Cyclobutene electrocyclization

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 stereochemistry of the former product was not assigned, but later, the exo-isomer was synthesized and found to be identical to the product generated from the 8200 material. Benzene might arise from the bicyclo[6.4.0.]dodeca-2,4,6,9,ll-pentaene which could be formed by a forbidden disrotatory retro cyclobutene electrocyclization of starting material, and at least two paths to the tricyclo[4.4.2.0]-tetraene can be envisioned. These are a 1,5-shift of the cyclobutene ring and... 

The butadiene-cyclobutene electrocyclic interconversions are predicted to occur thermochemically by way of [ 2s + 2J or [ 2g + 2J interactions, which again involves a conrotatory motion about the relevant bond axes. 

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). 

There are several general classes of pericyclic reactions for which orbital symmetry factors determine both the stereochemistry and relative reactivity. The first class that we will consider are electrocyclic reactions. An electrocyclic reaction is defined as the formation of a single bond between the ends of a linear conjugated system of n electrons and the reverse process. An example is the thermal ring opening of cyclobutenes to butadienes ... 

This compound is less stable than 5 and reverts to benzene with a half-life of about 2 days at 25°C, with AH = 23 kcal/mol. The observed kinetic stability of Dewar benzene is surprisingly high when one considers that its conversion to benzene is exothermic by 71 kcal/mol. The stability of Dewar benzene is intimately related to the orbital symmetry requirements for concerted electrocyclic transformations. The concerted thermal pathway should be conrotatory, since the reaction is the ring opening of a cyclobutene and therefore leads not to benzene, but to a highly strained Z,Z, -cyclohexatriene. A disrotatory process, which would lead directly to benzene, is forbidden. ... 

The cyclohexadiene-hexatriene system seems to be less complicated than the cyclobutene-butadiene system. Cyclohexadiene undergoes photochemical electrocyclic ring opening ... 

The Electrocyclic Ring Operung of Fluonnaled Cyclobutene Derivatives Dolbier, W R, Jr, Koroniak, H Mol Struct Energ S, 65-81 51 o... 

The best way to understand how orbital symmetry affects pericyclic reactions is to look at some examples. Let s look first at a group of polyene rearrangements called electrocyclic reactions. An electrocyclic reaction is a pericyclic process that involves the cycli/ation of a conjugated polyene. One 7r bond is broken, the other 7t bonds change position, a new cr bond is formed, and a cyclic compound results. For example, a conjugated triene can be converted into a cyclohexa-diene, and a conjugated diene can be converted into a cyclobutene. 

Compound 6 is a pivotal intermediate in Schreiber s synthesis. It was hoped that the conspicuous and strained bridgehead cyclobutene substructure in 6 would undergo a conrotatory electrocyclic ring opening upon thermolysis to give an isomeric 1,3-diene (8, Scheme 1). In the event, when a solution of cyclobutene 6 in toluene is confined to a sealed tube and heated to 180°C for 12 h, a stereoisomeric mixture of 1,3-dienes 7 and 8 is produced in an excellent yield of 95% (7 8 ca. 5 1). Finally, irradiation of the 5 1 mixture of cis-7 and trans-8, or of each independently, establishes a photostationary state in which the desired trans isomer 8 predominates (8 7 ca. 10 1). 

Table 13-1. Computed reaction barriers and isomer stabilities [kcal/mol] for the electrocyclic ring opening of cyclobutene (relative to cyclobutene 1, including zero-point vibrational contributions). Except for G2, the results were obtained using the 6-311+G(d,p) basis set.

The nucleophilic attack with 2-700 and 2-701 can proceed in a syn or anti manner to provide either 2-702 or 2-703, or both [357]. If2-703 is formed, it follows a charge-driven conrotatory opening of the cyclobutene ring with generation of the coiled 1,3,5,7-octatetraene 2-704. This intermediate is capable of a rapid helical equilibration [357] and a regioselective 8jt electrocyclic ring closure to give 2-705 [358]. 

The forerunner in the Co-catalyzed [2+2+2] cycloaddition domino processes was that identified by Vollhardt and colleagues [273], with their excellent synthesis of steroids. Reaction of 6/4-1 with [CpCo(CO)2] gave compound 6/4-3 with an aromatic ring B via the intermediate 6/4-2. In this process, trimerization of the three alkyne moieties first takes place, and this is followed by an electrocyclic ring opening of the formed cyclobutene to give o-quinodimethane. This then undergoes a Diels-Alder reaction to provide the steroid 6/4-3 (Scheme 6/4.1). 

Electrocyclic reactions are examples of cases where n-electron bonds transform to sigma ones [32,49,55]. A prototype is the cyclization of butadiene to cyclobutene (Fig. 8, lower panel). In this four electron system, phase inversion occurs if no new nodes are formed along the reaction coordinate. Therefore, when the ring closure is disrotatory, the system is Hiickel type, and the reaction a phase-inverting one. If, however, the motion is conrotatory, a new node is formed along the reaction coordinate just as in the HC1 + H system. The reaction is now Mobius type, and phase preserving. This result, which is in line with the Woodward-Hoffmann rules and with Zimmerman s Mobius-Hiickel model [20], was obtained without consideration of nuclear symmetry. This conclusion was previously reached by Goddard [22,39]. 

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]. 

Electrocyclic reactions can be brought about by heat, by ultraviolet irradiation and sometimes by use of metal catalysts. The thermal reaction is generally not reversible and as written above cyclobutenes have been converted to 1, 3 dienes by heating between 100° and 200°C. But the photochemical conversion can be carried out in either direction. Generally 1, 3 dienes can be converted to cyclobutenes rather than the reverse because the dienes because of n electrons are strong absorbers of light at the used wavelengths. 

The simplest example of an electrocyclic reaction involving 4n electron system is the thermal opening of cyclobutenes to 1,3 butadienes. The reaction can be done thermally or photochemically and under either conditions, it is stereospecific. 

We are also carrying out calculations 40) for the electrocyclic ring opening of cyclobutene (27) and bicyclobutane (28) to 1,3-butadiene (29). While.this work is not yet complete, we have established that 27 opens preferentially by... 

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