Cyclobutene, 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]. 

The first example illustrates how a 1,4-dehydroaromatic system with cyclohexane ring having two double bonds may be also disconnected according to a retro-Diels-Alder to give a diene and an acetylene as the dienophile [25]. The second example makes clear that even an aromatic double bond may be -in some instances-involved in a retrosynthetic pericyclic disconnection [26]. In the synthetic direction, the polycyclisation involves a conrotatory electrocyclic cyclobutene ring opening, (16 15) followed by an intramolecular Diels-Alder addition (see Scheme... 

This electrocyclic cyclobutene ring opening also gives the product as a single stereoisomer. 

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

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. 

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. 

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 opposite is true for the electrocyclic opening of cyclobutene—ring strain in the four-membered ring means that the reverse (ring-opening) reaction is preferred to ring closure. 

Periplanone B is the most active sex pheromone found in the alimentary tract and excreta of the American cockroach Periplaneta americana. An elegant total synthesis of this germacrane sesquiterpene was achieved by SCHREIBER and SANTINI Cyclodecatrienone 1 is an obvious precursor. One of the oxirane rings arises from epoxidation of the enone CC double bond, the other from [2-1-1]-cycloaddition of a carbene to the carbonyl bond of the enone. Oxidation of the methylene group introduces the additional carbonyl double bond. The CC double bond of the enone results from an elimination of HX in the a-X-substituted cyclodecadienone 2, which, on its part, is feasible by substitution of cyclodecadienone 3. An electrocyclic opening of the cyclobutene ring in 4 provides the 1,3-diene substructure in 3. 

The FMO model provides insight into one aspect of electrocyclic reactions that we have not yet discussed. In the electrocyclic opening of cyclobutenes to butadienes, the tendency of a substituent at C3 of the cyclobutene to rotate inward to form a cis product (equation 11.42) or outward to form a trans product (equation 11.43) has been termed torcfuoselectivity Steric effects... 

Orbital interactions producing tor-quoselectivity in the electrocyclic opening of 3-substituted cyclobutenes. (Adapted from reference 152.)... 

Sol 14. The compound I undergoes sequential cyclobutene ring opening to give cyclohexenofused [12]annulene (V), which then undergoes thermal Mobius TT-bond shifts to substimted di-trans isomer VI. The compound VI then forms the cage compound VIII in two steps thermal electrocyclization followed by [4 + 2] cycloaddition. 

In a new, stereospecific synthesis of functionalized butadienes, the elaborated norbornane (846 R = Me) undergoes a facile thermal retro-Diels-Alder reaction, and the intermediate cyclobutene (847) opens electrocyclically to a 2.5 1 mixture of E,E- and Z,Z-dienes. ... 

For some time it has been known that many pericyclic reactions can be greatly accelerated if they are run under single electron transfer (SET) conditions (also known as electron transfer catalysis, ETC). Examples include Diels-Alder reactions, electrocyclic openings of cyclobutenes, and retro [2-1-2] cycloadditions. From the beginning it has been debated whether these SET reactions really are concerted processes with aromatic transition states, or whether they are better thought of as stepwise processes involving radical cation intermediates. 

FIGURE 5.37. Conversion of cyclobutene to (a) the conrotatory and (b) the disro-tatory transition states for electrocyclic opening to butadiene. The C=C bond has been sketched in the diagram to show the orbital overlap more clearly. Dashed lines indicate the overlap of AOs. 

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],... 

The parent compound has notyetbeen synthesized [11]. However, substituted thiepins are stable and accessible by various routes. For instance, 3-amino-substituted thiophenes and activated alkynes undergo a (2 + 2)-cycloaddition followed by electrocyclic cyclobutene ring-opening (cf. p. 95) to give the thiepin 1 ... 

An unusual feature of the ( )-illudol (60) synthesis reported by Semmelhack and co-workers is the use of a cyclobutene ester (57) as dienophile. Because of the competitive electrocyclic opening of (57) the cycloaddition had to be performed at relatively low temperatures, and under these conditions it transpired that the trimethylsilyl enol ether (58) was sufficiently reactive whereas the corresponding methyl ether was not. 

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