Grignard allylic substitution

Yamano T, Taya N, Kawada M, Huang T, Imamoto T (1999) Tetrahedron Lett 40 2577 Brunner H, Nishiyama H, Itoh K (1993) Asymmetric hydrosilylation. In Ojima I (ed) Catalytic asymmetric synthesis. Wiley-VCH, New York, chap 6 Sawamura M, Kuwano R, Ito Y (1994) Angew Chem, Int Ed Engl 33 111 Kuwano R, Uemura T, Saitoh M, Ito Y (1999) Tetrahedron Lett 40 1327 Hayashi T (1993) Asymmetric allylic substitution and grignard cross-coupling. In Ojima I (ed) Catalytic asymmetric synthesis. WUey-VCH, New York, chap 7-1 Trost BM, Vranken DLV (1996) Chem Rev 96 395 Consiglio G,Waymouth RM (1989) Chem Rev 89 257... 

Initial studies on the application of these catalysts to allylic substitution reactions showed that the arenethiolate moiety functions as an excellent nontransferable group, and that the regioselectivity can be completely reversed by suitable changes in the reaction parameters [33]. If the reaction between geranyl acetate and n-BuM gl was carried out inTHFat—30°C with fast addition of the Grignard reagent to the reaction mixture, complete a selectivity was obtained. Raising the tempera-... 

The scope of the method turned out to be particularly broad (Table 12). The allylic substitution of cinnamyl bromide could also be performed with other linear alkyl Grignard... 

The use of the o-diphenylphosphanylbenzoyl leaving group in copper-catalysed allylic substitution reactions with a Grignard reagent has been studied extensively.7 ( ) High SN2 regiospecificity (>95%) and complete stereospecificity are observed at room temperature when the solvent is a dichloromethane - diethyl ethyl mixture. 

The Taniaphos catalyst (6) has been found to give S 2 products in excellent yields (90-98%) with a high enantioselectivity (90-98% ee) in the allylic substitution of (7e) several different leaving groups by Grignard reagents in the presence of CuBr.SMe2 in r-BuOMe at -78 °C.9. 

Metals other than palladium and molybdenum can be used for allylic substitution reactions. For example, nickel in the presence of the oxazolinylferrocenylphosphine 9 provides good asymmetric induction for the reaction of a Grignard reagent with allylic electrophilic systems such as acetates.151... 

Allylic substitution reactions [1] will be discussed in the 8 2 versus 8 2 (see Chapter 24) cyclization reactions from di-Grignard reagents will be discussed in Chapter 25 metal-catalyzed reactions will be covered in Chapters 29 and 30 the chemistry of acetylenes and Si are covered in Chapters 31 and 32 and while some asymmetric reactions will be discussed, the reader is encouraged to peruse through Chapter 28. 

Nickel catalysts also catalyze Grignard substitution to allylic compounds including allyl alcohol [230-233] ethers [230,231,234,235 Eq. (106) 231] amines, albeit in a low product yield [231] sulfides [231,236,237], including thioacetals [238] thiols [231] selenides [239] carboxylates [240] phosphates [94,121] and halides [Eq. (107) 230], most likely via intermediate / -allyl-Ni species. Monosubstitution of bis-allyl ether was possible [Eq. (108) 235]. Most of the literatures cited in the foregoing disclosed regiochemical outcome associated with these allylic substitutions. 

Enantioselective allylic substitution with Grignard reagents was carried out by chiral nickel complexes to show a maximum e.e. value as high as 94% [241]. Equations (112) [240] and (113) [242,243] illustrate examples. 

Although, generally speaking, nickel or copper is the catalyst of choice for allylic substitution with Grignard reagents, as shown in the foregoing discussions, the result of Eq. (160) clearly demonstrates that palladium still finds an advantage in allylic substitutions. 

Allylic ethers and alcohols have long been known to react with Grignard reagents in the presence of an appropriate Ni-based complex containing phosphine ligands [26]. These reactions are related to the well-studied Pd-catalyzed allylic substitution reactions that utilize soft nucleophiles [27], and a number of important mechanistic studies on the stereochemical outcome of this class of transformations have been carried out [28]. 

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