Diastereoselectivity ester, with imines

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. 

Potassium enolates derived from the chiral Schiff bases obtained by reaction of racemic a-amino esters with 2-hydroxypinan-3-one undergo diastereoselective protonation, as evidenced by release of optically active a-amino esters on subsequent cleavage of the imine (Scheme 5). ... 

In addition to copper and rhodium catalysts commonly used in the generation of metal carbene complexes, other transition metals have also been explored in the diazo decomposition and subsequent ylide generation.Che and co-workers have recently studied ruthenium porphyrin-catalyzed diazo decomposition and demonstrated a three-component coupling reaction of a-diazo ester with a series of iV-benzylidene imines and alkenes to form functionalized pyrrolidines in excellent diastereoselectivities (Scheme 20). ... 

Schunk and Enders [134] disclosed the first solid-phase synthesis of (5-1 actants via ester enolate-imine condensation employing an immobilized ester enolate in a simple three-step procedure (Scheme 31). The protocol showed high purity, excellent diastereoselectivity, and good yields of the product. The substrates were attached to the polymer with a Tl-triazene linker, which was cleaved traceless. The... 

High diastereoselectivities have been observed for the reaction of dimethylketene methyl trimethyl-silyl acetal with imines derived from (2S)-amino esters (equation 49). However, the scope of this method must be further investigated. 

Attempts to prepare homochiral -lactams using chiral reactants under Reformatsky conditions described above gave poor results.Good diastereoselectivities are observed in the reaction of lithium enolates with imines bearing a chiral group on either a nitrogen (equation 46)or carbon atom (equation 47). Esters derived from isobomeol-lO-diisopropylsulfonamide give enolates which condense with cinnamaldimines to yield cis -lactams with excellent enantioselectivity (equation 48). ... 

The cycloaddition of ester enolates with imines is of continuing interest and potassium rert-butoxide may be used to generate the enolate (94S805) but more usually tin, titanium or zinc enolates are employed. When enolates are generated from 2-pyridylthioesters, the stereochemistry of the tin enolate may be greater than and, in some cases, opposite to that for titanium enolates (94T5821). The effect of the lithium, zinc or titanium on the diastereoselectivity in addition reactions of the enolates of a-... 

Since the last review in this series in 1993 (10) and the publication of Ojima s paper summarizing his approach to the / -lactam (237), a number of new approaches for the asymmetric synthesis of the / -lactam taxol side chain have emerged. For example, chiral sulfonamide esters have been used as chiral auxiliaries to achieve diastereoselective cycloaddition with N-TMS-imine, to give lactam 7.1.1 in 94% yield. Benzoylation of 7.1.1 yielded the ready-to-couple lactam 7.1.2 in 96% yield (238). 

Farina et al. used the chiral imine 7.1.3 to effect diastereoselective condensation with acetoxy acyl chloride to give preferentially the desired lactam in 74% yield and 84% diastereomeric excess. Subsequent deprotection of the silyl ether followed by mesylation and elimination afforded the olefin 7.1.4 which was ozonized. The resulting keto ester was easily hydrolyzed to give the unprotected lactam 7.1.5 in five steps (259). 

The Bayliss-Hillman reaction is commonly used for the coupling of Michael acceptors with aldehydes to give /3-hydroxy-a-methylene esters/ketones/nitriles. The use of imines in place of aldehydes provides entry to the corresponding /3-amino products. Examples of the asymmetric Bayliss-Hillman reaction with imines are very rare. Aggarwal and co-workers have shown that indium(III) triflate in combination with 3-hydroxyquinuclidine (3-HQD) catalyzes the reaction of enantiomerically pure N-p-toluenesulfinimine with methyl acrylate in an asymmetric Bayliss-Hillman reaction (eq 15). Higher diastereoselectivity was observed in the reaction of A-tert-butanesulfinimines, however, the yields were much poorer. ... 

More recently, Davis and co-workers developed a new method for the asymmetric syntheses of aziridine-2-carboxylates through the use of an aza-Darzens-type reaction between sulfinimines (N-sulfinyl imines) and a-haloenolates [62-66]. The reaction is highly efficient, affording cis- N-sulfmylaziridine-2-carboxylic esters in high yield and diastereoselectivity. This method has been used to prepare a variety of aziridines with diverse ring and nitrogen substituents. As an example, treatment of sulfinimine (Ss)-55 (Scheme 3.18) with the lithium enolate of tert-butyl bromoacetate gave aziridine 56 in 82% isolated yield [66],... 

Amino acid synthesis (cf. 12,15). The reaction of 1 with chiral a-imino esters provides an enantio- and diastereoselective synthesis of amino acid derivatives. The imine (2), prepared from (S)-phenethylamine, reacts with 1 to give 3, which... 

The [lrCl(cod)]2-catalyzed reductive coupling of acrylates and imines provides trans-P-lactams with high diastereoselectivity (Equation 10.39) [67]. With regards to the reaction mechanism, in situ generated Ir-hydride reacts with acrylate 148 to produce an Ir enolate, which then reacts with the 147 to afford the P-amido ester 149. 

The initial medicinal chemistry route to the azabicyclo[3.3.0]octane-3-carboxylic acid produced the azabicyclo system in a diastereoselective but racemic manner, and required a classical resolution to achieve enantioenriched material (Teetz et al., 1984a, b 1988). Reaction of (R)-methyl 2-acetamido-3-chloropropanoate (43) and 1-cyclopentenylpyrrolidine (44) in DMF followed by an aqueous acidic work-up provided racemic keto ester 45 in 84% yield (Scheme 10.11). Cyclization of 45 in refluxing aqueous hydrochloric acid provided the bicyclic imine, which was immediately reduced under acidic hydrogenation conditions. The desired cis-endo product 46 was obtained upon recrystaUization. The acid was protected as the benzyl ester using thionyl chloride and benzyl alcohol, providing subunit 47 as the racemate. Resolution of 47 was accomplished by crystallization with benzyloxy-carbonyl-L-phenylalanine or L-dibenzoyl-tartaric acid. 

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