Substituents application strategies

There are, however, serious problems that must be overcome in the application of this reaction to synthesis. The product is a new carbocation that can react further. Repetitive addition to alkene molecules leads to polymerization. Indeed, this is the mechanism of acid-catalyzed polymerization of alkenes. There is also the possibility of rearrangement. A key requirement for adapting the reaction of carbocations with alkenes to the synthesis of small molecules is control of the reactivity of the newly formed carbocation intermediate. Synthetically useful carbocation-alkene reactions require a suitable termination step. We have already encountered one successful strategy in the reaction of alkenyl and allylic silanes and stannanes with electrophilic carbon (see Chapter 9). In those reactions, the silyl or stannyl substituent is eliminated and a stable alkene is formed. The increased reactivity of the silyl- and stannyl-substituted alkenes is also favorable to the synthetic utility of carbocation-alkene reactions because the reactants are more nucleophilic than the product alkenes. 

Several applications of this methodology are known. For the determination of the relative configuration of the stereocenter and the axial chiral unit of 71, the product of a diastereoselective ester enolate Claisen rearrangement of 70, with AgBF4 a cycli-zation to 72 was initiated. Then the carboxylic acid was reduced to alcohol 73 and the position of the substituents was investigated by NMR and by the use of NMR shift-reagents (Scheme 15.16) [32], Control experiments ensured the stereospecifi-city of the cyclization and the reduction step. There are further examples of this strategy [33]. 

The synthesis of chemical libraries loaded with structural diversity is an emerging field with direct applications in biomedical research. Strategies for library synthesis have mainly focused on combinatorial synthesis of molecules that vary substituents with a core... 

An application of the deracemization strategy has provided efficient entry to a novel amino acid substituent of the antifungal agents, polyoxins and nikkomycins, as shown in Scheme 8E.20. The versatile five-carbon building block was obtained from phthalimidation of the hydroxymethyl-substituted epoxide in 87% yield and 82% ee. Straightforward synthesis of polyoxamic acid was then accomplished by subsequent dihydroxylation and selective oxidation of the alkylation product. 

Another concise strategy for the synthesis of alkaloids related to crinine features the application of a general and useful procedure for the elaboration at a carbonyl center of a quaternary carbon atom bearing differentially functionalized alkyl substituents. The application of this methodology to the total syntheses of ( )-crinine (359) and ( )-buphanisine (361) (Scheme 46) commenced with the... 

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