Molecular editing with fluorine is a validated strategy for modulating the structure and function of organic systems. In the current arsenal of catalytic dihalogenation technologies, the direct generation of the vicinal difluoride moiety from simple olefins without a prefunctionalization step remains conspicuously absent. Herein we report a catalytic, vicinal difluorination of olefins displaying broad functional group tolerance, using inexpensive p-iodotoluene as the catalyst. Preliminary efforts toward the development of an enantioselective variant are also disclosed.

Contemporaneous reports describing the vicinal difluorination of olefins relying on I­(I)/I­(III) catalysis have augmented the arsenal of dihalogenation methods and provided a solution to this longstanding challenge in olefin functionalization. In both studies, success was contingent on the in situ generation of ArIF2 from a simple aryl iodide, HF source, and suitable terminal oxidant. The first report by Jacobsen and co-workers employed a resorcinol-derived aryl iodide/m-CPBA oxidant combination, while this laboratory relied on p-iodotoluene and Selectfluor. The complementarity of these approaches ensures that a wide variety of electronically distinct olefins are viable substrates for this transformation. This perspective describes our development of a catalytic difluorination of terminal olefins as a means to efficiently construct a hybrid, chiral bioisostere of the trifluoromethyl and ethyl groups in the broader context of molecular design and highlights key reports from other laboratories that accelerated the study.

A novel polymer-supported fluorinated organocatalyst has been prepared and benchmarked in the enantioselective Michael addition of aldehydes to nitroalkenes. The system has proven to be highly efficient and displays excellent selectivities (er and dr) with a wide variety of substrates. Detailed deactivation studies have given valuable insights, thus allowing the lifespan of this immobilized aminocatalyst to be significantly extended. These data have facilitated the implementation of enantioselective, continuous flow processes allowing either the multigram synthesis of a single Michael adduct over a 13 h period or the sequential generation of a library of enantiopure Michael adducts from different combinations of substrates (13 examples, 16 runs, 18.5 h total operation). A customized in-line aqueous workup, followed by liquid−liquid separation in flow, allows for product isolation without the need of chromatography or other separation techniques.

The enantioselective, organocatalytic aziridination of small, medium and macro-cyclic enals is reported using (S)-2-(fluorodiphenyl methyl)-pyrrolidine. Central to the reaction design is the reversible formation of a β-fluoroiminium ion intermediate, which is pre-organised on account of the fluorine-iminium ion gauche effect. This conformational effect positions the fluorine substituent synclinal-endo to the electropositive nitrogen centre thus benefiting from favourable stereoelectronic and electrostatic interactions (σC-H →σC-F *; F(δ-…︁) N(+) ). Consequently, one of the shielding groups on the fluorine-bearing carbon atom is positioned above the π-system, forming the basis of an enantioinduction strategy. Treatment of this intermediate with a "nitrene" source furnished a series of novel, optically active aziridines (e.r. up to 99.5:0.5). Further derivatisation of the product aziridines gives facile access to various amino acid derivatives, including β-fluoroamino acids. Crystallographic analyses of both the aziridines and their derivatives are disclosed.

The microwave (MW)-assisted addition of dialkyl phosphites to α-oxophosphonates

This work is dedicated to David Milstein in honor of his 70 th birthday.The deaminativeh ydrogenation of nitriles towards alcohols is au seful reaction to transform nitriles into alcohols with NH 3 as the sole byproduct. Using the simplea nd robust RuHCl-(CO)(PPh 3 ) 3 complexa sacatalyst, at low H 2 pressures as eries of aliphatic and aromaticn itriles could be transformed into the correspondinga lcohols. Suitable solvent systemsf or theser eactions were 1,4-dioxane/water and EtOH/water mixtures.I n most cases, the selectivity for the alcohols wase xcellent, and the corresponding amines were formed only in trace amounts.

The synthesis of hydroxy-methyl-20:350-354, 2009; Published online in Wiley InterScience (www.interscience.wiley.com).

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