A study of diastereoseleetive 1,4-addition of phenyl Grignard has been attempted on some chiral crotonates. The H-facial seleetivities in these reactions have been determined on the basis of specific rotations of the hydrolysis product, namely 3-phenyl butanoic acid (3PBA). Correlation of these results with the results obtained from 1H NMR shieldings arising due to phenyl anisotropy, has led to conformational correlation model for the determination of absolute stereochemistry of chiral alcohols~
The chiral pool of natural products has been widely used for total syntheses of natural products and has been applied for evolving new methodology for asymmetric C-C bond formation. A variety of chiral enoates including cc,13-tmsaturated-esters, -amides, -N-enoyl sultams and c~,13-ethylenic sulfoxides I have been utilized.
Of the cheaply available members of the chiral pooL camphor has been well exploited. 2 The success in the use of camphor is due to its rigid structure and the possibility of appropriate derivatization to allow greater stereoselection. 3"6 In line with above studies we have synthesized chiral crotonates 7-12 starting with appropriate isoborneols and borneols, 1-6. 7 1,4-addition reactions to crotonates, 7-12, were studied with Grignard reagents obtained from phenyl bromide, both with and without the use of Cu(I) (Scheme 1). Whereas the sulfide derivatives 7-9 did not react at lower temperatures (-78 and -40 oc) and gave a multiplicity of products at -10 oc, 10-12, gave the required adducts only at -10 oc. In the case of 11, the reaction took place at -10 oc in the presence of Cu(I) but was found to be sluggish and was therefore carried out at 0 oc.
The IH NMR spectra of products obtained in the Cu(I) catalysed reactions showed them each to be a mi~ure of two compounds, epimeric at newly formed stereogenic center. These diastereomers were not separable by column chromatography. The two most upfield methyl signals, in each of these fractions, were well resolved and assigned to 10'-H 3 resonances. From the integration of these signals, the diastereomeric ratios of 13:14, 15:16 and 17:18 were calculated to be 66:34, 40:60 and 57:43, respectively (Table 1). The absolute stereochemistry of the diastereomeric compounds, 13-18, were determined from the sign of rotation of 3phenylbutanoic acid (3PBA) obtained on hydrolysis of their respective 1,4-adduct mixtures with KOH in ethanol. The 3PBA obtained from phenyl adducts of 10, 11 and 12 showed .specific rotation of [c~]2~' D = +12.4 (c 9, benzene), [et]26 D = -10.2(c 5.44, benzene), and [(3~]26 D = +5.6 (c 7.13, benzene), respectively. Hence it was concluded that the 1,4-additions proceeded with the preferential formation of S-(+)-3PBA derivatives of 4 and 6 and R-(-)-3PBA derivative of 5. The diastereomeric ratios of the epimers, thus calculated from the known