Radical bromination-induced ipso cyclization–ortho cyclization sequence of N-hydroxylethyl-N-arylpropiolamides

A facile procedure is reported for the synthesis of various 2-bromo-1-phenyl-5,6-dihydro-3H,7aH-benzo[b]pyrrolo[2,1-c][1,4]oxazin-3-ones via a brominative spiro-tricyclization of N-arylpropiolamides in the presence of TBAB and oxone.

Practical Synthesis of the Fluorogenic Enzyme Substrate 4-Methylumbelliferyl α-l-Idopyranosiduronic Acid

A practical and concise synthesis of 4-methylumbelliferyl α-l-idopyranosiduronic acid, a fluorogenic enzyme substrate diagnostic for α-l-iduronidase, was accomplished. It features successive radical bromination and radical reduction of easily accessible methyl 4-methyl­umbelliferyl-2,3,4-tri-O-acetyl-β-d-glucouronate in four steps with 28% overall yield.

An Enantioconvergent Benzylic Hydroxylation Using a Chiral Aryl Iodide in a Dual Activation Mode

In this article we describe an enantioselective hydroxylation of benzylic C-H bonds with a unique activation mechanism. A chiral aryl iodide catalyst initially acts as precursor for a brominating reagent which subsequently brominates the benzylic C-H bond in a non-stereoselective fashion through a radical bromination. In the second step of this transofrmation, the same catalyst acts as a chiral ligand in a Cu-catalyzed enantioconvergent substitution. We present a broad substrate scope and an intial mechanistic proposal based on a plethora of control experiments.<br>

An Enantioconvergent Benzylic Hydroxylation Using a Chiral Aryl Iodide in a Dual Activation Mode

In this article we describe an enantioselective hydroxylation of benzylic C-H bonds with a unique activation mechanism. A chiral aryl iodide catalyst initially acts as precursor for a brominating reagent which subsequently brominates the benzylic C-H bond in a non-stereoselective fashion through a radical bromination. In the second step of this transofrmation, the same catalyst acts as a chiral ligand in a Cu-catalyzed enantioconvergent substitution. We present a broad substrate scope and an intial mechanistic proposal based on a plethora of control experiments.<br>

Synthesis of Tetrahydroisoquinolines by Visible-Light-Mediated 6-exo-trig Cyclization of α-Aminoalkyl Radicals

Starting from the respective tertiary α-silylmethyl amines, the intramolecular cyclization of α-aminoalkyl radicals to Michael acceptors produced tetrahydroisoquinolines. The reaction conditions included the use of 5 mol% of an iridium photoredox catalyst, dimethylformamide as the solvent, and equimolar amounts of water and cesium carbonate as the additives. 13 substrates were synthesized from ortho-alkylbenzaldehydes in a three-step procedure involving a carbonyl condensation, a radical bromination, and a substitution by a secondary α-silylmethyl amine. After optimization of the photocyclization, the reaction delivered tetrahydroisoquinolines in moderate to high yields (41–83%). A facial diastereoselectivity (dr ≅ 80:20) was observed with chiral substrates and a crystal structure provided evidence for the relative configuration of the major diastereoisomer. A catalytic cycle with direct electron transfer to the photoexcited metal catalyst is proposed.

Crystal structures of 2-bromo-1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane and 2-bromo-1,1,1,3,3,3-hexaisopropyl-2-(triisopropylsilyl)trisilane

The synthesis and crystal structures of two tris(trialkylsilyl)silyl bromide compounds, C9H27BrSi4 (I, HypSiBr) and C27H63BrSi4 (II, TipSiBr), are described. Compound I was prepared in 85% yield by free-radical bromination of 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane using bromobutane and 2,2′-azobis(2-methylpropionitrile) as a radical initiator at 333 K. The molecule possesses threefold rotational symmetry, with the central Si atom and the Br atom being located on the threefold rotation axis. The Si—Br bond distance is 2.2990 (12) Å and the Si—Si bond lengths are 2.3477 (8) Å. The Br—Si—Si bond angles are 104.83 (3)° and the Si—Si—Si bond angles are 113.69 (2)°, reflecting the steric hindrance inherent in the three trimethylsilyl groups attached to the central Si atom. Compound II was prepared in 55% yield by free-radical bromination of 1,1,1,3,3,3-hexaisopropyl-2-(triisopropylsilyl)trisilane using N-bromosuccinimide and 2,2′-azobis(2-methylpropionitrile) as a radical initiator at 353 K. Here the Si—Br bond length is 2.3185 (7) Å and the Si—Si bond lengths range from 2.443 (1) to 2.4628 (9) Å. The Br—Si—Si bond angles range from 98.44 (3) to 103.77 (3)°, indicating steric hindrance between the three triisopropylsilyl groups.

THE FREE RADICAL BRO MINA TION OF ETHYL PYRIDAZINES: THEORETICAL STUDIES

Theoretical studies on free radical bromination by N-bromosuccinimide were carried out on a range of ethyl-3-methoxy-pyridazine derivatives. The investigations of these reactions performed, in order to develop a convenient and rapid theoretical means of predicting selectivity. The geometry optimizations of the total energies of the reactants and the products were calculated using Semi-empirical; AMI, MNDO, PM3 e Hartree Fock, HF3- 21 G computational methods. The calculation performed using PM3 Hamiltonian gave the best qualitative predictions, thus providing a rapid method for the selectivity of the reactions used in the synthesis of novel heterocyclic analogs of neurotransmitters.