Electrophilic reactions allylic derivatives

If the ring becomes more strained in the transition state nucleophilic substitution should proceed more slowly than with similar, non-cyclic electrophiles. Thus, cyclopropyl derivatives are highly resistant towards nucleophilic substitution because the RCR angle is fixed at 60°, and only rarely can products of an Sn2 reaction at cyclopropyl derivatives be obtained [109]. Instead, allyl derivatives are usually the main products (Scheme4.23). 

The presence of five-membered rings such as cyclopentanes, cyclopentenes, and dihydrofurans in a wide range of target molecules has led to a variety of methods for their preparation. One of the most successful of these is the use of trimethylenemethane [3 + 2] cycloaddition, catalysed by pal-ladium(O) complexes. The trimethylenemethane unit in these reactions is derived from 2-[ (trimethylsilyl)methyl]-2-propen- 1-yl acetate which is at the same time an allyl silane and an allylic acetate. This makes it a weak nucleophile and an electrophile in the presence of palladium(0). Formation of the palladium 7t-allyl complex is followed by removal of the trimethylsilyl group by nucleophilic attack of the resulting acetate ion, thus producing a zwitterionic palladium complex that can undergo cycloaddition reactions. 

Metal-carbon (M—C) bonds are thermodynamically unstable with regard to their hydrolysis products. Water can attack M—C bonds either by proton transfer (H+, electrophilic reaction) or via the oxygen (OH2 or OH, nucleophilic reaction). Examples are shown in Scheme 1. Ligands such as carbon monoxide and ethylene are activated toward nucleophilic attack upon coordination to (low-valent) metals, e.g., Pd2+. A number of C—C-bond forming reactions derive from this activation. Allyl ligands are generated by proton attack to the terminal 1,3-diene carbon... 

Perhaps the most interesting developments in the area of selective lithiations to appear this year have been concerned with the control of absolute stereochemistry. The application of chiral amide bases to the enantioselective deprotonation of epoxides was first described some years ago by Whitesell and co-workers, but this year several groups have reported on other aspects of these useful reaqents. Symmetrically substituted ketones (5 R=Me, CH2Ph) have been shown by Simpkins to undergo an enantioselective deprotonation under kinetically controlled conditions to give, after reaction with an electrophile (iodomethane, allyl bromide or acetic anhydride), optically active ketones (6) or enol acetates (7) (Scheme 2). The ability of a number of bases to discriminate between the two prochiral protons present in (5) were evaluated and the most effective of those studied was the camphor derivative (8) deprotonation of (5 R=Me) proceeded in 74% enantiomeric excess... 

Aldehydes are generally accepted to be soft electrophiles towards allyl anions such as (82), and usually lead to good yields of y-adducts. However, with dithianyl derivatives, e.q. (84), the exposed nature of the a-site results in an increased level of reaction via this site. This may be suppressed if the normal lithium counterion is replaced by cadmium. The resulting organometa11ic complex gives good levels of y-selectivity with aldehydes (Scheme 28). The same authors have also studied the effect of added CdCl, to anions derived from a,B-unsaturated esters (85). The influence of an adjacent to... 

The coupling reactions with the benzoyl chloride and allyl iodide required the addition of 10% Cul as catalyst to yield the corresponding ketone and allyl derivatives. In the absence of copper iodide catalyst, the prementioned two electrophiles gave only low yields ofthe expected products. 1,2-Dibromoethane was used to remove the excess of magnesium when benzoyl chloride or ally iodide was used as electrophiles (entries 6 and 7), and it did not react with the Grignard reagents under the given reaction conditions. 

Annulations. The primary allylic halide 2-chloromethyl-3-trimethylsilyl-l-propene or the mesylate derived from the corresponding alcohol behaves as a hifunctional reagent possessing both nucleophilic and electrophilic reaction centers. For example, they have been shown to participate in [3 + 2] carbon annulations for the constmction of methylenecyclopentanes. The reaction proceeds through a Lewis acid-promoted conjugate addition (Sakurai reaction) followed by an internal alkylation of the derived ketone enolate (eq 3). 

The direct ruthenium catalysed allylation with allylic alcohol derivatives of various aromatic compounds and heterocycles such as furans and thiophenes was performed by Nishibayashi with cationic thiolate-bridged diruthenium(III, II) catalysts. The reaction is consistent with an electrophilic aromatic substitution by the electrophilically activated allyl moiety [68]. Allylation also takes place with the alkene metathesis Grubbs catalyst [69]. More importantly using (phosphine-sulfonate)ruthenium(II) catalyst Bmneau et al. have recently shown that allyl alcohols are activated generating an allyl-ruthenium(IV) intermediate leading to C3-allylation of indole with high regioselectivity in favour of the branched allyl derivative [(Eq. 84)] [167]. 

As with the silanes, some of the most useful procedures for synthetic applications of stannanes involve electrophilic attack on alkenyl and allylic derivatives. The stannanes are more reactive than the corresponding silanes because there is more anionic character on carbon in the C—Sn bond and it is a weaker bond. There are also a number of synthetic procedures in which organotin compounds act as carbanion donors in transition metal-catalyzed reactions. Organotin compounds are also used in free-radical reactions, as will be discussed in Chapter 10. 

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