Cyclobutenedione derivatives

A further example of the utility of the cyclobuta[ >]chroman system in synthesis (see 6.4.1.3) is provided by the conversion of the cyclobutenedione derivatives (19) into substituted xanthones. Compounds (19) are obtained in high yield from salicylaldehydes and squarate esters and their reaction with alkenyl, aryl and heteroaryl li compounds is both facile and high yielding <96JA12473>. 

P.A. Tempest, R.W. Armstrong, Cyclobutenedione derivatives on solid support toward multiple core structure libraries, J. Am. Chem. Soc. 1997, 119, 7607-7608. 

Thermal electrocyclizations of perhalogenated 1,3-butadienes yield perhalogenated cyclobutenes which can be solvolysed to 3,4-dihydroxy-3-cydobutene-l,2-dione ( squaric acid") and its derivatives (G. Maahs, 1966 H. Knorr, 1978 A.H. Schmidt, 1978). Double CO extrusion from fused cyclobutenediones has been used to produce cycloalkynes, e.g., benzyne from benzocyclobutenedione by irradiation in an argon matrix (O.L. Chapman, 1973) and cyc/o-Ci8, cyclo-Cn, etc. by laser desorption mass spectroscopy of appropriate precursors (see section 4.9.8). 

Conjugate addition of vinyl-, aryl-, heteroarylcuprates 90 to the cyclobutenedione 63, followed by in situ protection with (methoxyethoxy) methyl chloride of the enolates, provides a method for synthesizing substituted catechol derivatives 91 [44], Regiocontrolled synthesis is achieved by using cyclobutenedione monoacetals 92 as starting substrates. (Scheme 32)... 

The ethoxycarbocation intermediate (363) produced by the action of acid on the cyclobutenedione monoacetal (362) has been found to react with bis(trimethylsilyl)-acetylene to afford a 2-methylenecyclopent-4-ene-l,3-dione derivative (365). The authors426 proposed that the rearrangement results from an unprecedented cationic 1,2-silyl migration on the alkynylsilane, subsequent ring expansion via a vinyl cation intermediate (364), and re-closure by intramolecular addition of an acyl cation to a silylallene in a 5-exo-trig mode (see Scheme 90). 

Various kinds of substituents such as amino acid derivatives can be easily introduced into cyclobutenedione resulting in the formation of variety of chiral nonlinear optical materials... 

Even in such molecules with large ground state dipole moment, we observed the production of non-centrosymmetric crystal structures exhibiting SHG by introduction of asymmetric amino acid derivatives into the cyclobutenedione. (-)4-(4,-dimethylaminophenyl)-3-(2l-hydroxypropylamino) cyclobutene-1,2-dione (DAD) (3), (+)4-(4 -di-... 

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 most dramatic synthetic achievement with cyclobutenediones is the synthesis of deltic acid derivatives. As illustrated below, photolysis43 of diethyl squarate (16 d) yielded, among other products, diethyl debate (21). The bis-trimethylsilyl ester (16 e) of squaric acid similarly furnished a deltate ester which was successfully hydrolysed to deltic acid itself (22), the lowest member of the series of oxocarbon acids48). 

Over the years, squaric acid and its derivatives have found several uses in medicinal chemistry Squaric acid inhibits glyoxy-lase I (45) semisquaric acid (3-hydroxy-3-cyclobutenedione) is an inhibitor of pyruvate dehydrogenase and transketolase (46) and other derivatives serve as antagonists of the N -methyl-D-... 

Liebeskind and co-workers have published a series of papers dealing with the chemistry of cyclobutenones and cyclobutene-diones. Thus an unprotected stannyl derivative bearing an amino function was reacted with an appropriate aryl iodide, leading in excellent yield to a pyrido-annelation product [64] (Scheme 4-23). The reaction of a monoprotected derivative with chlorocyclobutenones led to benzannelated cyclobutenediones [65], and stannyl derivatives of p-benzoquinone also underwent benzannelation when treated with these substrates [66]. Acylation of cyclobutenediones via stannyl derivatives has also been carried out [67], as has functionalization of cyclobutenones [68]. 

Cleavage without decarbonylation has been observed with derivatives of cyclobutenedione ("cyclobutadienequinone ), the initial product being either a bis-ketene or a diacyl radical depending on whether the reacting excited state is singlet or triplet. Thus, the product of photolysis 93> of phenylcyclobutenedione in methanol was dimethyl phenylsuccinate plus an unidentified substance. The bis ketene intermediate (14) formed... 

Similar electrophilic Friedel-Crafts-Uke reactions allow the most reactive dichloride 17 to furnish 1,4-diarylcyclobutenedione derivatives [44,45] for example, l,4-thieno[3,2-fo]pyrrole-substituted cyclobutenedione 23 was prepared by this method and an oxygen-inserted conjugation system 24 was attained as a photochromic devise [46] (Scheme 4). 

The reaction of cyclobutenediones such as 50 with the appropriate alkenyllithium agent facilitates an alternative route to alkenyl butenones such as 51. Further synthetic utility of the Moore reaction can be illustrated by the efficient parallel synthesis of ( )-0-methylperezone 52 and, proceeding from the alkynyl derivative 53, its regioisomer ( )-0-methylisoperezone 54. ... 

Oimethoxyfuran reacts with dienophtles such as dimethylmaleic anhydride under high pressure 99 methylenecyclobutenone and cyclobutenedione (giving (96)1 react straightforwardly. The furan-derived ether (96a> fails to... 

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