Levoglucosenone Michael addition reaction

Shafizadeh s laboratory (31-34) reported the first successful studies of thiol addition. Our recent studies (35-37) and others (38) on the Michael addition reaction of reactive thiols to levoglucosenone and its isomer isolevoglucosenone (39) clearly indicate the complete stereoselectivity of the addition and its general synthetic approach to 1,4- and 1,2-thiodisaccharides (40). 

Interesting work continues on the cellulose pyrolysis product levoglucosenone (35)3 C- -branched-chain derivatives having been produced by Michael addition reactions. Direct adducts such as (36) were obtained but, in addition, a 2 1 product (37) was... 

Our laboratory has developed analogous domino thio-click Michael-aldol approach to heterocyclic thio-chromene systems [8], using 2-thio salicylic aldehyde. The base-catalyzed thio-click reaction proceeds via a conventional stereoselective Michael addition reaction of thiol to C-4 position of levoglucosenone and a concomitant domino cyclization of intermediate thio adduct to form C—C bond at C-3 of functionalized levoglucosenone as illustrated in Scheme 6.3. 

A variety of important synthetic reactions can he promoted by electrogenerated bases (EGB). The Michael addition and alkylation of compounds with activated hydrogen atoms are two examples in which using EGB has been very successful. The electrochemical method is very successful for functionalization of levoglucosenone as shown in Scheme 4.28.198... 

Regioselective Michael addition of imidazole to levoglucosenone 475 is effectively catalyzed by cathodic electrolysis. The electrochemical conditions are milder and provide higher yields as compared to the base-catalyzed reactions (Scheme 110) <1996JOC8786>. 

The conjugate system of the C-2 nitroalkenes should posses some interesting chemical reactivity and it should be an excellent Michael reaction acceptor with reactive nucleophiles. Moreover, the steric effect of the bulky 1,6-anhydro ring should be similar to that of levoglucosenone. As a consequence, nitroalkenes are excellent precursors for the stereoselective introduction of an additional sugar moiety at C-2 with subsequent additional functional group such as nitromethylene or its reduced/acetylated analog. Moreover, this unsaturated C-2 functionality additionally fixes the conformation of the system and most importantly sterically hinders the P-D-face of both enone molecules. 

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