Ring systems intramolecular coupling

Diene)Fe(GO)3 complexes have been used to construct 2-azaspiro[5.5]undecane and tricyclic ring systems. Intramolecular coupling reactions between diene-Fe(GO)3 complexes and a pendant olefinic group or pendant alcohols have been studied.The cyclization of allylic thioester-functionalized cyclohexadiene iron tricarbonyl... 

A total synthesis of the sesquiterpene ( )-illudin C 420 has been described. The tricyclic ring system of the natural product is readily quickly assembled from cyclopropane and cyclopentene precursors via a novel oxime dianion coupling reaction and a subsequent intramolecular nitrile oxide—olefin cycloaddition (463). 

The construction of ring systems through a tandem inter- and intramolecular coupling of two unsaturated compounds is also possible using the reagent 1. Thus, as exemplified in Eq. 9.65, s. p. 349, this transformation provides an efficient method for preparing cyclic compounds [113]. 

A sequence of an inter- and an intramolecular Heck coupling has been used to construct the 26-membered carbocyclic compound 60 from an acyclic precursor 59, which presents half of the target molecule (Scheme 20). The first step of this twofold coupling is favored to occur inter- rather than intramolecularly, because the latter would lead to a highly strained 13-membered ring system with a biaryl unit and a frans-configmed double bond. In the cyclizing second step, polymerization is disfavored by the orientation of the two side arms in the 3- and 3 -positions of the initially formed 1,1 -biaryl derivative. 

The halogenated derivatives of six membered heterocycles, like their carbacyclic analogues, usually participate readily in coupling reactions that involve the incorporation of an olefin or carbon monoxide. The insertion of carbon monoxide commonly leads to the formation of either a carboxylic acid derivative or a ketone, depending on the nature of the other reactants present. Intermolecular and intramolecular variants of the insertion route are equally popular, and are frequently utilized in the functionalization of heterocycles or the formation of annelated ring systems. 

Intramolecular versions of the Heck reaction are very useful for the construction of ring systems. The entropic advantage of having both coupling partners present in the same molecule increases the efficiency of the insertion reaction and leads to efficient reactions. Moreover the intramolecular version can be carried out on hindered substituted alkenes, whereas the intermolecular Heck reaction is largely restricted to monosubstituted alkenes. These reactions illustrate the syn stereochemistry of both the insertion reaction and the elimination. A number of multicyclic natural products have been synthesized using intramolecular Heck reactions to assemble the skeletons, and this has become a powerful synthetic tool for such compounds. 

As for the biaryl ether containing macrocycles, an array of bioactive macrocycles with an endo aryl-aryl bond exist in nature. A new palladium catalyzed reaction has been recently developed in which bis(pinacolato)diborane(4) mediated the process to reach such a structural motif. The reaction consists of a domino process involving a Miyaura s arylboronic ester synthesis and an intramolecular Suzuki-coupling. Synthesis of a bicyclic A-B-O-C ring system of RP-66453 273, a neurotensine receptor antagonist, with an endo aryl-aryl and an endo aryl-aryl ether bond was described (Scheme 53).141... 

Intramolecular pinacol coupling can also be used to prepare bicyclic ring systems, as demonstrated by Arseniyadis in a synthetic approach to paclitaxel (Taxol) (Scheme 5.8).19 Treatment of ketoaldehyde 5 with Sml2 furnished diol 6, a precursor to the A ring of the target, in high yield. 

A novel ring system, pyrrolo[3,2-f][l,2,5]benzotriazocine 84, was synthesized using a three-step sequence (Scheme 18 <1998JHC1535>). Diazotization of amino pyrrole derivative 83 in acetic acid afforded 1,2,5-triazocine ring in 75% yield by intramolecular coupling of diazonium group with ortho-position of benzyl substituent. 

Palladium-catalyzed coupling of dibromoarene and sulfoximine gives 1,5,6-oxithiazocine 138 ring system in 69% yield (Equation 25 <2002SL832>). The reaction sequence involves an intramolecular N-arylation followed by intramolecular ring closure. 

A Suzuki coupling of 2,6-dimethoxyiodobenzene with the dihydroaromatic boron compound 13 forms the basis of a synthesis of the dibenzo[6,t/]pyran ring system <03AG(E)2795> and naphtho[2,3-c]chromenes result from an intramolecular dehydro DA reaction on the diarylalkynes 14 <03SL1524>. 

From a synthetic point of view, bond forming steps are the most important reactions of radical ions [202]. Several principle possibilities have been described in Section 8.1 and are summarized in Scheme 52. Many carbo- and heterocyclic ring systems can be constructed by (inter- and intramolecular) radical addition to alkenes, alkynes, or arenes. Coupling of carbonyl radical anions leads to pinacols either intra-or inter-molecular which can be further modified to give 1,2-diols, acyloins or alkenes. Radical combination reactions with alkyl radicals afford the opportunity to synthesize macrocyclic rings. These radical ion-radical pairs can be generated most efficiently by inter- or intramolecular photoinduced electron transfer. 

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