Green synthesis of 6-cyano-2,2-dimethyl-2-H-1-benzopyran and its subsequent enantioselective epoxidation

Abstract

a b s t r a c tThe clean synthesis of 6-cyano-2,2-dimethyl-2-H-1-benzopyran epoxide starting from 3-methyl-2-butenal is reported using recyclable catalysts. H 4 PMo 11 VO 40 (PMo 11 V) and (PyH) 3 HPMo 11 VO 40 (Py 3 -PMo 11 V) Keggin-type heteropolyacids were used to synthesize 6-cyano-2,2-dimethyl-2-H-1-benzopyran in two steps with 35% yield. This is an alternative procedure to the traditional methodology with pyridine or picoline as catalyst, where 6-cyano-2,2-dimethyl-2-H-1-benzopyran is obtained by condensation of 4-cyanophenol with 1,1-diethoxy-3-methyl-2-butene. The 6-cyano-2,2-dimethyl-2-H-1-benzopyran epoxide was obtained using Jacobsen-type catalysts, and in situ generated dimethyldioxirane (DMD) as oxidizing agent, that in comparison to m-CPBA/4-NMO and NaOCl/4-PPNO did not degrade the catalyst. In presence of 4-phenylpyridine N-oxide (4-PPNO) at 4 • C, enantioselectivities of 87% for 3S,4S-epoxide and 68% for 3R,4R-epoxide were obtained with the S,S-and R,R-Jacobsen catalysts, respectively. Overall yield was approximately 17% for 3S,4S-epoxide.

Selective and metal-free epoxidation of terminal alkenes by heterogeneous polydioxirane in mild conditions

“…Dioxirane compounds as non-metal organic oxidants can efficiently transfer oxygen atoms to various substrates and their utility has been well known for various oxidation reactions such as epoxidation of various olefins (enol ether, silyl enol ether, 2,3-dimethylbenzofuran, enol ester, lactone and enol phosphate) [9], oxidation of sulfides, amines and carbonhydrogen bond [10]. Among them dimethyldioxirane (DMDO), known as Murray's reagent [11,12], is an oxidant used in organic synthesis and considered as an environment-friendly oxygen transfer reagent for suitable substrates without the need for a catalytic system containing transition metal [13][14][15]. However, DMDO is susceptible to decomposition especially in the presence of heat; it should be isolated at lower temperatures mostly as acetone solution.…”

Recent Applications of Heteropolyacids and Related Compounds in Heterocycle Synthesis. Contributions between 2010 and 2020

“…Within this group are pyrimidines, which are a class of six-membered heterocycles that contain two nitrogen atoms in positions 1 and 3 and are an important source for the discovery of many drugs due to their versatile properties such as anticancer, antiviral, antibacterial and insecticide activity [27][28][29][30][31][32]. This molecule can be functionalized with other biologically important molecule residues to improve its bioactivity, as in the case of 3,4-dihydropyrimidine-2 (1H) -ones (thiones), an important compound in organic synthesis due to its bioactivity [33]. The most suitable procedure for their preparation is the Biginelli synthesis, a multicomponent condensation reaction in an acid medium that involves an aldehyde, a β-dicarbonylcompound and urea or thiourea [34].…”

“…Our research group reported a green method for the synthesis of 6-cyano-2,2-dimethyl-2-H-1-benzopyran (6-CN-2,2-DMB) and its subsequent enantioselective epoxidation by the use of the heteropolyacids H 4 PMo 11 VO 40 (PMo 11 V) and (PyH) 3 HPMo 11 VO 40 (Py 3 -PMo 11 V), and homogeneous Jacobsen catalysts (Scheme 28) [33]. The reaction was carried out in three steps with a yield of 35%.…”