First Row Transition Metal Catalyzed Radical Transformations

The Co-catalyzed coupling of three-membered ring heterocycles with alkenes has provided a new synthetic route to challenging substrates such as cyclic homoallylic alkohols and amines starting form easily accessible materials. During the studies of this transformation, it has been discovered that the intermediate generated during the reaction (e.g. alkoxide formation after epoxide opening) is basic enough to deprotonate the metal hydride species generated at the end of the catalytic cycle, thus providing catalytic turnover without need of external reductants or stoichiometric amount of additional base. In a broader context, this discovery might inspire the design of novel atom-economical transformations involving the alkylation of different electrophiles (from a nucleophilic Co(I)-species) and generation of similar basic intermediates able to directly regenerate the active catalyst. In conclusion, a conceptually novel strategy for the synthesis of a broad array of primary amines building blocks through the synthesis of rare unprotected aminochlorides has been reported. These versatile intermediates can be generated for the first time from alkenes through the use of an operationally simple Fe-catalyzed aminochlorination reaction that uses a hydroxylamine-derivative reagent and benign NaCl as a stoichiometric chlorinating agent. This protocol tolerates a large scope of aliphatic and conjugated alkenes, including densely functionalized substrates, and gives perfect regioselectivy for the anti-Markovnikov installation of the amino group. The unique reactivity of this poorly studied class of amphoteric molecules enables a facile access to mono- and difunctionalized primary amine derivatives, such as linear or branched primary amines, aziridines, cyano amines, azido amines and allyl amines. This operationally simple Fe-catalyzed protocol thus provides a unified two-step strategy for the synthesis of a wide range of primary amine containing building blocks, formally addressing multiple longstanding challenges in catalysis, such as the catalytic synthesis of linear primary amines from alpha alkenes

Atom-economical cobalt-catalysed regioselective coupling of epoxides and aziridines with alkenes

We demonstrate that a simple cobalt complex can regioselectively couple epoxides and aziridines with alkenes to generate valuable homoallylic alcohols and amines. The intramolecular reaction exhibits complete atom economy and, in contrast to traditional Mizoroki–Heck reactions, does not require stoichiometric amounts of base. An indole derivative was also shown to be a suitable coupling partner. Finally, promising results regarding the development of an intermolecular process using both epoxides and aziridines are reported, as well as preliminary mechanistic studies suggesting a radical mechanism

Unlocking Mizoroki–Heck-Type Reactions of Aryl Cyanides Using Transfer Hydrocyanation as a Turnover-Enabling Step

A new transfer hydrofunctionalization strategy to turnover H-MII-X complexes has enabled both intra- and intermolecular Mizoroki–Heck (MH)-type reactions of aryl cyanides that are challenging to realize under traditional, basic conditions. Initially, a cascade carbonickelation/MH reaction of 2-cyanostyrenes was achieved using a key alkyne transfer hydrocyanation step. Mechanistic experiments supported the proposed catalytic cycle, including the turnover-enabling transfer hydrocyanation step. The reactivity was then extended to the intermolecular MH reaction of benzonitriles and styrenes

Efficient access to unprotected primary amines by iron-catalyzed aminochlorination of alkenes

Primary amines are essential constituents of biologically active molecules and versatile intermediates in the synthesis of drugs and agrochemicals. However, their preparation from easily accessible alkenes remains challenging. Here, we report a general strategy to access primary amines from alkenes through an operationally simple iron-catalyzed aminochlorination reaction. A stable hydroxylamine derivative and benign sodium chloride act as the respective nitrogen and chlorine sources. The reaction proceeds at room temperature under air; tolerates a large scope of aliphatic and conjugated alkenes, including densely functionalized substrates; and provides excellent anti-Markovnikov regioselectivity with respect to the amino group. The reactivity of the 2-chloroalkylamine products, an understudied class of amphoteric molecules, enables facile access to linear or branched aliphatic amines, aziridines, aminonitriles, azido amines, and homoallylic amines

Metabolic syndrome as a predictor of all-cause and cardiovascular mortality in type 2 diabetes: the Casale Monferrato Study

OBJECTIVE: The aim of this study was to assess in an 11-year survival follow-up of a population-based cohort of type 2 diabetes the predictive role of World Health Organization-defined metabolic syndrome, independent of conventional cardiovascular risk factors. RESEARCH DESIGN AND METHODS: During the follow-up (1991-2001), 1,565 patients were regularly examined with centralized measurements of HbA(1c). The independent role of the metabolic syndrome as a predictor of all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling. RESULTS: At baseline, the prevalence of the metabolic syndrome was 75.6% (95% CI 73.6-77.9). Results are based on 685 deaths (520 with the metabolic syndrome and 165 without it) in 10,890.2 person-years of observations. With respect to subjects without the metabolic syndrome, those with the metabolic syndrome had a similar hazard ratio (HR) of cardiovascular mortality after adjustment for age, sex, smoking, total cholesterol level, and coronary heart disease. In contrast, relative to subjects with diabetes only, the HR of subjects with only one component of the syndrome was 2.92 (1.16-7.33), independent of other risk factors. CONCLUSIONS: We found that 1) the prevalence of the metabolic syndrome in a population-based cohort of type 2 diabetes is high (75.6%); 2) the metabolic syndrome is not a predictor of 11-year all-cause and cardiovascular mortality; and 3) more than twofold higher cardiovascular risk, independent of conventional risk factors, is evident in diabetic subjects with only one component of the syndrome compared with those with diabetes only. Categorizing type 2 diabetic subjects as having or not having the metabolic syndrome does not provide further prediction compared with the knowledge of its single components