Substituted cyclobutane

The photosensitized dimerization of isoprene in the presence of henzil has been investigated. Mixtures of substituted cyclobutanes, cyclohexenes, and cyclooctadienes were formed and identified (53). The reaction is beheved to proceed by formation of a reactive triplet intermediate. The energy for this triplet state presumably is obtained by interaction with the photoexcited henzil species. Under other conditions, photolysis results in the formation of a methylcydobutene (54,55). 

Alkenes with electron-withdrawing groups may form cyclobutanes with alkenes containing electron-donating groups. The enamine reactions, mentioned above, are examples of this, but it has also been accomplished with tetracyanoethylene and similar molecules, which give substituted cyclobutanes when treated with alkenes of the form C=C—A, where A may be... 

Substituted cyclobutanes or benzene rings are formed by the reaction of imidazolides with suitable double-bond systems. 

This chapter contains a review of some photodimerizations and photo-condensations leading to the formation of substituted cyclobutanes. Since the literature in this field is indeed vast, it would be impossible to present here a comprehensive review of all the reactions reported to lead to such products. Instead, it is our goal to present a general survey of the various types of compounds known to produce cyclobutane compounds upon irradiation and to discuss mechanisms which have been proposed to account for some of these products. 

The following cleavage reactions depict the importance of these hetereoatom substituted cyclobutanes in organic synthesis. 

The second example is an intermolecular crystal-state reaction. Cross-conjugated 1,5-disubstituted 1,4-dien-3-ones in solution undergo both cis-trans photoisomerization and photodimerization, yielding complex mixtures of products, including die all-trans-substituted cyclobutane 2 in the case of 1,5-diphenyl-1,4-pentadien-3-one. In contrast, dienones such as 3a in whose crystals adjacent molecules lie parallel and strongly overlapped react in the solid to give 3b as the sole photoproduct. This isomerically pure tricyclic diketone results, formally, from an eight-center dimerization. It is not formed in the reaction in solution, and could be prepared by other methods only with considerable difficulty (4). 

In general, 2,3-dialkyl-p-benzoquinones exhibit site selectivity in that they tend to give predominantly Diels-Alder adducts resulting from diene attack on the external rather than the internal double bond. This external site selectivity is, however, dramatically reversed when a (substituted) cyclobutane ring is fused to p-benzoquinone. Paddon-Row and coworkers103 studied the reactions of p-benzoquinones such as 129 with several... 

Calculations based on this second model give the observed value for the entropy of activation. In addition, this model may be used to account for the observed isotope effect (Benson and Nangia, 1963). If the tetra-methylene biradical is involved then it is to be expected that appropriately substituted cyclobutanes might undergo cis-trans isomerization reactions. This will be referred to again later. One final point should be mentioned in connection with biradical intermediates in both cyclopropane and cyclobutane reactions. This concerns the absence of any effect of radical inhibitors on these systems, when it might be expected that they would interact with the biradicals. In fact calculations show that, under the conditions of formation, the biradicals have extremely short lifetimes sec) and hence, unless radical inhibitors are... 

The ciT-substituted cyclobutane ester 502 is of interest as intermediate for the synthesis of carbocyclic 503 (equation 218). Ring opening of the bicyclic (-l-)-Nopinone 501... 

Dimeric Phenolic Acid Constituents (Substituted Cyclobutanes) of Cell Walls... 

The only stem materials examined were from the Setaria anceps and Digitaria decumbens grasses. The major substituted cyclobutane dimers in these walls appeared, from the mass spectral data, to be mixed dimers of ferulic acid and coniferyl alcohol (FA-ConAlc type). Further examination of the aromatics of stems is required but if such dimers are present then they may well be involved in the biosynthesis of lignin (41,42). 

Cleavage of a C—C bond gives a distonic radical cation as an intermediate, while concerted cleavage of two C—C bonds yields the corresponding ArO and ArO in cycloreversion of aryl-substituted cyclobutane Therefore, the cycloreversion mechanism is related to dimerization of ArO where tt- and a-dimers are detected during PR of ArO such as... 

Table 1. Addition Reactions of Cyclobutenes To Give Substituted Cyclobutanes...

