Pyridyl alcohol, chiral, Asymmetric

Shibata T, Mraioka H, Tanji S, Hayase T, KodakaY, Soai K(1996) Enantioselective synthesis of chiral 5-carbamoyl-3-pyridyl alcohols by asymmetric autocatalytic reaction. Tetrahedron Lett 37 8783-8786. doi 10.1016/S0040 39(96)02031-X... 

Scheme 3 Asymmetric autocatalysis of a chiral pyridyl alcohol...

In 1972, Tsuchihashi disclosed that the carbanion (28 Ar = p-tolyl), generated from (/ )-methyl p-tolyl sulfoxide with lithium diethylamide, adds to benzaldehyde or a-tetialone to give an adduct (29) in a dia-stereomeric ratio of 50 50 or 64 36, respectively. Additions of this carbanion to various unsymmetrical ketones are also reported to be poorly diastereoselective (for example, EtCOMe 50 50, Bu COMe 55 45, Bu COPh 70 30). Note that in the case of Ar = 2-pyridyl a chiral sulfinyl group increases the asymmetric induction observed in the addition of the corresponding carbanion to carbonyl compounds (PhCHO 80 20, R-C9H19CHO 70 30). Since diastereomer pairs of (29) are separable, chromatographic separation followed by reductive desulfurization with Raney Ni provides a method for obtaining optically active alcohols (30 Scheme 9). 

Oguni has reported asymmetric amplification [12] ((-i-)-NLE) in an asymmetric carbonyl addition reaction of dialkylzinc reagents catalyzed by chiral ami-noalcohols such as l-piperidino-3,3-dimethyl-2-butanol (PDB) (Eq. (7.1)) [13]. Noyori et al. have reported a highly efficient aminoalcohol catalyst, 2S)-3-exo-(dimethylamino)isobomeol (DAIB) [14] and a beautiful investigation of asymmetric amplification in view of the stability and lower catalytic activity of the het-ero-chiral dimer of the zinc aminoalcohol catalyst than the homo-chiral dimer (Fig. 7-5). We have reported a positive non-linear effect in a carbonyl-ene reaction [15] with glyoxylate catalyzed by binaphthol (binol)-derived chiral titanium complex (Eq. (7.2)) [10]. Bolm has also reported (-i-)-NLE in the 1,4-addition reaction of dialkylzinc by the catalysis of nickel complex with pyridyl alcohols [16]. 

During the past two decades the homogeneous and heterogeneous catalytic enan-hoselective addition of organozinc compounds to aldehydes has attracted much attention because of its potential in the preparation of optically active secondary alcohols [69]. Chiral amino alcohols (such as prolinol) and titanium complexes of chiral diols (such as TADDOL and BINOL) have proved to be very effective chiral catalysts for such reactions. The important early examples included Bolm s flexible chiral pyridyl alcohol-cored dendrimers [70], Seebach s chiral TADDOL-cored Frechet-type dendrimers [28], Yoshida s BINOL-cored Frechet-type dendrimers [71] and Pu s structurally rigid and optically active BlNOL-functionalized dendrimers [72]. All of these dendrimers were used successfully in the asymmetric addition of diethylzinc (or allyltributylstannane) to aldehydes. 

Bohn and co-workers also studied diethylzinc addition to benzaldehyde with soluble polymeric catalysts [10]. Dendritic chiral catalysts consisting of poly(benzyl ethers) and chiral pyridyl alcohols (3) were used as organocatalysts for the asymmetric C-C linkage reaction. The enantiocontrol by the dendritic systems was slightly lower than that of the parent pyridyl alcohols (2-3% drop in ee) but the conversion toward the chiral secondary alcohol was actually slightly higher for the largest dendritic catalyst (84% versus 80% yield after 3 h of reaction time). In more... 

Fu reported the enantioselective addition of diphenylzinc to ketones catalyzed by chiral amino alcohol 6, and observed a slight asymmetric amplification [13]. Bolm also reported asymmetric amplification in enantioselective alkylations using diethylzinc promoted by a chiral 2-pyridyl alkanol 7 and (1-hydroxy sulfoximine 8 (Scheme 9.6) [14,15]. 

In the course of the continuing study [9a,b] on the enantioselective addition of dialkylzincs to aldehydes by using chiral amino alcohols such as diphenyl(l-methyl-2-pyrrolidinyl)methanol (45) (DPMPM) [48] A. A -dibutylnorephedrine 46 (DBNE) [49], and 2-pyrrolidinyl-l-phenyl-1-propanol (47) [50] as chiral catalysts, Soai et al. reacted pyridine-3-carbaldehyde (48) with dialkylzincs using (lS,2/ )-DBNE 46, which gave the corresponding chiral pyridyl alkanols 49 with 74-86% ee (Scheme 9.24) [51]. The reaction with aldehyde 48 proceeded more rapidly (1 h) than that with benzaldehyde (16 h), which indicates that the product (zinc alkoxide of pyridyl alkanol) also catalyzes the reaction to produce itself. This observation led them to search for an asymmetric autocatalysis by using chiral pyridyl alkanol. 

Asymmetric Diek-Alder Reactions The first efficient asymmetric synthesis of 7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylate by a highly diastereoselective fiiran Diels-Alder reaction was reported in 1986 by Koizumi and coworkers [47]. When the optically active 3-(2-pyridyl-sulfinyl)acrylate (S)s-54 was used as the chiral dienophUe, a mixture of endo- and exo-cycloadducts 55 and 56 was obtained in 69% combined isolated yield. With both isomers, high diastereoselectivities were encountered. The major endo) isomer could be readily transformed into the enan-tiomericaUy pure alcohol 57. Even higher diastereoselectivities (dr > 98 2) were found for the nitro-substituted analog (i.e., 58) [48]. Due to the enhanced reactivity of this dien-... 

---