摘要：

J. CHEM. SOC. PERKIN TRANS. 11 1983 Stereoselectivity in the Condensation Reactions of I-PhenylethylAlkyl and Phenyl Ketones with Organometallic Reagents Carlos Alvarez-lbarra, Odon Arjona, Rafael Perez-Ossorio," Alfredo Perez- Rubalcaba, Maria L. Quiroga, and Maria J. Santesmases Departmento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Complutense, Ciudad Universitaria, Madrid 3, Spain Stereochemical results of the condensation reactions of a series of ketones, PhCHMeCOR (R = Me, Et, Pr', But, Ph), with various organomagnesium and organolithium derivatives in ethers as solvents are reported. Results are accounted for on the basis of competition between two transition states which may adopt either Karabatsos- or Felkin-type conformations according to the nature of R, the reagent nucleo- philicity, and the polarity of solvent.Polar and steric analysis of this reaction allows highly stereoselective syntheses of diastereoisomeric a-phenylalkanols to be devised. In a previous paper,' we proposed that both steric and polar factors should be considered to account for the observed asymmetric induction in condensation reactions in solvents of different polarity of phenyl- and methyl-magnesium bromides with (+)-2-phenylpropanal (1) and (+-)-3-phenylbutan-2-one (2). In the case of condensation reactions of (2) the transition states TS,$and TSII$ (Scheme; R = Me) have been postulated; both have a Karabatsos-type geometry and yield, respect- ively, the SR- and RR-alcohols. The experimental results are consistent with the assumption of a selective stabilization of TS,$,whereby the phenyl group adopts an anti-arrangement to the nucleophilic attack (attack a, Scheme) upon increasing the solvent ET(30)parameter. This proposal is consistent with an increased inductive anisotropic effect of the phenyl group inducing the preferential entrance of the nucleophile on the face of the carbonyl group opposed to it.3 For the reactions of (1) with phenyl-and methyl-magnesium bromides a transition state TSIIIS(Scheme; R = H), characterized by a phenyl-nucleophile arrangement identical to TS,$ but yielding the diastereoisomeric alcohol, should be taken into account. This can be concluded from the lack of stereo- differentiating effect of the solvent.Lately, we have found new evidence for the contribution of polar effects to condensation processes of (2) with arylmetal reagents. The stereoselectivity increases upon increasing the nucleophilicity of the reacting species (PhLi > Ph2Mg > PhMgBr > Ph3A1 > PhMgRr-Cu'). Thus, reaction with PhLi is highly stereoselective (96% of the RS-diastereoisomer). The effect of an interaction (P~-Nu)~,~-~~~~, present in TS,$ but not in TS,,X and directly dependent from the polar parameters of the whole process (reagent nucleophilicity and solvent polarity), accounts for these result^.^ In addition, the stereoselectivity observed in the condensation of (2) with various X-ArMgBr species (X H, m-Me, p-Me, nz-MeO, ~ m-F, p-F, and p-CF,) is also consistent with this interpret- ati~n.~ In this paper we report the stereochemistry of the condens- ation processes of various carbonyl derivatives, PhCHMe- COR, having a common chiral centre.The effect of changing the R group [R Me (2), Et (3), Pr' (4), But (5), and Ph (6)], the organic residue of the organometallic reagent, R'X (R' = Me, Et, Pr', But, Ph), the metal (Li, Mg), and the ether solvent [Et,O, tetrahydrofuran (THF), and dimethoxy-ethane (DME)] are examined. The aim of this work is to generalize the hypothesis made for the condensation reactions of ketone (2).We try to gain a deeper insight into the polar influences affecting these processes and to devise highly stereoselective syntheses of a-phenylalkanols by suitable Me I rr' RJ R R a-attack b-attack b-attack TS{ TSlf Scheme. selection of the prochirality of the carbonyl group and of the experimental conditions.Results and Discussion In the Table are gathered the stereochemical results observed for the condensation reactions of the a-phenylketones

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