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The levels of diastereoselection resulting from the 1,3-dipolar cycloaddition of chiral and achiral azomethine ylides 2 (a–c) to chiral, unsaturated bicyclic lactams 1 (a–f) are described in terms of steric factors.

We describe a remarkably simple, high-yielding route to 2-H oxazolines 3 from a variety of β-amino alcohols 1

A four-step synthesis of optically pure 6α-phenyl pyrroloisoquinolines from chiral formamidines has been accomplished.

The oxazoline-mediated biaryl coupling reaction was applied successfully to the total synthesis of a series of dibenzocyclooctadiene lignans in chiral nonracemic form. The diastereoselectivities achieved in the coupling reaction varied in a predictable manner, primarily as a function of the ortho substituents on the phenyl Grignard reagent

The natural alkaloid cryptaustoline is (13R,7S)-(−)-1 due to the heretofore unprecedented inversion while the formamidine route led to the expected (13S,7R)-(+)-1

Generation of organolithium reagents using lithio ditert-butyl biphenyl (Freeman's Reagent) leads to facile additions to the naphthalene oxazolines.

The title compounds were prepared by addition of Grignard reagents to methoxyformamidines 6 and 8 in ether at room temperature. Hydrolysis gives the free secondary amines, or in cases of volatile products, their thiourea derivatives.

Excellent diastereofacial selectivities over a wide range of temperatures (−78 to 25 o C) were obtained with the title compounds with use of chiral oxazolines derived from (S)-valinol or (S)-tert-leucinol. These are the first useful levels of asymmetric induction observed without the presence of the chelating methoxyl groups. The dihydronaphthylcarbinols and aldehydes resulting from these additions were obtained in >98% ee

La synthese presentee s'effectue via la reduction du vinyl triflate 3-ethyle-1-methyle 2,5-dihydro-4-trifluoromesyloxypyrrole-1,3-dicarboxylate

The title compounds have been prepared from 3-acylpropionic acids 2 and (−)-R-phenylglycinol in a three-step sequence in >98% enantiomeric excess. The R group in 2 ultimately becomes the 2-substituent in the chiral pyrrolidine

The L-valinol-derived unsaturated lactam methyl 3-isopropyl-7a-methyl-5-oxo-2,3-dihydro-7aH-pyrrolo[2,1-b]oxazole-6-carboxylate functions as an excellent chiral dienophile in asymmetric Diets-Alder reactions. Diene approach occurs exclusively from the α-(endo) face to provide optically pure tricyclic lactams. In the presence of Lewis acids, increases in rate, regiospecificity, and ‘Alder endo’ stereoselectivity are observed. Elaboration of the cycloadducts provided an unexpected entry into cyclopropane-containing polycyclic systems via an N-acyliminium ion-enamide rearrangement. In addition, a number of optically pure carbocycles were readily prepared via this methodology.

Addition of RMgX to 2-methoxy-4-tert-butylpiperidine formamidine in dichloromethane or ether gives good to excellent yields of axial product.

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.

Excellent enantioselection is observed in the reduction of a wide variety of prochiral ketones using LiAlH4 modified with biphenol 4.

Use of a modified auxiliary allowed for the asymmetric synthesis of quaternary carbons adjacent to nitrogen in tetrahydroisoquinolines.

A series of synthetic manipulations on the naphthalene nucleus, containing a 1-(2-oxazolinyl) moiety, is described. Nucleophilic additions afford both regio- and stereoselective products in the 1- and 4-positions. The latter is oxidatively transformed in the 4-keto system 4 which can undergo various substitutions as well as carbonyl transpostions

o-Chloro-β-phenethylamines, transformed into the N-tert-butylformamidines, were found to be excellent precursors to indolines following benzyne formation. A series of methoxy-substituted o-chlorophenethylamines containing an N-alkyl or aryl substitutent were subjected to sec-butyllithium producing the ortho-lithiated aromatic which subsequently lost lithium chloride at temperatures ranging from -78 to -50 o C. The resulting benzyne was intramolecularly trapped providing the titled heterocycles. Quenching the reaction resulted in elimination of the tert-butyl isocyanide (isolated after aqueous workup as tert-butylformamide)

