Chiral imine acetal

In contrast to the allyltitaniums derived from acrolein cyclic acetals, such as 1,2-dicyclo-hexylethylene acetal shown in Scheme 9.8, those derived from acrolein acyclic acetals react with ketones and imines exclusively at the y-position. As shown in Eq. 9.29, the reaction with chiral imines having an optically active 1-phenylethylamine moiety proceeds with high diastereoselectivity, thus providing a new method for preparing optically active 1-vinyl-2-amino alcohol derivatives with syn stereochemistry [53], The intermediate allyltita-nium species has also found use as a starting material for a carbozincation reaction [54],... 

TiCl, on the silyl ketene acetal however, other data suggest that metal enolates may not be involved (73b). In subsequent studies, this reaction has been extended to chiral imines (81,82). 

In 2000, the group of Banik et al. reported the enantiospecific synthesis of 3-hydroxy-2-azetidinones by microwave assisted Staudinger reaction [51]. Chiral imines, derived from chiral aldehydes and achiral amines, reacted with methoxy- or acet-oxy-acetyl chloride to afford a single, optically pure c/s-p-lactam, (Scheme 7). 

The /3-aminoester 385, synthesized by coupling of a chiral imine with a ketene acetal, cyclized toward cis-3-hydroxy-4-phenylazetidin-2-one 386 in the presence of boron tribromide (Scheme 57) <1998BML1619>. 

BLA 28 is very useful in the double stereodifferentiation of aldol-type reactions of chiral imines [41], Reaction of (5)-benzylidene-a-methylbenzylamine with trimethyl-silyl ketene acetal derived from tert-butyl acetate in the presence of (R)-28 at -78 °C for 12 h provides the corresponding aldol-type adduct in 94 % de (Eq. 78). Including phenol in the reaction mixture does not influence the reactivity or the diastereoselec-tivity. The aldol-type reaction using yellow crystals of (R)-28.(5)-benzylidene-a-methylbenzylamine PhOH proceeds with unprecedented (> 99.5 0.5) diastereoselec-tivity (Eq. 79). In general, 28 is a more efficient chiral Lewis acid promoter than 27. 

Asymmetry in enolate alkylations can be induced by the presence of chiral imines formed from aldehydes, ketones or aminoesters. Chiral acetals or oxa-zolidines of keto- or aldehydo-esters can also be efficient reagents. 

Homoenolate and homoallenyl carbanion equivalents. Two routes to homo-cnolate species are based on the action of (propene)titanium diisopropoxide. Trialkoxy-titanates generated from acetals of acrolein react with aldehydes and imines. Chiral cyclic acetals are similarly cleaved to afford the nucleophiles. 3-Alkoxy-2-propyn-l-yl carbonates are transformed into (l-alkoxyallen)-l-yltitanates that add to carbonyl compounds with y-selectivity. ... 

P-Amino esters. By means of double stereodifferentiation using chiral imines and a chiral BINOL-boronate catalyst, the condensation with ketene silyl acetals is a simple method for the synthesis of /3-amino esters in optically active forms, a-Hydroxy-/3-amino esters are similarly accessible. ... 

The intramolecular cyclization route to a specific P-lactam often depends on the availability of a P-aminoester having the required stereochemistry. A review which considers the asymmetric synthesis of p-aminoesters is available (94MI475). Ytterbium promoted addition of benzylamine to 2-alkenoic esters having a stereogenic centre at the y-position (94CL827) and triphenyl borate mediated reaction of chiral imines with silylketene acetals have been utilised to give P-aminoesters stereoselectively (93BMC2337). 

Imino aldol reaction of ketene silyl acetals with the chiral imine derived from tartaric acid 83 in the presence of a cation-exchange resin provided the corresponding /i-amino esters 84 in a good yield and high diastereose-lectivity [68]. The esters 84, thus obtained, were subjected to the Grignard reagent which promoted S-lactam formation. After a sequence of reactions compound 84 was transformed into the ester 85 [68] which in the past was... 

Commerpon and his collaborators also reported a diastereoselective condensation of a chiral imine 7.1.6 with acetoxy acetyl chloride (7.1.7). Reaction gave a pair of diastereomers, with the desired one 7.1.8 in 50-60% diastereomeric excess. After cleavage of the acetate, cis-/ -lactam... 

