Enantioselective isomerization

The enantioselective version of the relay transformation by organic and metallic catalyses was successfully demonstrated by Gong and coworkers (Scheme 3.39) [83]. They accomplished the direct transformation of o propargylaniline derivatives into tetrahydroquinolines in a highly enantioselective manner through the hydroamina tion of alkynes/isomerization/enantioselective transfer hydrogenation (see Sec tion 3.3 for details) sequence under the relay catalysis of an achiral Au complex/ chhal phosphoric acid binary system. 

An isomerization/enantioselective intramolecular Alder-ene cyclization of enynes 467 was reported by Okamoto and co-workers (Scheme 2-54). The reaction was catalyzed by a cationic Rh(I)-(i )-BrNAP complex to afford various bicyclic and trycyclic dihydrobenzofurans and dihydronaphthofurans 469 in good yields and excellent enantioselectivity. Another example of an Alder-ene cyclization is the reaction of allylic ester 470, which yielded a-methylene-y-butyrolactone 471 in 50% yield. It was found that other transition metals, such as Pd, Ru, and Ti, were unable to catalyze this reaction (Scheme 2-55). ... 

Scheme 2-54. Isomerization/enantioselective Alder-ene cyclization of enynes.

An alkene isomerization/enantioselective intramolecular Alder-ene reaction cascade occurs using a cationic rhodium(I)/(7 )-BINAP complex as catalyst (Scheme 150). 0... 

Subsequently, the same group demonstrated an asymmetric synthesis of 3-amino aldehydes via catalytic double-bond isomerization/enantioselective aza-Petasis-Ferrier rearrangement reaction (Scheme 2.93) [128]. Similarly, the hemiaminal allyl ether substrates 346 were first isomerized by Ni(II) complexes to stereoselectively form Z-configured vinyl ethers 347, which then underwent a phosphoric acid-catalyzed... 

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). 

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... 

The synthetic problem is now reduced to the development of a feasible, large-scale preparation of enantiomerically pure (/ )-citro-nellal (36), which has a single stereogenic center. One way in which the aldehyde function in 36 could be introduced is through the hydrolysis of a terminal enamine. (/ )-CitronelIal (36) can thus be traced to citronellal ( )-diethylenamine (44), the projected product of an enantioselective isomerization of prochiral diethylgera-... 

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]. 

This interpretation was supported by further investigations by GiacomelH and coworkers [73]. Racemic 4-phenyl-l-hexene was kineticaUy resolved by isomerization of the double bond using a catalyst system consisting of Al Buj, (R)-N,N-di-methyl-l-phenylethylamine and Ni(mesal)2. Very poor enantioselectivities (ee < 0.3%) were observed for both the isomerization product and the unreacted alkene. The authors note that it is essential to first react the alane with the chiral amine. No... 

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. 

An especially important case is the enantioselective hydrogenation of a-amidoacrylic acids, which leads to a-aminoacids.29 A particularly detailed study has been carried out on the mechanism of reduction of methyl Z-a-acetamidocinnamate by a rhodium catalyst with a chiral diphosphine ligand DIPAMP.30 It has been concluded that the reactant can bind reversibly to the catalyst to give either of two complexes. Addition of hydrogen at rhodium then leads to a reactive rhodium hydride and eventually to product. Interestingly, the addition of hydrogen occurs most rapidly in the minor isomeric complex, and the enantioselectivity is due to this kinetic preference. 

BINAP-AgF gives good enantioselectivity, especially for the major anti product in the addition of 2-butenylstannanes to benzaldehyde.188 This system appears to be stereoconvergent, suggesting that isomerization of the 2-butenyl system occurs, perhaps by transmetallation. 

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. 

Hydrogenation of a series of /Z-isomeric mixtures of a-arylenamides with a MOM-protected /3-hydroxyl group catalyzed by a BICP-Rh complex or an Me-DuPhos complex leads to the formation of chiral /3-amino alcohol derivatives with excellent enantioselectivities.70b A 1,4-diphosphane 26 with a rigid 1,4-dioxane backbone is also very effective for this transformation (Equation (28)).76 DIOP -Rh72a and Me-DuPhos-Rh219 catalysts are also effective for this transformation. 

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