A main group-catalyzed method for the synthesis of aryl- and heteroarylamines by intermolecular C–N coupling is reported. The method employs a small-ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane) and a terminal hydrosilane reductant (phenylsilane) to drive reductive intermolecular coupling of nitro(hetero)arenes with boronic acids. Applications to the construction of both Csp2–N (from arylboronic acids) and Csp3–N bonds (from alkylboronic acids) are demonstrated; the reaction is stereospecific with respect to Csp3–N bond formation. The method constitutes a new route from readily available building blocks to valuable nitrogen-containing products with complementarity in both scope and chemoselectivity to existing catalytic C–N coupling methods.

A selective and mild method for the benzylic fluorination of aromatic azaheterocycles with Selectfluor is described. These reactions take place by a previously unreported mechanism, in which electron transfer from the heterocyclic substrate to the electrophilic fluorinating agent Selectfluor eventually yields a benzylic radical, thus leading to the desired C-F bond formation. This mechanism enables high intra- and intermolecular selectivity for aza-heterocycles over other benzylic components with similar C-H bond-dissociation energies.

Proctocolectomy (PC) with small bowel resection may lead to profuse ileostomy diarrhoea which can be difficult to treat. The effect of a recently developed long acting somatostatin analogue (SMS 201-995) on ileostomy output was investigated in 5 patients who had undergone PC and ileal resection (median 120 cm) and who suffered severe diarrhoea (4-7 litres/24 h). Gastric emptying, transit of a standard meal through the small bowel and the amounts of nutrients excreted were simultaneously determined during double blind infusion of SMS (25 micrograms/h) and placebo (isotonic saline 125 ml/h). SMS 201-995 significantly reduced ileostomy output (P less than 0.05) and water excretion (P less than 0.05) and prolonged small bowel transit time (P less than 0.05). Whilst having little effect on gastric emptying, or on the excretion of glucose or nitrogen, fat excretion was significantly increased (P less than 0.05). In two patients subcutaneous administration of SMS 201-995 (50 micrograms b.d.) has maintained a reduced ileostomy output for 4 and 6 months respectively.

Experimental, spectroscopic, and computational studies are reported that provide an evidence-based mechanistic description of an intermolecular reductive C−N coupling of nitroarenes and arylboronic acids catalyzed by a redox-active maingroup catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide, i.e., 1• [O]). The central observations include the following: (1) catalytic reduction of 1•[O] to P III phosphetane 1 is kinetically fast under conditions of catalysis; (2) phosphetane 1 represents the catalytic resting state as observed by 31 P NMR spectroscopy; (3) there are no long-lived nitroarene partial-reduction intermediates observable by 15 N NMR spectroscopy; (4) the reaction is sensitive to solvent dielectric, performing best in moderately polar solvents (viz. cyclopentylmethyl ether); and (5) the reaction is largely insensitive with respect to common hydrosilane reductants. On the basis of the foregoing studies, new modified catalytic conditions are described that expand the reaction scope and provide for mild temperatures (T ≥ 60 °C), low catalyst loadings (≥2 mol%), and innocuous terminal reductants (polymethylhydrosiloxane). DFT calculations define a two-stage deoxygenation sequence for the reductive C−N coupling. The initial deoxygenation involves a ratedetermining step that consists of a (3+1) cheletropic addition between the nitroarene substrate and phosphetane 1; energy decomposition techniques highlight the biphilic character of the phosphetane in this step. Although kinetically invisible, the second deoxygenation stage is implicated as the critical C−N product-forming event, in which a postulated oxazaphosphirane intermediate is diverted from arylnitrene dissociation toward heterolytic ring opening with the arylboronic acid; the resulting dipolar intermediate evolves by antiperiplanar 1,2-migration of the organoboron residue to nitrogen, resulting in displacement of 1•[O] and formation of the target C−N coupling product upon in situ hydrolysis. The method thus described constitutes a mechanistically well-defined and operationally robust main-group complement to the current workhorse transition-metal-based methods for catalytic intermolecular C−N coupling.

This report details a new method for site-selective methylene oxidation adjacent to azaheterocycles. A dual catalysis approach, utilizing both an iron Lewis acid and an organic hydroxylamine catalyst, proved highly effective. We demonstrate that this method provides complementary selectivity to other known catalytic approaches and represents an improvement over current heterocycle-selective reactions that rely on stoichiometric activation.