Electrocyclic opening

Strategies based on two consecutive specific reactions or the so-called "tandem methodologies" very useful for the synthesis of polycyclic compounds. Classical examples of such a strategy are the "Robinson annulation" which involves the "tandem Michael/aldol condensation" [32] and the "tandem cyclobutene electrocyclic opening/Diels-Alder addition" [33] so useful in the synthesis of steroids. To cite a few new methodologies developed more recently we may refer to the stereoselective "tandem Mannich/Michael reaction" for the synthesis of piperidine alkaloids [34], the "tandem cycloaddition/radical cyclisation" [35] which allows a quick assembly of a variety of ring systems in a completely intramolecular manner or the "tandem anionic cyclisation approach" of polycarbocyclic compounds [36]. 

Figure B14.2. Orbital correlation diagram for electrocyclic opening of cyclopropyl cation S, A and solid lines indicate disrotatory opening S, A and dotted lines indicate conrotatory opening.

The three-membered ring of the cycloproparenes is opened easily by an electrophile and the attack can be at either the a or the n framework. The reactions with halogens (non-photochemical)58-59,61 and acids250 give rise to benzyl derivatives that are best accounted for by 7t capture of the electrophile (E+) at the bridge, electrocyclic opening of the cyclopropyl cation to benzyl cation (path a, Scheme 21) and capture by the nucleophile. 

Construct correlation diagrams for conrotatory and disrotatory electrocyclic opening of each of the following ... 

An elegant synthesis of the neurotoxic alkaloid anatoxin has exploited the electrocyclic opening of the dibromobicyclo[5.1.0]octane followed by transannular cyclization (Scheme 13).238 Similarly, the thermal electrocyclic opening of the dichlorocyclopropane followed by intramolecular trapping of the developing allylic cation by a suitably positioned amine has been used in a homoaporphine synthesis.238... 

For example, the electrocyclic opening of the benzcyclobutene 2.146 gives a diene unit, which is trapped intramolecularly by the pendant vinyl group in... 

Electrocyclic opening and closing of some linearly conjugated ions... 

A halide ion departing initiates the electrocyclic opening of a cyclopropyl cation, without the cation itself being an intermediate. 

D-A = Diels-Alder EC = electrocyclic closing EO = electrocyclic opening GT = group transfer Ch = cheletropic Cy = cycloaddition 1,3-D = 1,3 dipolar cycloaddition con = conrotatory dis = disrotatory s = suprafacial. 

The photochromic properties of 2/7-chromene derivatives has generated much interest in recent years. Under UV irradiation these molecules can undergo reversible electrocyclic opening of the pyran ring to afford colored ortho-quinone methides <2005T11730, 2005T1681>. 

For some time the synthetic potential of this reaction as a source of Diels-Alder adducts underwent considerable study. One outcome of these studies was the realization that of the four possible o-xylylenol isomers, only ones with the enolic OH group pointed out (the F-photoenol ) reacted with dienophiles [23]. Mechanistic studies picked up in the 1970s, after Matsuura and Kitaura reported that, in the absence of dienophiles, benzocyclobutenols are formed from 2,6-dialkylphenyl ketones but not from simple o-alkylphenyl ketones [24]. Previously the absence of cyclobutenol products had been quite puzzling and led to suggestions that they were formed from the initial biradical but underwent rapid electrocyclic opening to the o-xylylenols. 

The first reaction is an electrocyclic opening of a cyclobutene ring. 

A few important points can be discerned from Table 5.5. The first step is the rate-determining step, with a barrier of 13-15 kcal mol , leading to the bicyclic intermediate 9 that is energetically slightly below 2. The second step is the Woodward-Hoffmann-allowed, disrotatory, electrocyclic opening of a cyclohexadiene ring. This step has a much lower barrier (1-2 kcal mol relative... 

Similarly, thermal (at 150°C) electrocyclic opening of cyclobutenes forms conjugated butadienes this mode of reaction is favoured by relief of ring strain. However, the reverse ring closure is not normally observed. Photochemical ring closure can be affected, but the stereospecificity is opposite to that of thermal ring opening. 

Few reactions of alkynes with C—X bonds are valuable for the preparation of four-membered hetero-cycles. Ynatnines react with aldehydes and ketones in the presence of Lewis acids to give unstable oxetene derivatives which undergo electrocyclic opening (Scheme 43). Open-chain products are also obtained with thiocarbonyl compounds,Schiff bases and iminium salts. Reactions of ynamines with carbon dioxide, ketenes, - ketenimines and isocyanates " often give mixtures of products and are of little preparative value. 

The opening of halocyclopropanes to allyl systems according to equation 124 can happen thermally or with the assistance of electrophiles and nucleophiles . Some recent examples include an efficient cyclopentenone synthesis (equation 125) ", an electrocyclic opening/cyclization sequence giving functionalized furan and pyran derivatives (equation 126), an elegant total synthesis of the very fast death factor alkaloid ( ) anatoxin and a nice application of the well known nucleophilic opening to the preparation of crystalline methylene aziridines (equation 127) . 

As noted earlier (Section I V.A.5), the addition of nucleophiles to cyclopropenes relieves ring strain. Electrocyclic opening of the anion generated in this manner competes with capture by an ambient electrophile (E" ) (equation 85). Cyclopropene 278 reacts with... 

For cyclobiitenophcnanthicnc (50) lwt> dilTcrcnt phoiochemical reaction pathways are conceivable (Michl, 1974b) the electrocyclic opening of the cyclobutene ring to form 51 and the cycloreversion reaction to give phenanthrene and acetylene. The HMO coefficients of the 2 and 2 positions in biphenyl have opposite signs in the HOMO and equal signs in the LUMO. Thus, the HOMO... 

The second reaction involves a reverse Diels-Alder reaction and an electrocyclic opening of the dobutene product. This is a four-electron conrotatory process. The two substituents may both. otate out to give the , -diene or both in to give the 2,Z-diene. 

Hassner, A., Naidorf, S. Cycloadditions. 31. Photochemical generation of vinylketenes by electrocyclic opening of cyclobutenones. Tetrahedron Lett. 1986, 27, 6389-6392. 

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