the asymmetric oxidative lactonizations of meso-diols to give the corresponding lactones in up to 81% ee.     

Catalytic asymmetric reductive amination of aldehydes via dynamic kinetic resolution

A novel organocatalytic asymmetric reductive amination of aldehydes has been developed. Treating racemic alpha-branched aldehydes with p-anisidine and a Hantzsch ester in the presence of our previously developed phosphoric acid catalyst, TRIP, gave beta-branched secondary amines in excellent yields and enantioselectivities via an efficient dynamic kinetic resolution. The process is applicable to several different aromatic aldehydes and amines but gives slightly reduced enantiomeric ratios with aliphatic aldehydes.