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The intramolecular Schmidt reaction of ketones and tethered azides is an efficient method for the generation of amides and lactams. This reaction is catalyzed by Lewis acids, which tightly bind the strongly basic amide product and result in product inhibition. We report herein conditions to achieve a catalytic Schmidt reaction using substoichiometric amounts of the heat-stable Lewis acid Sc(OTf)3. This species was shown to effectively release products of the Schmidt reaction in a temperature-dependent fashion. Thus, heat was able to promote catalyst turnover. A brief substrate scope was conducted using these conditions.

Depending on the method of activation, (2′-amino- N ′- tert -butoxycarbonyl-benzylidene)-3-alkenylamines ( 1 ) react with Lewis acids (TiCl 4 or TMSOTf) to afford either a novel Boc-assisted iminium ion formation/trapping sequence (giving hexahydropyrido[1,2-c]quinazolin-6-ones ( 2 ) or tetrahydropyrrolo[1,2-c]quinazolin-5-ones ( 4 )) or a pseudodimerization process (leading to iminodibenzo[b,f]diazocines ( 3 )).

Treatment of benzyl azide with triflic acid or titanium tetrachloride effects 1,2-phenyl migration with concomitant liberation of molecular nitrogen. The resulting N-phenyl iminium ion intermediate readily combines with enolizable carbonyl substrates to form Mannich bases.

The intramolecular Schmidt reaction was applied to the norbornane skeleton to examine an approach to sparteine. In so doing, the stereospecificity of intramolecular Schmidt reactions of e-azido ketones was demonstrated. The intramolecular Schmidt reaction was found to fail in a ketone containing a lactam moiety.

Intramolecular cycloaddition of the nitrones derived from a series of 5-alkenals and α-methylbenzyl hydroxylamine leads to mixtures of diastereomeric products in the range of 1.7/1 to 16/1. Cyclization of a series of fifteen 5-alkenyl nitrones with a chiral group on nitrogen afforded diastereomeric isoxazolidines in ratios ranging from 1.7/1 to 16/1. When R* = (S)-α-methylbenzyl, C6a of the major product was also S in those cases known.

A derivative of the Wieland-Miescher ketone can selectively be converted into either regioisomeric ring-expanded lactam. The synthesis of the diastereomeric N-α-methylbenzyl oxaziridine derivatives determines the regiochemistry of the product lactam and additionally allows the separation of a racemic substrate into regio- and enantioisomeric lactams.

A simple and efficient synthesis of chiral lactams utilizing a group-selective nitrogen insertion process has been investigated for a group of prochiral ketones. The preparation of a useful intermediate in benzomorphinan synthesis has been carried out in optically active form.

The reaction between β-substituted acrylate esters and α-methylbenzyl hydroxyl amine affords diastereoisomeric 5-isoxazolidinones, convenient precursors of simple optically pure 2-azetidinones.

A conceptually novel total synthesis of (−)-alloyohimbane is reported. The key step utilizes a group-selective nitrogen insertion process on a meso bicyclic ketone.

Potassium diisopropylamide (KDA) has been used to efficiently generate the anions of oxime ethers and dimethylhydrazones. As a deprotonating agent, KDA is superior to BuLi and LDA. The corresponding cuprates are extremely oxygen sensitive, but undergo 1,4-addition with cyclohexenone, and the resulting potassium enolates can be trapped with aqueous buffer or ClSiMe 3 . Attempted trapping with either Ac 2 O or AcCl in the presence of diisopropylamine fails.

The proton that bears a 1,3-diaxial relationship to the substituted nitrogen atom of some chiral oxaziridines appears in the NMR spectrum at unusually high field. This observation indicates that an unusual rotamer is substantially populated in these systems.