Masamichi Ogasawara

Rhodium-catalyzed asymmetric 1,4-addition of arylboron reagents to α,β-unsaturated esters

Abstract Reaction of arylboron reagents, arylboronic acids or arylborates, which are readily accessible by lithiation of aryl bromides followed by treatment with trimethoxyborane, with α,β-unsaturated esters in the presence of rhodium/( S )-binap catalyst proceeded with high enantioselectivity to give high yields of optically active β-aryl esters of up to 98% ee. The enantioselectivity depends on the steric bulkiness of the ester moiety.

Rhodium-catalyzed asymmetric 1,4-addition of 2-alkenyl-1,3,2-benzodioxaboroles to α,β-unsaturated ketones

Reaction of 2-alkenyl-1,3,2-benzodioxaboroles, which are readily accessible by hydroboration of alkynes with catecholborane, with α,β-unsaturated ketones in the presence of rhodium(S)-binap catalyst and triethylamine in dioxaneH2O (101) proceeded with high enantioselectivity at 100 °C to give high yields of optically active β-alkenyl ketones of over 90% ee. One pot synthesis of the 1,4-addition product is also successful in the rhodium-catalyzed asymmetric reaction by use of alkenylboranes generated in situ from alkyne and catecholborane.

Rhodium-catalyzed asymmetric 1,4-addition of arylboron compounds generated in situ from aryl bromides

Rhodium-catalyzed asymmetric 1,4-addition to α,β-unsaturated ketones is effected by use of arylborates, generated in situ by lithiation of aryl bromides followed by treatment with trimethoxyborane, to give the corresponding β-aryl ketones of up to 99% ee in high yields. The addition of 1 equiv. (to arylborate) of water is essential for high chemical yields.

Synthesis and application of novel chiral phosphino-oxazoline ligands with 1,1′-binaphthyl skeleton

Abstract C 1 -Symmetric phosphino-oxazolines, ( S,S )- and ( S,R )-2-[4-(isopropyl)oxazol-2-yl]-2′-diphenylphosphino-1,1′-binaphthyl, which possess both phosphine and oxazoline moieties, were prepared from racemic binaphthol and enantiomerically pure ( S )-(+)-2-amino-3-methyl-1-butanol in high yields. Reaction of 1,3-diphenyl-2-propenyl acetate with dimethyl sodiomalonate in the presence of 2 mol% of palladium catalysts bearing the new chiral ligands proceeded with high enantioselectivity to give allylic alkylation products of up to 91% ee.

Enantioselective Synthesis of Planar-Chiral Phosphaferrocenes by Molybdenum-Catalyzed Asymmetric Interannular Ring-Closing Metathesis

Enantioselective synthesis of planar-chiral phosphaferrocenes was realized for the first time by molybdenum-catalyzed asymmetric ring-closing metathesis (ARCM) in up to 99% ee, which is the first application of ARCM to induction of chirality in molecules devoid of stereogenic centers.

Palladium-Catalyzed Synthesis of Endocyclic Allenes and Their Application in Stereoselective [2 + 2]Cycloaddition with Ketenes

Palladium-catalyzed reactions of various 2-bromo-3-exo-methylenecycloalkenes with a stabilized nucleophile were examined. When the carbocycles were nine-membered or larger, the corresponding endocyclic allenes were isolated in excellent yields. In a reaction of the eight-membered cyclic substrate, initial formation of a cycloocta-1,2-diene derivative was detected; however, it dimerized slowly. The seven-membered carbocycle was inert to the reaction. Using a chiral Pd-catalyst, an axially chiral endocyclic allene was obtained in 65% ee. The cyclic allenes were applied to [2 + 2]cycloaddition with ketenes, and the stereoselectivity was studied.

Kinetic Resolution of Planar-Chiral (η6-Arene)Chromium Complexes by Molybdenum-Catalyzed Asymmetric Ring-Closing Metathesis†

