Laccase-Catalyzed Oxidation of Allylbenzene Derivatives: Towards a Green Equivalent of Ozonolysis

Laccase-based biocatalytic reactions have been tested with and without mediators and optimized in the oxidation of allylbenzene derivatives, such as methyl eugenol taken as a model substrate. The reaction primarily consisted in the hydroxylation of the propenyl side chain, either upon isomerization of the double bond or not. Two pathways were then observed; oxidation of both allylic alcohol intermediates could either lead to the corresponding α,β-unsaturated carbonyl compound, or the corresponding benzaldehyde derivative by oxidative cleavage. Such a process constitutes a green equivalent of ozonolysis or other dangerous or waste-generating oxidation reactions. The conversion rate was sensitive to the substitution patterns of the benzenic ring and subsequent electronic effects.

Photocatalytic three-component asymmetric sulfonylation via direct C(sp3)-H functionalization

The direct and selective C(sp3)-H functionalization of cycloalkanes and alkanes is a highly useful process in organic synthesis owing to the low-cost starting materials, the high step and atom economy. Its application to asymmetric catalysis, however, has been scarcely explored. Herein, we disclose our effort toward this goal by incorporation of dual asymmetric photocatalysis by a chiral nickel catalyst and a commercially available organophotocatalyst with a radical relay strategy through sulfur dioxide insertion. Such design leads to the development of three-component asymmetric sulfonylation involving direct functionalization of cycloalkanes, alkanes, toluene derivatives or ethers. The photochemical reaction of a C(sp3)-H precursor, a SO2 surrogate and a common α,β-unsaturated carbonyl compound proceeds smoothly under mild conditions, delivering a wide range of biologically interesting α-C chiral sulfones with high regio- and enantioselectivity (>50 examples, up to >50:1 rr and 95% ee). This method is applicable to late-stage functionalization of bioactive molecules, and provides an appealing access to enantioenriched compounds starting from the abundant hydrocarbon compounds.

Photocatalytic three-component asymmetric sulfonylation via direct C(sp3)-H functionalization

The direct and selective C(sp3)-H functionalization of cycloalkanes and alkanes is a highly useful process in organic synthesis owing to the low-cost starting materials, the high step and atom economy. Its application to asymmetric catalysis, however, has been scarcely explored. Herein, we disclose our effort toward this goal by incorporation of dual asymmetric photocatalysis by a chiral nickel catalyst and a commercially available organophotocatalyst with a radical relay strategy through sulfur dioxide insertion. Such design leads to the development of three-component asymmetric sulfonylation involving direct functionalization of cycloalkanes, alkanes, toluene derivatives or ethers. The photochemical reaction of a C(sp3)-H precursor, a SO2 surrogate and a common α,β-unsaturated carbonyl compound proceeds smoothly under mild conditions, delivering a wide range of biologically interesting α-C chiral sulfones with high regio- and enantioselectivity (> 50 examples, up to > 50:1 rr and 95% ee). This method is applicable to late-stage functionalization of bioactive molecules, and provides new access to enantioenriched compounds starting from the abundant hydrocarbon compounds.

Iridium-catalyzed enantioselective olefinic C(sp2)–H allylic alkylation

The first iridium-catalyzed enantioselective allylic alkylation of an olefinic C(sp2)–H bond – that of an α,β-unsaturated carbonyl compound, is developed in cooperation with Lewis base catalysis.

Synthesis, Characterization and Biological Activity of (E)-9-Benzylidene-5-phenyl-5,6,7,8,9,10-hexahydro-[1,2,4]triazolo[3,4-ɑ]quinazoline

Novel quinazoline derivatives were synthesized viathe reaction of unsaturated carbonyl compound subsidiaries with 3-aminotriazole. These compounds are convenient and important intermediates for the synthesis of a rangeof useful and novel heterocyclic compounds. The structures of these compounds were characterized using elemental analysis and IR, 1H NMR and mass spectroscopic methods.They were also tested with respect to their anti-bacterial activity against two types of bacteria,Staphylococcus aureusand Pseudomonas aeruginosa. Significant anti-bacterial activity was observed,and the results indicate the favorable effect of electron-releasing substituents on anti-bacterial activity

Trimethylphosphine-Promoted Alcoholysis of α,β-Unsaturated Imides and α,β-Unsaturated Esters

α,β-Unsaturated imides and α,β-unsaturated esters were found to undergo alcoholysis in the presence of trimethylphosphine. The reaction is initiated by nucleophilic addition of trimethylphosphine to the double bond of the α,β-unsaturated carbonyl compound. Saturated imides also undergo the alcoholysis in the presence of the corresponding α,β-unsaturated imide.

