Substitution reactions, stereoselective

Nucleophilic Substitution Reactions. Many of the transformations reali2ed through Michael additions to quiaones can also be achieved usiag nucleophilic substitution chemistry. In some iastances the stereoselectivity can be markedly improved ia this fashion (100), eg, ia the reaction of ben2enethiol with esters (R = CH C O) and ethers (R = 3) 1,4-naphthoquiaones. 2-Bromo-5-acetyloxy-l,4-naphthoquiQone [77189-69-6J, R = Br, yields 75% of 2-thiophenyl-5-acetyloxy-l,4-naphthoquinone [71700-93-1], R = SC H. 3-Bromo-5-methoxy-1,4-naphthoquinone [69833-10-9], R = Br, yields 82% of 3-thiophenyl-5-methoxy-l,4-naphthoquinone [112740-62-2] R = SC H. ... 

The optical stability of organotin compounds is then discussed and the stereoselectivity (or nonstereoselectivity) of a series of substitution reactions at the tin atom is described and used to distinguish between possible mechanisms. 

A fifth and last method is a stereoselective or -specific substitution reaction on an optically active organotin compound prepared by one of the four former methods. This last method will be discussed in Section 5. 

The optical purity of almost all the organotin compounds described in this chapter is not yet known. In order to determine the stereoselectivity of substitution reactions at the tin atom of these organotin compounds, it is almost always necessary to know the optical purity of the starting compound and of the final product. The method described in this section can be used not only for the resolution of racemic organotin compounds but also for the determination of their optical purity 50). It will be a valuable tool for the determination of the stereoselectivity of the reactions described in Chapter 5, and of other reactions which will be studied. 

Furthermore, a neighboring group participation of a phenylthio function is observed in the Lewis acid-catalyzed nucleophilic substitution reaction of various P-nitrosulfides. Because the P-nitrosulfides are readily available, by the Michael addition of thiols to nitroalkenes (see Michael addition Chapter 4), this reaction is very useful. The P-nitrosulfides are prepared stereoselectively, and the reaction proceeds in a stereo-specific way (retention of configuration) as shown in Eqs. 31-34.35... 

The isolated bicyclic derivatives induced very high stereoselectivity (ee s up to 99%) in the Pd catalyzed ally lie substitution reaction [85],... 

Introduction of a double bond between the triple bond and the leaving group leads to enyne electrophiles 45, which would give access to vinylallenes 46 if the attack of the nucleophile takes place at the triple bond in an SN2" (1,5) substitution reaction (Scheme 2.16). In addition to the regioselectivity, two types of stereoselectivity also have to be considered in this transformation, i.e. the configuration of the olefinic double bond of the vinylallene and the (relative or absolute) configuration of the allenic chirality axis. 

Aminoallenes constitute an important class of functionalized allenes with interesting chemical properties. They are known as attractive substrates for constructing three- to six-membered azacycles [78]. In 1999, Ohno and co-workers reported the stereoselective synthesis of chiral a-aminoallenes 179 and 181 by RCu(CN)M-medi-ated anti-SN2 substitution of chiral 2-ethynylaziridines 178 and 180 (Scheme 4.47) [79]. The X-ray data and specific rotations of the allenes were consistent with a net anti-S- 2 substitution reaction. 

When the allene moiety of 2,3-allenylamines was substituted with Br, an intramolecular nucleophilic substitution reaction led to a chiral 2,3-ds-ethynylaziridine 323. The diastereoselectivity depends on the absolute configuration of the allene moiety, i.e. typically for a matched-mismatched pair the S,aR-isomer afforded the product with much higher stereoselectivity [155, 156],... 

Stereoselective substitution reactions of chiral dienyl electrophiles have also been carried out. In analogy to the copper-promoted 8 2 reactions of simple allylic electrophiles [3], the corresponding 8 2 (1,3) substitutions of dienyl carbonates [43] have been reported to proceed with high anti selectivity. Interestingly, treatment of chiral dienyl acetal 63 with the Yamamoto reagent PhCu BFs gave rise to the formation of a 1 3 mixture of the anti-S l substitution product 64 and the syn-Sn2" (1,5) substitution product 65 (Eq. 4.28) [44]. A mechanistic explanation of this puzzling result has yet to be put forward, however. 

Borzilleri RM, Zheng X, Schmidt RJ, Johnson JA, Kim S-H, DiMarco JD, Fairchild CR, Gougoutas JZ, Lee FYF, Long BH, Vite GD. (2000) A novel application of a pd(0)-catalyzed nucleophilic substitution reaction to the regio- and stereoselective synthesis of lactam analogues of the epothilone natural products. J Am Chem Soc 122 8890-8897. 

Stereoselective construction of (Z)-fluoroalkene depsipeptide (60) through a Cu(l)-mediated allylic substitution reaction... 

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