1,3‐Dipolar cycloadditions. Reactions of nitrile imines with 1,2‐disubstituted alkenes

Abstract

Nitrile imines react with 1‐phenylsulphonyl‐2‐benzoyl (or methoxycarbonyl)alkenes to give 4‐phenylsulphonyl‐5‐benzoyl (or methoxycarbonyl) substituted pyrazolines. The cycloaddition regioselectivity is discussed in terms of Frontier Orbital energies and coefficients.

Tilcotil® Studies [3+2] additions with isothiazol‐3(2H)‐one 1,1‐dioxide

“…The theory proposes furthermore that, with 'normally'*) electron-deficient olefins, these processes should be dipole HO-controlled, except in the nitrile-oxide case, where dipole LU-control would be expected. Most peculiarities of 1,3-dipolar regiocontrol can be rationalized with these premises [ 131 [ 141; in fact, for the two reported cases [ 15][16] of 1,3-dipolar additions to a psulfoacrylic-acid moiety typical of 13, the actually observed selectivities are in agreement with the theory. In practice, the pivotal regiocontrolling factor seems to be simply the C=O group of both 13 and 14.…”

Methyl 3-Phenylsulfonyl-2-propenoate

“…It has been communicated that methyl (E)-3-phenylsulfonyl-2-propenoate (1) reacts with the nitrile imine generated in situ from phenylhydrazonyl chloride and triethylamine to afford a single regioisomeric 4,5-dihydropyrazole (eq 5) in 65% yield. 3 The regioselectivity of this process was rationalized in terms of frontier orbital theory. [4 + 2] Cycloaddition.…”

“…3 Methyl (Z)-3-phenylsulfonyl-2propenoate (2) is prepared in 88% yield by the Boric Acid mediated addition of Sodium Benzenesulfinate to Methyl Propiolate. 5,6 Handling, Storage, and Precautions: potential alkylating and vesicant.…”

Synthesis of novel pyrazoles via [2+3]-dipolar cycloaddition using alkyne surrogates

“…Several pharmaceutical drugs including celecoxib2 and rimonabant3 utilize the pyrazole as their core molecular entity,4,5 and a regioselective synthetic method for the synthesis of these and other substituted pyrazoles is still in demand 3,5-7. (Figure1) One of the most frequently used protocols for pyrazole synthesis is 1,3-dipolar cycloaddition, and the usual dipolarophiles for this purpose are alkynes8 and alkyne equivalents 6,9.…”