Highly activated disubstituted

New possibilities in hetero-Diels-Alder condensation have been opened by the introduction of highly active l-methoxy-3-trimethylsilyloxy-, 4-benzoyIoxy-l-methoxy-3-trimethylsilyloxy-, and 2-acetoxy-l-alkoxy-3-trimethylsilyloxy-l,3-butadienes ( Danishefsky dienes, 5). These compounds readily react under atmospheric pressure, in the presence of Lewis acids, with normal aldehydes (e.g., acetaldehyde, benzaldehyde, furfural) to furnish 2,3-disubstituted or 2,3,5-trisubstituted derivatives of 2,3-dihydro-4H-pyran-4-one 7 capable of readily functionalizing to sugars (Scheme 5) [26]. This approach... 

A similar but conceptually distinct approach to difunctionalization of terminal alkynes consists of sequential carboboration-palladium-catalyzed cross-coupling 137 equation (33) illustrates that this method also provides alkenes of high stereochemical purity by net syn Markovnikov addition. Benzyne-contain-ing molecules can act as highly activated substrates for vicinal difunctionalizations initiated by nucleophiles 138-140 thus, nucleophilic addition-electrophilic trapping can serve as an alternative to sequential directed metallation for the production of 1,2-disubstituted and 1,2,3-trisubstituted aromatic systems (equation 34).141... 

We chose to design and then synthesize a class of compounds heretofore unknown in the artemisinin area 8,8-disubstituted-D-norartemisinins. While the parent molecule 421 was not predicted in the CoMFA models to be highly active, homologues of 421 were.155... 

Di-Cl—TFMS and 2,4-Di-F-TFMS. Trepka et al. (5) found the 2,4-di-Cl— and 2,4-di-F—TFMS derivatives to be highly active against both grasses and broadleaves (see Table I). We may thus ask whether the appropriate Hansch relationships listed in Table XI for the mono-substituted TFMS derivatives can be used to predict the high activity of these disubstituted compounds. 

Masamune et al. examined the catalytic activity of several boron Lewis acids derived from BH3 THF and the p-toluenesulfonamides of simple a-amino acids towards the aldol reaction of benzaldehyde with TMS enolate 48 [121]. As a result, the borane catalysts derived from a,a-disubstituted glycine p-tolueriesulforiarriides were found to have high activity. The disubstitution would accelerate the second step (Step II) of the catalytic cycle (Scheme 10.43). On the basis of this observation, they developed chiral borane catalysts 47 c and 47 d, which enable highly enantioselective aldol reactions of KSA and thioketene silyl acetals (84—99% ee with 48). 

This class of compounds may be considered to have been obtained by removing the benzene ring from the quinoline nucleus of quinine. A number of 4-pyridy-lalcohols have been shown to possess high activity against P. berghei, P. falciparum and P. vivax in experimental animals. However, promising antimalarial activity was obtained with 2,6-disubstituted-4-pyridylalcohols, of which WR-148946 (27a), WR-172435 (27b), WR-180409 (enpiroline, 27c) and 27d have been studied in detail [45]. 

Of the disubstituted phenoxyalkanoic acids the 4-chloro-2-methyiphenoxy derivatives (MCPA, MCPP, MCPB) are also of high activity. 

The cationic chiral catalyst [RhCcodlC )]" showed high activity and selectivity in the presence of C02-philic counterions such as the BARF or triflate anion (Scheme 4.7-3) [21]. The DuPHOS-type ligand 7 is a fairly nonpolar alkyl phospholane and is especially useful in asymmetric hydrogenation of dehydroamino acids in conventional solvents [38]. The enantioselectivities in SCCO2 compared well to those in methanol for most substrates, and the asymmetric induction was considerably higher for p,p-disubstituted substrates (Table 4.7-2). 

It has also been found that highly active catalysts can be prepared in situ by reducing a platinum, palladium, or rhodium salt with sodium borohydride in the presence of a carbon support. Similar reductions of nickel salts produce colloidal nickel-boron, which is highly selective toward olefins of different structural types. The normal order of reactivity—i.e., terminal > disubstituted > trisubstituted—is observed, but the reactivity spread is sufficiently large that selective hydrogenation of polyenes is possible, as illustrated by a step in a synthesis of the natural product... 

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