Five-membered ring synthesis

5-hexynyllithiums bearing an alkyl, aryl, or trimethylsilyl substituent on the terminal alkyne carbon cyclize readily upon warming to room temperature and the exocyclic vinylic organolithium 14 derivative may be trapped by reaction with different electrophiles. The alkyl-substituted system such as dec-5-ynyllithium 13a (R = Bu) undergoes clearly first-order cyclization to l-(cyclopentylidene)pentyllithium 14a (R = Bu) with a half-life of 7 min at 28.8 °C, and the activation parameters that characterize this reaction indicate that the rate of cyclization is strongly dependent on the temperature. 

The pure E stereochemistry of the vinylsilane 21 clearly shows that the carbocylization proceeds in a totally stereoselective fashion to give, under these conditions (20 °C, 5 min) the configurationally stable (Z)-alkenylzinc bromide [21] 20 via a syn addition of the allenic zinc bromide to the acetylenic moiety. This carbocyclization represents a new desymmetrization of diynes such as 18 which serves to deliver functionalized exo- 

The organozinc bromide 23ZnBr undergoes a regiospecific 5-exo-dig cyclization to give 24, which was characterized by hydrolysis or iodinolysis to give 25 or 26, respectively as a single isomer [20]. 

The first intramolecular carbolithiation of stabilized carbanions to the alkoxyacetylene 

This cyclization reaction is not restricted to sulfone-stabilized carbanions. Indeed, phosphorus ylides, ester- and ketone-enolates participate also in the 5-endo-dig carbometallation reaction [17a]. The synthesis of fused bicyclo as well as spirobicyclo derivatives can be accomplished via the intramolecular carbometallation reactions of various stabilized carbanions with alkoxyacetylenes [17a]. Moreover, some asymmetric 

Takahashi et al. reported that acetylenes could be transformed into indan-l-ones under water gas shift condition with cobalt as the catalyst in 1990 [6]. Nevertheless, the reaction proceeded at harsh conditions (100 atm of CO and 220 °C), and eight examples were provided in moderate to good yields (Table 15.1). 

In order to obtain some detail about this transformation, a series of deuterium isotope-labeling experiments were conducted. By the treatment of diphenylacetylene with D2O instead of H2O, the deuterated indanone was 

A possible mechanism was outlined by the authors. Coordination of diphenylacetylene to the cobalt complex could induce an electronic attack of the central cobalt metal on the aromatic ring and migration of the aromatic hydrogen to the acetylenic carbon initialing the C-H metalation step. Insertion of CO into the cobaltocycle complex gives the indenone. The resultant indenone could be hydrogenated by the [Co]-H species formed under water gas shift reaction conditions to furnish the indanone formation as discussed previously. 

The formation of Af-alkyl isoindolin-l-one through the carbonyiative C-H activation of Af-alkyl benzaldimines with cobalt as the catalyst was achieved by Sen and coworkers in 2006 (Table 15.2) [7]. The author wants to exploit the formation of polypeptides from aldimines with CO after the analysis of the products with GCMS, NMR, and X-ray, it turns out to be the isoindolin-l-one scaffolds. Reactions run under high temperature and pressure (100 °C and 69 bar of CO), and deuterium experiments indicate that the [Co]-H species was generated by the C-H metalation step of the aromatic ring, followed by the insertion to the C=N bond of the benzaldimine affording the final products. 

In 2014, a cobalt-catalyzed carbonyiative synthesis of phthalimide motifs from benzamides was demonstrated by Daugulis and coworker [8]. Here it uses the 8-aminoquinoline as the Ar,AT-bidentate directing system. Reactions 

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Five-membered ring synthesis by formation of one bond 423... 

From five-membered rings Synthesis of pyrene derivatives from five-membered ring precursors by ring enlargement [13]. 

Trifluoromethyl-substituted nitrones have been prepared [78JFC-(12)153 88JFC(39)39, 88MI2 89JHC381] and used as building blocks for five-membered ring synthesis (Scheme 66). 

Five-membered Ring Synthesis by Formation of One Bond 334... 

Five-membered Ring Synthesis by Formation of Two Bonds 4.05.4.5.1 From [4+1] atom fragments... 

Intramolecular Carbometallation 7.2.2.1 Five-membered ring synthesis... 

Five-membered ring synthesis via cyclization of vinyllithium derivatives 306... 

In the case of the TMM-Pd procedure for cycloaddition, it is found that the oxazolidinone and camphorsultam systems do not translate well to five-membered-ring synthesis. 

The only pericyclic reactions we have used so far have been cycloadditions the Diels-AIder reaction (Chapter 17) and photochemical (Chapter 32) or thermal t Chapter 33) 2 + 2 cycloadditions. Electrocyclic and sigmatropic reaaions are also useful in synthesis and as each is the basis of a method of five-membered ring synthesis, they are conveniently grouped into one chapter here. 

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