CONFORMATIONS OF 4,5,6-TRIPHENYL-TETRAHYDRO-1,3-THIAZINE-2-THIONES AND THEIR N-ALKYL DERIVATIVES. UNUSUAL THIAZINETHIONE OR AZETIDINE FORMATION UPON REACTION OF 3-AMINO- AND 3-METHYLAMINO-1,2,3-TRIPHENYLPROPYL CHLORIDES WITH POTASSIUM ETHYLXANTHATE

Abstract

Reaction of 3-amino- or 3-methylamino-1,2,3-triphenylpropyl chlorides (6 or 7) with potassium ethylxanthate leads to 4.5.6-triphenyl-tetrahydro-,3-thiazine-2-thione 1 or 1-methyl-2,3,4-triphenylazetidine 8 depending on the N-substitution. Conformational distribution of all possible diastereoisomeric thiazinethiones 1 and their N-alkyl derivatives 2–5 is determined by means of ¹H NMR spectroscopy. Allylic strain caused by N- substituents in the trans,cis-isomers strongly shifts the equilibrium between conformations with a,a,e or e,e,a phenyl groups towards the conformer with an axial neighbouring Ph-4 group. Vicinal couplings data for the diastereoisomeric azetidine 8 show different ring geometry depending on the configuration.     

Efficient asymmetric addition of diethylzinc to aldehydes using 3‐hydroxyazetidine derivatives as chiral ligands

A new series of chiral 3‐hydroxyazetidines has been prepared from (S)‐1‐(4‐methoxyphenyl)ethylamine. These ligands have shown excellent catalytic activities and enantiomeric selectivities in asymmetric addition of diethylzinc to aromatic aldehydes. Copyright © 2008 John Wiley & Sons, Ltd.     

Selective Reductive Elimination at Alkyl Palladium(IV) by Dissociative Ligand Ionization: Catalytic C(sp3)−H Amination to Azetidines

A palladium(II)‐catalyzed γ‐C?H amination of cyclic alkyl amines to deliver highly substituted azetidines is reported. The use of a benziodoxole tosylate oxidant in combination with AgOAc was found to be crucial for controlling a selective reductive elimination pathway to the azetidines. The process is tolerant of a range of functional groups, including structural features derived from chiral α‐amino alcohols, and leads to the diastereoselective formation of enantiopure azetidines.     

Spirocyclic azetidines for drug discovery: Novel Boc-protected 7'H-spiro[azetidine-3,5'-furo[3,4-d ]pyrimidines]

A novel spirocyclic scaffold of 7'H-spiro[azetidine-3,5'-furo[3,4-d]pyrimidine] chemotype was synthesized in N-Boc-protected form. However, the scaffold was revealed to be unstable to storage when deprotected. The solution was found in the brief removal of the Boc protecting group and rapid acylation of the liberated NH-azetidine with a carboxylic acid imidazolide.     

Investigations on Novel 1,3-Diazetidine Based Four-Membered N-Heterocyclic Carbenes

Attempts towards the synthesis of two novel four-membered 1,3-diazetidine based N-heterocyclic carbenes (NHCs) containing an organic backbone with a carbonyl functionality were undertaken. These carbenes cannot be isolated but the respective carbene dimers are obtained in quantitative yield which undergo a degradation and rearrangement sequence upon thermal exposure. Some of the species involved in these thermal reactions could be isolated and characterized, others were observed by mass spectrometric experiments. Ab initio and density functional theory (DFT) calculations provide a mechanistic rationale for the experimental observations. Since dimerization is strongly favored, classic carbene trapping reactions remain a goal to achieve.     

Benzazetidines and Related Compounds: Synthesis and Potential

Benzazetidines are a class of N-heterocycles potentially very interesting for a variety of purposes, including biological applications and drug design. In the past, their high ring strain has hampered the development of trustable, general, and efficient synthetic methodologies for their preparation. In this review article, the aim is to disclose all the literature contributions about the synthesis of these compounds and the study of their reactivity, from the early examples to the most recent synthetic approaches. Recently, there has been a growth of interest for this heterocycle, driven by the publication of novel synthetic methodologies based on palladium-catalyzed intramolecular C−H amination and organocatalyzed ring-closure of 2-(N-Boc-anilino)-α-ketoesters/amides.     

Dynamic Phenomena and Complexation Effects in the α-Lithiation and Asymmetric Functionalization of Azetidines

In this work it is demonstrated that enantiomerically enriched N-alkyl 2-oxazolinylazetidines undergo exclusive α-lithiation, and that the resulting lithiated intermediate is chemically stable but configurationally labile under the given experimental conditions that afford enantioenriched N-alkyl-2,2-disubstituted azetidines. Although this study reveals the configurational instability of the diastereomeric lithiated azetidines, it points out an interesting stereoconvergence of such lithiated intermediates towards the thermodynamically stable species, making the overall process highly stereoselective (er > 95:5, dr > 85:15) after trapping with electrophiles. This peculiar behavior has been rationalized by considering the dynamics at the azetidine nitrogen atom, the inversion at the C-Li center supported by in situ FT-IR experiments, and DFT calculations that suggested the presence of η³-coordinated species for diastereomeric lithiated azetidines. The described situation contrasted with the demonstrated stability of the smaller lithiated aziridine analogue. The capability of oxazolinylazetidines to undergo different reaction patterns with organolithium bases supports the model termed “dynamic control of reactivity” of relevance in organolithium chemistry. It has been demonstrated that only 2,2-substituted oxazolinylazetidines with suitable stereochemical requirements could undergo C=N addition of organolithiums in non-coordinating solvents, leading to useful precursors of chiral (er > 95:5) ketoazetidines.