Chalcones thiophenol addition

Attempts to use polyamino acids as catalysts in other reactions have proved successful, notably in the coupling of thiophenol with chalcones. Employing poly-(L)-leucine, the -phenylthioether was obtained in up to 45% e.e., (Scheme 10). Studies indicated that the best results were obtained by slow addition of the thiophenol to the reaction mixture. 

A multigram preparation of a useful chiral building block was developed, using the Beckmann rearrangement as a key synthetic step (equation 115) °. The enantiomeric addition of thiophenol to a chalcone 313, catalysed by (+)-cinchonine, provided the chiral enantiomeric carbonyl compound 314. The Beckmann rearrangement of its oxime 315 gives the anilide of (R)-(- -)-3-phenyl-3-phenylsulfanylpropanoic acid 316. Alcoholysis produced the expected enantiomerically pure ethyl ester 317. 

Addition of thiophenols to chalcones in [bmim]PF6, catalysed by L-proline and cinchonine in CH2CI2, afforded products with <16% and 26% ee, respectively. The latter addition also occurred in neat ionic liquids in the absence of the latter catalysts but the rate of the reaction depended considerably on the structure of the ionic liquid.129... 

Optically pure (+)-(i )-3-phenylsulfanyl-l,3-diarylpropan-l-ones are readily available by the enantioselective Michael addition of thiophenols to chalcones. After reduction, acidic dehydration of the racemic alcohol affords a mixture of the racemic cis- and trans- 2,4-disubstituted thiochromans (Scheme 164). A detailed consideration of the stereochemical outcome of the reaction with unsymmetrically substituted diaryl derivatives suggests the involvement of a [1,3] PhS shift via a four-membered sulfonium intermediate and this is backed up by theoretical calculations <2003T3621>. 

The use of numerous polymer-supported optically active phase transfer catalysts was further extended by Kelly and Sherrington11351 in a range of phase transfer reactions including a variety of displacement reactions, such as sodium borohydride reductions of prochiral ketones, epoxidation of chalcone, addition of nitromethane to chalcone and the addition of thiophenol to cyclohexanone. Except in the chalcone epoxidation, all the examined resin catalysts proved to be very effective. However, with none of the chiral catalyst system examined was any significant ee achieved. The absence of chiral induction is a matter of debate, in particular over the possible reversibility of a step and the minimal interaction within an ion pair capable of acting as chiral entities in the transition state and/or the possible degradation of catalysts and leaching. 

The addition of thioacetic acid to tra 5-chalcones furnished only moderate enantioselectivity (33-65% ee with Takemoto s catalyst 11) [33]. Better results were obtained by the Chen group, with various thiols employing quinine-derived squaramide 13 [34]. It is worth noting that, in this case, substituted benzyl thiols, furfuryl thiol, and aliphatic thiols were better donors than thiophenol (Scheme 14.6). 

Very efficient Michael addition reactions of amines, thiphenol and methyl acetoacetate to chalcone in water suspension have been developed." For example, stirring a suspension of powdered chalcone in a small amount of water containing n-Bu NH and a surfactant, hexadecyltrimethylammonium bromide for 2 hr gave the adduct in 98% yield. Similarly adducts were obtained with thiophenol and methyl acetoacetate (Scheme 30). 

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