Acid-catalyzed additions of amines to alkenes are generally unsuccessful due to the buffering effect of the amine substrate. 1 Friedel-Crafts alkylations of arylamines are hindered by coordination of the amine to the Lewis acid catalyst. 2 A recent communication by Hartwig et al. reports that several common Brønsted acids catalyze the intramolecular hydroamination of tosyl-protected amino olefins. 3 Beller and co-workers have reported that alkylations of electron-rich anilines with styrene are promoted with HBF 4 ·Et 2 O. 2b,4 Herein we report the first homogeneous 5 acid catalyst that promotes both hydroamination and hydroarylation reactions of anilines and alkenes, including simple cyclic alkenes and dienes. These transformations are air-and moisture-tolerant and can be controlled to favor either N-H or Ar-H addition products based on reaction conditions and aniline substitution pattern. The key to the activity of this system is that the acid counteranion has a dramatic effect on reaction efficiency.In the course of our studies on metal-catalyzed hydroamination reactions, 6 we found that Ph 3 CB(C 6 F 5 ) 4 (1) catalyzes the reaction of norbornene with aniline. Both hydroamination (2) and ortho-hydroarylation (3) products are formed using 5 mol % of 1 (eq 1). 7(1)

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery.

[reaction: see text] Several tantalum imido complexes have been synthesized and shown to efficiently catalyze the hydroamination of internal and terminal alkynes. An unusual hydroamination/hydroarylation reaction of norbornene catalyzed by a highly electrophilic cationic tantalum imido complex is also reported. Factors affecting catalyst activity and selectivity are discussed along with mechanistic insights gained from stoichiometric reactions.

The synthesis and reactivity of dibenzyl cationic tantalum imido complexes is described. The trialkyl tantalum imido compounds Bn(3)Ta=NCMe(3) (1) and Np(3)Ta=NCMe(3) (2) were synthesized as starting materials for the study of dialkyl cationic tantalum imido complexes. Compound 1 undergoes insertion reactions with diisopropylcarbodiimide and 2,6-dimethylphenylisocyanide to give (bisamidinate)imido complex 5 and (bisimino-acyl)imido complex 6, respectively. Treatment of compound 1 with B(C(6)F(5))(3) gives the zwitterionic tantalum complex [Bn(2)Ta=NCMe(3)][BnB(C(6)F(5))(3)] (7) which is stabilized by eta(6)-coordination of the benzyl triaryl borate anion. Coordination of the aryl anion can be displaced by three equivalents of pyridine to give the Lewis base complex 8. Treatment of compound 1 with [Ph(3)C][B(C(6)F(5))(4)] gives the cationic tantalum imido complex [Bn(2)Ta=NCMe(3)][B(C(6)F(5))(4)] (3). This salt forms insoluble aggregates unless trapped by THF coordination or an insertion reaction with an alkyne or an alkene. Cation 3 undergoes migratory insertion reactions with diphenylacetylene, phenylacetylene, norbornene, and cis-cyclooctene to give the corresponding alkenyl or modified alkyl imido complexes. The characterization of these products and the significance of these insertion reactions with respect to Ziegler-Natta polymerizations and hydroamination reactions are described.

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