Sulfones reductive lithiation

The reductive lithiation of a-alkoxy phenylsulfides is a slow process (typically 0.5-1 h at -78°C) and lowering the LUMO of the electron acceptor by using, for example, an anomeric sulfone, leads to a much faster electron transfer [11]. Reductive lithiation of sulfone 22 is fast (less than 1 min) and leads to similar a-lithio reagents to those described above and Scheme 8 shows examples of simple a-C-2-deoxyglycosides 23 and 24 prepared by this protocol. The most interesting feature of anomeric sulfones is that alkylation prior to the reductive desulfonylation event is achievable. In this way, a one-pot four-step sequence... 

Our strategy for the Smij-promoted synthesis of l,2-cis-C-glycosides is illustrated in Figure 3. It was assumed that one-electron transfer to the LUMO of the aryl sulfone group in A would result in concomitant cleavage of the C1 -S bond liberating an anomeric radical intermediate, as previously observed in the reductive lithiation of glycosyl phenyl sulfones." If 5-exo cyclization onto the silicon-tethered alkene/alkyne is substantially favored over a second electron transfer from Smij, then the exocyclic carbon radical B would ultimately be formed. On the other hand, reduction of the Cl-radical by... 

An attractive flexibility in using anomeric phenyl sulfones is that a stereodivergent synthesis of C-glycosides is available by alkylation before the reductive desulfonylation event. Thus, a one-pot four-step sequence of sulfone deprotonation-electrophile quenching-reductive lithiation-methanol quenching on sulfone 14 provides stereoselectively P-C-glycosides 19 as shown with aldehyde 16 (Fig. 

Beau, J M, Sinay, P, Preparation and reductive lithiation of 2-deoxy-D-glucopyranosyl phenyl sulfones a highly stereoselective route to C-glycosides, Tetrahedron Lett., 26, 6185-6188, 1985. Crich, D, Lim, L B L, Synthesis of 2-deoxy-(3-C-pyranosides by diastereoselective hydrogen-atom transfer. Tetrahedron Lett., 31, 1897-1900, 1990. 

Difluoromethyl phenyl sulfone is lithiated by LiHMDS at -78°, and the lithio species attacks cyclic sulfates of 1,2-diols and 1,2-amino alcohols to afford a,a-difluoroalkyl sulfones. The benzenesulfonyl group can be reductively removed (Mg, HOAc, NaOAc) or eliminated to provide 1,1-difluoroalkenes with an allylic OH or NH2 group. 

Further methods involving reductive lithiation exploit anomeric sulfones which also lead to the formation of (3-C-glycosides [20]. Since C-1-lithiation of carbohydrates traditionally results in 1,2-(3-elimination, to afford the corresponding... 

Sulfonic acids are prone to reduction with iodine [7553-56-2] in the presence of triphenylphosphine [603-35-0] to produce the corresponding iodides. This type of reduction is also facile with alkyl sulfonates (16). Aromatic sulfonic acids may also be reduced electrochemicaUy to give the parent arene. However, sulfonic acids, when reduced with iodine and phosphorus [7723-14-0]y produce thiols (qv). Amination of sulfonates has also been reported, in which the carbon—sulfur bond is cleaved (17). Ortho-lithiation of sulfonic acid lithium salts has proven to be a useful technique for organic syntheses, but has litde commercial importance. Optically active sulfonates have been used in asymmetric syntheses to selectively O-alkylate alcohols and phenols, typically on a laboratory scale. Aromatic sulfonates are cleaved, ie, desulfonated, by uv radiation to give the parent aromatic compound and a coupling product of the aromatic compound, as shown, where Ar represents an aryl group (18). 

Sulfones are similar in some ways even more acidifying, and with a powerful ability to coordinate, but less likely to be attacked at S. As with sulfoxides, lithiation a to S competes, and ortholithiation is useful only with sulfones lacking a-protons.141 After lithiation, the removal of sulfones can sometimes be accomplished by transition metal-catalysed reduction or substitution 144 143... 

Bissulfones have been reductively converted to organolithiums (lithiated sulfones) such as 113 and 114, using lithium - naphthalene.92 Two successive lithiations lead to the pheromone 115 of the lesser tea tartrix. 

Lithiation of vinylic sulfones. Phenyl vinyl sulfones (1), prepared as indicated, react with methyllithium regiospecifically at — 95° at the a-vinyl position to give the lithium derivatives 2. As expected, 2 can be alkylated to give 3. The reaction of 2 with enolizable carbonyl compounds proceeds more satisfactorily by prior conversion to the vinylic Grignard reagent a. This sequence constitutes a route to disubstituted alkenes, since a sulfone group is reductively cleaved by sodium amalgam (7, 326). ... 

A serious obstacle to the use of the Julia alkenation for the synthesis of trisubstituted alkenes is illustrated in Scheme 31. Addition of cyclohexanone to the lithiated sulfone (86) gave intermediate (87), which could not be acylated under the reaction conditions because of the sterically hindered tertiary alk-oxide. Owing to an unfavorable equilibrium, (87) reverted back to starting materials. However, by reversing the functionality of the fragments a stable adduct (88) was formed in which the less hindered secondary alkoxide was acylated and the resultant -benzoyloxy sulfone (89) reductively eliminated to the alkene (90) in 54% overall yield. Trisubstimted alkenes have been generated by reductive elimination of 3-hydroxy sulfones ° but, in general, retroaldol reactions compete. 

A dramatic application was the asymmetric synthesis of epibatidine 70 by Simpkins.18 Diels-Alder reaction of the deactivated pyrrole 63 with the alkynyl sulfone 64 gave the bicyclic core 65 of epibatidine. Selective reduction gave the compound 66 needed for epibatidine, but in racemic form. A directed lithiation (chapter 7) and sulfonation led to achiral bis sulfone 67. 

---