Isomerization of allylic amines

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... 

Scheme 7. Stereochemical outcome of BINAP-Rh(i)-catalyzed asymmetric isomerization of allylic amines.

We now turn to the Takasago Process for the commercial synthesis of (-)-menthol (1),4 one of the most successful industrial applications of catalytic asymmetric synthesis. This exquisite synthesis is based on the BINAP-Rh(i)-catalyzed enantioselecdve isomerization of allylic amines, and has been in operation for the commercial production of (-)-menthol since 1984. 

Rh/(5)-BINAP Isomerization of allylic amine /.-Menthol Aroma and flavour chemical 96-98... 

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. 

Isomerization of allylic amines is another example of the application of the BINAP complex. Rh BINAP complex catalyzes the isomerization of N,N-diethylnerylamine 40 generated from myrcene 39 with 76-96% optical yield. Compound (R)-citronellal (R)-42. prepared through hydrolysis of (R)-41, is then cyclized by zinc bromide treatment.49 Catalytic hydrogenation then completes the synthesis of (—)-menthol. This enantioselective catalysis allows the annual production of about 1500 tons of menthol and other terpenic substances by Takasago International Corporation.50... 

The commercialization in 1983 of the process illustrated in Eq. (1) is undoubtedly one of the most significant triumphs of asymmetric catalysis to date [2]. Takasago Chemical Company produced more than 22 000 tons of menthol by this route during the period 1983-1996, consuming only 125 kg of the chiral Hgand in the process. Rh(I)/Tol-BINAP-catalyzed isomerizations of allylic amines are beheved to proceed through the pathway outlined in Eq. (2) [3]. 

For Rh(I)/BINAP-catalyzed isomerizations of allylic amines, the mechanistic scheme outlined in Eq. (2) has been proposed. The available data are consistent with the notion that Rh(I)/PF-P(o-Tol)2-catalyzed isomerizations of allylic alcohols follow a related pathway [11]. For example, the only deuterium-containing product of the reaction depicted in Eq. (9) is the l,3-dideuterated aldehyde, which estabhshes that the isomerization involves a clean intramolecular 1,3-migration. The data illustrated in Eqs. (10) and (11) reveal that the catalyst selectively abstracts one of the enantiotopic hydrogens/ deuteriums alpha to the hydroxyl group. 

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. 

Ar = 2-(n-C4H,0)-5-(t-C4H9)C5H3 Rh(I)-cataIyzed isomerization of allylic amines... 

RHODIUM-CATALYZED ENANTIOSELECTIVE ISOMERIZATION OF ALLYLIC AMINES... 

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

Ab Initio MO calculations of a model complex Rh(PH3)2(NH3)(CH2=CHCH2NH2) were earned out to shed light to the detailed mechanism of Rh(l)-catalyzed isomerization of allylic amines to enamines.5 This study suggests that the square-planar [RhiPHjyNHjXCf CHCHjNHj) complex is transformed to [Rh(PH3)2(NH3)(( )-CH3CH=CHNH2)]+ via intramolecular oxidative addition of the C(l)-H bond to the Rh(I) center, giving a distorted-octahedral Rh(lll) hydride intermediate, followed by reductive elimination accompanied by allylic transposition. 

Isomerization of allylic amines (11, 53-54 12, 56-57).1 The asymmetric isomerization of allylamines to enamines effected with ruthenium complexes of (R)-and (S)-l is applicable to C5-isoprenoids, even to ones with an allylic dialkylamino group at one end and an allylic O-function at the other end. Thus it can be used to... 

A few molecular orbital calculations have been reported for these metallacycles. An ab initio study of a postulated azoniumrhodacyclopropane produced a structure in good agreement with known azoniummetallacyclopropanes. This as yet unknown heterocycle was studied because it has been proposed as an intermediate in the stereoselective isomerization of allyl amines to enamines... 

In a similar maimer to the asymmetric isomerization of allylic amines, the new stereogenic center can be controlled by either the substrate or the configuration of the ligand on ruthenium [43],... 

L-Menthol, hydroxy-dihydro-citronellal, d-and L-citronellol Isomerization of allyl amine with Rh-binap >1000 t/y Takasago [5-7]... 

Rhodium(I)-catalyzed isomerization of allylic amines is also good route to P-substituted aldehydes [89]. 

RHODIUM-CATALYZED ENANTlOSri fCTIVE ISOMERIZATION OF ALLYLIC AMINES 101... 

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