Allyl leaving group approach

Recently, Lambert and co-workers645,646 have reported the preparation of the trimesityl-substituted Mes3Si+ cation 249 using the so-called allyl leaving group approach [Eq. (4.162)] instead of the hydride transfer reaction applied in earlier studies. The electrophile attacks the double bond and the intermediate carbenium... 

An alternative allyl leaving group approach was used by Lambert and coworkers38 in the preparation of the sterically hindered trimesitylgermyl and trimesitylstannyl cations (Scheme 3), analogous to their earlier preparation of the trimesitylsilyl ion39. 

Lambert JB, Zhao Y, Wu H, Tse WC, Kuhhnann B (1999) The allyl leaving group approach to tricoordinate silyl, germyl and stannyl cations. J Am Chem Soc 121 5001... 

Hie use of chiral catalysts as an approach to enantiomer icaliy enriched products by means of coppet-mediated substitution reactions is covered in this chapter. Reactions in which a chiral auxiliary resides in the leaving group of the substrate w ill also he dealt with, since these reactions provide direct and efBcient routes to single enantiomers of the desired products. Most studies so far have been concerned with allylic substrates, with a new chiral center being produced in the course of a selec-... 

Alkylation reactions are subject to the same constraints that affect all Sn2 reactions (Section 11.3). Thus, the leaving group X in the alkylating agent R—X can be chloride, bromide, iodide, or tosylate. The alkyl group R should be primary or methyl, and preferably should be allylic or benzylic. Secondary halides react poorly, and tertiary halides don t react at all because a competing E2 elimination of HX occurs instead. Vinylic and aryl halides are also unreactive because backside approach is sterically prevented. 

The first strategy involves discrimination between enantiotopic leaving groups (Type A). In the second approach, two enantiomers of a racemic substrate converge into a meso-n-al y complex wherein preferential attack of the nucleophile at one of either allylic termini leads to asymmetric induction, a process that may be referred to as a dynamic kinetic enantioselective transformation (Type B). The third requires differentiation between two enantiotopic transition... 

The SN21 reaction can theoretically take place by a nucleophilic attack on the allylic system either syn or anti to the leaving group (cf. 79 and 80). Although he never fully elaborated on it in print, Winstein (24-26) was the first to postulate that the nucleophilic attack should be syn. He suggested that the approach of the nucleophile displaces the n electrons in such a direction as to allow them to attack the C—X bond from the rear. The syn attack would therefore be favored for stereoelectronic reasons. 

The stereochemistry of Pd -catalyzed allylic alkylation is net retention (equation 62). This arises from sequential inversion steps. Initially, the Pd approaches from the face of the C3 unit opposite the leaving group, to form the jt-allyl complex. Subsequently, the nucleophile adds to the face of the TT-allyl opposite palladium. If a bulky or umeactive nucleophile is used with allylic acetates, the acetoxy group can add again to the complex. Ultimately, this results in the production of a mixture of stereoisomers upon nucleophihc addition. As an example of the range of allylic substrates that react, nitrogen nucleophiles, in particular primary and secondary amines, undergo palladium-catalyzed substimtion with aUyhc alcohols, acetates, and ethers (equation 63). 

In three dimensions the reaction is stereospecific with retention by double inversion. The palladium approaches the alkene from the opposite face to the leaving group and the nucleophile approaches from the opposite face to the palladium. This is clearly shown by reaction of the two diastereoisomers 237 and 240 with malonate. [Note These compounds are of course racemic and attack at either end of the achiral p3 allyl cation complexes 238 or 241 would give racemic material anyway.]... 

Figure 4 Electrophilic aromatic substitution, constituting the most likely mechanism for DMAT synthase. The diphosphate moiety dissociates to generate the allylic carbocation, which then attacks the activated carbon-4 of the indole ring system. Approach of the aromatic C-4 is opposite the diphosphate leaving group, as indicated by experiments with specifically mono-tritiated (T) DMAPP (Shibuya et al., 1990). 

A different approach to the cephalotaxine ring system also used tf-allyl palladium chemistry (Scheme 9.49). " Tetramethylguanidine (TMG), which is a stronger base than triethylamine by at least two orders of magnitude, was found to be the base of choice for the cyclization of allylic sulfone 9.171. The sulfone leaving group was also essential to the synthesis of the earlier intermediate 9.170 by allowing alkylation to introduce the aminopropyl side chain. ... 

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