Alkylations substituted alkene synthesis

Coupling with enol esters (7, 93). A new synthesis of an alkyl-substituted alkene involves coupling of a lithium dialkyl cuprate with an enol triflate,1 available from a ketone by reaction with triflic anhydride and 2,6-di-t-butylpyridine.2 A wide variety of organocuprates can be used and the geometry of the enolate is largely retained. Reported yields are in the range 60 100%. 

As a general mle, unless an anion-stabilizing group, such as phenyl, or a heteroatom such as sulfur is present, the alkylsilane is not readily deprotonated. The a-halosilane can be deprotonated but, unlike the readily available chloromethyltrimethylsilane, there are few general methods to this approach. Al-kyllithium reagents add to vinylsilanes ( ) to produce the carbanion (287). Silyl derivatives with heteroatoms, such as sulfur, selenium, silicon or tin, in the a-position (288) may be transmetallated (Scheme 41). Besides the difficulty in synthesizing the anion, alkene formation lacks specificity for simple di- and tri-alkyl-substituted alkenes. As a result, the Peterson reaction of an a-silyl carbanion with a carbonyl has found the greatest utility in the synthesis of methylene derivatives, (as discussed in Section 3.1.3), heterosubstituted alkenes and a,p-unsaturated esters, aldehydes and nitriles. 

Enamines 1 are useful intermediates in organic synthesis. Their use for the synthesis of a-substituted aldehydes or ketones 3 by reaction with an electrophilic reactant—e.g. an alkyl halide 2, an acyl halide or an acceptor-substituted alkene—is named after Gilbert Stork. 

The first step in this preparation, the epoxidation of 1,4,5,8-tetra-hydronaphthalene, exemplifies the well-known selectivity exerted by peracids in their reaction with alkenes possessing double bonds that differ in the degree of alkyl substitution.12 As regards the method of aromatization employed in the conversion of ll-oxatricyclo[4.4.1.01-6]-undeca-3,8-diene to l,6-oxido[10]annulene, the two-step bromination-dehydrobromination sequence is given preference to the one-step DDQ-dehydrogenation, which was advantageously applied in the synthesis of l,6-metliano[10]annulene,2,9 since it affords the product in higher yield and purity. 

The Hofmann elimination is useful synthetically for preparing alkenes since it gives the least substituted alkene. The reaction involves thermal elimination of a tertiary amine from a quaternary ammonium hydroxide these are often formed by alkylation of a primary amine with methyl iodide followed by reaction with silver oxide. The mechanism of the elimination is shown in Scheme 1.13 in this synthesis of 1-methyl-1-... 

Acetylene- and Diacetylene-Expanded Cycloalkanes and Rotanes. 201 1 -42 de Meijere A, Kozhushkov SI, Khlebnikov AF (2000) Bicyclopropylidene - A Unique Tetra-substituted Alkene and a Versatile Cj-Building Block. 207 89-147 de Meijere A, Kozhushkov SI, Hadjiaraoglou LP (2000) Alkyl 2-Chloro-2-cyclopropylidene-acetates - Remarkably Versatile Building Blocks for Organic Synthesis. 207 149-227 Dennig J (2003) Gene Transfer in Eukaryotic Cells Using Activated Dendrimers. 228 227-236 de Raadt A, Fechter MH (2001) Miscellaneous. 215 327-345 Desreux JF, see Jacques V (2002) 221 123-164... 

A modified version of the Brown-Negishi reaction using B-alkylcatechol-boranes was reported (Scheme 32). This novel method is based on a simple one-pot procedure involving the hydroboration of various substituted alkenes with catecholborane, followed by treatment with catalytic amount of oxygen/DMPU/water and a radical trap. Efficient radical additions to a,ft-unsaturated ketones and aldehydes have been reported. Primary alkyl radicals are efficiently generated by this procedure and the reaction has been applied to a 300 mmol scale synthesis of the y-side chain of (-)-perturasinic... 

Since reactivity of alkenes increases with increasing alkyl substitution, hydration is best applied in the synthesis of tertiary alcohols. Of the isomeric alkenes, cis compounds are usually more reactive than the corresponding trans isomers, but strained cyclic isomeric olefins may exhibit opposite behavior. Thus, for example, frans-cyclooctene is hydrated 2500 times faster than cw-cyclooctene.6 Similar large reactivity differences were observed in the addition of alcohols to strained trans cycloalkenes compared with the cis isomers. frans-Cycloheptene, an extremely unstable compound, for instance, reacts with methanol 109 faster at —78°C than does the cis compound.7... 

Ranu, B.C. and Hajra, A., Synthesis of alkyl-substituted pyrroles by three-component coupling of carbonyl compound, amine and nitro-alkane/alkene on a solid surface of silica gel/alumina under microwave irradiation, Tetrahedron, 2001, 57, 4767-4773. 

The majority of mono- and di-substituted alkenes undergo hydroboration to give trialkylboranes which are then available for a variety of synthetic procedures. With some alkenes, alkylation of borane does not go to completion and the resulting mono- or di-alkyl boranes are useful in synthesis as modified boranes. Thus, 2-methylbut-2-ene gives bis(3-methyl-2-butyl)borane (idisiamylborane). 

The regioselectivity of the Paterno-Biichi reaction with acyclic enol ethers is substantially higher than with the corresponding unsymmetrically alkyl-substituted olefins. This effect was used for the synthesis of a variety of 3-alkoxyoxetanes and a series of derivatives [55]. The diastereoisomeric cis-and tnms-l-methoxy-l-butenes were used as substrates for the investigation of the spin state influence on reactivity, regio- and stereoselectivity [56]. The use of trimethylsilyloxyethene 62 as electron rich alkene is advantageous and several 1,3-anhydroapiitol derivatives such as 63 could be synthesized via photocycloaddition with l,3-diacetoxy-2-propanone 61 (Sch. 17) [57]. 

---