David M. Casper

An improved procedure for the asymmetric aldol reaction of the titanium enolate of an N3-propionyl-3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one

Abstract The direct formation of the titanium enolate of N 3 -propionyl-3,4,5,6-tetrahydro-2 H -1,3,4-oxadiazin-2-one has been achieved through complexation with titanium tetrachloride at 25°C, followed by deprotonation with triethylamine (−78 to 25°C). The preformed titanium enolate has been reacted with D 2 O/DCl to afford deuterated derivative 6 and also reacted with a series of aromatic and aliphatic aldehydes affording aldol adducts 4a – f with crude diastereoselectivities ranging from 8:1 to 38:1.

X-Ray crystallographic and 13C nuclear magnetic resonance studies of 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-ones derived from ephedrine and pseudoephedrine ☆

Abstract 3,4,5,6-Tetrahydro-2H-1,3,4-oxadiazin-2-ones derived from (1R,2S)-ephedrine and (1S,2S)-pseudoephedrine have been synthesized and their conformational properties have been examined. The ephedrine heterocycles 5–7a appear to favor one set of equilibrating conformers while the pseudoephedrine heterocycles 5–7b exist as multiple conformers at room temperature. The observed conformational behavior of these heterocycles is attributed to allylic strain and a gauche effect arising from the torsional energy barrier between the lone pair electrons of the N3- and N4-nitrogens.

X-Ray Crystallographic and Proton Nuclear Magnetic Resonance Studies of β-Hydroxy-N-nitrosamines derived from α-Amino Acids and Ephedrine

Abstract β-Hydroxy-N-nitrosamines derived from l -leucine, l -valine, l -phenylalanine, d -phenylglycine and (1R,2S)-ephedrine have been synthesized and analyzed. These compounds all exhibit rotameric populations of (E)- and (Z)-stereoisomers that are a result of the barrier to rotation about the N-nitroso (N–NO) group. A correlation is made between the X-ray crystallographic data of the N-nitroso-ephedrine derivative 6 and the 1H NMR of the N-nitrosamines 4a–4d. From this comparison, the identities and ratios of (E)- and (Z)-rotamers were unambiguously assigned. Finally, the 1H NMR also provides some insight into the conformational changes that occur when the nitrosamine rotamers interconvert.

Synthesis of 3,4,5,6‐Tetrahydro‐2H‐1,3,4‐oxadiazin‐2‐ones Employing a Metal Hydride and Diethyl Carbonate: An Alternative Cyclization Method over 1,1′‐Carbonyldiimidazole

Abstract A series of 3,4,5,6‐tetrahydro‐2H‐1,3,4‐oxadiazin‐2‐ones have been synthesized from valine, leucine, ephedrine, and norephedrine. The synthesis is accomplished through a process of nitrosation, reduction, and cyclization. The cyclization protocol employed involves the use of a metal hydride (LiH or NaH) and diethyl carbonate rather than 1,1′‐carbonyldiimidazole.

(5R,6S)-4-Isopropyl-5-methyl-6-phenyl-3-propanoyl-2H-1,3,4-oxadiazinan-2-one

The title compound, C16H22N2O3, was synthesized during the course of a study on (1R,2S)-norephedrine-derived 1,3,4-oxadiazinan-2-ones. The conformation adopted by the isopropyl group is pseudo-axial relative to the oxadiazinan core. The allylic strain contributes to this conformational arrangement.

Preparation of Some Derivatives of N‐tert‐Butyldecahydro‐3‐isoquinoline Carboxamide

Abstract N‐tert‐Butyldecahydro‐3‐isoquinoline carboxamide (1) is a key structural fragment present in a variety of medicinally important HIV protease inhibitors. Derivatives of this carboxamide were prepared by alkylation with either 2‐iodoethanol, allyl bromide, or bromoacetaldehyde dimethylacetal. The corresponding aldehyde of the dimethylacetal derivative was prepared by reaction with BBr3 in CH2Cl2.