Enantioselective reactions isomerizations

While much of the interesting properties of bispidine complexes are based on this difference, it certainly is of interest to develop the coordination chemistry of the isomeric tetradentate ligand. (2.) While 14 and its complexes have Cs symmetry the ligand and complex of the isomer shown in Fig. 2(c) are C2 symmetric, and therefore chiral. If catalytically active (such as complexes based on 14), complexes derived from that shown in Fig. 2(c) should be interesting for enantioselective reactions. 

Hayashi, et al. developed an enantioselective formal aza [3+3] cycloaddition of a,p-unsaturated aldehydes and enamide (enecarbamate) providing tetrahydropyil-din-2-ol in excellent enantioselectivities and yield. Scheme 3.50 [66]. The reaction comprised four consecutive reactions ene reaction, isomerization of imine to enecarbamate, hydrolysis and hemiacetal formation. Noteworthy, examples of a,P-unsaturated aldehydes acting as enophile in intermolecular catalytic enantioselective ene reaction are rare, and the reaction developed by Hayashi represents one of the successful example in such category. 

Yang and his team developed a procedure for the oxidative carbonylation of terminal olefins to phenylsuccinate esters by using thioureas as hgands [38]. It was claimed that these hgands can prevent both palladium precipitation and double bond isomerization. Later on, the same authors synthesized a set of thiourea-oxazohnes (S,A-bidentate ligand) which also allowed for enantioselective reactions (Scheme 8.8) [39, 40]. 

Shibasaki et al. also reported that similar Morita-Baylis-Hillman-type products were obtained via asymmetric aldol reaction of a p,y-unsaturated ester with aldehydes using a chiral barium catalyst system (Table 3) [25]. The desired products formed in good yields with high enantioselectivities after isomerization. Several aromatic- and alphatic aldehydes were tested, and in all cases high a-(E) selectivities and high enantioselectivities were observed. Several aryl, heteroaryl, alkenyl, and alkyl aldehydes can be used as substrates in this reaction. 

Although metal-olefin complexation can be a source of enantioselection, reactions exploiting this mechanistic motif have not been developed much. Due to the facile enantioface interconversion process, the origin of the enantioselection often reverts back to Type C alkylation (Figure 8E. 1). To transfer chiral recognition of the coordination process to the ee of the product, kinetic trapping of the incipient it-allyl complex is required prior to any isomerization process. For this reason, few successful examples have come from the use of more reactive heteroatom nucleophiles (N, O and S) and/or intramolecular reactions. 

In contrast to 1, isomeric p-nitrophenyl nicotinate shows almost no catalysis. Thus, it is clear that substrate coordination to the metal ion complex plays the critical role for an enormous rate enhancement. The lipophilic ester (R = C5Hn) also undergoes a large rate enhancement indicating the importance of substrate binding into the micellar phase by hydrophobic interaction. A large rate enhancement can also be seen in lipophilic esters which lack the metal coordination site as given below with the enantioselective micellar reactions (Table 9, 10). 

In Ghosh s enantioselective total synthesis of the cytotoxic marine macrolide (+)-amphidinolide T1 (318) [143], the C1-C10 fragment 317 was constructed by CM of subunits 315 and 316 (Scheme 62). The reaction mediated by catalyst C (5 mol%) afforded in the first cycle an inconsequential 1 1 mixture of (E/Z)-isomeric CM products 317 in 60% yield, along with the homodimers of 315 and 316. The self-coupling products were separated by chromatography and exposed to a second metathesis reaction to provide olefins 317 in additional 36% yield [144]. 

As already discussed for aldol and Robinson annulation reactions, proline is also a catalyst for enantioselective Mannich reactions. Proline effectively catalyzes the reactions of aldehydes such as 3-methylbutanal and hexanal with /V-arylimines of ethyl glyoxalate.196 These reactions show 2,3-syn selectivity, although the products with small alkyl groups tend to isomerize to the anti isomer. 

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). 

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. 

One problem for the asymmetric hydrogenation of imine is (E)/(Z) isomerism of the substrate, which may have a significant effect on the enantioselectivity of the reaction. This problem was difficult to address because of the rapid interconversion of the E and Z isomers of the imines under reaction conditions (Fig. 6-8). 

A novd example of a catalytic enantioselective domino process1201 is the inter-intramolecular nitro-aldol reaction described by Shibasaki et al which generates substituted indanones. As catalyst a praseodym-heterobimetallic complex with binaph-thol as chiral ligand is employed. Treatment of keto-aldehyde 41 with nitromethane in the presence of the catalyst 46 at -40 °C and successive warming to room temperature affords diredly the produd 42 in an overall yield of 41 % and 96 % ee after several recrystallizations (scheme 9). As intermediates the nitromethane adduct 43 and the hemiacetal 44 can be proposed. In a second aldol reaction 44 leads to 45 which isomerizes to the thermodynamically more stable epimer 42. 

A corollary to the above argument is that enantioselectivities depend on alkene geometry. Indeed, isomeric enolsilanes provide enantiomeric products. Because obtaining enolsilanes such as 344 in high isomeric purity is difficult, enantioselectivities with these nucleophiles are reflective, Eqs. 214 and 215. Pyrrole-derived enolsilanes are accessible in very high isomeric purity (>99 1) thus providing a convenient solution to this problem. Their use in the catalytic amination reaction provides access to a-hydrazino acid derivatives in high enantioselectivity. 

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