Cyclobutene derivatives cycloaddition

Cycloaddition of norbornadiene with allene takes place to yield the cyclobutene derivative 10[5], Cyclodimerization of 1,2-cyclononadiene (11) affords a mixture of stereoisomers of the cyclobutane derivatives 12[6,7],... 

The few reported [2 + 2] cycloadditions of alkoxyallenes illustrated in Eqs 8.29 and 8.30 are probably of less synthetic importance. Cyclobutene derivative 162 could be prepared in good yield by cycloaddition of tetramethoxyallene 39 and acetylenedicar-boxylate 161 [105], whereas the reaction of 1,1-diethoxyallene 163 and phenylisocya-nate (164) gave the expected /3-lactam 165 [106]. Another example for a [2 + 2] cycloaddition is the dimerization of 39 described by Saalfrank et al. [107]. 

With the silyl-substituted difluoroallene 245 and molybdenum hexacarbonyl, the expected [2+ 2+ 1] cycloaddition is not observed. CO is not incorporated and the cyclobutene derivatives 246 can be isolated in good yields (Scheme 15.77) [148]. 

The meso-ionic 1,3-oxazol-S-ones show an incredible array of cycloaddition reactions. Reference has already been made to the cycloaddition reactions of the derivative 50, which are interpreted as involving cycloaddition to the valence tautomer 51. In addition, an extremely comprehensive study of the 1,3-dipolar cycloaddition reactions of meso-ionic l,3-oxazol-5-ones (66) has been undertaken by Huisgen and his co-workers. The 1,3-dipolarophiles that have been examined include alkenes, alkynes, aldehydes, a-keto esters, a-diketones, thiobenzophenone, thiono esters, carbon oxysulfide, carbon disulfide, nitriles, nitro-, nitroso-, and azo-compounds, and cyclopropane and cyclobutene derivatives. In these reactions the l,3-oxazol-5-ones (66)... 

Cyclobutanes can be conveniently prepared from cyclobutene derivatives through electrophilic addition, catalytic hydrogenation, nucleophilic addition, cycloaddition as well as light-induced addition reactions. 

The intermolecular [2 + 2]-cycloaddition of alkenes and alkynes utilizing an iron complex as a catalyst was reported by Rosenblum and Scheck [48]. The application of the [CpFe(CO)2]BF4 complex (Scheme 9.21) gave the desired cyclobutene derivatives 29 in up to 53% yield. 

The reaction of iron-carbonyl complexes with alkynes led to cyclobutenediones, which is formally a [2 + 1 + 1]-cycloaddition process for the formation of a cyclobutene derivative (Scheme 9.22) [49]. Nevertheless, in this reaction the liberation of the ligand is initiated by addition of stoichiometric amounts of copper] 11) salts and the use of various alkynes leads to interesting products such as 30 in good yields. 

The reaction of enamines with acetylenic compounds has been the subject of intensive studies. In general, alkyl acetylenedicarboxylates and propiolates undergo initial cycloaddition (Chapter 18) to form cyclobutene derivatives. These cyclobutenes rearrange, in most cases spontaneously, to form products whose structures depend on the starting enamine and on the reaction conditions126-128 (Scheme 45). 

For the synthesis of estradiol methyl ether 4-319, the cyclobutene derivative 4-317 was heated to give the orthoquinonedimethane 4-318 which cydized in an intramolecular Diels-Alder reaction [109]. The thermally permitted, conrotatory electrocyclic ring-opening of benzocyclobutenes [110] with subsequent intramolecular cycloaddition also allowed the formation of numerous complex frameworks (Scheme 4.70). 

The [2 -I- 2] cycloaddition of an alkene and an alkyne is a valuable route leading to cyclobutene derivatives. The ruthenium(0)-catalyzed [2 -1- 2] cycloaddition of a strained cycloalkene, norbornene 40, vith highly electron-deficient DMAD afforded the cyclobutene 74 (Scheme 4.28) [62]. As expected, the reaction took place at the exo face of 40 via the ruthenacyclopentene intermediate 75, that ivas formed by the oxidative cyclization of DMAD and norbornene. In addition to the parent 40, various norbornene derivatives can also be used as alkene components. When the Ru" precatalyst 17 ivas employed, electronically neutral alkynes participated in the [2 -1- 2] cycloaddition with norbornene and its derivatives [63]. A similar [2 -1- 2] cycloaddi-... 

Photoinduced [2 + 2] cycloaddition (Section 4.9) of alkenes (alkynes) to form cyclobutane (cyclobutene) derivatives is one of the best studied reactions in photochemistry.680 682 According to the Woodward Hoffmann orbital symmetry rules,336 the cycloaddition of one singlet excited (Si) and one ground-state alkene is allowed by a suprafacial suprafacial concerted stereospecific pathway (Scheme 6.45) 695 699 700 Rare concerted [4 + 2] and [4 + 4] photocycloadditions of conjugated singlet excited dienes must occur in a suprafacial antarafacial and suprafacial suprafacial manner, respectively.690 Since the suprafacial antarafacial reactant approach is geometrically difficult to achieve, [4 + 2] reactions usually proceed stepwise (involving biradical intermediates). [2 + 2] or [4 + 4] photocycloadditions can occur in either a concerted or stepwise fashion. 

In contrast to furan, the benzene ring in benzo[ ]furan (because of its large resonance energy) is dominant to such an extent that [4+2] cycloadditions are not possible. On the other hand, photochemical [2+2] cycloaddition occurs readily on the C-2/C-3 double bond leading, e.g. with an acetylene di-carboxylic ester, to the cyclobutene derivative 1 ... 

