Lithium enediolates

A full paper on the conjugate addition of organolithium reagents to free a, -unsaturated carboxylic acids (rather than esters) has now appeared. Methyl groups at the a- and /3-carbon of the alk-2-enoic acid decrease reactivity as acceptors, and foster deprotonation, respectively. The lithium enediolate resulting from the conjugate addition can be intercepted by electrophiles. PM3 calculations are in agreement with the substituent effects. 

Other studies have provided additional data on the relative stabilities of the lithium aldolates 14 and 15 derived from the condensation of dilithium enediolates 13 (Rj = alkyl, aryl) with representative aldehydes (eq. [ 10]) (16). Kinetic aldol ratios were also obtained for comparison in this and related studies (16,17). As summarized in Table 4, the diastereomeric aldol chelates 14a and ISa, derived from the enolate of phenylacetic acid 13 (R = Ph), reach equilibrium after 3 days at 25° C (entries A-D). The percentage of threo diastere-omer 15 increases with the increasing steric bulk of the aldehyde ligand R3 as expected. It is noteworthy that the diastereomeric aldol chelates 14a and 15a (Rj = CH3, C2HS, i-C3H7) do not equilibrate at room temperature over the 3 day period (16). In a related study directed at delineating the stereochemical control elements of the Reformatsky reaction, Kurtev examined the equilibration of both... 

The best reagents for reduction of olefinic aldehydes to olefinic alcohols are lithium aluminum hydride and sodium borohydride. Crotyl alcohol, CHjCH = CHCHjOH, and cinnamyl alcohol, CjH,CH =CHCHjOH, have been prepared in excellent yields. Cinnamyl alcohol is further reduced at higher temperatures to hydrocinnamyl alcohol. Citral, (CHj)jC =CHCHjCHjC(CH3)=CHCHO, may be selectively reduced to the ctOTesponding dienol by catalytic hydrogenation over platinum catalyst. A new method for the preparation of enediol esters of the type... 

Jutzi reported the formation of enediol compounds from the reaction of trimethyl-silyl lithium with CO (Eq. (5.51)) [56]. As shown above, they proposed a mechanism involving the dimerization of a lithioxy carbene, which is an acyllithium tautomer (Eq. (5.51)). A similar reaction suggests the possibility of further insertion... 

Bis(trimethylsilylmethyl)thorium gave an enediol compound (Eq. (5.64)) [74], which is again similar to the one observed for the lithium counterpart as shown in Eq. (5.23). Another example of the similarity of the acyllithium to the lanthanide can be seen in the reaction of a vinylsamarium complex with CO (Eq. (5.65)) [75]. Formally, the reaction (Eq. (5.65)) is almost identical to the reaction shown in Eq. (5.30) and those in Scheme 5-3 for a vinyllithium. The mechanisms suggested for each reaction are different, but none of these have yet been studied further in detail. 

Chiral lithium diphenylbinaphtholate (2) has been found to be an effective catalyst for the enantioselective aldol-Tishchenko reaction, affording 1,3-diol derivatives with three contiguous chiral centres and high stereoselectivities (up to 99% ee) ° A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide (3) as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. 

Acyloins (la) [29,30] and bis-silylated derivatives of their enediols (lb) [31] have been demonstrated to be useful acyl anion equivalents (RCO ) and have been employed in an indirect but facile way for the preparation of ketones (3) (Equation 7.1). The hydroxy ketones (2), which are the key intermediates in this method, have been prepared by the reaction of acyloins (la) with organic halides in the presence of sodium hydroxide in dimethyl sulfoxide [29, 30] according to the Hein s procedure [32] or using sodium hydride in 1,2-dimethoxyethane (DME) (glyme) [33]. They also have been prepared by the alkylation of lithium enedi-olates of acyloins prepared from the corresponding lb and methyllithium [31]. These reactions proceed with C-alkylation however, the reaction conditions employed are quite basic which would limit substrate choice. 

As an alternative to the use of auxiliaries for the asymmetric alkylation of carboxylic acid derivatives, in 2011, Zakarian and Stivala reported on the direct stereoselective alkylation of arylacetic acids with chiral lithium amide bases.This method offers an alternative to traditional auxiliary-based methods and operates through the formation of enediolates also, it builds on earlier work by Shioiri and Ando and by Koga and Matsuo . Zakarian and Stivala examined several C2-symmetric tetramines for their enan-tiodirecting power. After significant experimentation, conditions were established that used 4 equivalents of -BuLi and a slight excess of the tetramine that provided clean formation of the desired product. The enantioselectivity was found to be dependent on the quality of the -butyllithium. The reaction scope was examined with a variety of... 

---