Allylic enantioselective isomerization

The disclosure, in 1982, that cationic, enantiopure BINAP-Rh(i) complexes can induce highly enantioselective isomerizations of allylic amines in THF or acetone, at or below room temperature, to afford optically active enamines in >95 % yield and >95 % ee, thus constituted a major breakthrough.67-68 This important discovery emerged from an impressive collaborative effort between chemists representing Osaka University, the Takasago Corporation, the Institute for Molecular Science at Okazaki, Japan, and Nagoya University. BINAP, 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (Scheme 7), is a fully arylated, chiral diphosphine which was introduced in... 

Takasago A catalytic process for the enantioselective isomerization of allylic amines. The catalyst is a chiral rhodium complex. Used in the manufacture of (-)menthol. Named after Takasago International Corporation, the Japanese company which commercialized the process in 1983. 

Although the asymmetric isomerization of allylamines has been successfully accomplished by the use of a cationic rhodium(l)/BINAP complex, the corresponding reaction starting from allylic alcohols has had a limited success. In principle, the enantioselective isomerization of allylic alcohols to optically active aldehydes is more advantageous because of its high atom economy, which can eliminate the hydrolysis step of the corresponding enamines obtained by the isomerization of allylamines (Scheme 26). 

The first enantioselective isomerization of allylic alcohols was carried out by using RhH(CO)(PPh3)3/(—)-DIOP. However, the enantioselectivity was very low (Equation (14)).50... 

The enantioselective isomerization of allylic alcohols using cationic rhodium(l)/BINAP complex was reported.9,11 Although the enantioselectivities were lower than those achieved by the isomerization of the corresponding enamines, 3,3 -disubstituted allylic alcohols were isomerized to the corresponding aldehydes in moderate yield and enantioselectivity (Scheme 27). 

Metal-catalyzed C-H bond formation through isomerization, especially asymmetric variant of that, is highly useful in organic synthesis. The most successful example is no doubt the enantioselective isomerization of allylamines catalyzed by Rh(i)/TolBINAP complex, which was applied to the industrial synthesis of (—)-menthol. A highly enantioselective isomerization of allylic alcohols was also developed using Rh(l)/phosphaferrocene complex. Despite these successful examples, an enantioselective isomerization of unfunctionalized alkenes and metal-catalyzed isomerization of acetylenic triple bonds has not been extensively studied. Future developments of new catalysts and ligands for these reactions will enhance the synthetic utility of the metal-catalyzed isomerization reaction. 

BINAP (40a) was first reported as a ligand in an enantioselective hydrogenation in 1980 [172], and provides good selectivity for the reductions of dehydroamino acid derivatives [173], enamides, allylic alcohols and amines, and a,p-unsaturated acids [4, 9, 11, 12, 174, 175]. The fame of the ligand system really came with the reduction of carbonyl groups with ruthenium as the metal [11, 176]. The Rh-BINAP systems is best known for the enantioselective isomerizations... 

The growing interest in enantioselective isomerization of meso oxiranes to allylic alcohols arises from the ready availabihty of starting materials and the synthetic value of the homochiral products. First apphed to simple meso cycloalkene oxides, this methodology has been successfully exteuded to fuuctioualized meso oxiranes, and even to the kinetic resolution of racemic oxiranes, demonstrating its potential in accessing highly advanced synthons. 

Numerous HCLA have been developed and used for the enantioselective isomerization of oxiranes to allylic alcohols and, in most cases, their efficiency strongly depends on the structure of the oxirane. The HCLA species can be divided into two groups monohthiated vicinal diamines or ether-amines and dilithiated diamines or amido-alcoholates. 

One of the landmark achievements in the area of enantioselective catalysis has been the development of a large-scale commercial application of the Rh(I)/BINAP-catalyzed asymmetric isomerization of allylic amines to enamines. Unfortunately, methods for the isomerization of other families of olefins have not yet reached a comparable level of sophistication. However, since the early 1990s promising catalyst systems have been described for enantioselective isomerizations of allylic alcohols and aUylic ethers. In view of the utility of catalytic asymmetric olefin isomerization reactions, I have no doubt that the coming years will witness additional exciting progress in the development of highly effective catalysts for these and related substrates. 

