A. I. Meyers

The chemistry of 2-oxazolines (1985–present)

Abstract 2-Oxazolines have permeated numerous sub-disciplines in synthetic organic chemistry in the 100 years since their discovery. This versatile heterocycle has served as protecting group, coordinating ligand, and activating moiety, often exhibiting all of these characteristics in a single transformation. The well-defined reactivity of chiral oxazolines has given rise to numerous highly efficient strategies for asymmetric synthesis including their use as ligands in asymmetric catalysis. Various unique properties have dictated their use in a multitude of dissimilar applications: as monomers in polymer production, as moderators in analytical processes, and as conformationally rigid peptide mimics in medicinal chemistry. Even natural systems have chosen to incorporate oxazolines into their chemical arsenal, as evidenced by the rapidly growing number of identified natural products and their attendant pharmacological properties. Future studies will undoubtedly uncover unexpected properties and applications. The number of important publications detailing oxazoline-related chemistry is growing, suggesting that research in this area, as in synthetic organic chemistry in general, has yet to mature.

Reinvestigation of a modified Hantzsch thiazole synthesis

Abstract A recently reported modified Hantzsch reaction was reinvestigated and conditions were found to reach enantiomerically pure thiazole amino acid derivatives.

Recent progress using chiral formamidines in asymmetric syntheses

Abstract The ability to generate a carbanion next to nitrogen in a chiral environment has led to a number of useful asymmetric routes to alkaloids and related substances. Mechanistic studies have been conducted to understand the nature of these alkylations.

Stereoselectivity in the aldol reaction: The use of chiral and achiral oxazolines as their boron azaenolates

Abstract Chiral oxazolines, as their boron enolates derived from various boron triflates, react with aldehydes to give erythro -selectivity (97% + %) with enantiomeric purities of 50–60%. Achiral oxazolines as their boron enolates derived from diisopinocampheylborane give, on reaction with aldehydes, β-hydroxy esters with high threo -selectivity (90+%) in 77–85% ee. A variety of structurally different oxazolines were also studied and many show high erythro -selectivity.

The oxidation of 2-oxazolines to 1,3-oxazoles

Abstract Oxazolines are readily oxidized to 1,3-oxazoles using NBS/peroxide or light or, more efficiently, by the Kharasch-Sosnovsky Reaction.

An asymmetric synthesis of chiral phthalides via chiral lithiated oxazolines

Abstract Chiral aromatic oxazolines were prepared for utilization in asymmetric C-C bonding reactions. Lithiation of aryloxazolines could not be accomplished directly but were efficiently lithiated via halogen metal exchange of the o-bromo derivative 16. The resulting lithio compound 9 reacted smoothly with carbonyls to give adducts 19 but with poor stereoselectivity. Hydrolysis gave the phthalides 4 in poor ees (20–25%). When the lithio-oxazolines 9 were transformed into21, they now served as chiral electrophiles. Addition of organometallics to 21 gave, particularly with Grignard reagents, useful levels of asymmetric induction which, after hydrolysis, gave phthalides 4 in 40–80% ee.

Asymmetric routes to azasugars from chiral bicyclic lactams. Synthesis of 1,4-dideoxy-1,4-imino-D-lyxitol; L-deoxymannojirimycin; rhammo-1-deoxynojirimycin and 1-deoxy-6-epicastanospermine

Abstract By employing the appropriate chiral bicyclic lactams, the asymmetric total synthesis of four enantiopure azasugars mentioned in the title were successfully achieved. A series of diastereoselective oxidations ( OsO 4 NMO ) followed by diastereoselective reductions (BH3, 9-BBN) gave good yields of the trisubstituted (16) and tetrasubstituted (2,3,4) pyrrolidine and piperidines respectively.

An asymmetric synthesis of 4,4- and 6,6-dialkylcyclohexenones and 4,4- and 5,5-dialkylcyclopentenones. Application to the total synthesis of (-)-silphiperfol-6-ene

Abstract Chiral amino alcohols have been transformed into bicyclic lactams 1 and 6 which, after metalation and alkylation, gave high diastereomeric ratios of 2,2-dialkyl quaternary products, 29 and 12 , respectively. Addition of organolithium reagents to the carbonyl of these lactams, followed by acidic cleavage, leads to enantiomerically pure cyclohex-2-enones and cyclopent-2-enones. This process was also applied to a key, chiral cyclopentenone 39 , which was used by Curran, in racemic form, to prepare the angular triquinane, silphiperfol-6-ene. The total asymmetric synthesis was carried out in 6.6% yield over nine steps.

Total synthesis of (−)-bistatramide C

Abstract The total synthesis of macrocyclic hexapeptide Bistatramide C is reported from enantiomerically pure oxazole and thiazole amino acids.

An oxazoline based approach to (S)-Gossypol

Abstract (S)-Gossypol (S)-1 , a yellow pigment of cottonseed, has been accessed by a total asymmetric synthesis. The sequence leading to (S)-gossypol (S)-1 was highlighted by four oxazoline mediated reactions, including coupling of ortho-(methoxy)aryloxazolines with Grignard reagents, butyllithium based ortho-lithiation of aryloxazolines, stereocontrolled Ullmann couplings of bromonaphthyloxazolines, and ethoxyvinyllithium hexamethylphosphoric triamide complex based ortho-lithiation of aryloxazolines.