Keto sulfones, addition reactions

In addition to procedures for pyridine ring closure based on the use of 3-amino-thiophene derivatives, there are alternative methods for the construction of thieno [3,2-Z>]pyridines. One approach made use of cyclic (3-keto sulfones, which proved to be convenient synthons for the modified Hantzsch synthesis of fused pyridines (1986KGS1563, 1990JHC1453, 2000MI1, 2002USP6191140). For example, the reactions of benzothiophene 1,1-dioxide 168 with enamines 169 or methylene-active compounds 170 in the presence of NH4OAc produced fused dihydropyridines 171 (1990JHC1453). 

As discussed in the sections above, the sulfonylmethane anion reacts with ketones and aldehydes che-moselectively in the presence of an ester or amide. It is possible to obtain the keto sulfone on addition to an ester (448) when the reaction is carried out without competing carbonyl groups (equation lOS). The... 

Malonate esters and vinylogous malonates, as well as 1,3-diketones, readily undergo diazo transfer. In addition, the less acidic -keto phosphonates (138 equation 55) ° and p-keto sulfones (140 equation 56) have been shown to participate in this reaction. 

Iminium activation has been recently used to achieve the enantioseleclive conjugate addition of geminal bis(sulfone)s and p-keto sulfones to a,P-unsaturated aldehydes. Almost simultaneously, different groups have reported the efficient use of catalyst 22a in the addition of bis(phenylsulfonyl)methane [200] and fluorobis(phenylsulfonyl) methane [201] to a wide variety of enals to yield the corresponding Michael adducts in excellent yields and enantioselectivities (Scheme 2.72). This reaction is particularly attractive since allows the preparation of interesting chiral building blocks by further synthetic transformations over the aldehyde moiety and reductive desulfonylation [91] of the bis(phenylsulfonyl) group. 

Aleman J, Marcos V, Marzo L, Garci a-Ruano JL. Influence of the reaction conditions on the evolution of the Michael addition of (3-keto sulfones to alpha,beta-unsaturated aldehydes. 7. Org. Chem. 2010 (23) 4482 491. 

Nitroalkenes react with lithium dianions of carboxylic acids or with hthium enolates at -100 °C, and subsequent treatment of the Michael adducts with aqueous acid gives y-keto acids or esters in a one-pot operation, respectively (Eq. 4.52).66 The sequence of Michael addition to nitroalkenes and Nef reaction (Section 6.1) provides a useful tool for organic synthesis. For example, the addition of carbanions derived from sulfones to nitroalkenes followed by the Nef reaction and elimination of the sulfonyl group gives a,P-unsaturated ketones (Eq. 4.53).67... 

The reactions of lithiated anions of chiral hydrazones 1.76 (Samp, Ramp) with a,P unsaturated esters or sulfones are highly stereoselective at -78°C. By a sequence of 1,4-addition and removal of the chiral auxiliary with O3, Enders and coworkers [161, 1441, 1442, 1443] prepared 5-keto-3,4-dialkylesters and 5-keto-3-alkylsulfones with high selectivities (figure 7.60). When -bromo-a,P-un-saturated esters or sulfones are used as Michael acceptors, cyclic ketoesters or... 

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