Alkene-acetylene cyclization

Intramolecular alkene-acetylene cyclization of terf-butyl enynoate proceeds to afford the titanacycle, which in turn reacts regioselectively with electrophiles at... 

A major initial limitation of the benzocyclobutene approach to o-quinodimethanes was the lack of efficient, large-scale syntheses for many specifically substituted derivatives. Fortunately, recent developments have lemov much of this impediment. Q>nceptually, the synthesis of benzocyclobutenes from aromatic precursors can be envisaged in only a limited number of ways. These include [2 -i- 2] cycloadditions involving benzynes and alkenes, intramolecular cyclization on to a benzyne, cyclizations involving arene anions, and electrocyclic closure of o-quinodimethanes. Benzocyclobutene derivatives can also be prepared by aromatization of bicyclo[4.2.0]octanes. Detailed discussion of variations to these approaches can be found in the cited reviews. The cobalt catalyzed co-oligomerization of 1,5-hexadiynes with al-kynes, especially bis(trimethylsilyl)acetylene, has also been employed for the preparation of specifically substituted benzocyclobutenes. In the latter case the cyclobutenes are often not isolated but converted directly to o-quinodimethanes and subsequent products. ... 

Some 2//-pyrans were obtained by cyclization of alkenic acetylenes after their activation involving C=C — C=C exchange in initial reaction steps. Thus, diacetylenic alcohol PhCH(OH)C=C—C=CPh (56) was found to cyclize to 2//-pyrans readily after the addition of secondary amines RR NH (82CZ296). Similarly, acetylenic ketone PhCOC=C—CH=CHOMe (57) gave appropriate 2//-pyrans after the addition of aqueous bromine or benzthiamide (83AP454). 

Simple acetylenic allylic alcohols can be cyclized easily by tarf-butoxide, and since this base initiates prototropic shifts the vinylic link may.be E or Z such cyclizations proceed via exomethylene furans similar to 15.65 If necessary, UV irradiation can effect both the isomerization of an to a Z-alkene and the cyclization, leaving only the final adjustments to be made chemically.66 In a variation, methoxide plays the role of leaving group allowing very good yields to be attained (Scheme 10).67... 

Recently, addition of organorhodium species to nitriles has been reported.420 4203 4201 Intermolecular reaction of benzonitrile with phenylborate (accompanied with r//w-aryiation) (Equation (65)), arylative cyclization of acetylenic nitriles (Equation (66)), and cyclization of 2-cyanophenylboronic acid with alkynes or strained alkenes (Equation (67)) are proposed to proceed via this process. 

ELECTROPHILIC ADDITIONS TO CARBON-CARBON MULTIPLE BONDS A. Chlorinating agents Sodium hypochlorite solution 7V-Chloro succi n i m i de Antimony pentachloride Formation of chlorohydrins from alkenes Chlorination with solvent participation and cyclization Controlled chlorination of acetylenes... 

Many cyclization reactions via formation of metallacycles from alkynes and alkenes are known. Formally these reactions can be considered as oxidative cyclization (coupling) involving oxidation of the central metals. Although confusing, they are also called the reductive cyclization, because alkynes and alkenes are reduced to alkenes and alkanes by the metallacycle formation. Three basic patterns for the intermolecular oxidative coupling to give the metallacyclopentane 94, metallacyclopentene 95 and metallacyclopentadiene 96 are known. (For simplicity only ethylene and acetylene are used. The reaction can be extended to substituted alkenes and alkynes too). Formation of these metallacycles is not a one-step process, and is understood by initial formation of an tj2 complex, or metallacyclopropene 99, followed by insertion of the alkyne or alkene to generate the metallacycles 94-96, 100 and 101-103 (Scheme 7.1). 

The polymer-supported distannane 90 was used as a source of stannyl radicals in several radical cyclization reactions, such as the photochemical radical chain addition of f-butyl iodide to acetylenes yielding the Z/E mixture of alkenes or the photochemical cyclization of citronellyl bromide to give menthane in high yields164 (Scheme 44). 

The first report of a catalytic intermolecular cyclization was made by Pauson and Khand in 1974 [22], but the scope was limited to gaseous acetylene as the alkyne partner, strained olefins such as norbornene and norbornadiene as the alkene component, and TON s (turnover numbers) were modest (8-11). Several subsequent reports detailed the production of cyclopentenones from a substoi-chiometric amount of Co2(CO)g, but none were as efficient as Pauson s initial work [23,24]. Using ethylene as the alkene component, Rautenstrauch demonstrated the first efficient catalytic Pauson-Khand cyclization with a TON of 220, Eq. (5) [25]. A more general catalyst system employing (indenyl)Co(cod) was recently reported by Chung and Jeong, Eq. (6) [26]. The reaction was quite effec-... 

Celecoxib 24, a highly selective COX-2 inhibitor and a nonsteroidal anti-inflammatory drug (NS AID), is used for the treatment of arthritis and pain. The core skeleton of Celecoxib 24 is a 3-trifluoromethylpyrazole ring, which has been synthesized by [2 - - 3] cyclization and condensation of 1,3-diketones or their equivalents. Figure 12.3 summarizes three synthetic approaches toward 3-trifluoromethylpyrazole compounds via condensation of 1,3-diketones or a,[3-unsaturated ketones with arylhydrazine (route A, Schemes 12.1-12.3), via [2 - - 3] cycloaddition of trifluor-oacetamide with substituted ethenes or acetylene (route B, Schemes 12.4 and 12.5), and via cycloaddition of CFa-alkene with C-N=N unit (route C, Scheme 12.6). 

In addition to alkenes and acetylenes, carbonyl-containing compounds also participate in [2+2] cycloaddition reactions with indoles. The first example of oxetane formation via the photoreaction of indoles with a carbonyl group (a type of Patemo-Biichi reaction) was reported by Machida and coworkers [34, 35] (Scheme 16), who carried out the intramolecular cyclization of iV-acetylindole with phthalimide tethered with appropriate linkers 67a-d. Interestingly, only the... 

Radical cyclization of acetylenic esters." Cyclization of alkynyl esters 1 with Bu.ySnH/AIBN in refluxing benzene results in the (E)-exocyclic alkene, (E)-2, as the major product. In contrast, cyclization of 1 with tris(trimethyl-silyl)silane/AIBN provides a mixture of (E)- and (Z)-2, with the latter predominating. A different stereoselectivity obtains from cyclization of 1 with BuySnH or (TMSjySiH initiated by triethylborane/02. Actually the high (E)-selectivity in BujSnH/AlBN is a result of isomerization of (Z)-2 to (E)-2, promoted by BuySnH at high temperatures. In any case, this isomerization is an unexpected example of regiocontrol in radical cyclizations. 

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