Double cyclization generation

A facile acid-catalyzed double cyclization of A,A-dibenzylaminoacetaldehyde dialkyl acetals of type 125 has been known to generate l-azadibenzo[c,/]bicy-clo[3.3.1]nona[3,6]dienes 126 in high yields 120,121,147). A novel and convenient synthesis of ( )-amurensinine (25) and ( )-reframine (28) (Scheme 25) proceeds from the quaternary salt 127, where proper choice of base and reaction... 

Double cyclization of iodoenynes is proposed to occur through a Rh(I)-acetylide intermediate 106, which is in equilibrium with vinylidene lOS (Scheme 9.18). Organic base deprotonates the metal center in the course of nucleophilic displacement and removes HI from the reaction medium. Once alkenylidene complex 107 is generated, it undergoes [2 + 2]-cycloaddition and subsequent breakdown to release cycloisomerized product 110 in the same fashion as that discussed previously (Scheme 9.4). Deuterium labeling studies support this mechanism. 

Terminal perfluoroolefins have two fluorine atoms at the double bond. The carbon atoms of the latter bear a significant positive charge, and the nucleophilic agents easily replace the fluorine atoms at the multiple bond. The reactions of binucleophilic reagents with terminal perfluoroolefins form heterocyclic systems. The first step of the reaction involves a nucleophilic attack at the carbon atom of the double bond, generating a carbanion. The latter is stabilized by elimination of the fluoride ion and formation of a new double bond. Subsequent cyclization by the intramolecular attack of the nucleophilic center at the double bond leads to the formation of a heterocyclic system. For example, when a reaction mixture of hexafluoropropylene and sodium dialkylaminodithiocarbamate in dimethylacetamide is heated with aqueous sodium tetraphenylborate, one obtains the tetraphenylborate salt of 2-dialkylamino-4-trifluoromethyl-4,5-difluoro-l,3-dithiolan-2-yl (78JFC(12)193). This compound is formed by intramolecular cyclization of the S-nucleophilic center. 

If a molecule has a multiple bond and a nucleophilically mobile chlorine atom, then the fluoride ion attacks the double bond, generating a carbanion stabilized by two trifluoromethyl groups, and intramolecular nucleophilic cyclization forming a five-membered heterocycle 48 is possible. 

In many of these applications, the ethynyl group is present in the starting material only in latent form, e.g. as a chlorovinyl substituent, from which it is liberated during the pyrolysis step. That even non-terminal acetylenes can be employed in these cycloaromatizations is illustrated by the protected cross-conjugated diacetylene 43 in Scheme 11. When this was subjected to hydropyrolysis at 900 °C, the diacetylene 44 was generated in situ and double-cyclized to corannulene (40) immediately [23]. 

The anodic behavior of A -substituted alkenes can be described as the oxidation of an electron-rich double bond. Tetraamino-substituted alkenes are extremely easily oxidized. Tetrakis(dimethylamino)ethylene exhibits two reversible one-electron processes at —0.75 and —0.61 V vs. SCE at a dropping mercury electrode in acetonitrile [140]. The anodic behavior of A, A -dimethylaminoalkenes has been studied intensively by cyclic voltammetry and electron spin resonance (ESR) spectroscopy [141]. The anodically E° = 0.48 V vs. SCE) generated cation radical of l,l-bis(iV,iV-dimethylamino)ethylene is shown to undergo C-C coupling, forming l,l,4,4-tetrakis(A, iV-dimethylamino)butadiene, which subsequently is further oxidized to its dication at —0.8 V [141,142]. With vicinal diamino ethylenes, usually two reversible one-electron oxidations are observed [143], while gem-inal diamino ethylenes exhibit an irreversible behavior [141]. Aryl-substituted vicinal diamino ethylenes (endiamines) can undergo a double cyclization to give an indolo-oxazoline when oxidized at 0.4 V vs. SCE in acetonitrile in the presence of 2,6-lutidine [144] ... 

Incorporation of an cc,P-cis double bond generates dehydrosecodine, the putative biosynthetic intermediate. By using the piperidone (77) as a starting material the reaction can be directed to either the aspidosperma or iboga skeleton. The ketone (77) cyclizes to (80) but conversion to the TMS enol ether (78) results in the iboga structure (79) (Scheme 149) <86JOC2913>. 

Intramolecular sequential [2+2+2] cycloaddition of linear hexaynes 2.86 that include a 1,3-diyne unit leads through a double cyclization to the biaryl derivatives 2.87. Axial chirality is generated between... 

The addition, therefore, follows Markovnikov s rule. Primary alcohols give better results than secondary, and tertiary alcohols are very inactive. This is a convenient method for the preparation of tertiary ethers by the use of a suitable alkene such as Me2C=CH2. Alcohols add intramolecularly to alkenes to generate cyclic ethers, often bearing a hydroxyl unit as well. This addition can be promoted by a palladium catalyst, with migration of the double bond in the final product. Rhenium compounds also facilitate this cyclization reaction to form functionalized tetrahydrofurans. 

---