Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization (original) (raw)
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Multicomponent synthesis of dihydrobenzoxazepinones by coupling Ugi and Mitsunobu reactions
Various dihydrobenzo[f ] [1,oxazepin-5-ones have been convergently prepared in 2-3 steps by coupling Ugi and Mitsunobu reactions. Two alternative methodologies were used: in the first one the Ugi condensation was followed by a Mitsunobu cyclization (2 steps); in the second one an intermolecular Mitsunobu reaction was followed by a deprotection step and then by an intramolecular Ugi reaction. Also a "convertible" isocyanide was used.
An efficient diversity-oriented synthetic approach to annulated 9H-benzo[b]pyrrolo[1,2-g][1,2,3]triazolo[1,5-d][1,4]diazepines has been developed using a Sc(OTf) 3 -catalyzed two-component tandem C-2 functionalization−intramolecular azide−alkyne 1,3-dipolar cycloaddition reaction. The reaction shows high substrate tolerance and provides a library of fused heterocycles that may lead to novel biologically active compounds or drug lead molecules.
Beilstein Journal of Organic Chemistry, 2021
A novel catalyst-free synthetic approach to 1,2,3-triazolobenzodiazepinones has been developed and optimized. The Ugi reaction of 2-azidobenzaldehyde, various amines, isocyanides, and acids followed by microwave-assisted intramolecular azide-alkyne cycload-dition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkynes. 678
One-Step Synthesis of Oxazoline and Dihydrooxazine Libraries
Journal of Combinatorial Chemistry, 2007
Oxazolines appear in numerous medicinally active compounds and natural products of biological significance. 1 Additionally, they are valuable as synthetic intermediates or protecting groups 2 in organic synthesis, 3 and commonly appear in ligands for asymmetric synthesis ). 4 The most common mode of oxazoline synthesis involves preparation of a β-hydroxy amide followed by cyclization. Typical cyclization reagents include Burgess reagent, 5 PPh 3 /DIAD, 6 DIC/Cu(OTf) 2 ,7 molybdenum oxide, 8 and DAST/Deoxo-Fluor. 9 The six-membered homologous dihydrooxazines have been prepared by various methods that include [4+2] cycloadditions between N-acyl imines and alkenes, 10 1,4-dipolar cycloaddition reactions between olefins and aminomethyl ions, 11 and from stereochemically defined Nthioacyl-1,3-amino alcohols in the presence of Bu 4 NF and EtI. 12
Acylation of 4-a-furyl-4-N-benzylaminobut-1-enes with maleic anhydride gave 4-oxo-3-aza-10-oxatricyclo[5.2.1.0 1,5 ]dec-8-ene-6-carboxylic acid via amide formation followed by intramolecular Diels–Alder reaction of furan (IMDAF). The cycloaddition proceeded under mild reaction conditions (25 C) and provided only the exo-adduct in quantitative yield. Treatment of this compound with PPA gave isoindolo[2,1-b][2]benzazepine derivatives via ring opening, aromatization and intramolecular electrophilic alkylation. In order to extend the scope of the reaction sequence, 7-oxo-5,11b,12,13-tetrahydro-7H-isoindolo[2,1-b][2]benzazepine-8-carboxylic acids were further transformed into useful synthetic intermediates.
European Journal of Organic Chemistry, 2009
A flexible route for the stereoselective synthesis of a variety of structurally diverse (1R)-1-alkyldihydro and tetrahydrobenzazepin(ones) has been developed. The key step is a highly diastereoselective 1,2-addition process applied to a stereopure aromatic hydrazone combined with a ring-closing [a] 3741 metathesis reaction to secure the formation of the sevenmembered azaheterocycle ring system. (Scheme 2. Synthesis of the styrenic enehydrazides 4a-g.
Synlett, 2015
Commercially available reagents were used throughout without further purification unless otherwise stated. Reactions were routinely carried out under a nitrogen or argon atmosphere using oven or flame-dried glassware. Fully characterized compounds were chromatographically homogeneous. Melting points were determined on a Fisher Scientific hot stage melting point apparatus and are uncorrected. 1 H and 13 C NMR spectra were recorded using a Bruker Avance-500, Avance-400 or Avance-300 spectrometer operating at 500 MHz, 400 MHz and 300 MHz respectively (1 H frequency, corresponding 13 C frequencies are 125 MHz, 100 MHz and 75 MHz). In the 13 C NMR spectra, signals corresponding to CH, CH 2 , or CH 3 groups are assigned from DEPT. IR spectra were recorded on a Nicolet Avatar 360 FT-infrared spectrometer. Mass spectra were recorded on a Micromass 70-250S double focusing mass spectrometer (EI) or Waters ZQ Single Quad mass spectrometer (ESI). Anhydrous THF and toluene was obtained from an Innovative Technologies 'Pure-Solve' SPS-400-4 system. Anhydrous DMF (Drisolv®) was obtained from EMD and used as received. Inorganic bases (Cs 2 CO 3 , K 2 CO 3 , K 3 PO 4) were dried under vacuum at >160 °C for 4 hours and stored in a desiccator prior to use. n-Butyllithium (2.5 M solution in hexanes) and sec-butyllithium (1.6 M in hexanes) were purchased from Sigma-Aldrich and titrated biweekly according to the method of Chong and coworkers. 1 Internal temperatures for low temperature reactions were measured using a Barnant thermocouple thermometer. Flash chromatography was carried out using Silicycle Silicaflash P60 silica gel.