Stereocontrolled Synthesis and Cycloaddition of 1,2,4-Trioxygenated 1,3-Dienes

Abstract

A new stereocontrolled synthetic pathway to 1,2,4-trioxygenated 1,3-dienes from pyruvic aldehyde dimethyl acetal (14a) is described. Reacting the cyclohexylamine-derived imine of this starting material with chloroalkyl ethers under basic conditions affords ketoacetals 18-20, which were then transformed into eight different enoxysilanes 12. A delta-elimination triggered by tert-butyllithium yields 1,2,4-trioxygenated dienes 13. Increasing the bulkiness of the silyloxy group or that of the acetal moiety leads stereoselectively to the (1E,3E) or (1Z,3E) isomers of 13, respectively. Hyperbaric [4 + 2] cycloadditions between 13 (13c, 13d, 13g) and N-methylmaleimide or methyl- and phenylacrylates give access to the expected cycloadducts with fine stereo- and regiocontrol.

The Stepwise Diels–Alder Reaction of 4‐Nitrobenzodifuroxan with Danishefsky’s Diene

“…The high susceptibility to hydrolysis of a trimethylsilyloxy moiety by adventitious water present in the reaction mixture is a well-known perturbation in Diels-Alder reactions that involve trimethylsilyloxy butadienes or related derivatives. [23] Based on the X-ray structure of 16, the cycloadduct 14 formally appears to be the result of a normalelectron-demand process with the C4=C5 double bond of NBDF as the dienophile component. Notably, the configuration of 14, a cis arrangement of H5 and the 4-NO 2 group, is similar to the one established from previously isolated NBDF adducts such as 17-20.…”

A Domino Knoevenagel/1,6‐Heteroelectrocyclization Sequence to Access Phosphono‐2H‐thiopyrans

“…Two kinds of reaction conditions were tested. The first (Method A) used “classical” Knoevenagel conditions:14 the reagents were warmed at reflux in benzene or cyclohexane15 in the presence of a catalytic amount of piperidine. The second (Method B), based on Lenhert's work,16 consisted of the use of a Lewis acid catalyst (TiCl 4 ) to promote the phosphonate/aldehyde condensation, in THF at room temperature and in the presence of an excess of pyridine.…”

Arginine-specific protein modification using α-oxo-aldehyde functional polymers prepared by atom transfer radical polymerization

“…Synthesis of methylglyoxal 1,1-dimethylacetal cyclohexylimine (2). 2 was prepared following a modified protocol from Pichon et al 22 Methylglyoxal 1,1-dimethylacetal (1, 10 g, 85 mmol) was added under inert atmosphere to a flame-dried 100 mL roundbottom flask containing 50 mL anhydrous diethyl ether, cyclohexylamine (9.23 g, 93 mmol) and granular calcium chloride (0.5 g, 4.5 mmol). The contents of the flask were stirred overnight at 45 C and then the solvent and 1 removed at 70 C in vacuo (8 mbar) on a rotary evaporator.…”