Prolinol propionamide

Recently, both enantiomeric forms of callosobruchusic acid (170), a pheromone of the azuki bean weevil, Callosobruchus chinensis L., which induces the male to extrude his genital organ and to attempt copulation, were synthesized by Mori et al.178), applying Evan s alkylation method in natural product synthesis as the key step. Thus, (S)-prolinol propionamide was converted to its enolate (164) by treatment with LDA. 

Then it was alkylated with iodide (168) in the presence of HMPA. Finally the reaction was quenched to produce (169) in 46% yield with 96.6% diastereomeric purity. The amide (169) was hydrolyzed to produce (R)-(170) with 93% e.e. In the same manner, by alkylating (R)-prolinol propionamide with (168), the amide (169 ) was obtained. Acid hydrolysis of (169 ) produced (S)-( 170) with 92% e.e. 

Myers has studied the remarkable chemistry of cyclic silyl ketene acetals 14 prepared from optically active (5)-prolinol propionamides and dichlorodimethylsi-lane (Eq. (8.5)) [7]. The reactive species is generated upon deprotonation of the prolinol amide and treatment with the silyl dichloride. The enoxysilane may be purified by distillation under reduced pressure and utilized in aldol additions to afford on/i-adducts 15 in >99% diastereomeric purity. 

Myers et al. found that silyl enolates derived from amides undergo a facile non-catalyzed aldol addition to aldehydes at or below ambient temperature [90]. In particular, the use of cyclic silyl enolate 27, derived from (S)-prolinol propionamide, realizes high levels of diastereoface-selection and simple diastereoselection (anti selectivity) (Scheme 10.27). It has been proposed that this non-catalyzed highly stereoselective reaction proceeds via attack of an aldehyde on 27 to produce a trigonal bipyramidal intermediate 29 in which the aldehyde is apically bound 29 then turns to another isomer 30 by pseudorotation and 30 is then converted into 28 through a six-membered boat-like transition state (rate-determining step). 

The diacid corresponding to 114 is callosobruchic acid (115), and forms part of the copulation release pheromone of the azuki bean weevil, Callosobruchus chinensis Both chiral isomers have been synthesized by Mori et al. from methyl geranate epoxide (123). After scission of the epoxide group, the iodide 124 was made conventionally, then the chiral group was introduced using the Evans (R)- or (5)-prolinol propionamide enolate anion (125) (made with lithium diethylamide in tetrahydrofuran on the amide). Removal of the proline group... 

Myers disclosed the unusual chemistry of tethered silyl ketene acetals 117 prepared from (S)-prolinol-derived propionamides and Me2SiCl2 (Equation 12) [73, 74]. When treated with aldehydes, 117 affords anti adducts such as 119 in >99% diastereomeric excess. Analysis of the X-ray structures of the adducts led to the proposal that the additions occur through transition state structures such as 118. The significance of the silicon-tethered enol derivative was demonstrated by the fact that the corresponding acyclic bis-0-TMS-derived silyl ketene acetals afford only 1.8 1 mixtures of antijsyn aldol adducts [73]. 

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See also in sourсe #XX -- [ ]

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