Isomerization of allylamines to enamines

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... 

The mechanism of the BINAP rhodium complexes catalysed isomerization of allylamines to enamines has been published280. The reaction course and its intermediates have been probed by ab initio calculations281. 

The crossover product, propionaldehyde-l,3-d-3- C 12, clearly demonstrated that the isomerization occurred via intermolecular 1,3-hydrogen shift. These results are consistent with a modified metal hydride addition-elimination mechanism which involves exclusive 1,3-hydrogen shift through oxygen-directed Markovnikov addition of the metal hydride to the carbon-carbon double bond (Scheme 12.2). The directing effect of functional groups on the selectivity of transition metal catalysis is well presented [9], and an analogous process appears to be operative in the isomerization of allylamines to enamines [10]. 

The isomerization of allylamines could be more selective compared to their oxygen homologues due to the higher coordination property of nitrogen. This assumption was clearly exemphfied by the discovery of the cobalt-catalyzed isomerization of allylamines to enamines. With the introduction of cationic rhodium complexes of BINAP, the reaction has became one of the most successful asymmetric reactions [32]. 

From the synthetic point of view, the isomerization of allylamines to enamines is very attractive, since allylamines can easily be prepared by borohydride reduction of pyridinium salts. 

During the past decade, metal-catalyzed asymmetric reactions have become one of the indispensable synthetic methodologies in academic and industrial fields. The asymmetric isomerization of allylamine to an optically active enamine is a typical example of the successful application of basic research to an industrial process. We believe that Takasago s successful development of large-scale asymmetric catalysis will have a great impact on both synthetic chemistry and the fine chemical industries. The Rh-BINAP catalysts, though very expensive, have become one of the cheapest catalysts in the chemical industry through extensive process development. 

Asymmetric hydrogenation was boosted towards synthetic applications with the preparation of binap 15 by Noyori et al. [55] (Scheme 10). This diphosphine is a good ligand of rhodium, but it was some ruthenium/binap complexes which have found spectacular applications (from 1986 up to now) in asymmetric hydrogenation of many types of unsaturated substrates (C=C or C=0 double bonds). Some examples are listed in Scheme 10. Another important development generated by binap was the isomerization of allylamines into enamines catalyzed by cationic rhodium/binap complexes [57]. This reaction has been applied since 1985 in Japan at the Takasago Company for the synthesis of (-)-menthol (Scheme 10). 

Table 1. Asymmetric Isomerization of Allylamines to Optically Active ( )-Enamines with Cationic Rh(l) Chiral Diphosphane Complexes R2 R2...

Tani, K., T. Yamagata, S. Otsuka et al., 1982. Cationic rhodium (I) complex-catalyzed asymmetric isomerization of allylamines to optically active enamines. 600-601. 

The synthesis of a variety of chiral aliphatic aldehydes of high optical purity through the enantioselective isomerization of allylamines found many applications in organic synthesis. The enantioselective isomerization of diethylgeranylamine, which was prepared from myrcene, furnished (R, )-diethylenamine in >98% yield with >98% ee. This enamine is converted to (—(-menthol stereospecifically in high chemical yield (yield of each step >92%, Scheme 4).9 11... 

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). 

Olefinic double-bond isomerization is probably one of the most commonly observed and well-studied reactions that uses transition metals as catalysts [1]. However, prior to our first achievement of asymmetric isomerization of allylamine by optically active Co(I) complex catalysts [2], there were only a few examples of catalytic asymmetric isomerization, and these were characterized by very low asymmetric induction (<4% ee) [3], In 1978 we reported that an enantioselective hydrogen migration of a prochiral allylamine such as AVV-diethylgerany-lamine, (1) or N V-diethylnerylamine (2) gave optically active citronellal ( )-enamine 3 with about 32% ee utilizing Co(I)-DIOP [DIOP = 2,3-0-isopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane] complexes as the catalyst (eq 3.1). 

Iron carbonyls have been used in stoichiometric and catalytic amounts for a variety of transformations in organic synthesis. For example, the isomerization of 1,4-dienes to 1,3-dienes by formation of tricarbonyl(ri4-l,3-diene)iron complexes and subsequent oxidative demetallation has been applied to the synthesis of 12-prostaglandin PGC2 [10], The photochemically induced double bond isomerization of allyl alcohols to aldehydes [11] and allylamines to enamines [12,13] can be carried out with catalytic amounts of iron carbonyls (see Section 1.4.3). 

