Planar Chirality − Synthesis and Transformations of 8- to 10-Membered Heterocycles Bearing (E)-Olefins

Abstract

Medium‐sized heterocycles (8‐membered to 10‐membered) are prevalently found in organic chemistry as key intermediates in the synthesis of more complex structures or as core structures in natural products or pharmaceutically important compounds. At present, the production of such rings remains a challenge in organic synthesis. During the past decade, an increasing amount of interest has focused on the generation of cyclic lactones and peptides, as well as on hairpins and β‐turn mimics, and such medium‐sized rings were thought to represent suitable fragments. Furthermore, heterocyclic structures of this type are a characteristic of a range of complex natural products, and total synthesis of these is a broad field for organic chemists to test new strategies and to develop new methods. The aim of this review is to discus some modern strategies for synthesizing unsaturated 8‐ to 10‐membered heterocycles, with the scope restricted to the production of ring systems incorporating a N, O, and S function in combination with (E)‐olefins. The planar‐chiral properties thus induced have been exploited for further stereoselective and regioselective reactions. Although a number of conversions has described only the generation of simple structures without complicated stereogenic properties, most of them seem to offer undiscovered potential in terms of stereoselective syntheses. However, the emphasis of the methods is focused on stereoselective processes. The review is subdivided into two major chapters: ring‐closure and ring‐enlargement reactions, and additional information is given on cycloadditions and fragmentations.

Flow Photochemical Syntheses of trans‐Cyclooctenes and trans‐Cycloheptenes Driven by Metal Complexation

“…Flow photoisomerization has provided access to functionalized trans-cyclooctenes capable of stereospecific, transannular cyclization reactions. While stereospecific, transannular cyclizations of (E)-cycloalkenes have been studied with larger ring systems, [125][126][127][128] few studies had been carried out on transcyclooctene derivatives. (E)-Thiacyclooct-4-ene has been shown to undergo acid catalyzed transannular cyclization, [129] as does the anion of (E)-4,5-epoxy-1-thiacyclooctane-1,1dioxide.…”

Métodos de preparação de lactonas de anel médio

“…Por outro lado, no que se refere ao rearranjo de Claisen e às reações de Diels-Alder, deve-se notar que são métodos de aplicação pontual, normalmente restritos a um único tipo de substrato. Já os β-hidróxi-éteres cíclicos mostraram-se bastante promissores 102 como substratos para a síntese de lactonas de anel médio, através da clivagem oxidativa promovida por RuO 4 . Finalmente, é importante ressaltar que há uma tendência crescente do emprego da metátese olefínica em lactonizações, assunto este que talvez já mereça uma revisão à parte.…”

The Belluš–Claisen Rearrangement

“…70 ) generates predominantly the Z ‐enolate structure corresponding to 71 because of minimized 1,3‐diaxial and other steric interactions. As a result, 3,4‐ trans ‐difunctionalized 2‐azonines 73 are the major diastereomers produced by the reaction. Because of restricted flipping of the E double bond with respect to the ring, in nine‐ and ten‐membered lactams, such as 66 , 73 , and 74 , planar‐chirality phenomena frequently occur 45d. One can take advantage of these phenomena in introducing new stereogenic centers in total syntheses of bicyclic natural products, such as the pumiliotoxins 45e…”

“…Because of restricted flipping of the E double bond with respect to the ring, in nine‐ and ten‐membered lactams, such as 66 , 73 , and 74 , planar‐chirality phenomena frequently occur 45d. One can take advantage of these phenomena in introducing new stereogenic centers in total syntheses of bicyclic natural products, such as the pumiliotoxins 45e…”