Stereoselectivity substitution reactions

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. 

CHAPTER 6 Stereospecific and Stereoselective Substitution Reactions of Organolithiums 241... 

Many stereoselective substitution reactions (Sj 2) were first studied and optimized with steroidal substrates, because this class of compounds provides a large variety of pure enantiomers with just one reactive chiral center. Furthermore, the... 

Then, the stereoselective substitution reaction of cation (42) by water generated 1-phenyl prop-2-en-l-ol (44) and/or ( )-3-phenylprop-2-en-l-ol (45). Finally, (37) assisted by FeCl2 oxidized (44) or (45) to the product (ii)-3-phenylprop-2-enal (46). The cleavage of the allyl sp C-H bond in the rate-determining step was supported... 

Ketones, in which one alkyl group R is sterically demanding, only give the trans-enolate on deprotonation with LDA at —12°C (W.A. Kleschick, 1977, see p. 60f.). Ketones also enolize regioseiectively towards the less substituted carbon, and stereoselectively to the trans-enolate, if the enolates are formed by a bulky base and trapped with dialkyl boron triflates, R2BOSO2CF3, at low temperatures (D A. Evans, 1979). Both types of trans-enolates can be applied in stereoselective aldol reactions (see p. 60f.). 

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 formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

Hetero-substituted 2-alkenyllithium compounds, however, show useful levels of regio- and stereoselectivity in reactions with aldehydes, in particular if the cation is held at one terminus of the allylie system by electron-withdrawing or chelating groups. 

Both of the 4,5-tran.v-diaslereomers of 4,5-dihydro-4-(4-methoxyphenyl)-5-methyl-3-[(7 )-(4-methylphenylsulfinyl)methyl]isoxazole (24) show excellent stereoselection in reactions with aldehydes. Despite the bulky substituents at the 4,5-dihydroisoxazole nucleus, the stereochemical outcome of the reaction is controlled by the sulfoxide stereogenicity. The pairs of 4,5-dihydro-3-(2-hydroxyalkyl)-4-(4-methoxyphenyl)-5-methylisoxazoles, obtained by desulfurization of the corresponding aldol adducts, have the same configuration at the hydroxy-substituted carbon (C-2 ) and opposite configuration in the 4- and 5-positions of the dihydroisoxazole ring24. 

P-Allyl-to-(isopinocampheyl)borane exhibits high stereoselectivity in reactions with chiral a-substituted aldehydes.40 The stereoselectivity is reagent controlled, in that there is no change in stereoselectivity between the two enantiomeric boranes in reaction with a chiral aldehyde. Rather, the configuration of the product is determined by the borane. Both enantiomers of (Ipc)2BH are available, so either enantiomer can be prepared from a given aldehyde. 

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. 

The first example of a stereoselective substitution at tin was the reaction of (—)- -butylneophylphenyltin hydride (65) ([with diazomethane in the presence of copper in diethyl ether to form optically active methylneophylphenyl-t-butyltin (84) ([o g5 - 1.5) 20 44- >. 

In general, the Henry reaction gives a mixture of diastereomers and enantiomers. The lack of selectivity is due to the reversibility of the reaction and the easy epimerization at the nitro-substituted carbon atom. Existing reviews have hardly mentioned the stereochemistry of the Henry reaction. Recently, Shibasaki has found that the modification of the Henry reaction can control the stereochemistry to give (3-nitro alcohols with high diastereo- and enantio-selectivity.6 In Section 3.3, the progress of the stereoselective Henry reaction and its application to biologically active compounds are discussed. 

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... 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

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. 

The stereoselective elimination reaction of suitably substituted allylic compounds is a reasonable approach to the construction of the propadiene framework. Central chirality at the allylic position is transferred to axial chirality of the allene by stereoselective /3-elimination (Scheme 4.53). 

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],... 

The condensation of the cinnamaldehyde derivative (18) with ethoxycarbonyl-pentyltriphenylphosphorane in DMF gave a mixture of tram-trans- and trans-cis-products.22 A general method to prepare l-substituted-m-9-alkenes (19), using a stereoselective Wittig reaction, has been described.23 2,2-Dimethyl-3-butenal (20)... 

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