Addition reactions continued high enantioselectivity

Carbonyl ylides continue to be targets of opportunity because of their suitability for trapping by dipolar addition. High enantiocontrol has been achieved in the process described by Eq. 16 [109], but such high enantioselectivity is not general [110] and is dependent on those factors suggested by Scheme 11. Using achiral dirhodium(II) catalysts, Padwa and coworkers have developed a broad selection of tandem reactions of which that in Eq. 17 is illustrative [111] these... 

Initial preparative work with oxynitrilases in neutral aqueous solution [517, 518] was hampered by the fact that under these reaction conditions the enzymatic addition has to compete with a spontaneous chemical reaction which limits enantioselectivity. Major improvements in optical purity of cyanohydrins were achieved by conducting the addition under acidic conditions to suppress the uncatalyzed side reaction [519], or by switching to a water immiscible organic solvent as the reaction medium [520], preferably diisopropyl ether. For the latter case, the enzymes are readily immobilized by physical adsorption onto cellulose. A continuous process has been developed for chiral cyanohydrin synthesis using an enzyme membrane reactor [61]. Acetone cyanhydrin can replace the highly toxic hydrocyanic acid as the cyanide source [521], Inexpensive defatted almond meal has been found to be a convenient substitute for the purified (R)-oxynitrilase without sacrificing enantioselectivity [522-524], Similarly, lyophilized and powered Sorghum bicolor shoots have been successfully tested as an alternative source for the purified (S)-oxynitrilase [525],... 

The asymmetric catalytic reduction of ketones (R2C=0) and imines (R2C=NR) with certain organohydrosilanes and transition-metal catalysts is named hydrosilylation and has been recognized as a versatile method providing optically active secondary alcohols and primary or secondary amines (Scheme 1) [1]. In this decade, high enantioselectivity over 90% has been realized by several catalytic systems [2,3]. Therefore the hydrosilylation can achieve a sufficient level to be a preparative method for the asymmetric reduction of double bond substrates. In addition, the manipulative feasibility of the catalytic hydrosilylation has played a major role as a probe reaction of asymmetric catalysis, so that the potential of newly designed chiral ligands and catalysts can be continuously scrutinized. 

In summary, the intramolecular oxypalladation followed by Pd—elimination is undoubtedly useful for synthesizing 0-heterocycles. In addition, some reactions of this type serve as useful probes for developing novel catalyst systems of paUadium(II). A highly enantioselective oxypalladation has been developed by incorporation of chiral hgands in the catalyst systan. However, it does not appear that the catalyst system applies to a broad range of substrates. Efforts focusing on the control of chirality are expected to continue in this field. 

Enantioselective Mannich-type addition of enolate equivalents to imines continues to be an attractive strategy for the preparation of chiral p-amino carbonyl compounds. In the area of copper-catalyzed enantioselective Mannich reactions, a number of outstanding examples have appeared in this decade. In particular, work from Kobayashi s laboratories has led this field in recent years. Kobayashi and coworkers have developed a Cu(OTf) 2/diamine catalyst (121) for highly enantioselective addition of enolate equivalents to N-acylimino esters [36]. This methodology... 

The introduction of the activated allylic bromides and Morita-Baylis-HiUman acetates and carbonates pioneered the development of a number of phosphine-catalyzed reactions in subsequent years [45]. Interestingly, the asymmetric variant of this type of transformation only appeared in the literature seven years later. In 2010, Tang, Zhou, and coworkers disclosed a highly enantioselective intramolecular ylide [3-1-2] annulation using spirobiindane-based phosphine catalyst 31 (Scheme 20.27). BINAP was found inactive in this reaction even at an elevated temperature (70°C). Notably, both optically active benzobicyclo[4.3.0] compounds 32 and 32 with three continuous stereogenic centers could be obtained as major products in high yields and stereoselectivities just by a choice of an additive [Ti(OPr )4], which can block the isomerization of the double bond [46]. 

As most pharmaceuticals are heterocyclic, there is continuing interest in methods for the direct enantioselective construction of heterocycles. Greg Fu of reports (J. Am. Chem. Soc. 125 10778, 2003) that the addition of the dipole 1 to alkynes is catalyzed by Cul, and that in the presence of the planar-chiral ligand 2 the reaction proceeds in high enantiomeric excess. The is maintained with aryl-substituted alkynes, and is higher when there are alkyl substituents on the heterocyclic ring of 1. 

The chiral molecular receptor (35) has been used to effect enantioselective cyclization of the enone (36). The complex of (36) and (35) undergoes energy transfer from the ketonic acceptor to (36) and results in its conversion into the cyclobutanes (37) and (38) in a total yield of 21%. Bach et aV have continued their investigations of enantioselective additions mediated by the chiral lactam hosts (39). The present reactions involve intra and intermolecular additions of quinolone systems (40) at -60°C in toluene as solvent. The irradiation affords the cycloadducts (41) and (42). As can be seen, the ee of the products is high and the chemical yields are also good. An extension of the work to intermolecular reactions of the quinolone (43) was also reported. The additions of the alkenes... 

In the enantioselective synthesis of anthracyclinone AB building blocks Japanese workers continue to successfully exploit their methodology based on the addition of Grignard reagents to the a-carbonyl group of the ketals obtained from tetralone and (2S,3S)-l,4-dimethoxybutane-2,3-diol (60) [76]. This highly diastereoselective reaction was apphed in the synthesis of (-)-7-deoxydaunomycinone [77,78]. Later it was extended to the synthesis of AB segment 58, an intermediate in the first enantioselective synthesis of (-)-y-rhodomycinone (65) [71,79]. 

---