Electrocydization

Of note, Quintela and coworkers used a related aza-Wittig/l,5-electrocydic ring-closure process to obtain access to multiheterocydic structural elements such as py-... 

The combination of pericyclic transformations as cycloadditions, sigmatropic rearrangements, electrocydic reactions and ene reactions with each other, and also with non-pericyclic transformations, allows a very rapid increase in the complexity of products. As most of the pericyclic reactions run quite well under neutral or mild Lewis acid acidic conditions, many different set-ups are possible. The majority of the published pericyclic domino reactions deals with two successive cycloadditions, mostly as [4+2]/[4+2] combinations, but there are also [2+2], [2+5], [4+3] (Nazarov), [5+2], and [6+2] cycloadditions. Although there are many examples of the combination of hetero-Diels-Alder reactions with 1,3-dipolar cycloadditions (see Section 4.1), no examples could be found of a domino all-carbon-[4+2]/[3+2] cycloaddition. Co-catalyzed [2+2+2] cycloadditions will be discussed in Chapter 6. 

To date, only a few examples are known where a domino reaction starts with an electrocydic reaction, although the value of this approach is clearly demonstrated by the beautiful synthesis of estradiol methyl ether 4-319 through a domino elec-trocyclic/cycloaddition process. There is also an impressive example of a double thermal electrocyclization being used however, the starting material for this domino reaction was prepared in situ by a transition metal-catalyzed transformation, and is therefore discussed in Chapter 6. 

Sorensen and coworkers used a domino conrotatory electrocydic ring-opening/ 6ji-disrotatory electrocyclization for the formation of ring C in the total synthesis of ( )-viridin (4-327) (Scheme 4.72) [112]. Heating 4-325 in the presence of a base followed by in-situ oxidation with DDQ afforded the tetracyde 4-326 in 83% yield. 

Thiemann and coworkers [68] sought novel types of steroids with different biological activity, and in doing so prepared areno-annulated compounds such as 6/1-133 (Scheme 6/1.35). This is achieved with a Heck reaction of 6/1-132 with an acrylate, followed by an electrocydic ring closure of the formed hexatriene. The reaction is then terminated by removal of the nitro group, with formation of the aromatic ring system. 

For example, McNab and coworkers have discovered that flash-vacuum pyrolysis (FVP) (1000 °C, 0.01 Torr) of pyrrole 10-114 led to the formation of pyrrolo[2,l-a]isoindol-5-one 10-117 in 79% (Scheme 10.29) [44]. The transformation is proposed to proceed via an initial 1,5-aryl shift to give intermediate 10-115, which then undergoes an elimination of methanol. Finally, electrocydization of the ketene 10-116 results in the formation of 10-117. 

An attractive strategy to functionalized cyclohep-tenes was developed by West al1181 As illustrated in scheme 7, the substrate 30 is exposed to FeCl3 as Lewis acid at -30 °C to induce a Nazarov electrocyd-ization to give the carbocation 31. Under the reaction conditions 31 undergoes a [4+3]-cycloaddition... 

Although not involving a pure hydrocarbon, the thermal isomerization of the methylenecyclobutene 268 to the benzocyclobutene 271 shows some typical allene hydrocarbon behavior (see below). In the first step of this sequential reaction, the substrate opens to give a vinylallene , 269, which, at the same time is also a derivative of the (Z)-bisallene 230 already referred to. As such, it readily electrocydizes to the o-xyly-lene 270, which, in a last and also characteristic step, ring closes to 271 [113]. 

The initially generated o-diallenylarene 273 electrocydizes to the annelated o-xyly-lene 274, which can either ring close to a naphtho[fo]cyclobutene or be trapped with a dienophile to yield the Diels-Alder adduct 275. Instead of the terminal hydrogen atom, the ethynyl functions can also carry alkyl and aryl substituents. 