Cycloaddition reactions of the indole 2,3-double bond are not limited to alkenes as partners. Acetylenic compounds have also been used in photochemical cycloaddition reactions with indoles to produce cyclobutenone derivatives. There have been extensive studies on the reaction of indoles with dimethyl acetylenedi-carboxylate (61, DMAD), which produce a number of structurally distinct products [31]. By devising a photosensitized cycloaddition reaction of DMAD to activated indoles 60 in the presence of acetophenone, Neckers and Davis were able to produce the cyclobutene derivatives 62 in good yields (Scheme 14) [32]. The resulting cyclobutenes can then be converted to the corresponding benzazepines 63 via thermal ring-opening reactions. 

The formal [2+2] cycloaddition also provides an interesting approach for stereoselective synthesis of chiral cyclobutane derivatives. Ishihara and co-workers [70] reported the enantioselective [2 + 2] cycloaddition of unactivated alkenes 113 with a-acyloxyacroleins (Scheme 6.26). The reaction is catalyzed by chiral anunonium salt 114 and gives highly functionalized cyclobuten derivatives 115 with high... 

Scheme 1 gives a postulated reaction pathway for all these metathesis like reactions. The heteroallenes or the heteroalkenes are supposed to react in a 2 + 2 cycloaddition reaction with Cl3(dme)WCtBu to form metalla cyclobutene derivatives. Electrocyclic ringopening reactions of these (not isolated) metallacycles yield tungsten imido or 0X0 complexes with sigma bonded vinyl, iminyl, ketenyl or keteniminyl ligands. 

The direct reductive elimination from intermediates 2 leads to the formation of products 5 which present a very constrained structure. Usually, a con-rotatory thermal opening leads to the formation of vinylcycloalkenes 6. Only when the electrocyclic opening of the cyclobutene is not favoured, due to geometrical, steric or electronic reasons, the cyclobutene derivative can be isolated. This is the case with a substrate such as 9 which undergoes cycloisomerization via a formal [2+2] cycloaddition to give the polycyclic compound 10 (Eq. 2) [5],... 

Irradiation of a mixture of anisole and acrylonitrile in acetonitrile provides a facile synthesis of the cyclobutene derivative (29) by way of the [2 + 2] cycloadduct (28), and Lukas et al. have established that [2 -I- 2] cycloadditions of alkynes to alkenes, leading to cyclobutenes, can be realized in the presence of Lewis acids, e.g. (30) (31). 

Irradiation of butadiene in addition to cyclobutene derivatives also gives bicyclobutanes. Show formation of bicyclobutane is cycloaddition process. 

Pentalenes.—The X-ray structure of the tri-t-butylpentalene (60) has been determined the compound is planar and the double bonds are localised. Pentalenes (62), together with dimers, are produced by the action of acetylenes RC=CH (R = C02Me, CHO, or CN) on l,3-di-t-butyl-6-dimethylamino-fulvene (61). The aldehyde (62 R = CHO) dimerized to yield mainly compound (63), whereas the head-to-tail dimer (64) was isolated from the cyano-derivative (62 R = CN). The latter adds water under acidic conditions to give the alcohol (65), while dimethylamine affords the rearranged adduct (66). Cycloaddition reactions of the pentalene di-ester (67) proceed differently with dicyanoacetylene and cyclopentadiene the former yields the cyclobutene derivative (68), the latter the Diels-Alder product (69). ... 

A rather early example for a formal iron-catalyzed [2+2] cycloaddition was reported by Rosenblum et al. in 1982. The reaction of propiolic ester with olefins is catalyzed by the (dicarbonyl)(T -cyclopentadienyl)iron(II) cation (Fp ) (Scheme 4-300). The corresponding cyclobutene derivatives are obtained in moderate yields and excellent stereoselectivity. ... 

The [2+2] cycloaddition of acetylenes with alkenes remains to be the main pathway to cyclobutene derivatives [439], Theoretically, this... 

Reactions Leading to Destruction of the Thiophen Ring.— The product formed in the reaction between tetramethylthiophen and dicyanoacetylene in the presence of AlCh, and believed to be a thiepin derivative, was later shown to be a cyclobutene derivative (207) formed by a [2 + 2] cycloaddition. Thermally, (207) is rearranged to (208) by a [3,3]... 

Oxa and aza-benzonormornadienes undergo [2 + 2] cycloaddition with alkynes in the presence of NiCl2(PPh3)2, PhjP and Zn powder in toluene to afford the corresponding exo-cyclobutene derivatives in fair to excellent yields [116,117]. 

CycIoa.ddltlons. Cyclobutene adducts are formed from the reaction of acetylenic derivatives and maleic anhydride through a 2 + 2 cycloaddition (48). The reaction is photochemicaHy cataly2ed (see Photochemical technology). 

Aumann et al. have observed an unusual formal [6S+2C] cycloaddition reaction when they performed the reaction between an alkynylcarbene complex and 1-aminobenzocyclohexenes. The solvent used in this reaction exerts a crucial influence on the reaction course and products of different nature are obtained depending on the solvent chosen. However, in pentane this process leads to cyclooctadienylcarbene complexes in a reaction which can be formally seen as a [6S+2C] cycloaddition [117] (Scheme 71). The formation of these compounds is explained by an initial [2+2] cycloaddition reaction which leads to a cy-clobutenylcarbene derivative which, under the reaction conditions, undergoes a cyclobutene ring opening to furnish the final products. 

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