The preparation of cyclobutanols by a homoallyl rearrangement has been described previously (see Houben-Weyl. Vol. 4/4, p 62), e.g. treatment of the but-3-enyl p-toluenesulfonate 1 with potassium methoxide in dioxane yielded the dicyanomethoxycyclobutane derivative 2 (61 %). It is also possible to introduce hydrogen into the cyclobutane product by the use of hydrides, for example, borohydrides. Methoxy- or ethoxy-substituted cyclobutanes are formed with alkoxides, while cyano compounds are obtained with potassium cyanide (Table 1). Electronegative substituents in the 1-position of the starting alkene are necessary for a good result in this preparative method. 

Other cyclobutanecarboxylic acid derivatives have also been converted to nitrogen-substituted cyclobutanes.37 43 47,339 For example, ran.s-2-(cyanomethyl)cyclobutanecarbohydrazide reacted with sodium nitrite/hydrochloric acid in methanol to give methyl traw-2-(cyanomethyl)-cyclobutylcarbamate (3).43... 

On the other hand, it has been reported that the bridgehead-substituted cyclobutane 3-chlorotet-racyclo[3.3.0.02,8.03 6]octan-4-one (11) was dehalogenated in good yield (82%) by sodium in tert-butyl alcohol if protected as the acetal 12.145 When 11 was not protected, ring opening to e c o-tricyclo[2.2.1.02 6]heptane-3-methanol resulted. 

Dcsilylation of a substituted cyclobutane gave the deuterated compound in good yield.155... 

The thermal rearrangement products of buta-l,3-dienyl substituted cyclobutanes are usually cyclohexenes.39 The vinyl group may be part of a phenyl ring, e.g. as in the case of 5,46,47 in which case rapid rearomatization follows the ring enlargement. 

Scheme 3 shows the pathway leading to each product. Arrows with loops designate bond rotation preceding ring closure. The proportions reflect the preference for formation of the trans-substituted cyclobutane and the relative rates of bond rotation and of ring closure. Analysis of the data revealed that bond rotation is ten times faster than closure.24... 

Three isomers of the substituted cyclobutanes 33, 34 and 35 are obtained by the [2+2] cycloaddition of isoprene, and separated at low temperature from other cooligomers without undergoing Cope rearrangement. When the mixture was subjected to hydroboration and oxidation, the alcohol 37 was obtained from the isomer 34, and easily separated from 35 and the diol 36. The alcohol 37 is a pheromone called grandisol [11]. Although overall yield was 15%, this is the shortest synthetic route to this pheromone. 

Stork, G. Cohen, J. F. Ring size in epoxynitrile cyclization. A general synthesis of functionally substituted cyclobutanes. Application to ( )-grandisol. /. Am. Chem. Soc. 1974, 96, 5270-5272. 

Compared with the parent system and those with identical substitution in all four carbons, the structure of other derivatives should be affected by the substitution pattern and by the nature of the substituents. For 1,2-disubstituted derivatives, structure type C, in which the doubly substituted cyclobutane bond is weakened (and lengthened), or a related structure type in which the bond is cleaved, should be favored. This is born out by several observations mentioned earlier. For example, the geometric isomerization of 1,2-diaryloxycyclobutane (Sect. 4.1) can be rationalized by one-bond rotation in a type C radical ion. Similarly, the fragmentation of the anti-head-to-head dimer of dimethylindene (Sect. 4.4) may involve consecutive cleavage of two cyclobutane bonds in a type C radical ion. The (dialkylbenzene) substituents have a lower ionization potential (IP 9.25 eV) [349] than the cyclobutane moiety (IP 10.7 eV) [350] hence, the primary ionization is expected to occur from one of the aryl groups. 

The photochemical cycloaddition of two different alkenes leads to multiply substituted cyclobutanes, and allows for a general access to this class of compounds. More specifically, ever since Ciamician observed the light-induced isomerization of carvone (1 —> 2) (Scheme 6.1) in 1908 [1], the inter- and intramolecular reaction between an a,(3-unsaturated carbonyl compound and an alkene has become the most intensively studied and most widely used class of [2 + 2]-photocycloaddition reactions [2-9]. 

The imidazolinone shown in Sch. 25 has been dimerized by irradiating in acetone [37]. The fe-urea substituted cyclobutane that was obtained has been further modified to produce several high energy explosives. The most energetic product is the nitrourea shown. It is hydrolytically and thermally stable, but sensitive to impact. 

NaBH4 reduction of compound (42) opens both heterocyclic rings giving the 1,2,3,4-tetra-substituted cyclobutane (43), whose stereochemistry assigns the configuration of the precursor (42) <71JA3493>. 

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