RHODIUM-CATALYZED ENANTIOSELECTIVE ISOMERIZATION OF ALLYLIC AMINES... 

RHODIUM-CATALYZED enantioselective isomerization of ALLYLIC AMINES 103... 

Although various transition-metal complexes have reportedly been active catalysts for the migration of inner double bonds to terminal ones in functionalized allylic systems (Eq. 3.2) [5], prochiral allylic compounds with a multisubstituted olefin (Rl, R2 H in eq 2) are not always susceptible to catalysis or they show only a low reactivity [Id]. Choosing allylamines 1 and 2 as the substrates for enantioselective isomerization has its merits (1) optically pure citronellal, which is an important starting material for optically active terpenoids such as (-)-menthol, cannot be obtained directly from natural sources [6], and (2) both ( )-allylamine 1 and (Z)-allylamine 2 can be prepared in reasonable yields from myrcene or isoprene, respectively, The ( )-allylamine 1 is obtained from the reaction of myrcene and diethylamine in the presence of lithium diethylamide under Ar in an almost quantitative yield (Eq. 3.3) [7], The (Z)-allylamine 2 can also be prepared with high selectivity (-90%) by Li-catalyzed telomerization of isoprene using diethylamine as a telomer (Eq. 3.4) [8], Thus, natural or petroleum resources can be selected. 

The desymmetrization of meso-e poxides such as cyclohexene epoxide (55, Scheme 13.27) has been achieved both by enantioselective isomerization, e.g. to allylic alcohols (56, path A, Scheme 13.27) or by enantiotopos-differentiating opening by nucleophiles, affording trans-/ -substituted alcohols and derivatives (57, path B, Scheme 13.27). As indicated in Scheme 13.27, the allylic alcohols 56 can also be prepared from the ring-opening products 57 by subsequent elimination of the nucleophile. 

Enantioselective Isomerization of meso-Epoxides to Allylic Alcohols... 

Enantioselective isomerization of olefins for preparation of optically active olefins has great synthetic potential with a long tradition [1] and the non-stereoselective version is probably the most intensively investigated reaction in transition metal catalysis [2]. In particular, stereoselective hydrogen migration in a-functionalized olefins, for example allyl alcohols and allylamines [3], affording optically active aldehydes, ketones and amines, is part of the standard repertoire of enantioselec-... 

Enantioselective Isomerization of Allylamines, Ally I Alcohols and Allyl Ethers... 

Scheme 2. Enantioselective isomerization of allyl compounds bearing oxygen or nitrogen containing groups.

Similar to the reaction of allylamines, allyl alcohols also undergo enantioselective isomerization in the presence of [Rh(BINAP)(COD)]+ [10]. Yields and enantio-selectivity are usually moderate, however. Considerable improvement was recently achieved by application of Rh(I) catalysts bearing phosphaferrocenes, 27, as chiral ligands (Scheme 7) [11]. These air-stable complexes, which can be recovered after the reaction, afford chiral aldehydes with up to 93 % ee. 

Scheme 7. Chiral aldehydes produced by enantioselective isomerization of allyl alcohols with [Rh(phosphaferrocene) (COD)]+ catalysts, THF, 70-100°C, 24 h.

Enantioselective isomerization can be advantageously used for the kinetic resolution of racemic allyl alcohols. For example treatment of 4-hydroxy-2-cyclopente-none (rac-28) in the presence of Rh[(R)-BINAP](MeOH)2 + gives rise to the enan-tiomerically enriched allyl alcohol (R)-29 (Scheme9) [13]. This unsaturated hydroxy ketone is an important building block for the synthesis of prostaglandins... 

Finally, another important application of BINAP is found in the Takasago process for the commercial production of (-) menthol from myrcene. The catalyst used is a rhodium complex of BINAP. Figure 6.35 gives the reaction scheme [58]. The key reaction is the enantioselective isomerization of the allylamine to the asymmetric enamine. It is proposed that this reaction proceeds via an allylic intermediate. 

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