Chiral 8-phenylmethyl

Okamoto and his colleagues60) described the interesting polymerization of tri-phenylmethyl methacrylate. The bulkiness of this group affects the reactivity and the mode of placement of this monomer. The anionic polymerization yields a highly isotactic polymer, whether the reaction proceeds in toluene or in THF. In fact, even radical polymerization of this monomer yields polymers of relatively high isotacticity. Anionic polymerization of triphenylmethyl methacrylate initiated by optically active initiators e.g. PhN(CH2Ph)Li, or the sparteine-BuLi complex, produces an optically active polymer 60). Its optical activity is attributed to the chirality of the helix structure maintained in solution. 

Darzens reaction of (-)-8-phenylmethyl a-chloroacetate (and a-bromoacetate) with various ketones (Scheme 2) yields ctT-glycidic esters (28) with high geometric and diastereofacial selectivity which can be explained in terms of both open-chain or non-chelated antiperiplanar transition state models for the initial aldol-type reaction the ketone approaches the Si-f ce of the Z-enolate such that the phenyl ring of the chiral auxiliary and the enolate portion are face-to-face. Aza-Darzens condensation reaction of iV-benzylideneaniline has also been studied. Kinetically controlled base-promoted lithiation of 3,3-diphenylpropiomesitylene results in Z enolate ratios in the range 94 6 (lithium diisopropylamide) to 50 50 (BuLi), depending on the choice of solvent and temperature. ... 

There are only a few reports on chiral phase transfer mediated alkylations". This approach, which seems to offer excellent opportunities for simple asymmetric procedures, has been demonstrated in the catalytic, enantioselective alkylation of racemic 6,7-dichloro-5-methoxy-2-phenyl-l-indanone (1) to form ( + )-indacrinone (4)100. /V-[4-(tnfluoromethyl)phenylmethyl]cinchoninium bromide (2) is one of the most effective catalysts for this reaction. The choice of reaction variables is very important and reaction conditions have been selected which afford very high asymmetric induction (92% cc). A transition state model 3 based on ion pairing between the indanone anion and the benzylcinchoninium cation has been proposed 10°. 

Pioneering work by Pracejus et al. in the 1960s, using alkaloids as catalysts, afforded quite remarkable 76% ee in the addition of methanol to phenylmethyl-ketene [26-29]. In 1999 Fu et al. reported that of various planar-chiral ferrocene derivatives tried, the azaferrocene 35 performed best in the asymmetric addition of methanol to several prochiral ketenes [30, 31]. In the presence of 10 mol% catalyst 35 (and 12 mol% 2,6-di-tert-butylpyridinium triflate as proton-transfer agent), up to 80% ee was achieved (Scheme 13.16). 

Takagi, R., Nakamura, M., Hashizume, M., Kojima, S., and Ohkata, K. (2001) Stereoselective cyclopropanation of 3-aryl-2-phosphonoacrylates induced by the (—)-8-phenylmethyl group as a chiral auxiliary. Tetrahedron Letters, 42, 5891—5895. 

Chiral glycine enolate synthons have been employed in diastereoselective alkylation reactions [15]. A complementary approach to the synthesis of a-amino acids is the electrophilic amination of chiral enolates developed by Evans [16]. Lithium enolates derived from A-acyloxazolidinones 38, reacted readily with DTBAD to produce the hydrazide adducts 39 in excellent yields and diastereoselectivities (Scheme 18). Carboximides 38 were obtained by A-acylation of (S)-4-(phenylmethyl)-2-oxazoli-dinone and the lithium-Z-enolates of 38 were generated at -78 °C in THF under inert atmosphere using a freshly prepared solution of lithium diisopropylamide (LDA, 1.05 equiv.) [17]. 

Analogously, after enolization with Ihmds, hypervalent iodine compounds such as PhI(OAc)2 have been used for the stereoselective synthesis of 2,3-disubstituted succinates by using the chiral oxazolidinone auxiliary (45 )-4-(phenylmethyl)-2-oxazolidinone (equation 19) . 

Atazanavir 11 (Figure 16.4A) is an acyclic aza-peptidomimetic, a potent HIV protease inhibitor [43,44] approved recently by the U.S. Food and Drug Adminstration for treatment of autoimmune diseases (e.g., AIDS). An enzymatic process has been developed for the preparation of (lS,2/ )-[3-chloro-2-hydroxy-l-(phenylmethyl)pro-pyljcarbamic acid, 1,1-dimethylethyl ester 13 (Figure 16.4B), akey chiral intermediate... 

Asymmetric reaction of the sulfides bearing a tricarbonyl(ri -arene)chromi-um complex was shown to be successful by Gibson and Simpkins [48,49]. The benzyhc methylene groups in tricarbonyl(ri -phenylmethyl alkyl sulfide)chro-mium(O) and tricarbonyl(ri -l,3-dihydroisobenzothiophene)chromium(0) were highly asymmetrically functionahzed by deprotonation with a chiral bis-Uthium amide and subsequent electrophihc reactions (Tables 4 and 5). 

The monomers with relatively small N-substituents such as N-methyl methacrylamide afford polymers rich in syndiotacti-city. The bulkier N-isopropyl, N-t-butyl, and N-phenyl derivatives result in polymers with a slightly reduced syndio-tacticity. However, radical polymerization of bulky N-[di (4-butylphenyl)phenylmethyl] methacrylamide (DBuTrMAM, 67) and N-triphenylmethylmethacrylamide (TrMAM, 68) produces a nearly complete isotactic polymer due to helix formation of the polymer chain. When the radical polymerization of these monomers was carried out in the presence of optically active menthol, single-handed helical, optically active polymers were produced. Because poly(TrMAM) was insoluble in solvents, its CD spectra were measured in the solid state to support the chiral structure. 

Several examples can serve to illustrate the use of chiral auxiliaries. First, the chiral, heterocyclic, amino-add-derived lactam, (5)-4-(phenylmethyl)-2-oxazolidinone, is capable of conversion into an anion on treatment with butyllithium [CH3(CH2)2CH2Li]. Acylation at nitrogen with propanoyl chloride produces chiral propionamide. 

Treatment of (R,R)-l,2-bis(l-acetoxy-l-phenylmethyl)-ferrocene with azidot-rimethylsilane in the presence of a catalytic amount of a Lewis acid such as Cu(OTf)2 and Sc(OTf)3 (10mol%) gave a mixture of two diasteromeric ferrocenyl diazides in a 80/20 ratio [157]. The major isomer was formed with retention of configuration at both benzylic chiral centers whereas the minor isomer was produced with inversion of configuration at one of the two chiral centers. 

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