Shawn R. Hitchcock

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.

β-Amino Alcohol Derived β-Hydroxy- and β-(o-Diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides: An Ester−Amide Ligand Structural Model for the Palladium-Catalyzed Allylic Alkylation Reaction

A commercially available collection of beta-amino alcohols have been converted to their corresponding beta-hydroxy- and beta-(o-diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides 11a-f and 12a-f and have been employed in the Tsuji-Trost asymmetric alkylation reaction with 1,3-diphenylpropenyl acetate. With the exception of ligands 11b and 11f, the beta-hydroxybenzoyloxy(o-diphenylphosphino)benzamide ligands 11a-f primarily afforded the (R)-enantiomer of the product. In contrast, the bis(phosphine) ligands 12a-f consistently afforded the (S)-enantiomer. The best ligand (12c) was derived from cis-(1R,2S)-2-amino-1,2-diphenyl-1-ethanol, and when applied in the asymmetric allylic alkylation reaction, it yielded the product in an enantiomeric ratio of 97.8.22 favoring the (S)-enantiomer. A computational study was conducted on the conformation that this ligand might adopt in the palladium-catalyzed alkylation reaction as compared to that of the Trost ligand 1a.

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, X-Ray Crystallography, and Reactions of N-Acyl and N-Carbamoyl Succinimides

Abstract A collection of N-acyl and N-carbamoyl succinimides were prepared by acylation of succinimide with acyl chlorides or by ethylene dichloride (EDC) coupling of carboxylic acids. The x-ray crystal structures of N-benzoyl and N-p-nitrobenzoyl succinimides were determined. The N-acyl succinimides were effective in acylating primary amines, a secondary amine, and an aromatic amine. Supplemental materials are available for this article. Go to the publishers online edition of Synthetic Communications® to view the free supplemental file. GRAPHICAL ABSTRACT

Enantiomerically enriched vic-amino alcohols from 2-iminobornanes

Abstract Enantiomerically enriched vic-amino alcohols derived from d -camphor have been synthesized by condensation of the highly electrophilic N-nitroimine of d -camphor with ethanolamine, (R)-phenylglycinol and (1R,2S)-norephedrine to afford imines 8a–c. The iminobornanes were reduced with lithium aluminum hydride to afford the corresponding amines in good yield (78–88%). The stereochemistry of the reduction was confirmed by X-ray crystallographic studies of the N-nitrosated norephedrine–camphor derivative 12.

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.

(6S)-2,4-Di-tert-butyl-6-[(4S,5R)-3-iso-propyl-4-methyl-5-phenyloxazolidin-2-yl]phenol.

The title oxazolidine compound, C27H39NO2, was synthesized from N-isopropylnorephedrine. The dihedral angle between the aromatic rings is 70.33 (5)°. The N atom of the heterocycle is oriented to allow intramolecular O—H⋯N hydrogen bonding with the hydroxy substituent.

(5S,6R)-3,4,5,6-Tetra­hydro-5-methyl-6-phenyl-4-propyl-2H-1,3,4-oxadiazin-2-one

The title compound, C13H18O2N2, was isolated during the preparation of new chiral auxiliaries. Notably, this compound is unlike previously reported structures in that it does not contain an imide moiety. The crystal structure indicates the presence of intermolecular N—H⋯O hydrogen bonds.

(6S)-2-tert-Butyl-6-[(4S,5R)-3,4-dimethyl-5-phenyloxazolidin-2-yl]phenol

The title compound, C21H27NO2, exhibits hydrogen bonding between the phenolic H atom and the heterocyclic N atom. The absolute configuration of the molecule is known from the synthetic procedure.