Sultam-derived dipolarophiles

TABLE 2.38. SELECTIVITIES OBSERVED IN THE DIPOLAR CYCLOADDITION OF SULTAM DERIVED DIPOLAROPHILES... 

Figure 2.13. Proposed transition state for chral sultam derived dipolarophiles.

The 3 + 2-cycloaddition of commercially available Me3SiCHN2 with camphor sultam-derived dipolarophiles produces 3-trimethylsilyl-substitutcd-A1 -pyrazolincs which on acid treatment convert into optically active A2-pyrazolines.60 The nucleophilic addition of ethyl diazoacetate with /V-cthoxycarbonyl-/V-(2,2,2-trichlorocthylidcne)a-mine produces a new diazo intermediate (35), which by 1,3-dipolar cycloaddition followed by a sigmatropic rearrangement of the cycloadduct (36) furnishes a substituted pyrazole (37) (Scheme 13).61. 

The sultam (146) yields the 1,2,4-dithiazolidine (174), thiazolidine (175) or 1,2,4-thiadiazolidine derivatives (176) on heating with an excess of several heterocumulene dipolarophiles (Scheme 29). It is formally acting as a masked 1,3-dipole resulting from elimination of the sulfene moiety (PhCH SOj) <78JOC4951>. 

In synthetic efforts toward the DNA reactive alkaloid naphthyridinomycin (164), Gamer and Ho (41) reported a series of studies into the constmction of the diazobicyclo[3.2.1]octane section. Constmction of the five-membered ring, by the photolytic conversion of an aziridine to an azomethine ylide and subsequent alkene 1,3-dipolar cycloaddition, was deemed the best synthetic tactic. Initial studies with menthol- and isonorborneol- tethered chiral dipolarophiles gave no facial selectivity in the adducts formed (42). However, utilizing Oppolzer s sultam as the chiral controlling unit led to a dramatic improvement. Treatment of ylide precursor 165 with the chiral dipolarophile 166 under photochemical conditions led to formation of the desired cycloadducts (Scheme 3.47). The reaction proceeded with an exo/endo ratio of only 2.4 1 however, the facial selectivity was good at >25 1 in favor of the desired re products. The products derived from si attack of the ylide... 

The chiral dipolarophiles of Garners and Dogan, which were derived from Oppolzer s sultam, have been previously discussed in Section 3.2.1 and, in an extension to these results, the sultam moiety was used as the stereodirecting unit in enantiopure azomethine ylides (56). The ylides were generated either by thermo-lytic opening of N-substituted aziridines or by the condensation of the amine functionality with benzaldehyde followed by tautomerism. These precursors were derived from the known (+)-A-propenoylbornane-2,10-sultam. Subsequent trapping of the ylides with A-phenylmaleimide furnished the cycloaddition products shown in Schemes 3.60 and 3.61. 

Cyclic sulfonamides are Lermed sultams. From the enantiomeric 10-camphorsulfonic acids, both enantiomers of camphorsultam (49) are readily available by reduction of the intermediate sulfon-imide 484fi 50 and are commercially available. They have been used for the formation of amides with unsaturated acids, which are useful chiral dienophiles and dipolarophiles (Sections D. 1.6,1.1.1- and D. 1.6.1.2.1.) or undergo osmium tetroxide catalyzed dihydroxylations (Section D.4.4.). Other amides may be used for enolate reactions (Sections D.1.1.1.3.1., D.l.5.2.1. and D.4.3.). The. V-fluorinated derivative was obtained by direct fluorination of the sultam with 10% fluorine in nitrogen at low temperature5 , and has been used for the enantioselective formation of C —F bonds (Section D.3.). 

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