Planar-chiral (h-arene)chromium complexes are useful chiral scaffolds in asymmetric synthesis, and have found widespread application as chiral ligands for asymmetric catalysis, or as chiral building blocks for natural product syntheses. Typical methods for the preparation of enantiomerically enriched planar-chiral (arene)chromium species are based either on the optical resolution of racemates or on stereoselective transformations, which include diastereoselective complexation, diastereoor enantioselective ortho-lithiation by utilizing a chiral directing group or a chiral base, and diastereoor enantioselective nucleophilic addition/hydride abstraction. Whereas these methods require a stoichiometric amount of chiral reagents or auxiliaries, asymmetric catalysis is an attractive and effective alternative for preparing optically active (h-arene)chromium complexes. Since the first report on such a catalytic process by Uemura et al. in 1993, only a handful of examples of the desymmetrization of prochiral (arene)chromium substrates have been reported by Gotov and Schmalz, K ndig and co-workers, and Uemura and co-workers 11] . Recently, we reported the preparation of phosphinechelate (h-arene)chromium complexes by Ru-catalyzed ringclosing metathesis. We also demonstrated that Mo-catalyzed asymmetric ring-closing metathesis (ARCM) was highly effective for the asymmetric synthesis of the various planarchiral ferrocenes. Thus, we are interested in controlling the planar chirality of (h-arene)chromium complexes by ARCM. Indeed, the kinetic resolution of racemic (h1,2-disubstituted benzene)chromium complexes proceeds efficiently in the presence of a chiral Mo-alkylidene species to give the planar-chiral chromium complexes with excellent enantiomeric purity. Furthermore, a highly enantiomerically enriched (h-bromoarene)chromium complex that was prepared by using the present method is an excellent precursor to various planar-chiral (arene)chromium derivatives. A (phosphinoarene)chromium species was derived from the (hbromoarene)chromium complex and applied as a chiral ligand in Rh-catalyzed asymmetric reactions, which achieved excellent enantioselectivity of up to 99.5%. The (h-arene)chromium complexes (rac-1) that were used in this study contain an h-(2-substituted alkenylbenzene) ligand, which constructs the planar-chiral environment upon coordination to the chromium atom, and an alkenylphosphine ligand. The chiral catalysts were screened by using racemic [(h-2-methylstyrene)Cr(CO)2(methallyldiphenylphosphine)] (1a) as a prototypical substrate. The asymmetric reactions were carried out in benzene at 40 8C in the presence of an appropriate chiral Mo catalyst (10 mol%), which was generated in situ from the Mo precursor [(pyrrolyl)2Mo(= CHCMe2Ph)(=NC6H3-2,6-iPr2)] and an axially chiral biphenol derivative (Table 1). Under these conditions, the Mo catalyst that was generated with (R)-L1 gave the ARCM product 2 a in 32% yield with an ee value of 79 %, and unreacted 1a was recovered in 66% yield with an ee value of 50% (entry 1). The krel value ([reaction rate of the fastreacting enantiomer]/[reaction rate of the slow-reacting enantiomer]; selectivity factor) for this reaction is estimated to be 14. The Mo catalyst that was generated with (R)-L2 gives better enantioselectivity and the krel value improved to 41 (entry 2). Lowering the temperature worsened the selectivity; the krel value was 12 at 23 8C (entry 3). It was found that the reaction with the Mo catalyst coordinated with (S)-L3 shows excellent enantioselectivity; 2a was obtained in 96 % ee and 44 % yield, and 1a was recovered in 88% ee and 50% yield. The krel value for the reaction is 114 (entry 4), and a nearly perfect kinetic resolution of the two enantiomers of rac-1a was achieved. Considering the structural similarity between L1, L2, and L3, these results are quite surprising and indicate that the slight structural modification to the Mo catalysts affects the enantioselectivity of the asymmetric reaction. After the optimization studies, the Mo/(S)-L3 species was applied to the other substrates. The substrate rac-1b, which has an ethyl substituent in place of the ortho-methyl group in 1a, was also resolved as above. The enantioselectivity and the reaction efficiency (krel = 75 (entry 5)) of the kinetic resolution of rac-1b were still high. Substrate 1 c contains an hbromostyrene ligand. As the bromo substituents in 1c/2c can be easily replaced by other functional groups by standard organic transformations (see below), they serve as versatile precursors to various planar-chiral compounds. The reaction of rac-1c under the optimized conditions afforded complex 2c in 97 % ee and 47% yield. Unreacted 1c was also recovered in 89% ee and 50 % yield. The krel value for this reaction is 198 [*] Prof. M. Ogasawara, S. Arae, Dr. S. Watanabe, Prof. T. Takahashi Catalysis Research Center and Graduate School of Life Science Hokkaido University, Kita-ku, Sapporo 001-0021 (Japan) E-mail: ogasawar@cat.hokudai.ac.jp

Asymmetric hydrogenation of prochiral carboxylic acids catalyzed by the five-coordinate ruthenium(II)-hydride complex [RuH(binap)2]PF6 (binap = (R)- or (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl)

Abstract The five-coordinate complex [RuH(binap)2]PF6 (I, binap = (R)- or (S)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) has been found to have sufficient catalytic activity for asymmetric hydrogenation of itaconic acid and other prochiral carboxylic acids under mild conditions. The catalytic hydrogenation of itaconic acid by I was examined under a variety of conditions, and the addition of triethylamine was found to effect high enantioselectivities (> 90% ee). 1H and 31P NMR examinations of reaction mixtures of I and itaconic acid under conditions similar to the hydrogenation suggested the formation of ruthenium species containing one binap chelate.

Asymmetric transfer hydrogenation of prochiral carboxylic acids catalyzed by a five-coordinate Ru(II)-binap complex☆

Abstract Asymmetric transfer hydrogenation of representative prochiral carboxylic acids was performed, using [RuH(binap) 2 ]PF6 as a catalyst and 2-propanol or ethanol as a hydrogen source.

Asymmetric hydrogenation of prochiral carboxylic acids and functionalized carbonyl compounds catalysed by ruthenium(II)-binap complexes with aryl nitriles (binap = (R)- or (S)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl)

Abstract Complexes RuCl2(ArCN)2(binap), II (binap = (R)- or (S)-2,2′-bis(diphenylphosphino)- 1,1′-binaphthyl; ArCN = benzonitrile, a; 2-furancarbonitrile, b; pentafluorobenzonitrile, c) were prepared, and their solution properties were investigated by 31P NMR measurements. The catalytic activities and enantioselectivities for IIa–c catalysed hydrogenation of some prochiral acids were very similar to those provided by Ru2Cl4(binap)2(NEt3), I. In the hydrogenation of β-functionalized carbonyl compounds, however, IIa–c showed considerably lower activities and/or selectivities, compared with complex I. The differences in IIa–c catalysed reactions are discussed in relation to the coordinating abilities of ArCN in II.