Asymmetric ally lation

A formal enantioselective synthesis of the antibiotic L-azatyrosine was developed. The asymmetric ally lation of hydrazono esters with ally lsilanes in the presence of a catalytic amount of ZnF2-chiral diamines in aqueous media generated (benzoyl)hydrazino-4-pentenoates in high enantioselec-tivity(Eq. 11.46).77... 

Keck and Tagliavani reported within months of each other the asymmetric ally-lation reactions with allyltri-n-butylstannane and various aldehydes with BINOL-Ti(IV) catalysts 451 and 452, respectively [289, 2901. Although the two catalysts give similar yields and enantioselectivities with a range of aldehydes, the diiso-propoxide catalyst 451 has been used more extensively. Keck and co-workers have shown that a variety of aldehydes react with allyl and methallyltri-n-butyl-stannane in modest to excellent yield and with good to excellent enantioselection using (/ )-451 as the catalyst (Table 11-25) [289, 296, 2971. 

Chiral /3-amino sulfoxides served as chiral ligands in Pd-catalyzed allylations. Chiral j8-aminoethyl sulfoxides 31a-f-palladium complexes catalyzed asymmetric ally-lations of 33 to give (5)-34 with 29% ee. o-Aminophenyl sulfoxides 32a,b provided much higher enantioselectivity (50%), presumably due to the sterically fixed structure of the intermediary palladium complex 35 (Scheme 17). 

With environmental consideration in mind, the group has developed a version in concentrated media, i.e. without dichloromethane and only three equivalents of isopropanol. ° For instance, the ketone 64 was converted into the alcohol 65 in 93% yield and 95% enantiomeric excess using only 10 mol% of titanium-BINOL catalyst (Conditions B, Scheme 7.36). A slight decrease of efficiency was observed using 5 mol% of catalyst (Conditions C). The efficiency of the method was illustrated by a tandem asymmetric ally-lation/diastereoselective epoxidation reaction of cyclic enones that is based on the use of the allylation catalyst for a subsequent epoxidation with TBHP, as illustrated in Scheme 7.37. ° ... 

Asymmetric Ally lation of Carbonyl Compounds via Organoboranes... 

Several enantioselective approaches to vitamin E (1), based on resolution of the products, the use of enantiopure natural building blocks, auxiliary controlled reactions and asymmetric oxidations have been described. In addition, a palladium-catalyzed asymmetric allylic alkylation reaction to build up the chiral chroman framework has been employed by Trost. Tietze and coworkers have developed asymmetric syntheses of the chiral chroman moiety using either the selective ally-lation of an alkyl methyl ketone or a Sharpless dihydroxylation as the key step. However, none of these methods is efficient enough for an industrial approach. ... 

The Katsuki-Sharpless asymmetric epoxidation of racemic diol ( )-406 (obtained by ally-lation of ( )-crotonaldehyde) gives, after chromatographic separation, the eryt/tro-epoxide (-i-)-407 (33% yield, >95% ee) and (—)-406 (O Scheme 102). These intermediates have been converted into (-t-)-D-olivose and (-r)-D-ditoxose [517,518,519]. In a similar manner, asymmetric epoxidation of dienol ( )-408 leads to (-r)-409, which has been converted into (-r)-oliose, and to (—)-408, which has been converted into (-r)-cymarose [520,521]. 

The activation of the carbonyl group by Lewis acids was another leap made in the 1960s as typified by Mukaiyama-aldol reaction. In sharp contrast to the conventional carbonyl addition reactions that had been run under basic conditions, this new method allowed the addition of various nucleophiles under acidic conditions with high chemo- and stereocontrol and, consequently, the scope of the carbonyl addition reaction was extensively expanded. The Lewis acid-promoted ally-lation with allylmetals and ene reaction also received as much attention as the aldol-type reaction. It should be further pointed out that the catalytic versions of asymmetric reactions, which represent one of the most exciting topics in recent synthetic chemistry, owe their development strongly to the Lewis acid activation protocol. The design of a variety of chiral ligands for metals has produced luxuriant fruits in this field. 

Another enantioselective route to 116, that features catalytic asymmetric induction, is shown here (see Prostaglandins-12 for another example). This synthesis begins with racemic allylic acetate 123. A palladium-mediated ally-lation of dimethyl malonate in the presence of chiral ligands (for the Pd) provided 124 with excellent enantioselectivity. This material was converted to 116. Alkylation as per the Mori synthesis (Juvabione-16) gave 117, which was converted to 125 using another Pd-mediated malonate allylation. Malonate 125 was converted to 126 via an intermediate tetraol. The synthesis of juvabione (15) was then completed using a short reaction sequence. 

There have been numerous Other applications of BINOL-Ti-catalyzed ally-lation reactions in complex molecule syntheses [30, 32], In the construction of the terminal portion of mucocin, Evans documented the asymmetric addition of an allylstannane to unsaturated aldehyde 202, giving adduct 203 in 98 2 dr (Equation 14) [125]. In another example, Roush disclosed the addition of an allylstannane to aldehyde 204, en route to the synthesis of the superstolides (Equation 15) [126]. These examples underscore the Ti-cata-lyzed enantioselective allylation process as a general approach to useful, functionalized chiral fragments. 

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See also in sourсe #XX -- [ ]

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