Ether compounds asymmetric reactions, chiral auxiliaries

However, most asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides with alkenes are carried out without Lewis acids as catalysts using either chiral alkenes or chiral auxiliary compounds (with achiral alkenes). Diverse chiral alkenes are in use, such as camphor-derived chiral N-acryloylhydrazide (195), C2-symmetric l,3-diacryloyl-2,2-dimethyl-4,5-diphenylimidazolidine, chiral 3-acryloyl-2,2-dimethyl-4-phenyloxazolidine (196, 197), sugar-based ethenyl ethers (198), acrylic esters (199, 200), C-bonded vinyl-substituted sugar (201), chirally modified vinylboronic ester derived from D-( + )-mannitol (202), (l/ )-menthyl vinyl ether (203), chiral derivatives of vinylacetic acid (204), ( )-l-ethoxy-3-fluoroalkyl-3-hydroxy-4-(4-methylphenylsulfinyl)but-1 -enes (205), enantiopure Y-oxygenated-a,P-unsaturated phenyl sulfones (206), chiral (a-oxyallyl)silanes (207), and (S )-but-3-ene-1,2-diol derivatives (208). As a chiral auxiliary, diisopropyl (i ,i )-tartrate (209, 210) has been very popular. 

The range of alkenes that may be used as substrates in these reactions is vast Suitable catalysts may be chosen to permit use of ordinary alkenes, electron deficient alkenes such as a,(3-unsaturated carbonyl compounds, and very electron rich alkenes such as enol ethers. These reactions are generally stereospecific, and they often exhibit syn stereoselectivity, as was also mentioned for the photochemical reactions earlier. Several optically active catalysts and several types of chiral auxiliaries contained in either the al-kene substrates or the diazo compounds have been studied in asymmetric cyclopropanation reactions, but diazocarbonyl compounds, rather than simple diazoalkanes, have been used in most of these studies. When more than one possible site of cyclopropanation exists, reactions of less highly substituted alkenes are often seen, whereas the photochemical reactions often occur predominantly at more highly substituted double bonds. However, the regioselectivity of the metal-catalyzed reactions can be very dependent upon the particular catalyst chosen for the reaction. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

The first asymmetric synthesis of (20 S)-camptothecin using catalytic asymmetric induction was achieved by Fang et al. in 1994 [74], They carried out a catalytic enantioselective synthesis of Comins s intermediate (23) in order to avoid the use of the expensive chiral auxiliary, 8-phenylmenthol, or similar compound. Intramolecular Heck reaction of pyridine derivative (26) gave the cyclic olefins (27) and (28) in a ratio 1 8. The allylic ether (27) can be isomerized to (28) upon treatment with Wilkinson s catalyst [75], Asymmetric Sharpless dihydroxylation of (28) proceeded successfully when 2,5-diphenyl-4,6-bis(9-0-dihydroquinidyl)pyrimidine [(DHQD)2-PYR] was used as the chiral catalyst [76], and subsequent oxidation gave (29) in 94% ee. Treatment of (29) with acid gave the target molecule (23, Scheme 2.5), which was converted to (20S)-camptothecin in 2 steps using the Comins s procedure [73]. 

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