Preparation of spiro[benzoisothiazole‐isoxazole] dioxides from dilithiated c(α),O‐oximes and methyl 2‐(aminosulfonyl)benzoate

Abstract

Several dilithiated C( ),O-oximes were prepared in excess lithium diisopropylamide-tetramethylethylenediamine (LDA/TMEDA) and condensed with methyl 2-(aminosulfonyl)benzoate followed by acid cyclization of intermediates to spiro(benzoisothiazole-isoxazole) dioxides, a new spiro and fused-ring system. Distortionless enhancement by polarization transfer (DEPT) and liquid chromatography mass spectrometry (LCMS) for all products, as well as X-ray single crystal analysis on a representative product, were especially relevant for structure confirmation in this synthesis.

Regioselective carbon–carbon bond formation of 5,5,5-trifluoro-1-phenylpent-3-en-1-yne

“…The addition of HMPA or DMPU was detrimental and no trace amount of 4 , 5a , nor 6a was detected (Table 1, entries 10 and 11). However, TMEDA affected this process to some extent (Table 1, entries 5 vs 12) [16–18], and the addition of 2 equiv each of LDA and TMEDA produced the regioisomeric 5a and 6a in better yields of 68% and 11%, respectively (Table 1, entry 13). The recovery of 15% of the substrate 4 under these conditions prompted further raise in their amount to 3 equiv, but again, no significant improvement was noticed (Table 1, entries 13 vs 14).…”

Preparation of 2‐(1H‐pyrazol‐5‐yl)benzenesulfonamides from polylithiated C(α),N‐carbo‐tert‐butoxyhydrazones and methyl 2‐(aminosulfonyl)benzoate

“…The anticipated C-acylated intermediates could be more difficult to cyclize to 4 or 5 as a result of the orthobenzenesulfonamide moiety bonded to the carbonyl carbon. Unexpectedly, spiro(benzoisothiazole-isoxazole)-dioxides 6 [15] resulted and not the projected isoxazoleortho-benzenesulfonamides 4. Intermediates resulting from condensation-cyclization of dilithiated phenylhydrazones 3' with lithiated ester-sulfonamide 1' (from 1) resulted in N-phenylpyrazolyl-ortho-benzenesulfonamides 5 [16].…”

Preparation of 2H‐spiro[benzo[d]isothiazole‐3,3′‐pyrazole]‐1, 1‐dioxide‐2′(4′H)‐carboxylates from dilithiated C(α),N‐carboalkoxyhydrazones and methyl 2‐(aminosulfonyl)benzoate

“…In this laboratory, BIDs and pyrazoles have been synthesized by the condensation‐cyclization of polylithiated intermediates, prepared in excess lithium diisopropylamide (LDA), with methyl 2‐(aminosulfonyl)benzoate 1 , Scheme . Specifically, anionic electrophile 1' has been condensed‐cyclized with dilithiated oximes 2 to afford spiro(BID‐isoxazoles) 3 [5]; with dilithiated β‐ketoesters 4 (R = OMe or OEt) to afford BID‐β‐ketoesters 5 (R = OMe or OEt); with dilithiated β‐diketones 4 (R = Ar) to afford BID‐β‐diketones 5 (R = Ar); or with trilithiated β‐ketoamides 4 (R = NLiC 6 H 5 ) resulting in BID β‐ketoamides 5 (R = NHC 6 H 5 ) [6].…”