Cyclobutenes acetylene derivatives

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). 

Koltzenburg et have shown that sensitized photoaddition of MA to acetylene gives, in addition to the cyclobutene derivatives 46, a 2 1 MA acetylene derivative 47. They further showed that the cyclobutene adduct... 

This chapter concerns selected reactions discovered in years, 2000-2012 initiated by the availability of some unusual acetylene derivatives. These reactions have led to the creation of novel carbocyclic and heterocyclic compounds. Historically, most of the studies were performed by, or with the participation of, Russian researchers. The cycloaddition reactions include various pathways to cyclobutene and cyclohexadiene derivatives, the heterocyclization reactions have demonstrated additional pathways to various nitrogen- and sulfur-containing heterocycles. 

Simple cyclobutanes do not readily undergo such reactions, but cyclobutenes do. Ben-zocyclobutene derivatives tend to open to give extremely reactive dienes, namely ortho-c]uin(xlimethanes (examples of syntheses see on p. 280, 281, and 297). Benzocyclobutenes and related compounds are obtained by high-temperature elimination reactions of bicyclic benzene derivatives such as 3-isochromanone (C.W. Spangler, 1973, 1976, 1977), or more conveniently in the laboratory, by Diels-Alder reactions (R.P. Thummel, 1974) or by cycliza-tions of silylated acetylenes with 1,5-hexadiynes in the presence of (cyclopentadienyl)dicarbo-nylcobalt (W.G, Aalbersberg, 1975 R.P. Thummel, 1980). 

Titanated vinylallenes generated from the coupling of acetylenes and propargyl carbonates [38] undergo facile, unidirectional electrocyclization to give cyclobutene derivatives under extremely mild reaction conditions as shown in Eq. 9.17 [39]. 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

The triplet states of maleic anhydrides and maleimides add to olefins and to acetylenes to yield cyclobutane and cyclobutene derivatives.436,437 A host of sensitizers are effective in promoting the reaction,436 and in some cases the reaction does not proceed at all unless sensitized. Interestingly enough, many such additions have been reported to be stereospecific.438... 

The addition of substituted alkenes with electron-withdrawing groups to ruthenium acetylide complexes results in the formal [2 + 2] cycloaddition of the olefin to the acetylene moiety. Facile ring opening of the resultant ruthenium cyclobutene complex (103) generates the ruthenium butadienyl species (104). Subsequent displacement of a phosphine ligand leads to the Tj3-allylic product (105) [Eq. (93)] (90-92). The intermediate cyclobutene complex has been isolated in one instance for the monocarbonyl derivative 106 [Eq. (94)] (92). 

Cyclic active-methylene compounds react in Michael reactions not only with a,/J-unsaturated acceptors, but also with acetylene dicarboxylates, propiolates, and their derivatives (Scheme IV/8). If, for instance, acetylene carboxylic esters are added to a variety of cyclic-active methylene compounds, ring-expanded products generally are formed directly. In other cases, it is possible to isolate the intermediate cyclobutene derivatives, which can be converted to the ring enlarged compounds in a second reaction step. 

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). 

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. ... 

In addition, Swenton and cowm kers have reported that the dianion derivatives of certain pyrimidine-acetylene photoadducts undergo an electrocyclic reaction which may involve an anion-accelerated cyclobutene ring opening see R. N. Comber, J. S. Swenton and A. J. Wexler, /. Am. Chem. Soc., 1979,101, 5411. 

Reaction with enamines and related substances. Brannock el al. found that the enamines derived from acyclic aldehydes and ketones react with dimethyl acetylene-dicarboxylate to give products derived by rearrangement of cyclobutenes initially formed by 1,2-cycloaddition. Thus, N,N-dimethylisobutcnylamine (1) reacts with dimethyl acetylenedicarboxylate in refluxing ether to give dimethyl 2-dimethylamino-methylenc-3-isopropylidencsuceinate (2) in 49 % yield. 

When the 1 1 cycloadducts, generated in situ by addition of an equimolar amount of a phosphaalkyne R C=P to an imidovanadium(v) complex RN=VCl3, are treated with an excess of an acetylene R C CR, quantitative formation of the corresponding 177-1,2-azaphospholes 5 is observed (Scheme 2). Compounds 5 are isolated pure in 31-71% yields and the reaction is regiospecific. A large number of 177-1,2-azaphospholes have been prepared by this route. The formation of the 1,2-azaphospholes proceeds via an insertion of the acetylene into the P-C bond of the vanadium cyclobutene derivative, followed by a reductive elimination <20008417, 2003ZNB44>. 

The ketene (2) also undergoes cycloaddition to acetylenes to give 2-cyclobutene-1 -one derivatives in 40-80% yield.5 Thus /-butylcyanoketene reacts with phenylacetylene in benzene at room temperature to give the cyclobutenone (10). Only one of the two possible products of cycloaddition is formed thus the reaction is regiospecific. The structure... 

Pyrolytic scission of cyclobutenes leads to a diene which promises to be useful in a Diels Alder approach to catechols. Heating of the sllyl derivative of the acyloin product from dimethyl glutarate in the presence of dlenophiles affords adducts of the transient diene. The adduct obtained with dimethyl acetylene dicarboxylate was converted in several steps to phthalic acid derivative. ... 

One typical example is given by G. Kaupp with the [2+2] cycloaddition of diphenyl-acetylene to 1,4-dioxene leading to a bicyclic cyclobutene in good yield (cf. iv of this chapter). Another example is presented by T. Miyashi starting from naphthoquinonor-bomadiene. In an intramolecular reaction a quadricyclane derivative is quantitatively formed upon irradiation at X > 400 nm. It is assumed that this process involves the diketo-norbomadiene in its triplet state. Although the spin multiplicity of intermediates have not... 

A useful reaction for the synthesis of unsaturated seven-membered heterocycles is the (2 + 2)-cycloaddition of heteroaromatic compounds, e.g., 1 //-pyrrole, furan, or thiophene derivatives, with acetylenes. In combination with a subsequent intramolecular (2 + 2)-cycloreversion (Section IV,B,2) of the annulated cyclobutene moiety, ring enlargement with two carbon atoms can be achieved. 1-Heterocycloheptatrienes, such as benzol6]azepines,26,27,65,66 benzo[fc]oxepins,67,68 benzo[6]-thiepins,69,70 and thiepins,18,71 have been successfully prepared in this way other routes are either nonexistent or laborious.72 In these compounds the reacting carbon-carbon double bond constitutes part of a (4n + 2)7r-electron system and in the (2 + 2)-cycloaddition the resonance energy of the aromatic nucleus is lost. Just like the nonaromatic heterocycles, heteroaromatic compounds have been reported to undergo (2 + 2)-cycloaddition reactions both with electron-deficient and with electron-rich acetylenes. 

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 ... 

The metathesis copolymerization of the cyclobutene derivative, 7,8-bis(trifluoro-methyl)tricyclo[4.2.2.0 ]deca-3,7,9-triene (MO (7 in Ch. 13), with norbomene or cyclopentene (M2) gives copolymers that are readily converted into acetylene copolymers by elimination of l,2-bis(trifluoro)benzene from the Mi units, but the compositional sequence distribution in these copolymers is difficult to establish (Ramakrishnan 1989b). 

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 action of zinc on the same cyclobutene derivative was also studied [6]. When the reaction was carried out in the presence of either dimethylacetylene or dimethyl acetylenedicarboxylate, hexa-methylbenzene and dimethyl tetramethylohthalate were isolated from the respective reaction mixtures. These products could arise by trapping of the cyclobutadiene by the acetylenes, and ring-opening of the adducts to give benzene derivatives. 

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