Catalytic Asymmetric Cycloaddition Reactions

J0rgensen and Juhl reported the first organocatalytic enantioselective inverse-electron-demand hetero-Diels-Alder reaction of aldehydes (e.g., 71) and enones (e.g., 72) with excellent diastereo- and enantioselectivity. Scheme 3.26 [41], The reaction utilizes a chiral enamine intermediate as an alkene in catalytic asymmetric cycloaddition reactions. 

A catalytic asymmetric cycloaddition reaction between norbomadiene and methylenecyclopropane can also be achieved in the presence of a [Ni(cod)2]-(—)-benzylmethylphenylphosphine catalyst to give the cycloadduct (72) in an optically active form. This reaction may proceed via a metallocyclopentane intermediate. The reactions of methylenecyclopropane with [Ni(cod)2l-phosphine systems do not appear to involve cleavage of the three-membered ring. However, the bis(acrylonitrile)nickel-catalysed cycloaddition reaction of methylenecyclopropane with methyl acrylate, which yields 3-methoxy-carbonylmethylenecyclopentane (73), does involve C—C bond cleavage. Reaction with the deuterium-substituted compound CHD=CDC02Me gives the cyclopentane derivative (74). An intermediate of the type (75) may be involved in this reaction. 

Various a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanols have been prepared from (R,R)-tartrate, which are called TADDOLs by Seebach et al. They studied the influence of the Ti catalyst preparation methods, the presence of molecular sieves, and the TADDOL structure in the enantioselective Diels-Alder reaction of acryloyl oxazolidinones [41] (Eq. 8A.22). Seebach also prepared polymer- and dendrimer-bound Ti-TADDOLates and used in catalytic asymmetric cycloadditions [42],... 

In the last decade a variety of catalytic asymmetric DA reactions wifh alkenes has been developed most, however, involve the use of a cychc diene, particularly cyclopentadiene. There are a few examples of catalytic asymmetric reactions of siloxydienes with alkenes. Corey et al. have reported enantioselective cycloaddition of sil-oxydiene 106 to mefhacrolein as the key step of fhe asymmetric synfhesis of cassiol (Scheme 10.116) [314]. Recently, Rawal et al. have demonstrated that Cr(III)-salen complex 108a catalyzes the cycloaddition of l-amino-3-siloxy-l,3-dienes to a, -unsa-turated aldehydes wifh high enantioselectivity [315]. The highly functionalized cyclohexene products have been used for alkaloid synthesis. Ghosez et al. have introduced asymmetric DA reaction of siloxy-substituted azadienes 109 under catalysis by Cu(II)-box complex 70a [316]. 

A few studies reporting an asymmetric Diels-Alder reaction involving vinyl-boronates have been hitherto published. A catalytic asymmetric cycloaddition has been developed using 3- 3-boronyl-propenoyl)-l,3-oxazolidin-2-ones as dienophiles and a chiral titanium catalyst in the presence of molecular sieves [57]. Adducts were obtained as single isomers in good yield and high enantioselectivity (>93% ee) (Scheme 9.25). Cyclopentadiene gave a mixture of endo and exo isomers (-95 5). 

Cycloaddition of diverse types of ketenes and imines leading to the formation of P-lactams is reported. The reactions of chiral ketenes with achiral imines, chiral imines with achiral ketenes, chiral imines with chiral ketenes, and catalytic asymmetrical Staudinger reactions have been investigated. In general, a higher level of asymmetric induction is achieved using either chiral ketenes or chiral imines derived from chiral aldehydes in comparison to the use of a chiral imine derived from an achiral aldehyde with an achiral ketene. Both carboxylic acid chlorides and carboxylic acids themselves have been used as ketene precursors. 

The [2 + 2] cycloaddition reaction of A -benzyl-l,4-dihydropyridine 34b with acrylonitrile, followed by catalytic reduction gave two pairs of diastereoisomeric amides 36 and 37 with a low diastereomeric excess, probably due to the large distance between the asymmetric center and the site of acrylonitrile attack. Compounds 36 and 37 were resolved into the four individual diastereoisomers (ca 5% for compound 36 and 15% for 37) [97JCR(M)321], Irradiation of 1,4-dibenzyl-1,4,5,6-tetrahydropyridine 38 in the presence of 29 gave two stereoisomers. 

Catalytic asymmetric Diels-Alder reactions are presented by Hayashi, who takes as the starting point the synthetically useful breakthrough in 1979 by Koga et al. The various chiral Lewis acids which can catalyze the reaction of different dieno-philes are presented. Closely related to the Diels-Alder reaction is the [3-1-2] carbo-cyclic cycloaddition of palladium trimethylenemethane with alkenes, discovered by Trost and Chan. In the second chapter Chan provides some brief background information about this class of cycloaddition reaction, but concentrates primarily on recent advances. The part of the book dealing with carbo-cycloaddition reactions is... 

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