Cyclopropane amino acids: 2,3- and 3,4-Methanoamino acids

Natural Occurrence, Syntheses, and Applications of Cyclopropyl-Group-Containing α-Amino Acids. 1. 1-Aminocyclopropanecarboxylic Acid and Other 2,3-Methanoamino Acids

Heterocyclic compounds are of outstanding importance as pharmaceuticals, agrochemicals, fine and bulk chemicals, and ligands for catalysis.1 Among the different heterocycles, 2-oxazolines have been widely studied and reviewed,2 especially chiral oxazolines3 and bis(oxazolines),4 due to their wide application as ligands for asymmetric catalysis. Compared to 2-oxazolines, the sulfur analogues, that is, the 2-thiazolines, have received less attention. To the best of our knowledge, there is only one review, published by Fustero et al. in 2001,5 which focuses on the preparation and to some extent synthetic applications of both 2-alkyl2-thiazolines and 2-alkyl-2-oxazolines. Recently, various groups have paid attention to the chemical properties of 2-thiazolines, mainly because of the unique properties of sulfur. In different reports, a reactivity that often dramatically differs from that of the corresponding oxazoline derivatives was pointed out. In this contribution, we wish to give an overview of the chemistry of 2-thiazolines, including new methodologies for their preparation, and recent applications, such as their growing use in organic synthesis in the biological field and asymmetric catalysis as ligands. The methods enabling access to thiazolines will first be underlined. Then the reactivity and applications in the fields of organic synthesis, biomolecules (natural or not), and catalysis will be documented. The structure of the thiazolines treated in this review is illustrated in Figure 1. Compounds bearing atoms other than carbon at the 2-position, including 2-H-thiazolines, 2-aminothiazolines, or 2-halogenothiazolines, are beyond the scope of this review. Cited references are restricted to journals, reviews, and books. Literature coverage for this review extends up to September 2007.

Overview of the chemistry of 2-thiazolines.

Ring opening of donor–acceptor cyclopropanes with various N-nucleophiles provides a simple approach to 1,3-functionalized compounds that are useful building blocks in organic synthesis, especially in assembling various N-heterocycles, including natural products In this review, ring-opening reactions of donor–acceptor cyclopropanes with amines, amides, hydrazines, N-heterocycles, nitriles, and the azide ion are summarized 1 	Introduction 2 		Ring Opening with Amines 3 	Ring Opening with Amines Accompanied by Secondary Processes Involving the N-Center 31 	Reactions of Cyclopropane-1,1-diesters with Primary and Secondary Amines 311 	Synthesis of γ-Lactams 312 	Synthesis of Pyrroloisoxazolidines and -pyrazolidines 313 	Synthesis of Piperidines 314 	Synthesis of Azetidine and Quinoline Derivatives 32 	Reactions of Ketocyclopropanes with Primary Amines: Synthesis of Pyrrole Derivatives 33 	Reactions of Сyclopropane-1,1-dicarbonitriles with Primary Amines: Synthesis of Pyrrole Derivatives 4 	Ring Opening with Tertiary Aliphatic Amines 5 	Ring Opening with Amides 6 	Ring Opening with Hydrazines 7 	Ring Opening with N-Heteroaromatic Compounds 71 	Ring Opening with Pyridines 72 	Ring Opening with Indoles 73 	Ring Opening with Di- and Triazoles 74 	Ring Opening with Pyrimidines 8 	Ring Opening with Nitriles (Ritter Reaction) 9 	Ring Opening with the Azide Ion 10 	Summary

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Ring Opening of Donor–Acceptor Cyclopropanes with N-Nucleo­philes

A general method for ring opening of various donor–acceptor cyclopropanes with the azide ion through an SN2-like reaction has been developed. This highly regioselective and stereospecific process proceeds through nucleophilic attack on the more-substituted C2 atom of a cyclopropane with complete inversion of configuration at this center. Results of DFT calculations support the SN2 mechanism and demonstrate good qualitative correlation between the relative experimental reactivity of cyclopropanes and the calculated energy barriers. The reaction provides a straightforward approach to a variety of polyfunctional azides in up to 91 % yield. The high synthetic utility of these azides and the possibilities of their involvement in diversity-oriented synthesis were demonstrated by the developed multipath strategy of their transformations into five-, six-, and seven-membered N-heterocycles, as well as complex annulated compounds, including natural products and medicines such as (−)-nicotine and atorvastatin.

https://chemistry-europe.onlinelibrary.wiley.com/doi/pdf/10.1002/chem.201500456

Ring Opening of Donor–Acceptor Cyclopropanes with the Azide Ion: A Tool for Construction of N‐Heterocycles

Synthesis of E and Z 1-amino-2-aryl(alkyl)-cyclopropanecarboxylic acids via meldrum derivatives

Reaction of 4-methylene-5(4H)-oxazolones with diazomethane: 4-Methylene-5(4H)-oxazolones with Diazomethane

Reaction of 5(4h)-thiazolones with diazomethane

The reaction of diazomethane with some (E) and (Z)-2-substituted-4-methylene-5(4)-oxazolones (1a-c) under two different conditions, has been studied. (E) and (Z)-1,2-disubstituted-7-oxo-6-oxa-4-azaspiro[2.4]-hept-4-enes (3a-c, 4a-c) were mainly obtained, together with multiple addition compounds. The reaction showed to be stereoselective only when the substituents were aromatic. Acid hydrolysis of compounds 3a and 4a produced a mixture of (E) and (Z)-3,5-disubstituted-tetrahydrofuran-2-ones (8a, 9a). Smooth methanolysis of the ring led to (E) and (Z)-1-benzamido-cyclopropanecarboxylic esters (10a-c, 11a-c), which, on acid hydrolysis, gave (E) and (Z)-1-amino-2-phenylcyclopropanecarboxylic acids 12a and 13a. The pmr spectra have been analyzed by an iterative computer method, and the computed best values obtained have been used to deduce the stereochemistry of the spiroderivatives.

I. Arenal

Papers

Synthesis of E and Z 1-amino-2-aryl(alkyl)-cyclopropanecarboxylic acids via meldrum derivatives

Reaction of 4-methylene-5(4H)-oxazolones with diazomethane: 4-Methylene-5(4H)-oxazolones with Diazomethane

Reaction of 5(4h)-thiazolones with diazomethane

Reaction of 4‐methylene‐5(4H)‐oxazolones with diazomethane