An efficient procedure for the preparation of the title compounds in high enantiomeric purity has been realized starting from 3-acylpropionic acids. Stereoselective reduction of chiral bicyclic lactams 2a-h, prepared from the corresponding γ-keto acid and (R)-phenylglycinol, using alane or triethylsilane with titanium tetrachloride provided the N-substituted pyrrolidines and pyrrolidinones, respectively. Subsequent cleavage of the phenylglycinol returned the desired amines and lactams. The enantiomeric purity of these compounds was determined to be >98% by chiral stationary-phase HPLC

The asymmetric synthesis of (S)-(+)-cryptaustoline was accomplished and found to differ in sign of rotation with the natural «S»-(-)-material. The previously assigned absolute configuration was found to be incorrect and is now corrected. The reversal in stereochemistry came about through an unusual manner involving (S)-(+)-laudanosoline (3) cyclizing to (R)-(-)-cryptaustoline ((-)-1c). The mechanism was explored by oxidation of a series of deuterio derivatives of laudanosoline, all of which retained deuterium in the resultant cryptaustoline

Conjugate additions of RCuCNLi to the chiral α,β-unsaturated lactam 4 gives almost exclusive exo addition-a reversal in stereochemistry when cuprates were added to chiral lactam 1. The lactams 5 were transformed into 4-substituted pyrrolidinones 8 via a three-step sequence which involved decarbalkoxylation, silane reduction and metal-ammonia benzylamine cleavage. The chemical yields as well as the enantiomeric purity were very high for this process. As an example of the usefulness of this scheme, the antidepressant (-)-Rolipram was prepared in good overall yield

An efficient synthesis of the phytoalexin, lacinilene C-7 methyl ether, via its probable biosynthetic precursor, 2-hydroxy-7-methoxycadalene is described. A related synthesis of a HIV-1 reverse-transcriptase inhibitor is briefly discussed.

A rapid synthesis of the enantiomerically pure biary catalyst (S)-1 was accomplished by a stereoselective Ullmann reaction (Scheme 1).

By utllizing S-serine, both enantiomers of the reduced methoxyamino alcohol (12) were efficiently prepared. The corresponding oxazolines, prepared from these auxiliaries, showed favorable properties toward additions to naphthalenes 22 and cyclohexene, 27

Treatment of oxazolines with chloromethyl methyl ether followed by diisobutylaluminum hydride leads to good yields of the carbinols.

The formation of chiral amino alcohols by reduction of amino acids has been the subject of considerable effort due to their importance in asymmetric synthesis? peptide and pharmaceutical chemistry: resolution of racemic mixtures: synthesis of insecticidal compounds: and others. From the earliest reports by Karrer in 1921, amino alcohols were prepared by reduction of the corresponding amino acid esters with sodium in ethanol.& Subsequently, lithium aluminum hydride6b and sodium borohydride& were employed and furthermore, free amino acids were shown to be reduced directly by sodium bis(2-methoxyethoxy)aluminum hydride? the borane-dimethyl sulfide complex activated by boron trifluoride-etherate,w lithium aluminum hydride? lithium borohyride with trimethylchl~rosilane,~~ sodium borohydride-trimethyl~hlorosilane,~g or boron trif l~orideetherate.~~ Very recently, while this manuscript was being prepared, a report appeared describing an efficient reduction of amino acids and derivatives using sodium borohydride and sulfuric

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

Highly diastereoselective additions of lithiosilanes to chiral naphthalenes can be performed in ether/ THF. Trapping of the resulting azaenolate, followed by protodesilylation, allows access to 1,1-disubstituted tetralins or dihydronaphthalenes in good yields and high enantiomeric excess

A route to the titled compounds in >99% ee was achieved from sequential diastereoselective alkylations of chiral, nonracemic bicyclic lactams 6 and 15. An intramolecular addition of the organolithium species derived from 17a-c and 28a-d gave, after hydrolysis, diketones 25a-c and 30a-d, which were cyclized to the titled compounds 4a-c and 31a-d. As an example of the versatility of this method, the ABC ring system of the triterpene stelliferin A, isolated from marine organisms, was prepared in high enantiomeric excess

Treatment of various carbonyl compounds with the carbanion of the 2-trimethylsilymethyl formamidine 2 gives the enamidine 3 which is readily transformed into the homologated nitriles 6.

High diastereoselectivities (93:7) were observed in the biaryl coupling of 2′,6′-disubstituted aryl Grignard reagents of 1 with aryloxazolines 2. The diastereoselectivities observed in the coupling reaction varied primarily as a function of the chelating properties of the ortho substituents on the aryl Grignard reagent.