Inversion benzyllic carbon

Diaziridines also show slow nitrogen inversion, and carbon-substituted compounds can be resolved into enantiomers, which typically racemize slowly at room temperature (when Af-substituted with alkyl and/or hydrogen). For example, l-methyl-3-benzyl-3-methyl-diaziridine in tetrachloroethylene showed a half-life at 70 °C of 431 min (69AG(E)212). Preparative resolution has been done both by classical methods, using chiral partners in salts (77DOK(232)108l), and by chromatography on triacetyl cellulose (Section 5.08.2.3.1). 

It is of interest to note that in the case of oxaazaphosphospholidines 302 derived from (-)-ephedrine (42), some inversion at the benzylic carbon occurred giving a mixture of the P-epimeric derivatives 303 (Scheme 71) [108], Halide exchange with inversion of configuration in the intermediate was suggested as the most likely explanation for the loss of stereospecificity. 

In a-methyl-benzylcalcium and a-Me3Si-benzylcalcium complexes, energy barriers for inversion of the chiral benzylic carbon (17-19 kcal mol-1) are concentration independent, suggesting that a dissociative mechanism is involved that involves Ca-Ca bond breakage. The a-methyl-benzylcalcium compounds are less stable and show a... 

The reaction of 2 - a r v I - N - io s v I a / i r i d i n es was studied in water containing /i-cyclo-dextrin, which formed an inclusion complex with the aziridine 49 The products were formed from attack at the benzyl carbon with inversion of configuration. The yields were high. 

It was hoped that the resulting benzylic carbinols 59 could be stereose-lectively reduced by catalytic hydrogenation to the required protected kainoid derivatives 60 (Scheme 24). The reduction of benzylic alcohols varies in stereospecificity depending on the catalyst employed.53 Hydrogenation over Raney nickel generally proceeds via retention of configuration, whereas hydrogenation over palladium on charcoal leads to inversion at the benzylic carbon. 

Cleavage of (2S,3S)-3-phenylglycidol (1). This epoxide (1) is cleaved by a number of nucleophiles regioselectively at the benzylic carbon to give 1,2-diols. The cleavage usually occurs with almost complete inversion at the benzylic center (>99 1). Trimethylaluminum, however, reacts with retention (32 1, equation I). Triethylaluminum reacts with 1 to give the corresponding adducts in a 1 1 ratio. 

The Hammett p value of—4.1 suggests a carbocation intermediate as does the regioselectivity of the reaction (MeOH attacks the benzylic position) but the stereochemistry (the reaction occurs with inversion) and a modest negative entropy of activation (AS = —48 J mol-1 K 1) suggest rather an S]sj2 reaction with a loose transition state having substantial positive charge at the benzylic carbon. Neither piece of evidence alone would be enough to define the mechanism. 

The reaction of Pd complexes (such as Pd(PhsP)4) with organic halides and related compounds has been used to prepare a number of stable Pd alkyl and vinyl compounds. This reaction with alkyl halides has the characteristics of an Sn2 reaction. Primary halides react faster than secondary halides. Also, when a chiral halide is used, such as (X)-(-F)-benzyl-o -D chloride, the benzyl palladium product is formed with inversion of configuration at the benzylic carbon (equation 8). With vinylic halides, retention of configuration at the double bond is observed... 

Solvolysis of electrophilic cyclopropanes with alcohols and phenols readily occurs as illustrated by the following examples of equations 166-168. It is worthwhile to note that methanolysis at 126 °C of ( + )-( ) methyl l-cyano-2-phenylcyclopropanecarboxylate (495) gives rise to (— )-(S)-methyl 2-cyano-4-methoxy-4-phenylbutanoate (496), indicating that the nucleophilic substitution reaction at the benzylic carbon of the cyclopropane proceeds with essentially complete inversion of configuration (equation 169). ... 

In a study by Berti et al., acid-catalyzed hydrolysis of styrene oxide was reported to occur with 67% inversion and 33% retention at the benzyl carbon.45 In a later study, it was reported that the styrene glycol product formed in the acid-catalyzed hydrolysis of chiral styrene oxide is completely racemic, which would indicate an A-l mechanism.46 As these two results indicate quite different mechanisms for this reaction, the glycol product from acid-catalyzed hydrolysis of chiral styrene oxide was converted to its bis-( + )-a-(methoxy-a-trifluoromethyl)phenylacetate diester derivative, and the composition of the diastereomeric diester mixture was determined by H NMR.47 This study agreed with those of Berti et al. and showed that acid-catalyzed hydrolysis of styrene oxide occurs with 67% inversion and 33% retention at the benzyl carbon. Acid-catalyzed methanolysis of styrene oxide is reported to occur with 89% inversion at the benzyl carbon.48 The fact that the diol product from acid-catalyzed hydrolysis of chiral styrene oxide is not completely racemic demonstrates that the lifetime of the carbocation is not sufficiently long for it to become symmetrically solvated. 

An SN2-like mechanism is likely on primary carbon atoms whereas the reaction probably has high SnI character for compounds containing tertiary or benzylic carbon atoms. For this S l mechanism, however, inversion of configuration is also expected, because rotation around the sigma bond is difficult because of steric interaction of the large groups with the catalyst surface. 

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