Lewis Acid Coordination Redirects S-Nitrosothiol Signaling Output.

S-Nitrosothiols (RSNOs) serve as air-stable reservoirs for nitric oxide in biology. While copper enzymes promote NO release from RSNOs by serving as Lewis acids for intramolecular electron-transfer, redox-innocent Lewis acids separate these two functions to reveal the effect of coordination on structure and reactivity. The synthetic Lewis acid B(C6 F5 )3 coordinates to the RSNO oxygen atom, leading to profound changes in the RSNO electronic structure and reactivity. Although RSNOs possess relatively negative reduction potentials, B(C6 F5 )3 coordination increases their reduction potential by over 1 V into the physiologically accessible +0.1 V vs. NHE. Outer-sphere chemical reduction gives the Lewis acid stabilized hyponitrite dianion trans-[LA-O-N=N-O-LA]2- [LA=B(C6 F5 )3 ], which releases N2 O upon acidification. Mechanistic and computational studies support initial reduction to the [RSNO-B(C6 F5 )3 ] radical anion, which is susceptible to N-N coupling prior to loss of RSSR.

Copper-Catalyzed C(sp3 )-H Amidation: Sterically Driven Primary and Secondary C-H Site-Selectivity.

Undirected C(sp3 )-H functionalization reactions often follow site-selectivity patterns that mirror the corresponding C-H bond dissociation energies (BDEs). This often results in the functionalization of weaker tertiary C-H bonds in the presence of stronger secondary and primary bonds. An important, contemporary challenge is the development of catalyst systems capable of selectively functionalizing stronger primary and secondary C-H bonds over tertiary and benzylic C-H sites. Herein, we report a Cu catalyst that exhibits a high degree of primary and secondary over tertiary C-H bond selectivity in the amidation of linear and cyclic hydrocarbons with aroyl azides ArC(O)N3 . Mechanistic and DFT studies indicate that C-H amidation involves H-atom abstraction from R-H substrates by nitrene intermediates [Cu](κ2 -N,O-NC(O)Ar) to provide carbon-based radicals R. and copper(II)amide intermediates [CuII ]-NHC(O)Ar that subsequently capture radicals R. to form products R-NHC(O)Ar. These studies reveal important catalyst features required to achieve primary and secondary C-H amidation selectivity in the absence of directing groups.

Elusive Terminal Copper Arylnitrene Intermediates.

We report herein three new modes of reactivity between arylazides N3 Ar with a bulky copper(I) ß-diketiminate. Addition of N3 ArX3 (ArX3 =2,4,6-X3 C6 H2 ; X=Cl or Me) to [i Pr2 NN]Cu(NCMe) results in triazenido complexes from azide attack on the ß-diketiminato backbone. Reaction of [i Pr2 NN]Cu(NCMe) with bulkier azides N3 Ar leads to terminal nitrenes [i Pr2 NN]Cu]=NAr that dimerize via formation of a C-C bond at the arylnitrene p-position to give the dicopper(II) diketimide 4 (Ar=2,6-i Pr2 C6 H3 ) or undergo nitrile insertion to give diazametallocyclobutene 8 (Ar=4-Ph-2,6-iPr2 C6 H2 ). Importantly, reactivity studies reveal both 4 and 8 to be "masked" forms of the terminal nitrenes [i Pr2 NN]Cu=NAr that undergo nitrene group transfer to PMe3 , t BuNC, and even into a benzylic sp3 C-H bond of ethylbenzene.

Gold(I)-catalyzed homologation of aryl aldehydes with trimethylsilyldiazomethane.

A methodology is described herein for the synthesis of 2-aryl acetaldehydes from aryl aldehydes using TMSCHN2 under Au(I) catalysis. A diazoorgano Au(I) complex was shown to be an intermediate that reacts with ArCHO to give ArCH2CHO products. This homologation protocol was used to synthesize a wide range of 2-aryl acetaldehydes with high functional group compatibility.

Copper(ii) ketimides in sp3 C-H amination.

Commercially available benzophenone imine (HN[double bond, length as m-dash]CPh2) reacts with ß-diketiminato copper(ii) tert-butoxide complexes [CuII]-O t Bu to form isolable copper(ii) ketimides [CuII]-N[double bond, length as m-dash]CPh2. Structural characterization of the three coordinate copper(ii) ketimide [Me3NN]Cu-N[double bond, length as m-dash]CPh2 reveals a short Cu-Nketimide distance (1.700(2) Å) with a nearly linear Cu-N-C linkage (178.9(2)°). Copper(ii) ketimides [CuII]-N[double bond, length as m-dash]CPh2 readily capture alkyl radicals R˙ (PhCH(˙)Me and Cy˙) to form the corresponding R-N[double bond, length as m-dash]CPh2 products in a process that competes with N-N coupling of copper(ii) ketimides [CuII]-N[double bond, length as m-dash]CPh2 to form the azine Ph2C[double bond, length as m-dash]N-N[double bond, length as m-dash]CPh2. Copper(ii) ketimides [CuII]-N[double bond, length as m-dash]CAr2 serve as intermediates in catalytic sp3 C-H amination of substrates R-H with ketimines HN[double bond, length as m-dash]CAr2 and t BuOO t Bu as oxidant to form N-alkyl ketimines R-N[double bond, length as m-dash]CAr2. This protocol enables the use of unactivated sp3 C-H bonds to give R-N[double bond, length as m-dash]CAr2 products easily converted to primary amines R-NH2 via simple acidic deprotection.