Alkenes

The α-C–H functionalization of piperidine catalyzed by tantalum complex 1 to pro­duce amine 2 was developed (Org. Lett. 2013, 15, 2182) by Laurel L. Schafer at the University of British Columbia. An asymmetric diamination of diene 3 with diaziri­dine reagent 4 under palladium catalysis to furnish cyclic sulfamide 5 was developed (Org. Lett. 2013, 15, 796) by Yian Shi at Colorado State University. Enantioenriched β-fluoropiperdine 8 was prepared (Angew. Chem. Int. Ed. 2013, 52, 2469) via amino­fluorocyclization of 6 with hypervalent iodide 7, as reported by Cristina Nevado at the University of Zurich. Erick M. Carreira at ETH Zürich disclosed (J. Am. Chem. Soc. 2013, 135, 6814) a ruthenium-catalyzed hydrocarbamoylation of allylic formamide 9 to yield pyrrolidone 10. Hans-Günther Schmalz at the University of Köln disclosed (Angew. Chem. Int. Ed. 2013, 52, 1576) an asymmetric hydrocyanation of styrene 11 with Ni(cod)₂ and phosphine–phosphite ligand 12 to yield exclusively the branched cyanide 13. A simi­lar transformation of styrene 11 to the hydroxycarbonylated product 15 was catalyzed (Chem. Commun. 2013, 49, 3306) by palladium complex 14, as reported by Matthew L. Clarke at the University of St Andrews. Feng-Ling Qing at the Chinese Academy of Sciences found (Angew. Chem. Int. Ed. 2013, 52, 2198) that the hydrotrifluoromethylation of unactivated alkene 16 to 17 was catalyzed by silver nitrate. The same transformation was also reported (J. Am.Chem. Soc. 2013, 135, 2505) by Véronique Gouverneur at the University of Oxford using a ruthenium photocatalyst and the Umemoto reagent 18. Clark R. Landis at the University of Wisconsin, Madison reported (Angew. Chem. Int. Ed. 2013, 52, 1564) a one-pot asymmetric hydroformylation using 21 followed by Wittig olefination to transform alkene 19 into the γ-chiral α,β-unsaturated carbonyl compound 20. Debabrata Mati at the Indian Institute of Technology Bombay found (J. Am. Chem. Soc. 2013, 135, 3355) that alkene 22 could be nitrated stereoselectively with silver nitrite and TEMPO to form alkene 23. Damian W. Young at the Broad Institute disclosed (Org. Lett. 2013, 15, 1218) that a macrocyclic vinylsiloxane 24, which was synthesized via an E-selective ring clos­ing metathesis reaction, could be functionalized to make either E- or Z-alkenes, 25 and 26.

Experimental and Theoretical Investigation of the Reaction of Secondary Amines with Maleic Anhydride

The reaction of secondary amines, namely 1-methylpiperazine, pyrrolidine, morpholine, 2-methylpiperidine, and diethylamine, with maleic anhydride has been investigated experimentally and theoretically at the DFT level. Under kinetic control, i.e. at −78°C or −15°C, amines add across the C=O functionality exclusively and the initially formed addition products isomerize to the corresponding N-substituted maleimic acid derivatives. In contrast to the acyclic α,β-unsaturated carbonyl compounds, amine does not add across the C=C functionality in maleic anhydride even under thermodynamic control. This behaviour of maleic anhydride can be rationalized on the basis of the local condensed Fukui functions, which reveal that the carbonyl carbon atoms in maleic anhydride are much harder than in an acyclic α,β-unsaturated carbonyl compound, such as acrolein. This prompts the amines to attack the carbonyl group in maleic anhydride exclusively.