Enantioselective conjugate allylation

Enantioselective conjugate allylation of o y unsaturated carbonyl compounds has remained to be studied until a very recent report is disclosed using a chiral copper catalysts (Scheme 3-104)J Choice of a substrate with appropriate reactivity appears to be the key of the success. Conjugate addition across nitro olefins followed by reduction of the nitronate products with TiCU gives a-allylketones (Scheme 3-105). ... 

Catalytic enantioselective conjugate addition and allylic alkylation reactions using Grignard reagents... 

Catalytic enantioselective conjugate addition TABLE 13. The allylic substitution of 3-bromopropenyl esters using Cu/Taniaphos... 

Enantioselective allylation, via indium compounds, 9, 672 Enantioselective conjugate additions, in C-G bond formation copper nucleophiles, 10, 373 lithium nucleophiles, 10, 370 magnesium nucleophiles, 10, 371 zinc nucleophiles, 10, 374 Enantioselective reactions... 

The formation of asymmetric carbon-carbon and carbon-heteroatom bonds by lithiation-substitution at a carbon adjacent to nitrogen can be accomplished by deprotonations or des-tannylations, followed by reaction with electrophiles. Apphcations of these sequences for amine elaboration are summarized for reactions controlled by chiral hgands and chiral auxiliaries. Notable features include syntheses of alkaloids, the ability to make both enantiomers with a single chiral ligand and diastereoselective and enantioselective conjugate additions with benzylic and allylic lithiation intermediates. The sequences are classified, where information is available, in terms of stereocontrol in the lithiation or substitution step. 

Moreover, Shibasaki developed a direct catalytic enantioselective conjugate addition of allyl cyanide 37 to a,(3-unsaturated thioamides (Scheme 2.25). A sequential Cu(i)-catalysed intramolecular cyclisation gave rise to enantioenriched fused isothiazoles 41 via Z-olefins 40. 

Scheme 2.25 Enantioselective conjugate addition of allyl cyanide to a,p-unsaturated thioamides with the use of chiral Cu(i) complex and Li(OC6H4-j3-OMe).

A nickel-catalyzed carbozincation in which an allylzinc adds across the double bond of an unsaturated acetal has also been reported (Scheme 79). ] This procedme effectively provides a reverse-polarity approach to the functionalization of unsaturated carbonyl derivatives. Non-allylic Grignard reagents, however, add to cychc unsaturated acetals with the opposite regiochemistry. This latter procedure provides the basis for an enantioselective conjugate addition to cyclic enones (in 53% ee for the cyclopentenyl substrate and 85% ee for the cyclohexenyl homologue). ... 

Scheme 5.109 Copper-catalyzed enantioselective conjugate addition of dimethyl zinc and enolate trapping by palladium-catalyzed allylic alkylation to ketone 427. Application to a synthesis of pumiliotoxin C.

Scheme 5.112 Rhodium-catalyzed enantioselective conjugate addition and subsequent diastereoselective aldol addition/allylation of boron enolate 438. Model for rationalizing the stereochemical outcome.

The catalytic enantioselective addition of vinylmetals to activated alkenes is a potentially versatile but undeveloped class of transformations. Compared to processes with arylmetals and, particularly alkylmetals, processes with the corresponding vinylic reagents are of higher synthetic utility but remain scarce, and the relatively few reported examples are Rh-catalysed conjugate additions. In this context, Hoveyda et al. reported very recently an efficient method for catalytic asymmetric allylic alkylations with vinylaluminum reagents that were prepared and used in Thus, stereoselective reactions... 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

High levels of asymmetric induction can be achieved intramolecularly if the substrate functionality and the heteroatom ligand are contained in the same molecule. Chiral amido(a]kyl)cuprates derived from allylic carbamates [(RCH= CHCH20C(0)NR )CuR undergo intramolecular allylic rearrangements with excellent enantioselectivities (R = Me, n-Bu, Ph 82-95% ee) [216]. Similarly, chiral alkoxy(alkyl)cuprates (R OCuRLi) derived from enoates prepared from the unsaturated acids and trans-l,2-cyclohexanediol undergo intramolecular conjugate additions with excellent diasteroselectivities (90% ds) [217]. 

Reactions where NLE have been discovered include Sharpless asymmetric epoxi-dation of allylic alcohols, enantioselective oxidation of sulfides to sulfoxides, Diels-Alder and hetero-Diels-Alder reactions, carbonyl-ene reactions, addition of MesSiCN or organometallics on aldehydes, conjugated additions of organometal-lics on enones, enantioselective hydrogenations, copolymerization, and the Henry reaction. Because of the diversity of the reactions, it is more convenient to classify the examples according to the types of catalyst involved. 

New catalyst design further highlights the utility of the scaffold and functional moieties of the Cinchona alkaloids. his-Cinchona alkaloid derivative 43 was developed by Corey [49] for enantioselective dihydroxylation of olefins with OsO. The catalyst was later employed in the Strecker hydrocyanation of iV-allyl aldimines. The mechanistic logic behind the catalyst for the Strecker reaction presents a chiral ammonium salt of the catalyst 43 (in the presence of a conjugate acid) that would stabilize the aldimine already activated via hydrogen-bonding to the protonated quinuclidine moiety. Nucleophilic attack by cyanide ion to the imine would give an a-amino nitrile product (Scheme 10). 

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