Intermolecular reactions vinylic substitution

In contrast to intermolecular reactions intramolecular substitutions may offer higher diastereoselectivities but again, complete lack of stereoselectivity is often encountered. Allylsi-lanes can serve as precursors for the stoichiometric preparation of 7c-allylpalladium(II) complexes12. If a stereogenic center is present in the molecule, diastereomeric complexes are formed, whose ratio can be determined by H NMR. Ionization of the dimeric complex 3 with triphenylphosphane gives a zwitterion which cyclizes in a 3-exo-trig mode to the vinyl cyclopropane derivative 4 with unknown diastereomeric ratio. For the cyclization step, dimethylsul-foxide and acetonitrile arc effective solvents, whereas with tetrahydrofuran and methylene chloride no reaction is observed. 

The Heck reaction, a palladium-catalyzed vinylic substitution, is conducted with olefins and organohalides or pseudohalides are frequently used as reactants [15, 16], One of the strengths of the method is that it enables the direct monofunctionalization of a vinylic carbon, which is difficult to achieve by other means. Numerous elegant transformations based on Heck chemistry have been developed in natural and non-natural product synthesis. Intermolecular reactions with cyclic and acyclic al-kenes, and intramolecular cyclization procedures, have led to the assembly of a variety of complex and sterically congested molecules. 

Photogenerated nitrenes can undergo cycloaddition with alkenes intermolecular reaction leads to aziridine products (5.38), and intramolecular reaction in vinyl azides gives azirines (5.39). The bicyclic azirine from phenyl azide has not been isolated, but it is the intermediate that best accounts for the formation of a substituted azepine when this azide is irradiated in the presence of a secondary amine (5.401. 

Alkyl halides with (3-hydrogens generally undergo only elimination reactions under the conditions of the vinyl substitution (100 C in the presence of an amine or other base). Exceptions are known only in cases where intramolecular reactions are favorable. Even alkyl halides without (3-hydrogens appear not to participate in the intermolecular alkene substitution since no examples have been reported, with the exception of reactions with benzyl chloride and perfluoroalkyl iodides. 

Cyclopropane formation occurs from reactions between diazo compounds and alkenes, catalyzed by a wide variety of transition-metal compounds [7-9], that involve the addition of a carbene entity to a C-C double bond. This transformation is stereospecific and generally occurs with electron-rich alkenes, including substituted olefins, dienes, and vinyl ethers, but not a,(J-unsaturated carbonyl compounds or nitriles [23,24], Relative reactivities portray a highly electrophilic intermediate and an early transition state for cyclopropanation reactions [15,25], accounting in part for the relative difficulty in controlling selectivity. For intermolecular reactions, the formation of geometrical isomers, regioisomers from reactions with dienes, and enantiomers must all be taken into account. 

In this sense Organ and coworkers [80] have developed intriguing syntheses of polysubstituted olefins based upon consecutive intermolecular reactions such as allylic and allylic-vinylic halide coupling sequences. Therefore, l-acetoxy-4-chloro but-2-ene can be readily submitted as a template for Pd-catalyzed allylic substitutions with two different carbon or nitrogen nucleophiles, leading to unsymmetrically substituted butene derivatives 66-70 in good yields (Scheme 22). Mechanistically, the chloro substituent is replaced... 

In the Heck reaction, an aryl or vinyl halide (R-X) and an alkene (H2C=CHR ) are converted to a more highly substituted alkene (R-CH=CHR ) under Pd catalysis. Base is used to neutralize the by-product (HX). The Heck reaction can be carried out in intra- or intermolecular fashion. In intermolecular reactions, the reaction proceeds best when the alkene is electrophilic. In intramolecular reactions, more highly substituted alkenes can be used. 

In 2001, Mauleon et al. reported an unusual palladium-cascade arylation of a,P-unsaturated phenyl sulfones 23 under Heck reaction conditions [12]. Contrary to the work of Fuchs and others [13], Mauledn et al. described the intermolecular reaction of a,P-unsaturated sulfones with a large excess of iodobenzene (or / -substituted iodoarenes) in the presence of Ag COj as base, which occurred mainly through a complex cascade reaction in which three molecules of iodobenzene and one molecule of vinyl sulfone were involved, forming fused polycyclic compounds 25 rather than the Heck trisubstituted olefin expected. The authors propose a mechanism involving Heck reaction and C-H activation pathways (Scheme 6.5). 

Carbonates of y-vinyl alcohols such as 87 undergo the intermolecular nucleophilic acyl substitution reaction to afford the corresponding alkyltitanium complex 88 having a lactone moiety (Scheme 12.59). The titanium-carbon bond in the... 

Intermolecular befera-Diels-Alder reactions of enamino ketones with highly substituted vinyl ethers. Effect of high pressure on the kinetics and diastereoselectivity [77]... 

In addition to siloxy- and alkoxy-substituted VCPs, alkyl- and H-substituted VCPs are also effective in the intermolecular [5 + 2]-cycloaddition reaction (Scheme 11). In general, an increase in the steric bulk of the cyclopropane substituent (H vs. Me vs. Pr1) leads to increased reaction rates, putatively through preferential population of the more reactive as-oid arrangement of the vinyl and cyclopropane moieties.43... 

The inter- and intramolecular Heck reactions provide other routes to substituted pyridines . Although electron-deficient 2-bromopyridines are resistant to substitution under Heck conditions, the aminopyridine 142 affords a high yield of the adduct 143 (Equation 68) <1998T6311>. The intermolecular Heck reaction of a 3-pyridyltriflate with ethyl acrylate is accelerated by LiCl <1999SL804>. An efficient Heck vinylation of 3-substituted-2-bromo-6-methylpyridines with methyl acrylate has been developed <2005T4569>. 

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