Five membered carbocycles, synthesis

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. 

Over the last twenty years there has been considerable interest in the application of the cyclobutylmethyl rearrangement to complex organic molecule synthesis. This attention is a result of the quest for intriguing and varied frameworks of organic compounds containing five-membered carbocycles.1 6 However, due to the enormous amount of literature, as well as the lack of systematization in connection with such rearrangements, a comprehensive coverage of the activities in this area is not feasible in this context. For this reason, the examples selected in this section reflect the personal interests of the author. 

Synthesis of Five-Membered Carbocyclic and Heterocyclic Ring Systems... 

The chemistry of oligounsaturated five-membered carbocycles has fascinated chemists for more than 100 years, since Thiele published the first synthesis of the aromatic cyclopentadienyl (Cp) anion 1 [1], In the last couple of decades, knowledge about fully unsatu-... 

Compound I must be activated by the strongly acidic medium. One possible protonation site is the basic pyrrolidinium nitrogen atom (structure X), which would favor the formation of carbenium ion XI (see Scheme 16.3). This intermediate would gain additional stabilization from the polar solvent. Conditions for an SnI substitution would prevail to yield XII, whose fragmentation would resemble, formally speaking, the retro cycloaddition process used in the synthesis of I (i.e., VIII - I). The resulting ketone (XIII) would contain the elements required for the construction of a five-membered carbocycle with the desired incorporation of the functional carbon of one of the nitrile groups, as... 

J SYNTHESIS OF FOUR- AND FIVE-MEMBERED CARBOCYCLIC RINGS... 

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. ... 

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. 

Three-Carbon Synthon for [3 + 2] Annulations. Danheiser and co-workers have exploited allenylsilanes as the three-carbon components in a [3 + 2] annulation strategy for the synthesis of a variety of five-membered carbocycles and heterocycles. The pathway by which a typical annulation proceeds is shown in eq 6. Reaction of the 2-carbon component (the allenophile ) at C-3 of the allenylsilane is followed by rapid rearrangement of the silicon-stabilized vinyl cation. Ring closure then affords the five-membered product. 

Synthesis of Five-Membered Carbocycles. 1-Substituted al-lenylsilanes react with Q ,/3-unsaturated carbonyl compounds in the presence of titanium tetrachloride to produce cyclopentenes. For example, carvone and 1-methyl-l-(trimethylsilyl)allene react smoothly to give a ds-fused bicyclic system (eq 7). ... 

The Nazarov reaction is a conrotatory [4rt]electrocychzation. Overall, the transformation involves conversion of a divinyl ketone 1 into a cyclopentenone 5 (Scheme 3.1). The reaction is triggered by complexation of the ketone with a Lewis acid (LA) or protonation, leading to the formation of the pentadienyl cation 2. This intermediate undergoes cyclization to yield the oxyallyl cation 3, which, after deprotonation, affords the cychc dienol 4, which tautomerizes to the final cyclopentenone 5. Owing to the frequent occurrence of five-membered carbocycles in natural products, the usefulness of the Nazarov reaction in total synthesis becomes evident. 

The generation of trimethylenemethanes from diazines limits their wide applicability in synthesis. Consequently, Trust s report of the annulation reactions of alkenes with 134 was an important advance in the field (Scheme 18.23) [104]. The process is catalyzed by Pd(0) and has been developed into a powerful method for the construction of five-membered carbocycles [39]. The intermediacy of a symmetrical // -bonded intermediate 136 has been suggested on the basis of labeling studies in which aU three methylene positions were shown to be equivalent [105]. The [3 -r 2]-cydoaddition reactions of 136 with electron-deficient olefins were found to be highly diastereoselective. 

Dipolar cycloaddUions. Interest in 1,3-dipolar cycloadditions increased dramatically during the past 20 years, largely because of the pioneering studies of Huisgen [7, 2] The versatility of this class of pericychc reactions in the synthesis of five-membered-ring heterocyclic compounds is comparable with that of the Diels-Alder reaction in the synthesis of six-membered-ring carbocyclic systems (equation 1)... 

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