Rare and amphoteric intermediates, in situ generation: controlled reactivity in diverse cascade reactions, over 100 examples.

Lignin is the most abundant renewable aromatic-containing macromolecule in Nature. Intensive research efforts are underway to obtain additional value from lignin beyond current low-value heating. Aerobic oxidation has emerged as one promising alternative for the selective depolymerization of lignin, and a variety of models for the most abundant β-O-4 linkage have been employed. In this work, aerobic oxidation of the simple β-O-4 lignin models 2phenoxyethanol (2) and 1-phenyl-2-phenoxyethanol (3) were investigated using the oxovanadium complex (HQ) 2 V V (O)(O i Pr) (HQ = 8-oxyquinolinate) and CuCl/TEMPO/2,6-lutidine as catalysts in several different solvents at 100 °C (TEMPO = 2,2,6,6tetramethylpiperidine-1-oxyl). Using the vanadium catalyst, reactions proceed more readily in pyridine (vs dimethyl sulfoxide) presumably via an initial base-assisted alcohol dehydrogenation followed by oxidative C−C and C−O bond cleavage to afford phenol, formic acid and CO 2 . In contrast, the copper-catalyzed reactions suffer from extensive formylation of the substrate and radical coupling to give TEMPO-functionalized products. These results suggest that use of more complex β-O-4 lignin models is required for accurate comparison of selective oxidation catalysts.

Nitrogen-substituted isocyanates are rarely utilized but powerful building blocks for the development of cascade reactions in heterocyclic synthesis. These reactive amphoteric intermediates can be accessed in situ via an equilibrium that allows controlled reactivity in the presence of bifunctional partners such as α-amino esters. A cascade reaction has been carried out that forms 3-aminohydantoin derivatives using simple phenoxycarbonyl derivatives of hydrazides and hydrazones as precursors of N-substituted-isocyanates. This method allows rapid assembly of complex aminohydantoin derivatives, including analogues of medicinally-relevant compounds, using simple reactants.

A Cascade Synthesis of Aminohydantoins Using in situ-Generated N-SubstitutedIsocyanates. -Simple hydrazides and hydrazones are used as precursors of the required N-substituted isocyanates. They are generated in situ and treated with a series of -amino esters. In the case of optically active amino acids such as (II), racemization takes place during the process. The substitution/cyclization sequence allows access to broad variety of complex aminohydantoin derivatives [cf. (V)], azumolene analogues (XVII), and thio analogue (XIX). -(VINCENT-ROCAN, J.-F.; CLAVETTE, C.; LECKETT, K.; BEAUCHEMIN*, A. M.; Chem. -Eur. J. 21 (2015) 10, 3886-3890, http://dx.doi.org/10.1002/chem.201405648 ; Dep. Chem., Univ. Ottawa, Ottawa, Ont. K1N 6N5, Can.; Eng.) -Lehmann 28-170

A detailed study concerning the use of N‐isocyanates, generated in situ, is carried out.