Sulfinamides

The utility of methanesulfinyl chloride lies in its great chemical reactivity. Through its ready hydrolysis, it serves as a convenient source of methanesulfinic acid. It reacts at low temperature with aromatic amines to form sulfinamides, and with alcohols to form sulfinate esters. When it is hydrolyzed in the presence of an equimolar quantity of sulfenyl chloride, a thiol-sulfonate ester is produced. 

Sulfenamides arc usually oxidized to sulfonamides tns(tnfluorotnetliane-sulfenyl) and bis(tnfluoromethanesulfenyl)arnineare converted to the corresponding sulfonamides by sodium hypochlorite at 20 tor 3 h m 61 and 92% yield, respecbvely [111] Oxidation of pentafluorobenzenesulfendimde by manganese dioxide yields a sulfinamide intermediate that can be trapped [772] (equabon 102)... 

Although carbanionic and enolate species are most often sulfinylated using sulfinate esters, particularly homochiral ester 19, other tricoordinate S(IV) compounds may be used in their place. Sulfinamides (66) and cyclic sulfite ester-amides (67) are two examples of such compounds. 

Finally, although strictly outside the scope of this chapter (and book), we mention a study of the transmission of electronic effects in iV-alkylidene-sulfenamides, -sulfinamides and -sulfonamides, XC6H4SO N=CHC6H4OH-2, through measuring the PMR chemical shifts of the o-OH148. The p values lie in the order S < SO > S02 (cf. above) which is attributed to a complex interplay of factors. 

Double asymmetric induction operates when the azomethine compound is derived from a chiral a-amino aldehyde and a chiral amine, e.g., the sulfin-imine 144 [70]. In this case, the R configuration at the sulfur of the chiral auxihary, N-tert-butanesulfinamide, matched with the S configuration of the starting a-amino aldehyde, allowing complete stereocontrol to be achieved in the preparation of the diamine derivatives 145 by the addition of trifluo-romethyl anion, which was formed from trifluoromethyltrimethylsilane in the presence of tetramethylammonium fluoride (Scheme 23). The substituents at both nitrogen atoms were easily removed by routine procedures see, for example, the preparation of the free diamine 146. On the other hand, a lower diastereoselectivity (dr 80 20) was observed in one reaction carried out on the imine derived from (it)-aldehyde and (it)-sulfinamide. 

Another intriguing behavior of some proteases is their ability to hydrolyze sulfur-nitrogen bond in N-acyl sulfinamides. Thus, when some N-acyl... 

Scheme 5.24 Subtilisin-Carlsberg-catalyzed hydrolysis of sulfinamides.

By modification of the elegant method of preparation of optically active sulfinates previously reported by Mikolajczyk and coworkers , an efficient stereospecific method for the conversion of readily available optically active sulfinamides to optically active sulfinates of inverted configuration at the sulfinyl function, has been recently reported by Hiroi and coworkers . The same authors subsequently reported the thermal rearrangement of several optically active cis- and trans-y-substituted allylic p-toluenesulfinates to optically active chiral sulfones with high stereoselectivity. For example, trans and cis (S)-( — )-crotyl p-toluenesulfinates rearranged to optically active (S)-(-l-)- and (R)-( — )-a-methylallyl p-tolyl sulfone, respectively (equation 19). 

Hogeveen and co-workers <82JOC1909 83JOC4275> also reported the synthesis of tricyclic sulfinamides by the reaction of cyclobutadiene aluminum halide o complexes (65 or 66) with 53 at low temperature. Treatment of 65 or 66 with 53 at -60 °C resulted in the formation of 67 or 68 in 52% and 55% yields, respectively (Scheme 18). 

Harmata and co-workers also discovered that 2,1-benzothiazines could be conveniently converted into 2-alkenylanilines by treatment with KDMSO in DMSO <91JOC5059 91T8855>. For example, the reaction of benzothiazine 185 with KDMSO for 20 minutes at 70 °C resulted in the formation of the 2-alkenyl sulfinamide 189 in 90% yield (Scheme 51). 

The 2-alkenyl sulfinamides appeared to be slightly unstable. They could, however, be quickly converted into anilines by base-catalyzed hydrolysis in good yields (Scheme 52) <91JOC5059 91T8855>. This general route to 2-alkenyl anilines is regioselective, but not stereoselective. 

Radical cyclization of acyclic sulfinamides 239 provides easy access to cyclic sulfinamides 241 <06AG(E)633>. Conceivably, the reaction pathway involves thiophilic attack by the aryl radical with a concomitant or successive expulsion of the p-tolyl or tert-butyl radical. 

Catalyst 41 (Fig. 29.29) is based on a sulfmyl imine, with the stereogenic center at the sulfinamide group. The best catalyst in this series, 41a, gave 94% ee in the hydrogenation of substrate 1 [54], The catalyst has low activity, with 5 mol% catalyst being required. 

It is also known (Mikolajczyk et al., 1976) that treatment of an optically active sulfinamide with an alcohol in the presence of two moles of strong acid as catalyst results in the formation of optically active sulfinate esters of inverted configuration (152), although the degree of stereoselectivity depends on the... 

The relative ease with which aryl benzyl sulfoxides undergo homolytic dissociation (Rayner et al., 1966) as compared to aryl benzyl sulfides or sulfones is supportive of this idea that ArSO radicals are easier to form than ArS or ArS02 radicals. Another interesting set of observations is the following. Booms and Cram (1972) found that optically active arene-sulfinamides ArS(0)NRPh (R = H or CH3) racemize thermally very readily at room temperature and that this racemization is the result of a free radical chain reaction (160) that is initiated by the dissociation of some of the sulfinamide into an ArSO and a PhNR radical (159). While the length of the inhibition... 

The first term obviously reflects the thiol-dependent 7V-hydroxyarylamine formation while the second term stands for the rearrangement to the sulfinamide (see Scheme 1). Correspondingly, product ratios were found to correlate with thiol concentrations in the following manner22,25 ... 

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