Cyclization carbo

Annelation of carbocycle to heterocycle and cyclizations with simultaneous formation of carbo- and heterocyclic fragments 98JCS(P1)983. 

Steps 1-2 of Figure 27.14 Epoxide Opening and Initial Cyclizations Cyclization is initiated in step 1 by protonation of the epoxide ring by an aspartic acid residue in the enzyme. Nucleophilic opening of the protonated epoxide by the nearby 5,10 double bond (steroid numbering Section 27.6) then yields a tertiary carbo-cation at CIO. Further addition of CIO to the 8,9 double bond in step 2 next gives a bicyclic tertiary cation at C8. 

The preparation of several medium- and large-sized 2-carbo-methoxycycloalkanones has been accomplished by treatment of the cycloalkanone with sodium triphenylmethyl, followed by carbonation with dry ice, and esterification with diazomethane. 1 The yields are good but the procedure is laborious. The synthesis of 2-carbomethoxycycIooctanone via the Dieckmann cyclization of dimethyl azelate with sodium hydride yields 48% of this product when the procedure is carried out over a 9-day period.3... 

Wang et al. reported that FeCls- and FeBrs-promoted cyclization/halogenation of alkynyl diethyl acetals formed ( )-2-(l-halobenzylidene or alkylidene)-substi-tuted five-membered carbo- and heterocycles. It was found that the 1 1 molar ratio... 

Polyene Cyclization. Perhaps the most synthetically useful of the carbo-cation alkylation reactions is the cyclization of polyenes having two or more double bonds positioned in such a way that successive bond-forming steps can occur. This process, called polyene cyclization, has proven to be an effective way of making polycyclic compounds containing six-membered and, in some cases, five-membered rings. The reaction proceeds through an electrophilic attack and requires that the double bonds that participate in the cyclization be properly positioned. For example, compound 1 is converted quantitatively to 2 on treatment with formic acid. The reaction is initiated by protonation and ionization of the allylic alcohol and is terminated by nucleophilic capture of the cyclized secondary carbocation. 

Proposed mechanism for asymmetric Zr-catalyzed diene cyclization this represents the intramolecular variant of the catalytic carbo-magnesation shown in Scheme 6.2. 

The oxidative coupling/cyclization process occurs via stoichiometric carbo-palladation using a Pd(II) species, typically Pd(OAc)2. In an early example, submission of diphenylamines 3 to the palladium(II)-promoted oxidative intramolecular cyclization conditions yielded carbazoles 4 [15-... 

Five-membered carbo- or heterocycles can be prepared with the aid of heteroatom-substituted carbene complexes in several different ways. In the following sections the focus will be on cyclization reactions in which the carbon-metal double bond plays a decisive role. 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Negishi E, Wang G, Zhu G (2006) Palladium-Catalyzed Cyclization via Carbopalladation and Acylpalladation. 19 1-48... 

On the other hand, the analogous iodo derivative 81 with (TMS)3SiH at room temperature afforded a linear fused five-membered carbo-cycle in two isomeric forms and with an overall yield of 74% (Reaction 7.89) [102]. In this case, the cascade proceeds through 5-cxo, 5-cxo, and 5-exo modes of cyclization. 

Radical cyclization of polyfunctional 5-hexenyl halides mediated by Et2Zn and catalyzed by nickel or palladium salts has been demonstrated to produce stereoselectively polyfunctional 5-membered carbo- and heterocycles [56, 57]. Based on this strategy a formal synthesis of methylenolactocin (11) was achieved (Scheme 20). The acetal 130, readily being built up by asymmetric alkylation of aldehyde 127 followed by reaction with butyl vinyl ether and NBS, served as the key intermediate for the construction of the lactone ring. Nickel(II)-catalyzed carbometallation was initiated with diethylzinc to yield exclusively the frans-disubstituted lactol 132, which could be oxidized directly by air to 134. Final oxidation under more forcing conditions then yielded the lactone (-)-75 as a known intermediate in the synthesis of (-)-methylenolactocin (11) [47aj. 

As part of our efforts to develop new efficient one-pot methodologies to access novel heterocyclic structures, we also reported an efficient synthesis of spiro[4,61-lactones and lactames by sequential multicomponent reaction/metal-catalyzed carbo-cyclizations from simple five-membered cyclic (3-ketoesters and (3-ketoamides,... 

Amino-1,2,3-triazoles with a substituent at the 4-position have been prepared (i) from azides and active methylene nitriles (ii) from azides and ynamines (iii) from diazomethane and carbo-diimides (iv) from azides and 1,1-diaminoethenes and (v) from the rearrangement of 3-hydrazono-1,2,4-oxadiazoles. Among these, the first method, a regiospecific process, is the most versatile and convenient although it is suitable only for 5-NH2-substituted triazoles. Other methods are used to prepare 5-NHR , 5-NR R - and 5-NHCOR-substituted triazoles. Intramolecular cyclization of suitable precursors also gives 5-aminotriazoles. For example, a-imino-a-piperidyl phenylhydrazones (838), in the presence of copper acetate, give 5-piperidyl-triazoles (839) (Equation (85)) <94H(38)739>. 

Acylpalladium intermediates can be involved in intramolecular processes leading to the formation of carbo- or heterocycles. In this chapter we discuss the cyclizations via the attack of acylpalladium intemediates at carbon centers and formation of new G-G bonds. The basic scheme (Scheme 7) of such processes includes the oxidative addition of Pd(0) to G(j )-X bonds (X = halogen or triflate), migratory insertion of GO, and subsequent intramolecular addition of acylpalladium intermediate to double or triple bonds to yield cyclic ketones. 

The synthesis of 207 is based on an intramolecular aminolysis of the (3-lactam ring in 206. This latter compound was prepared by stereoselective alkylation of 203 with l-bromo-3-butene and subsequent oxidative cleavage of the double bond to give the carboxylic acid 204, which next was coupled with 205. The resulting peptide product 206 rapidly cyclized to a ten-membered ring compound, on reductive deprotection of the hydrazine group, and then coupled with /V-carbo-benzoxytyrosine to give 207. 

A fair number of carbo-ammonium dicationic species and related systems have been reported. These distonic superelectrophiles have been directly observed and shown to be useful in synthetic methodologies. For example, the acid-catalyzed Grewe-cyclization is a well-known reaction used in the preparation of morphine analogues.37 The conversion involves formation of the distonic superelectrophile (102) from an appropriate... 

The synthesis of five-membered carbo- and hetero-cyclic compounds, including fused rings, has been reported using acetate as a nucleophile in the cyclization of 1,6-enynes under palladium(II) catalysis (Scheme 91). The reaction is initiated by trans-acetoxypalladation of the alkynes and quenched by either trans- or ra-deaceloxypal-ladation in the presence of 2,2/-bipyridine as the ligand.134... 

Marco-Contelles and de Opazo utilised 8-ewd< -trig and 1-exo-Aig cyclizations, mediated by B113S11H, in their construction of chiral, polyfunctionalised medium-sized carbo-cycles670. For example, treatment of iodide (104) with BujSnll under standard radical conditions afforded 7-membered carbocycles (105) in moderate yield (equation 79). Prado and coworkers reported the synthesis of benzolactams by 11 -endo aryl radical cyclization, an example of which is highlighted in equation 80675. 

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