The best known example is the thermal isomerization of 1,5-hexadiyne, which involves a [3.3]-sigmatropic shift to 1,2,4,5-hexatetraene (12) followed by an electrocydic ring closure to 3,4-bismethylencydobutene (324) for reviews, see (a) W. D. Huntsman, in The Chemistry of Ketenes, AUenes and Related Compounds, S. Patai (ed.), Wiley Chichester, 1980, Vol. 2, Chapter 15, pp. 521-667 (b) A. Viola, J. J. Collins, N. Fillip, Tetrahedron 1981, 37, 3765—3811 for quantum chemical calculations on this and related isomerizations, see K. A. Bleck,... 

An interesting possibility for the construction of a tetracyclic system 174 with two cyclobutane rings arises by addition of lithiated alkoxyallenes 120 to 173 followed by two consecutive electrocydic reactions. Products such as 174 are useful precursors for benz[a]anthracene-7,12-diones (Scheme 8.43) [110]. 

The unsymmetricall allene 189 dimerized to give pyranopyran 190. A hetero-Diels-Alder reaction was followed by the subsequent electrocydic ring closure reaction [8]. 

Vinylallenes and bisallenes participate in the Diels-Alder-type cycloaddition as the diene component, providing a powerful tool for the construction of complex ring systems. They also undergo thermal electrocydic ring closure to form methylenecy-clobutene derivatives. 

The electrocydic ring opening of the cydobutene 196 at 140 °C in 1,4-CHD produced in situ the enyne-allene 197 (Scheme 20.41) [78]. Cycloaromatization to the biradical 198 followed by hydrogen-atom abstractions then produced the phenol 199. 

Figure 12.3 uses a four-center electrocydic reaction [29] to illustrate the sensitivity to initial conditions. There are two simple yes/no questions. One is Did or did not... 

Electrocydization is another major mode of reaction utilizing the vinylidene complexes of Group 6 metals. It should be noted that the first example of this type of reaction was reported by Merlic et al. using a ruthenium complex employing nonaromatic diene-yne substrates [26]. 

Akiyama et al. extended this reaction to alkynylimines for the preparation of quinoline derivatives [28]. Treatment of N-aryl(alkynyl)imines 99 with 20 mol% W (CO)5(thf) in THF at reflux followed by oxidative work-up using NMO gave 2-arylquinolines 100 in reasonable yield through electrocydization of the vinylidene intermediate (Scheme 5.31). 

These reactions, called electrocydic rearrangements,365 take place by pericyclic mechanisms. The evidence comes from stereochemical studies, which show a remarkable stereo-specificity whose direction depends on whether the reaction is induced by heat or light. For example, it was found for the thermal reaction that cw-3,4-dimethylcyclobutene gave only cis,trans-2,4-hexadiene, while the trans isomer gave only the trans-trans diene 366... 

The reactions of alkenes and related compounds are grouped here into nine sections. The first five deal essentially with photoisomeriza-lion processes—geometrical isomerization about a carbon-carbon double bond, concerted (electrocydic) cyclization, concerted shifts (usually of hydrogen) along the ir-system, the di-jr-methane reaction. 

Electrocydic processes are one major group of concerted reactions far alkenes, that is, reactions in which all the bond-making and bond-breaking events occur in a single reaction step. In electrocyclic... 

Photochemical electrocycltc ring-closure in a 4-electron system works well for many acyclic dienes (2.17) and related cyclic systems 12.18). The situation with conjugated trienes is more complex, and they can act as 6-electron systems (2.19) leading to cydohexa-1,3-dienes, or as 4-electron systems (2.20) giving cyclobutenes. In addition they can undergo other photochemical reactions such as geometrical isomerization about the central double bond Iwhich must be c/s if a 6-electron electrocydic ring-closure is to take place). 

An important group of conjugated diene/triene systems are those in the vitamin D series. The key reactions in the commercial manufacture of vitamin D (and probably also in its formation in skin exposed to daylight) are a photochemical, conrotatory electrocydic ring-opening in the provitamin, and a thermal 1.7-shift of hydrogen in the previtamin so formed (2.23). High conversions to the vitamin are not normally possible because all three species absorb appreciably at the... 

The anion (103) underwent an interesting 6tt-electron electrocydization to give (104)... 

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