Tsutomu Miyake

BINAP-Ru(II) and BINAP-Rh(I)-catalyzed asymmetric hydrogenation of olefins without heteroatom-functionalities

Abstract Asymmetric hydrogenation of 1,1′-disubstituted olefins which have no heteroatom functionalities to allow additional interactions with catalyst centers, have been investigated by use of Ru(II) and Rh(I) complexes of BINAP as catalysts. Enantioselectivities and the sense of asymmetric induction are highly dependent on the structure of substrates and the nature of catalysts. Hydrogenation of 1-methyleneidan (1a), a five-membered methylenecycloalkane, gave the highest optical yield (78%) when Ru(OAc)2((R)-binap) was used as catalyst, while the use of the catalyst system [RhI(cod)]2/(R)-BINAP afforded the highest ees (71–82%) for six-membered analogs, 1-methylenetetralin (4a) and its derivatives. In contrast, hydrogenation of seven-membered analog 7 and acyclic olefins 10 resulted in only moderate enantioselectivities by use of these catalysts. The BINAP-Ru(II) catalyzed hydrogenation exhibited a remarkable dependence of enantioselectivities on solvents, while a large anionic ligand effect was observed for the reaction with the BINAP-Rh(I) system. Based on these experimental results, mechanistic aspects of these asymmetric hydrogenation have been discussed.

Asymmetric hydrogenation of unsaturated carbonyl compounds catalyzed by BINAP-Ru(II) complexes. Enantioselective synthesis of γ-butyrolactones and cyclopentanones

Abstract Asymmetric hydrogenation of 2- and 4-alkylidene-γ-butyrolactones and 2-alkylidenecyclopentanones catalyzed by BINAP—Ru(II) complexes affords the corresponding γ-butyrolactones and cyclopentanones in 94–98% ee. Hydrogenation of (E)- and (Z)-2-propylidene-γ-butyrolactone catalyzed by the same catalyst gave the products with the same absolute configuration and in almost equal enantioselectivities, which shows that olefin geometry does not affect the stereochemistry and enantioselectivity.

An efficient synthesis of optically active 4-methyloxetan-2-one: asymmetric hydrogenation of diketene catalysed by binap–ruthenium(II) complexes [binap = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl]

Highly enantioselective hydrogenation of diketene with the catalytic system derived from {RuCl[(S)- or (R)-binap](benzene)}Cl and triethylamine or with Ru2Cl4[(S)- or (R)-binap]2(NEt3)[binap = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl] in tetrahydrofuran gives optically active 4-methyloxetan-2-one in up to 97% selectivity and 92% enantiomeric excess (e.e.).

Synthesis of a novel chiral 1, 3-benzoxazinone auxiliary and its application to highly diastereoselective aldol reaction

Abstract Condensation of l -menthone with salicylamide followed by isomerization of the adduct withDBU afforded a novel chiral 1, 3-benzoxazinone auxiliary, the usefulness of which was demonstrated by highly diastereoselective aldol reaction with aldehydes.

A facile synthesis of the key intermediate for penems, carbapenems, and related β-lactam antibiotics

Abstract Michael addition of the hydroxylamine 14 to the N-acryloyl-1, 3-benzoxazinone 13 followed by the titanium enolate-mediated aldol reaction with acetaldehyde gave syn-aldol 16 in a high yield with excellent diastereoselectivity. Silylation of 16 followed by treatment with BnOLi and acetylation gave benzyl ester 19 together with the recovered chiral auxiliary 12 both in high yields. Mild hydrogenolysis of 19 furnished the β-amino acid derivative 20 which was transformed into acetoxyazetidinone 3, the key intermediate of penems 1 and carbapenems 2.

A novel synthesis of a key intermediate for penems and carbapenems utilizing lipase-catalyzed kinetic resolution

Abstract Titanium enolate-mediated aldol reaction of N-phthaloyl-β-alanyl-1, 3-benzoxazinone 5 with acetaldehyde gave the (±)-syn-aldol (±)-6 in a high yield with high diastereoselectivity. Lipase-catalyzed hydrolysis of the corresponding laurate (±)-7b furnished enantiomerically pure (2S, 3R)-N-(2-phthaloylaminomethyl-3-hydroxybutyryl)-1,3-benzoxazinone6 in 49% yield. Silylation of the hydroxy group of (2S, 3R)- 6 follwed by deprotection of the amino and carboxy groups gave the β-amino acid derivative 9 which was transformed into the acetoxyazetidinone 3, a key intermediate of penems and carbapenems.