Within 14 years of the seminal experiments of J. D. Roberts
leading to the first proposal of the structure of benzyne (1), synthetic organic chemists recognized the potential to exploit this highly reactive intermediate (and its substituted variants) in the total synthesis of natural products. More specifically, it was recognized that arynes offered the strategic advantage of rapidly functionalizing an aromatic ring by forming multiple carbon− carbon or carbon−heteroatom bonds in a single operation, often in a regioselective manner. Initially, the scope of synthetic
applications was somewhat limited by the harsh conditions
required to produce the aryne species. Many of these methods required strong bases, such as n-BuLi, or high temperatures (Scheme 1). However, with the development of milder methods for the generation of arynes came increased interest in employing them in the synthesis of more complex polycyclic systems. Most recently, the use of o-silyl aryl triflates as aryne precursors has allowed generation of the reactive intermediate under almost neutral conditions.
To date, over 75 individual natural products have been
prepared using arynes to generate key synthetic intermediates. Herein are recounted the reports of total syntheses that utilize arynes in ways that build complexity or introduce motifs essential to the completion of their targets. The methods by which the authors featured in this review accomplish this task reflect the versatility of arynes as reactive intermediates for synthesis (Scheme 2). For the purposes of organization, the syntheses are divided into subgroups on the basis of the type of aryne transformation: (i) nucleophilic additions or multicomponent reactions, (ii) σ-bond insertion reactions, (iii) [4 + 2]- and [2 + 2]-cycloaddition strategies, and (iv) metal-catalyzed aryne reactions.

A Comprehensive History of Arynes in Natural Product Total Synthesis

The use of arynes in organic synthesis

o-Quinodimethanes: Efficient Intermediates in Organic Synthesis.

Intramolecular [4+2] and [3+2] Cycloadditions in Organic Synthesis

This report describes efforts to develop transition-metal-catalyzed acetylene cyclization as an attractive and versatile synthetic tool. Syntheses of indans, tetralins, anthraquinones, benzocyclobutenes, polycycles and heterocycles are discussed. In particular, cobalt-catalyzed cyclooligomerization of acetylenes is described with a brief discussion of reaction mechanisms. (DDA)

Transition-metal-catalyzed acetylene cyclizations in organic synthesis

Letter: A formal regio- and stereoselective total synthesis of estrone. A convenient synthesis of D-homoestrone.

A stereoselective total synthesis of estrone by an intramolecular cycloaddition reaction of olefinic o-quinodimethane.

A formal regio- and stereoselective total synthesis of estrone. a convenient synthesis of d-homoestrone

PURPOSE:To prepare the d-isomer of 2-(6-methoxy-2-naphthyl)propionic acid, useful as medicine, in high optical purity in an industrial scale, easily and economicaly by optical resolution of d,l-2-(6-methoxy-2-naphthyl)propionic acid with L-(-)-alpha-phenylethylamine. CONSTITUTION:d-2-(6-Methoxy-2-naphthyl)propionic acid expressed by the formula is prepared by optical resolution of d,l-2-(6-methoxy-2-naphthyl)propionic acid with L-(-)-alpha-phenylethylamine. The resolution is carried out as follows. The acid and the amine (0.5-1.0mol on the basis of 1mol of the acid) are dissolved in a solvent. Preferably the solvent is the one which completely dissolves both compounds but poorly dissolves the formed salt, and a preferable example is the mixed solvent of methanol and ethyl acetate. The amine salt of the acid rich in the d-isomer slowly precipitates when the reaction solution is left to stand at room temperatures for 0.5-48hr. The product is further treated with the hot methanol- ethyl acetate mixutre to increase the ratio of the d-isomer, and the salt is decomposed to give the desired product.

Preparation of dd22*66methoxyy22naphthyl**propionic acid

PURPOSE: To prepare 2-hydroxyacrylonitriles and their keto cpds., useful as intermediates for analgesics, antiphlogistics, antipyretics, etc., by decarboxylation of glycidic acid, obtd. by neutralization of glucidic acid alkali salt or by hydrolysis of glycidic acid ester. COPYRIGHT: (C)1979,JPO&Japio

Keiko Shiroyama

Papers

Letter: A formal regio- and stereoselective total synthesis of estrone. A convenient synthesis of D-homoestrone.

A stereoselective total synthesis of estrone by an intramolecular cycloaddition reaction of olefinic o-quinodimethane.

A formal regio- and stereoselective total synthesis of estrone. a convenient synthesis of d-homoestrone

Preparation of dd22*66methoxyy22naphthyl**propionic acid

Preparation of nitriles