Scheme 4-292. Example for the pentacarbonyliron-catalyzed isomerization of silylated allylamines to enamines.

Treatment of allylamines with potassium amide on alumina causes their isomerization to enamines in good yields (124b). When allylamines are heated to about 55° the same type of isomerization takes place (I24c). 

The enantioselective BINAP-Rh +-catalyzed isomerization of an achiral allylamine, such as diethylgeranylamine, to give an optically active enamine (e. g., 2) (for configurational assignment, see p 436)56. 

As described above, hydrolysis of the optically active enamine 3 proceeds without racemization and produces an optically active aldehyde, citronellal, with a very high optical purity (>98% ee). The optical purity of citronellal) available from natural sources is known to be no more than 80% ee [5], The present asymmetric isomerization of the allylamine 1 is utilized as the key step for the industrial production of (-)-menthol (Scheme 3.3). 

In a similar reaction, allylamines can be isomerized to afford enamines. Photochemical isomerization of the silylated allylamine in the presence of catalytic amounts of pentacarbonyliron provided exdusively the E-isomer of the enamine, whereas a thermally induced double bond shift provided a 4 1 mixture of the E- and Z-enamines (Scheme 1.38) [13],... 

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. 

Sauer and Prahl258 showed that the main product from the base-catalysed transformation of allyldimethylamine and several other allylamines, including 1-allylpiperidine and 1-allylpyrrolidine, is the Z-enamino isomer. Seebach and coworkers145 isomerized 4-allylmorpholine with r-BuOK in DMSO to a mixture of Z- and E-4-(l-prope-nyl)morpholine in a 87 13 ratio. The E-enamine which presumably arose by a subsequent isomerization of the (Z) isomers was shown to be the thermodynamically stable isomer. 

Only few examples of preparative isomerizations of cyclic allylamine to cyclic enamine have been reported. Thus, 1-methyl-1,2-dihydro-1-benzazocine (70) was converted into enamine 71 by reaction with t-BuOK-DMSO at room temperature262, 1-methyl-1,2-dihydroquinoline (72) was isomerized under the same conditions to enamine 73 and the indoloquinolizines 74 were isomerized with t-BuOK-DMSO at 100 °C to enamines... 

Rivire and Lattes used LiNH2 and NaNHj in liquid ammonia at — 70°C, in hexamethylphosphortriamide at room temperature or t-BuOK/HMPA at room temperature for allylamine enamine isomerizations. An anion formed by deprotonation of the allylamine at C was considered to be the intermediate species in the isomerization. Intramolecular transfer of hydrogen in the transition state of the isomerization was suggested to explain both the kinetic formation of the Z-enamine and the absence of exchange with deuteriated base during the isomerization. Quantum chemical calculations showed that the Z-carbanion (61) is actually more stable than the -carbanion (62). 

Effects of additives in the isomerization of substrate 45 by catalyst 17 were studied under the conditions of [S]=0.24 mol L [S] [C] =100 at 60 °C in THE The results are briefly summarized in Table 1, and are important both for mechanistic studies and improvements of the catalyst activity. Simple tertiary amines retard the reaction drastically, which suggests the coordination order of amines to Rh-BINAP species to be proportional with the order of basicity of simple tertiary amines, allylamines and enamines. Without the presence of simple tertiary amines, this phenomenon enables the fast replacement of the enamine formed from the catalyst by a substrate molecule that permits a smooth catalytic cycle. The presence of chelate diolefins like COD also disturbs the catalytic cycle. An over-isomerized by product, dienamine 44, acts as a strong catalyst poison. 

Scope and limitation of allylamine substrates were studied extensively by employing Rh-BINAP complexes 17 as the catalyst (THF, 60 °C). The structure of the substrates influenced the reaction drastically. The first limitation is P-substi-tuted allylamines, thus N,i -dimethyl-2-methyl-2-butenylamine was not isomer-ized, presumably due to the thermodynamic stability of the substrate. The second is the a-substitution, namely N,AT-dimethyl-l-methyl-2-propenylamine gave polymeric products. This fact is in accordance with the thermal instability of enamines derived from small acyclic methyl ketones. However, the cyclic allylamine, 3-diethylaminocyclohex-l-ene 50 was isomerized selectively to the corresponding enamine 51,Eq. (11). 

---