Intramolecular asymmetric methods

Intramolecular asymmetric hydrosilylation-oxidation of (alkenyloxy) hydrosilanes provides an efficient method for the preparation of optically active polyols from al-lylic alcohols. Cyclization of silyl ethers 54 of a meso-type allyUc alcohol in the pres-... 

This collection begins with a series of three procedures illustrating important new methods for preparation of enantiomerically pure substances via asymmetric catalysis. The preparation of 3-[(1S)-1,2-DIHYDROXYETHYL]-1,5-DIHYDRO-3H-2.4-BENZODIOXEPINE describes, in detail, the use of dihydroquinidine 9-0-(9 -phenanthryl) ether as a chiral ligand in the asymmetric dihydroxylation reaction which is broadly applicable for the preparation of chiral dlols from monosubstituted olefins. The product, an acetal of (S)-glyceralcfehyde, is itself a potentially valuable synthetic intermediate. The assembly of a chiral rhodium catalyst from methyl 2-pyrrolidone 5(R)-carboxylate and its use in the intramolecular asymmetric cyclopropanation of an allyl diazoacetate is illustrated in the preparation of (1R.5S)-()-6,6-DIMETHYL-3-OXABICYCLO[3.1. OJHEXAN-2-ONE. Another important general method for asymmetric synthesis involves the desymmetrization of bifunctional meso compounds as is described for the enantioselective enzymatic hydrolysis of cis-3,5-diacetoxycyclopentene to (1R,4S)-(+)-4-HYDROXY-2-CYCLOPENTENYL ACETATE. This intermediate is especially valuable as a precursor of both antipodes (4R) (+)- and (4S)-(-)-tert-BUTYLDIMETHYLSILOXY-2-CYCLOPENTEN-1-ONE, important intermediates in the synthesis of enantiomerically pure prostanoid derivatives and other classes of natural substances, whose preparation is detailed in accompanying procedures. 

On the other hand, unsaturated aldehydes and ketones were obtained using allylic alcohols as alkene components [68]. Similarly, allyl f-butyldimethylsilyl ether and N-allylamides gave silyl enol ethers [69] and enamides [70], respectively. The ruthenium-catalyzed alkene-alkyne coupling was successfully combined with the palladium-catalyzed intramolecular asymmetric allylic alkylation [71] to provide a novel one-pot heterocyclization method [72]. 

These latter results demonstrating intramolecular asymmetric hydroacylation reactions show promising potential for further useful applications of this method in stereoselective organic synthesis. 

A significant study of the synthesis of chiral chromans by the Pd-catalysed intramolecular asymmetric allylic alkylation of readily available phenol allyl carbonates has established the optimum conditions for this highly efficient method and demonstrated its value by the total syntheses of (+)-clusifoliol and (-)-siccanin (Scheme 6) <04JA11966>. A biomimetic enantioselective synthesis of (-)-siccanin also features this approach to the chroman moiety <04JA12565>. 

Methods for the enantioselective synthesis of 3-substituted indolines by means of the asymmetric intramolecular carbolithiation of 2-bromo-A,-allylanilines in the presence of (-)-sparteine were reported simultaneously by Bailey <00JA6787> and Groth <00JA6789>. Thus, addition of 89 to 2.2 equiv of /BuLi in the presence of the chiral ligand generates the lithium intermediate 90 which upon quenching with methanol affords the chiral indoline 91 in a process that is highly solvent dependent. 

Palladium-catalyzed arylation of olefins and the analogous alkenylation (Heck reaction) are the useful synthetic methods for carbon-carbon bond formation.60 Although these reactions have been known for over 20 years, it was only in 1989 that the asymmetric Heck reaction was pioneered in independent work by Sato et al.60d and Carpenter et al.61 These scientists demonstrated that intramolecular cyclization of an alkenyl iodide or triflate yielded chiral cyclic compounds with approximately 45% ee. The first example of the intermolecular asymmetric Heck reaction was reported by Ozawa et al.60c Under appropriate conditions, the major product was obtained in over 96% ee for a variety of aryl triflates.62... 

The most spectacular application of the donor/acceptor-substituted carbenoids has been intermolecular C-H activation by means of carbenoid-induced C-H insertion [17]. Prior to the development of the donor/acceptor carbenoids, the intermolecular C-H insertion was not considered synthetically useful [5]. Since these carbenoid intermediates were not sufficiently selective and they were very prone to carbene dimerization, intramolecular reactions were required in order to control the chemistry effectively [17]. The enhanced chemoselectivity of the donor/acceptor-substituted carbenoids has enabled intermolecular C-H insertion to become a very practical enantioselective method for C-H activation. Since the initial report in 1997 [121], the field of intermolecular enantioselective C-H insertion has undergone explosive growth [14, 15]. Excellent levels of asymmetric induction are obtained when these carbenoids are derived... 

M. Hirama u. S. Ito, Heterocycles 28, 1229-1247 (1989) . .Asymmetric Induction in the Intramolecular Conjugate Addition of y- or d-Carbamoyloxy-a,/ -unsaturated Esters. A New Method for Diastcreo-selective Amination and Divergent Syntheses of 3-Amino-2,3,6-trideoxyhcxoscs". 

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