Prenyl Grignard reagent

X-Substituted Allyl Anions. Allyl anions with alkyl substituents almost always react with carbonyl electrophiles at the more substituted a position, as in the reaction of the prenyl Grignard reagent with aldehydes to give the product 4.39, presumably because the metal attaches itself preferentially to the less-substituted end of the allyl system and then delivers the electrophile in a six-membered transition structure 4.38. In contrast, alkylation of a similar anion with an alkyl halide gives mainly the product 4.40 of y attack, which is normal for an X-substituted allyl anion when a cyclic transition structure is not involved. 

A complete reversed selectivity has been observed by Yamamoto [46] who, more recently, reported the chemoselective reaction of prenyl Grignard reagent 73 with primary allylic chlorides 76, versus allylic acetates in the presence of CuCN -2LiCl at 0°C to give the 8 2 product 78 with high selectivity, as shown in Eq. (24). 

The synthetic utility of the prenyl Grignard reagent has been extended by its regioselective a-alkylation with alkyl halides induced by cuprous iodide, and by its y-alkylation with alkyl tosylates. The former conditions have been utilized in a straightforward new synthesis of geraniol (Scheme 28). Chromous-salt induced... 

With allylic Grignard reagents, the carbophilic addition on the thiocarbonyl of phenylisothiocyanate occurred as expected exclusively with inversion of the allylic chain. From crotyl and prenyl magnesium halides the compounds (4f) and (4g) were obtained in yields of 77 and 72%, respectively. 

Fujisawa [67] found that the stereoselective introduction of a prenyl alcohol moiety, with an -configuration, into a vinyl oxirane was readily achieved by a copper-catalyzed 8 2 reaction. Thus, addition of a Grignard reagent 160 to a solution of isoprenyl oxirane and copper(I) iodide (5 mol%) in THF/Me2S (20 1) at — 20"C afforded the allylic alcohol 161 in 95% yield in a 97 3 F/Z ratio [Eq. (54)]. 

A similar cyclization reaction proceeded on treatment of 2-haloethanal allyl acetal and allyl 2-halophenyl ether with Grignard reagents in the presence of an Fe(II) salt catalyst [177]. Addition of phenylmagnesium bromide to a solution of 2-iodoethanal prenyl acetal 176a in the presence of a catalytic amount of Fe(ll)Cl2 gave the isopropenyl-substituted tetrahydrofuran derivative 177 in 52% yield with an isopropyl-substituted product 180 (13%) (Scheme 3.164). 

Considering these results, it can be clearly concluded that Grignard reagents do not react with thioketones exclusively according to a thiophilic mechanism. However, the same conclusion appears to be justifiable also with respect to other organometallic reagents. According to a very recent paper," adamantanethione is indeed subject to a thiophilic attack by butyl-lithium to a certain extent, but a C-alkylation product is formed preferentially by its reaction with prenyl-lithium (Scheme 4). 

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