Stereoselectivity substitution

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-... 

Stereoselective substitution of the hydroxyl group in chiral cyanohydrins... 

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- >. 

Effenberger, F. and Gaupp, S. (1999) Stereoselective substitution of (/ )-2-(sulfonyloxy)nitriles with sulfur nucleophiles. Tetrahedron Asymmetry, 10, 1765—1776. 

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. 

Ohmori, K., Ushimaru, N., and Suzuki, K., Stereoselective substitution of flavan skeletons synthesis of dryopteric acid, Tetrahedron Lett., 43, 7753, 2002. 

If an organomagnesium reagent bears a remote leaving group, cyclizations can be achieved. Starting from the tosylate 133, a stereoselective substitution using CuCN-2LiCl... 

The second approach starts from achiral allylic substrates and uses a chiral metal catalyst. Among all ligands which have been tested binaphtol-derived phosphoramidites like 174 have led to excellent regio- and enantioselectivities (equation 103) °. Highly stereoselective substitutions are also obtained using ligand 175 (Taniaphos, equation 104... 

Treatment of functionalized vinyllithium, 28, with allylmaghesium bromide in the presence of zinc bromide leads to a stereoselectively substituted, metallated cyclopropane, 29, via a tandem metalla-Claisen-cyclization reaction (equation 48 )M. The produced cyclo-... 

The reactions of vinyl sulfones with various nucleophiles are usually stereoselective. Substituted vinyl sulfones are less reactive toward nucleophiles than the analogous vinyl ketones or esters 10 and are quite inert toward thiols. Peptide vinyl sulfones do not react with thiols such as glutathione under enzyme assay conditions. The reaction of thiols with aryl vinyl sulfones has been reported, however, it is performed in the presence of base. 11 ... 

Ono, N. Hamamoto, I. Kaji, A. Regio- and stereoselective /-substitution of allylic nitro compounds with lithium dialkylcuprates. 

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

If nucleophilic attack is slowed down by steric hindrance, for example in the formation of a trans decalin system (Table 13, entry 17)14, stereoscrambling can occur but otherwise complete retention of configuration is observed (Table 13, entries 15, 16 and 18). The starting material is readily available by palladium-catalyzed 1,4-chloroacylation of 1,3-dienes followed by chemo- and stereoselective substitution of the allylic chloride. 

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... 

Total syntheses of racemic muscarine and allomuscarine were achieved by Pirrung and DeAmicis 11), who used a new approach to formation of the stereoselectively substituted tetrahydrofuran nucleus (Scheme 8). The key step in this procedure was the stereospecific photochemical ring expansion of a cyclobutanone derivative. The cycloaddition of silyl enol ether with methylchloroketene generated by zinc dechlorination of 2,2-dichloropropionyl chloride followed by reductive removal of the halogen produced the methylsiloxycyclobutanone intermediate. Irradiation of the... 

Cyclopropane adducts prepared from the addition of dibromocarbenes to alkene substrates are proving to be extraordinarily valuable intermediates in the synthesis of alternatively substituted cyclopropanes. A number of workers have now demonstrated the stereoselective substitution of the bromine atoms for alkyl groups using alkyl copper re agents. 

Schmitt A, Reissig H-U (1995) Stereoselective substitution at phenyl-substituted y-iactois with organometaiiic reagents. Chem Ber 128 871-876... 

Entries 1-5 constitute the first examples of stereoselective substitutions of halogens by alkynyl groups in P-stereogenic compounds. Grignard reagents were also effective in the substitution, albeit in low or moderate yield (entries 6 and 8). Contrary to expectations, the bromide was found to be a more suitable leaving group than the iodine in some cases (compare entry 1 with entry 2 and... 

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... 

The synthesis of ( )-Epibatidine 76b and analogs thereof was realized by regioselective chloroacetoxylation of 2-aryl-l,3-cyclohexadiene [99]. Subsequent stereoselective substitution of the chlorine atom by tosylamide with either... 

Another approach starts from achiral allylic substrates and uses a chiral metal catalyst. Binaphtol-derived phosphoramidites like 132 have led to best regioselectivities and enantioselectivities among a vast number of tested ligands (Scheme 2-48, eq. (a)). Highly stereoselective substitutions have been described using the ligand 133... 

Homoallylalcohols are obtained by an iron-catalyzed regioselective and stereoselective substitution of Y,5-epoxy-a,P-unsaturated esters and amides with Grignard reagents (Scheme 4-201). The reaction proceeds with inversion of the configuration at the attacked C4 carbon atom and involving an Ti -allyliron intermediate. ... 

---