Benzylic C-H functionalisation by [Et3SiH + KOtBu] leads to radical rearrangements in o-tolylaryl ethers, amines

Reaction of Et 3SiH+KO tBu with diaryl ethers, sulfides and amines that feature an ortho alkyl group leads to rearrangement products. The rearrangements arise from formation of benzyl radicals, likely formed through hydrogen atom abstraction by triethylsilyl radicals. The rearrangements involve cyclisation of the benzyl radical onto the partner arene, which, from computation, is the rate determining step. In the case of diaryl ethers, Truce-Smiles rearrangements arise from radical cyclisations to form 5-membered rings, but for diarylamines, cyclisations to form dihydroacridines are observed. (Figure presented.)

Et3SiH + KOtBu provide multiple reactive intermediates that compete in the reactions and rearrangements of benzylnitriles and indolenines

The combination of potassium tert-butoxide and triethylsilane is unusual because it generates multiple different types of reactive intermediates simultaneously that provide access to (i) silyl radical reactions, (ii) hydrogen atom transfer reactions to closed shell molecules and to radicals, (iii) electron transfer reductions and (iv) hydride ion chemistry, giving scope for unprecedented outcomes. Until now, reactions with this reagent pair have generally been explained by reference to one of the intermediates, but we now highlight the interplay and competition between them

Isothiourea-catalyzed enantioselective α-alkylation of esters via 1,6-conjugate addition to para-quinone methides

Funding: We thank the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013)/E.R.C. grant agreement n° 279850, AstraZeneca and EPSRC [EP/M506631/1 (J.N.A.)], Syngenta and the EPSRC Centre for Doctoral Training in Critical Resource Catalysis [CRITICAT, EP/L016419/1 (W.C.H.)], and EPSRC [EP/M508214/1 (C.M.)] for funding. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. We thank the EPSRC UK National Mass Spectrometry Facility at Swansea University.The isothiourea-catalyzed enantioselective 1,6-conjugate addition of para-nitrophenyl esters to 2,6-disubstituted para-quinone methides is reported. para-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the para-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of para-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides, in up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er).Publisher PDFPeer reviewe

Ru-Catalyzed C-H Arylation of Fluoroarenes with Aryl Halides

We gratefully acknowledge the Engineering and Physical Sciences Research Council (EPSRC, EP/I038578/1 and EP/ K039547/1) for funding and the European Research Council for a Starting Grant (to I.L.).

Isothiourea-catalyzed enantioselective addition of 4-nitrophenyl esters to iminium ions

The authors thank AstraZeneca and the EPSRC (grant codes EP/M506631/1; J.N.A. and EP/J018139/1; A.B.F.) for funding. The European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC Grant Agreement No. 279850 is also acknowledged. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.Isothioureas catalyze the enantioselective addition of 4-nitrophenyl esters to tetrahydroisoquinoline-derived iminium ions. 4-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the 4-nitrophenyl ester, is used to facilitate catalyst turnover in this reaction process. Optimization showed that 4-nitrophenyl esters give the best reactivity in this protocol over a range of alternative aryl esters, with the observed enantioselectivity markedly dependent upon the nature of the iminium counteri-on. Highest yields and enantioselectivity were obtained using iminium bromide ions generated in situ via photoredox catalysis using BrCCl3 and Ru(bpy)3Cl2 (0.5 mol%) and commercially available tetramisole (5 mol%) as the Lewis base catalyst. The scope and limitations of this procedure was developed, giving the desired β-amino amide products in up to 96% yield, 79:21 dr and ermajor (2R,1′S) 99.5:0.5.PostprintPeer reviewe

New reductive rearrangement of N-Arylindoles triggered by the Grubbs-Stoltz reagent Et3SiH/KOtBu

N-Arylindoles are transformed into dihydroacridines in a new type of rearrangement, through heating with triethylsilane and potassium tert-butoxide. Studies indicate that the pathway involves (i) the formation of indole radical anions followed by fragmentation of the indole C2-N bond, and (ii) a ring-closing reaction that follows a potassium-ion dependent hydrogen atom transfer step. Unexpected behaviors of ‘radical-trap’ substrates prove very helpful in framing the proposed mechanis

Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides

The isothiourea-catalyzed enantioselective 1,6-conjugate addition of para-nitrophenyl esters to 2,6-disubstituted para-quinone methides is reported. para-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the para-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of para-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides at up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er)

Isothiourea-catalyzed enantioselective addition of 4-nitrophenyl esters to iminium ions

Isothioureas catalyze the enantioselective addition of 4-nitrophenyl esters to tetrahydroisoquinoline-derived iminium ions. 4-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the 4-nitrophenyl ester, is used to facilitate catalyst turnover in this reaction process. Optimization showed that 4-nitrophenyl esters give the best reactivity in this protocol over a range of alternative aryl esters, with the observed enantioselectivity markedly dependent upon the nature of the iminium counteri-on. Highest yields and enantioselectivity were obtained using iminium bromide ions generated in situ via photoredox catalysis using BrCCl3 and Ru(bpy)3Cl2 (0.5 mol%) and commercially available tetramisole (5 mol%) as the Lewis base catalyst. The scope and limitations of this procedure was developed, giving the desired β-amino amide products in up to 96% yield, 79:21 dr and ermajor (2R,1′S) 99.5:0.5

CCDC 1420695: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 1420658: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures