Yuzo Inouye

Solvent effect in a partial asymmetric synthesis—I

Abstract The cis/trans ratio as well as trans -(−)-( R : R )/(+)-( S : S ) ratio of cyclopropane products in the NaH-catalyzed Michael type condensations of (−)-menthyl chloropropionate with methyl methacrylate, conducted in media of varying dielectric constant, unequivocally showed the dependence of stereoselectivity of the reaction on solvent polarity. The stereochemical results were explicable in terms of electrostatic stabilization and non-bonded interactions in the postulated transition state conformations stabilized by orbital overlap in the rate- and therefore, stereochemistry-determining cyclization step. The solvent effect was also correlated fairly well in quantitative terms by the Kirkwood-Onsager theory.

NADH model reaction. Importance of hydroxy-groups in the asymmetric reduction of ethyl benzoylformate

Ethyl benzoylformate has been reduced with an NADH analogue, N-{(1S)-2-hydroxy-1-[(S)-α-hydroxybenzyl]ethyl}-1-propyl-1,4-dihydronicotinamide, to give (S)-mandelate in 2.9–28.5% e.e. The asymmetric yield was remarkably affected by the amount of magnesium perchlorate present and continuously changed throughout the reaction. The possible functions of hydroxy-groups in the model compound are discussed in the light of the resultant stereochemical outcome.

Role of hydroxyl groups in the stereochemistry of hydrogen transfer from chiral NAD(P)H model to carbonyl

Abstract Asymmetric reduction of α-ketoester with a chiral dihydronicotinamide was significantly affected by chiral aromatic additives, capable of exerting an attractive interaction with dihydropyridine ring, which was further consolidated through with magnesium.

Asymmetric reduction of α-ketoesters with Hantzsch esters (dialkoxycarbonyldihydropyridines)

Single and double asymmetric inductions were achieved by the reduction of pyruvates and benzoylformates with 2,6-dimethyl-3,5-dialkoxycarbonyl-1,4-dihydropyridine in the presence of a mono-ionised zinc species; differentiation is made between enantiotopic faces of the substrate carbonyl by diastereotopic hydrogen, and between diastereotopic faces by equivalent and diastereotopic hydrogen.

The Wittig rearrangement of fluorenyl ethers in two-phase system

Abstract The Wittig rearrangement of fluorenyl ethers by the use of potassium hydroxide as base in solid phase was readily effected by crown ethers and onium salts, while diamines moderately catalyzed the reaction.

Asymmetric reduction of ethyl benzoylformate with chiral NADH model systems: Mechanistic and stereochemical consideration of the reactions based on the complexation properties of the model compounds

Abstract Asymmetric reductions of ethyl benzoylformate were conducted by use of NADH model compounds with C1 or C2 symmetry in the presence of magnesium perchlorate. It was found that NADH model compounds which form 2 : 1 chelation complexes with the magnesium ion showed the dependence of optical yield on the reaction conversion. The stereochemical behaviors of the model compounds were classified into three reaction types on the basis of the component ratio in the chelation complex between the reductants and the magnesium ion.

Asymmetric induction in the allylic rearrangement of chiral amine oxide

The [2,3]-sigmatropic rearrangement of (R)-NN-dimethyl-3-(1-phenyl-phenyl-trans-but-1-enyl)amine oxide to give (S)-O-trans-1-phenyl-but-2-enyl-NN-dimethylhydroxyl-amine was effected thermally with nearly complete transfer of chirality from tetramally carbon to trigonal carbon via a cyclic half-chair transition state conformation.

Asymmetric reduction with L-proline amide derivatives of 1,4-dihydronicotinamide

The magnesium perchlorate-, zinc chloride-, and cobalt chloride-catalysed asymmetric reduction of ethyl benzoylformate with 1,4-dihydronicotinamides carrying an L-proline amide in the 3-carbamoyl side-chain afforded R-mandelate, the asymmetric yields being greatly affected by the catalyst metal species (5–83%).

NADH Model Reaction: Asymmetric Reduction of Non-activated Carbonyl Compounds with N-Anionized Hantzsch Ester

As model compounds for NADH coenzymes, three chiral Hantzsch ester-type dihydro-pyridines were prepared. By their use and 2,6-dimethyl-3,5-dicarbo-( — )-menthoxy-1,4-dihydropyridine that had already been prepared, asymmetric reductions of unactivated prochiral ketones were conducted under the action of alkali metal derivatives at room temperature in a non-polar solvent, and the alcohol product were obtained in a 36~80% chemical yield and 30~60% enantiomeric excess.

Self-immolative asymmetric synthesis in the allylic rearrangement of an optically active amine oxide

Transfer of chirality of tetraco-ordinate nitrogen to carbon atom occurred in the thermal sigmatropic rearrangement of (+)-N-trans-but-2-enyl-N-ethyl-p-toluidine oxide to (+)-O-1-methylprop-2-enyl-N-ethyl-p-tolylhydroxylamine, whose absolute configuration was correlated with (S)-(+)-butan-2-ol.