Benzyl halides stereochemistry

Alkyl halides that do not readily undergo nucleophilic attack may oxidatively add to a metal by radical mechanisms. Oxidative addition reactions that occur by radical mechanisms show loss of stereochemistry, nomeproducible rates, inhibition by radical inhibitors, and acceleration by O2 or light. Reactions of lr(Cl)(CO)(PMe3)2 with methyl and benzyl halides showed no indication of radical behavior, but other saturated alkyl halides, vinyl, and aryl halides showed characteristics consistent with a radical-chain pathway. 

Keywords benzyl halide, density functional calculation, organosilane, silyllithium compound, stereochemistry... 

The optically active benzyl halide PhCHDCl reacts with [Pd(PEt3)3] to give [Pd(PhCHD)Cl(PEt3)2] with net (72%) inversion of configuration at carbon as established by the reaction sequence in Scheme 7, in which the stereochemistry... 

The reactions of some optically active benzyl halides have provided further evidence for the nucleophilicities of the [Pd(PR3)j] species (Lau et al., 1974, 1976 Wong et al., 1974 Stille and Lau, 1976). The salient features of these studies are summarised in Scheme 6. The stereochemistry of the addition is established by reaction of the palladium-alkyl complex with carbon monoxide (this insertion is known to take place by an intramolecular migration process, with retention of configuration in the migrating alkyl group), and subsequent formation of an ester from this acyl complex. 

Treatment of benzyl halides with dihalomethane and NaHMDS affords vinyl halides with anti-Markovnikov selectivity and -stereochemistry [207] This conversion tends to work quite well following a Wittig-type process using CX or CHX [212,214, 215], Care must be exercised with this chemistry due to a propensity to generate the haloalkyne instead of the ge/n-dihalo species. Non-Wittig approaches have also been devised [210]... 

The oxidative addition is quite general with alkyl, allyl, benzyl, vinyl, and aryl halides as well as with acyl halides to afford the palladium (II) complex VII. The frans-bis( triphenylphosphine )alkylpalladium halides can also be carbonylated in an insertion reaction to give the corresponding acyl complexes, the stereochemistry of which (17, 18) proceeds with retention of configuration at the carbon bonded to palladium. The acyl complex also can be formed from the addition of the corresponding acid halide to tetrakis (triphenylphosphine) palladium (0). 

Most benzylic organolithiums, unless they bear an a heteroatom, are configurationally unstable over a period of seconds or more (see section 5.1.11), so any stereoselectivity in lateral lithiation is rarely detectable. However, as implied above, the lateral lithiation of tertiary 1-naphthamides 344 is stereoselective, and yields a single diastereoisomeric atropisomer of the organolithium 346b.159-139-140 Both diastereoisomers of 346 were characterised by NMR. These organolithiums react with most electrophiles to give 372 with retention of stereochemistry, but with trialkyltin halides with inversion (see section 6.1.4). 

Retention in the reactions of 15 is established both from presumed retention in the Sn-Li exchange step of a stannylation-destannylation sequence and by evidence that the s-BuLi-(-)-sparteine complex used to make the organolithium reliably removes the pro-/ proton adjacent to a carbamate (see below for crystallographic evidence involving a similar compound).11 The stereochemistry of the products 16, almost all formed essentially in enantiomerically pure form, was proved for the C02 adduct and the Mel adduct by comparison with known compounds. The only electrophiles for which incomplete retention of stereochemistry has been observed are the benzylic or allylic halides. These probably react in part by single electron transfer SE1 mechanisms, rather than by partial SE2inv.15 For example, 15 reacts with allyl bromide to give 16 (E = allyl) with only 42% ee. 

The absolute configurations of a number of arsonium ions and arsines have been correlated with one another on the basis of the stereospecificity of cathodic cleavage of the benzyl group from an arsonium ion and the quaternization of an arsine by benzyl and other alkyl halides, both of which occur with retention of configuration. Scheme 1 gives the connection between the stereochemistries of various optically active arsonium ions and arsines related to (S)-(+)-62. 

The SN1 reaction is almost always followed by tertiary halides, and also by secondary halides and, for example, tosylates, especially when at least one of the substituents is an aryl group. From this latter case the carbocation is now benzylic. The nature of the intermediate carbocation in an SN1 reaction is illustrated in Figure 7.3, which shows the three substituents in a coplanar arrangement and with an empty p-orbital. This structure provides a clue as to the stereochemistry of the subsequently formed tetrahedral product. 

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