It was originally suggested by Swindell that acylation of baccatin III with protected N-benzoyl-3-phenylisoserine proceeds through an oxazinone intermediate (286). He then developed a synthesis of the side chain methyl ester by hydrolysis of a protected oxazinone intermediate 7.6.3, which was itself prepared in 70% yield by a Diels-Alder type reaction between the imine 7.6.1 and the chiral ketene acetal 7.6.2. Hydrolysis of 7.6.3 and removal of protecting groups gave the side chain methyl ester in 93% yield (287). 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

Enamines of cyclohexylamine have been enantioselectively cyclized to bicyclo[3.3.1] nonanedione systems, using acryloyl chloride and chiral pyrrolidine catalysis. Enantio-pure A-sulflnylimines have been used in asymmetric synthesis of isoquinolone alkaloids, and a stereocontrolled synthesis of 3,4,5,6-tetrahydropyrimidine-based amino acids from imino ethers has been reported. Diastereoselective additions of chiral acetals of (2-lithiophenyl)acetaldehyde to arylimines have been used in an asymmetric synthesis of 1-aryltetrahydroisoquinolines. " Organolithiums react with chiral imines, in the presence of Lewis acids or bases, to give amines in up to 100% de. Diastereoselective additions of copper reagents to imines derived from (5)-l-phenylethylamine have been reported. 

The reaction of l,3-diphenylprop-2-enyl acetate (3) with dimethyl malonate to give (4) is catalysed by Pd complexes containing chiral imine-sulfide chelate ligands (5) derived from amino acids. Values of ee around 90% were realised in the most favourable cases. The steric and electronic factors which underlie the high enan-tioselectivity were examined by experiments involving about 12 different ligands (i.e. various R, R, R ). It was concluded that the enantioselectivity is ultimately controlled by the subtle steric environment of the chiral imine-sulfur chelate ligand, which predisposes the allyl unit of the reaction intermediate to a preferred reaction trajectory. ... 

The origin of enantioselectivity which accompanies the allylic acetate substitution reaction of l,3-diphenylprop-2-enyl acetate with dimethyl malonate, catalysed by palladium complexes having chiral imine-sulfide chelate ligands, has been explored. 

A chiral boron reagent, derived from equimolar amounts of (R)-or (5)-binaphthol and triphenyl borate, promotes the condensation of chiral imines with t-butyl acetate silyl ketene acetal in high diastereomeric excess (eq 12). ... 

TiCU-mediated additions of silyl ketene acetal (98) to chiral imines (99) and (100) (R = Et, Pr", Bu", Bu ) are described in equations (33) and (34) good diastereoisomeric ratios were obtained using imines (100), derived from (S)-valine methyl ester, which form with TiCU the chelated complex (101). Znh-catalyzed additions of acetate-derived silyl ketene acetals to chiral a. -dialkoxy nitrones (102 R = H) were reported to proceed with good yield (86-100%) and high diastereofacial selectivity ca, 90 10) in favor of the anti isomer (103 R = H, R = CHPh , R = Bu ) or of the syn isomer (104 R = H, R = CH2Ph, R- = Me) depending on the steric hindrance of R and (Scheme 8). Addition to nitrone (102 R = Me) gave the anti isomer (103 R Me, R = CHMePh, R = Me) in quantitative yield and 100% diastereofacial selectivity. This material was further elaborated to A/-benzoyl-L-daunosamine (Scheme S). ... 

In contrast to the low stereoselections realized in the above syntheses utilizing imines of various chiral aldehydes79-8 1, an almost complete stereoselectivity is reported for the Ugi reaction of 2,3 4,5-bis-O-isopropylidenearabinose with ammonia, acetic acid and cyclohexyl isocyanide giving the 2-acetamino-2-deoxyglueono amides as the exclusive products84. 

Ethyl (bornylideneamino)acetate (2) and the imines of (-)-(lf ,2, 5 )-2-hydroxy-3-pinanone and glycine, alanine and norvaline methyl esters were particularly successful as Michael donors. The chiral azaallyl anions, derived from these imines by deprotonation with lithium diisopropylamide in THF at — 80 C, add to various a,/i-unsaturated esters with modest to high diastereoselectivity (see Section 1.5.2.4.2.2.5.). Thus, starting with the imine 2, (R1 = CH,) and ethyl ( )-2-butcnoate, the a,/i-dialkylated glutamate derivative 3 is obtained as a single diastercomer in 90% yield91-92. 

Scheme 27 Addition of nitronates, enolates and silyl ketene acetals to chiral a-amino imines and iminium ions...

Moreover, a few chiral ferrocenylsulfur-imine ligands were investigated in the palladium-catalysed asymmetric allylic alkylation of 1,3-diphenylpropenyl acetate and cyclohexenyl acetate with dimethyl maionate (Scheme... 

A titanium catalyst 20 that incorporates binaphthyl chirality along with imine and phenolic (salen) donors is highly active in addition of silyl ketene acetals to aldehydes.160... 

Allyltitanium complexes derived from a chiral acetal have been reacted with carbonyl compounds and imines [63], While the chiral induction proved to be low with carbonyl compounds, high induction was observed with imines. This complex represents the first chiral homoenolate equivalent that reacts efficiently with imines. Finally, the reactions with electrophiles other than carbonyl compounds and imines, namely a proton source, NCS, and I2, furnished the corresponding alkene, chloro, and iodo derivatives in good yields [64]. 

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