Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with ?-ketoesters and ?-ketoamides.
ABSTRACT: Two regiodivergent approaches to intermolecular cyclization of 2-aminobenzothiazoles with ?-ketoesters and amides have been developed, controlled by the reagents employed. With the Brønsted base KOt-Bu and CBrCl3 as radical initiator, benzo[d]imidazo[2,1-b]thiazoles are synthesized via attack at the ?-carbon and keto carbon of the ?-ketoester moiety. In contrast, switching to the Lewis acid catalyst, In(OTf)3, results in the regioselective nucleophilic attack at both carbonyl groups forming benzo[4,5]thiazolo[3,2-a]pyrimidin-4-ones instead.
Project description:Although ?-diazo-?-ketoesters are synthetically versatile intermediates, methodology for introducing this functionality into complex molecules is still limited, most frequently involving a carboxylic acid precursor, which is then activated and transformed into a ?-ketoester, with the diazo group being subsequently added with a diazo transfer reagent. While introducing this highly functional moiety in a convergent one step process would be ideal, such an objective is limited by the relatively few studies which address functionalization of the ?-diazo-?-ketoester at the ?-position. In the present investigation, we evaluate strategies, both new and established, for functionalizing ?-diazo-?-ketoesters, particularly with regard to generating compounds prospectively useful in the synthesis of C1-substituted carbapenems. We report the first ?-aldehydo-?-diazo-?-ketoester as well as a method for its oxidation to the corresponding methyl ester, and the formation of a new substituted pyrazole under basic conditions.
Project description:The regiodivergent addition of substituted phenols to allylic oxides has been demonstrated using C2-symmetric palladium complexes. Complex phenol donors tyrosine, estradiol, and griseofulvin follow the predictive model.
Project description:A method for the regiodivergent arylboration of dienes is presented. These reactions allow for the formation of a diverse range of synthetically versatile products from simple precursors. Through mechanistic studies, these reactions likely operate by initial addition of a Cu-Bpin complex across the diene followed by Pd-catalyzed cross coupling with an aryl halide or pseudohalide.
Project description:A titanocene-catalyzed regiodivergent radical arylation is described that allows access to either enantiomerically pure tetrahydroquinolines or indolines from a common starting material. The regioselectivity of epoxide opening that results in the high selectivity of heterocycle formation is controlled by two factors, the absolute configuration of the enantiopure ligands of the (C5 H4 R)2 TiX2 catalyst and the inorganic ligand X (X=Cl, OTs). The overall reaction is atom-economical and constitutes a radical Friedel-Crafts alkylation.
Project description:An intramolecular Ir(III)-catalyzed regiodivergent oxyamination of unactivated alkenes provides valuable ?-lactams, ?-lactones and ?-lactams. The regioselectivity is controlled by the electronically tunable cyclopentadienyl Ir(III)-complexes enabling oxyamination via either 5-exo or 6-endo pathways. With respect to the mechanism, we propose a highly reactive [3.1.0] bicycle intermediate derived from Ir(V) nitrene-mediated aziridination to be a key intermediate toward the synthesis of ?-lactams.
Project description:A mild and metal-free regiodivergent addition of carbon nucleophiles to ?,?-unsaturated electrophiles was developed. Total 1,2-regioselectivity was observed in the addition of nitrobenzyl chloride derivative 1 to ?,?-unsaturated aldehydes 2 in the presence of TDAE. Moreover, the reaction between p-nitrobenzyl chloride 1a and ?,?-unsaturated iminium salts 4 led to the formation of the 1,4-adduct with total regioselectivity.
Project description:A catalytic enantioselective and regiodivergent arylation of alkenes is described. Chiral copper(II)bisoxazoline complexes catalyze the addition of diaryliodonium salts to allylic amides in excellent ee. Moreover, the arylation can be controlled by the electronic nature of the diaryliodonium salt enabling the preparation of nonracemic diaryloxazines or ?,?'-diaryl enamides.
Project description:A number of (1H-1,2,3-triazol-1-yl)benzo[d]thiazoles were synthesized utilizing a versatile Cu-catalyzed azide-alkyne click reaction (CuAAC) on tautomeric benzo[4,5]thiazolo[3,2-d]tetrazole (1) and 2-azidobenzo[d]thiazole (2) starting materials. Moreover, one of the resulting products of this investigation, triazolbenzo[d]thiazole 22, was found to possess significant neuroprotective activity in human neuroblastoma (SH-SY5Y) cells.
Project description:A magnesium-catalyzed regiodivergent C-O bond cleavage protocol is presented. Readily available magnesium catalysts achieve the selective hydroboration of a wide range of epoxides and oxetanes yielding secondary and tertiary alcohols in excellent yields and regioselectivities. Experimental mechanistic investigations and DFT calculations provide insight into the unexpected regiodivergence and explain the different mechanisms of the C-O bond activation and product formation.