Five-membered carbocycles reactions

Asymmetric Pauson-Khand reaction in syntheses of heterocycles fused with five-member carbocyclic fragment 980PP121. 

An interesting strategy for the diastereoselective synthesis of five-membered carbocycles was achieved by the reaction of alkenylcarbene complexes and lithium enolates derived from simple methyl ketones [79]. The use of more or less coordinating solvents (THF or Et20) or the presence of cosolvents such as PMDTA allows the selective synthesis of one or the other diastereoisomer of the final cyclopentene derivative (Scheme 32). 

The Pauson-Khand reaction (PKR) [96] consists of the synthesis of cyclopen-tenones by reaction of an alkene with a dicobalthexacarbonyl complexed alkyne (Scheme 57) and has recently emerged as one of the methods of choice for the obtainment of five-membered carbocyclic rings [97]. Its unique atom connectivity, which involves the two unsaturated carbons of the reagents and the carbon atom of a carbon monoxide ligand of cobalt usually in a regioselective manner (Scheme 57), has brought to refer to PKR as a [2 -I- 2 + 1] cycloaddition. 

The work reported by Eaton and coworkers can be summarized as reactions where an allene system in conjugation with a further unsaturated functionality reacts with carbon monoxide in the presence of an iron-carbonyl complex such as Fe(CO)5 under photochemical and thermal conditions when Fe2(CO)9 is used. When diallenes are used (X=R2C=C, Scheme 9.24), five-membered carbocyclic products are obtained [51, 52], whereas when allenyl ketones (X = O) are applied, five-membered lactones are generated [53, 54]. The use of allenylimines (X = NR) leads to five-membered lactams under these conditions [55]. 

Although a number of multistep procedures are available for the introduction of five-membered carbocycles, their direct formation in a thermal cycloaddition is rare.6 Interest in the potential application of such a three-carbon + two-carbon cyclopentane cycloaddition has been derived from the expectation that such a process could prove to be an effective complement to the four-carbon + two-carbon Diels-Alder reaction which is used extensively in the regio- and stereocontrol led preparation of functionalized six-membered carbocycles. 

The synthetic value of the photoinduced electron-transfer reactions of ketones has been expanded (Scheme 8.62) by generating a five-membered carbocyclic framework, as shown in the preparation of compound 226. 

Dipolar cycloaddition of nitrile oxides to unsaturated five-membered carbocyclic and heterocyclic systems gives fused 1,2-oxazolines. Steric effects are apparently of far greater importance than electronic ones, especially with regard to the orientation of the dipolarophile towards the nitrile oxide in the cycloaddition reaction. Originally, only one... 

The formation of ring systems by the anionic cyclization of olefinic alkyl, aryl and vinyl-lithiums is an interesting synthetic transformation that provides a regiospecific and highly stereoselective route to five-membered carbocycles and heterocycles99. Most importantly, it is possible to functionalize the initially formed cyclization product by a tandem reaction with electrophiles, a reaction that is not generally possible in the case of radical cyclizations. 

Reaction of asymmetric (2-butene-l,4-diyl)magnesium with a,to-alkylene dihalides usually gives two isomeric products. For example, treatment of (2-phenyl-2-butene-l,4-diyl)magnesium with 1,3-dibromopropane at — 78°C, followed by warming to room temperature, resulted in the generation of two five-membered carbocycles, 1-phenyl-1-ethenylcyclopentane and a-cyclopentylstyrene, with a ratio of 77 23, in a 76% isolated yield. 

Although there are only a few examples of alkylations of carboxylate enolates which are exocyclic to five-membered carbocyclic rings, the usual steric factors seem to control the stereoselectivity of these reactions. Thus, the dienolate (111) underwent reaction with 4-bromo-l-butene anti to the methoxymethyl substituents with high diastereoselectivity " and enolates derived from norbomane-2-carboxylates (112)... 

The 1,2-silyl migrative [3+2] cycloadditions of allylsilanes are applicable to a variety of electron-deficient multiple bonds. High diastereoselectivity is usually observed. These silicon-directed reactions are, therefore, valuable for stereocontrolled syntheses of highly functionalized five-membered carbocycles and heterocycles. 

An interesting approach to the substituted 6,8-bisdehydro[13]annulenone (238) includes a double Knoevenagel reaction of the mixed acetonedicarboxylic ester (235) with aldehyde (236) in the presence of piperidine to give (237). Oxidative coupling of the acetylene moieties in (237) with Cu(OAc)2 in pyridine affords (238) in 10% yield (Scheme 47).2 a,p-Unsaturated malonodinitriles are suitable intermediates for the synthesis of a variety of carbocyclic systems. Cyclization of the benzylidene malonodinitrile (239) to form a five-membered carbocyclic ring (240) can be achieved upon treatment with acid and subsequent hydrolysis (Scheme 48). A similar cyclization of (241) affords six-mem-bered carbocyclic ring systems. ... 

Five-membered carbocycles Ethoxycyclopropane reacted with TCNE in various sob vents. In dioxane and acetonitrile 3-ethoxy-1,1,2,2-cyclopentane-tetracarbonitrile 375 was the only product. Performing the reaction in benzene also yields a ring-opened enol ether, which reacts further with TCNE . 

Synthesis of Five-Membered Carbocycles An annulation of chromium arylcarbenes by alkynes without CO-insertion leads to five-membered rings. It has been observed as a side reaction along the benzannulation which may become predominant depending on the nature of the carbene heteroatom substitution pattern, [72] the metal [40] and its coligands [73] and the solvent [43] used. In this respect, indene derivatives have been obtained from arylcarbene complexes of chromium and tungsten. [73,74]... 

This reaction has general application in the synthesis of five-membered carbocycles and heterocycles. 

General Methods.—Cycloaddition reactions between allyl anions and carbon-carbon multiple bonds constitute an attractive foute to five-membered carbocycles. 

Examples of Mizoroki-Heck cyclizations forming five-membered carbocycles are scarce for cycUc vinyl haUdes or triflates, presumably due to the strained reaction products. Grigg et al. [27] tested 31, a cyclic derivative of 4a (Scheme 5.2), giving regioselectively the... 

When investigating the first syntheses of five-membered carbocycles (Section 5.2), Grigg et al. [8, 9] at the same time also revealed Mizoroki-Heck cyclizations forming the structurally related six-membered ring systems. Cyclization of 2-bromo-l,7-octadiene 79 gave 80 with a 4 1 ratio of exocyclic to endocyclic double-bond isomers in 86% yield, and without any 7-endo-ttig product (79 80, Scheme 5.17). Reaction of 81 was less successful, only providing 66% yield and a 2.5 1 ratio of double-bond isomers (81 82). Both products 80 and 82 were later successfully employed in Diels-Alder... 

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