Domino pericyclic

Brandi A., Cicchi S. Domino Processes Involving Pericyclic reactions in Seminars in Organic Synthesis. 23th Summer Sch A. Corhella 1998 3, Ed. Trombini, Pb. Soc. Chim. Ital. 

For the reason of comparison and the development of new domino processes, we have created a classification of these transformations. As an obvious characteristic, we used the mechanism of the different bond-forming steps. In this classification, we differentiate between cationic, anionic, radical, pericyclic, photochemical, transition metal-catalyzed, oxidative or reductive, and enzymatic reactions. For this type... 

Another anionic pericyclic domino process is a Pummerer-type rearrangement/... 

A very attractive anionic/anionic/pericyclic/anionic fourfold domino sequence was developed by Kuehne s group, as illustrated in Scheme 2.147 [336]. Herein, on treatment of the enantiopure tryptophane-derived diester 2-644 with a, 3-unsatu-rated aldehydes 2-645 at 70 °C in benzene with benzoic acid and freshly activated... 

A trifold anionic/pericyclic domino reaction was used for the synthesis of the dioxapyrrolizidine 2-655 combining a nitro aldol condensation, SN-type cyclization, SN-type etherification, and an intramolecular 1,3-dipolar cyclization as described by Rosini and coworkers (Scheme 2.148) [339]. 

Besides morefold anionic domino processes with one pericyclic reaction, domino sequences combining two initiating anionic with two pericyclic steps have also been developed. For example, the group of Nesi and Turchi reported on the synthe-... 

Several other anionic/pericyclic domino processes use a Horner-Wadsworth-Emmons (HWE) or a Wittig olefmation as the first step. 

The latter reaction belongs to the group of domino anionic/pericyclic reactions, which consists of three steps and will be discussed in the following section. 

As expected, some sequences also occur where a domino anionic/pericyclic process is followed by another bond-forming reaction. An example of this is an anionic/per-icyclic/anionic sequence such as the domino iminium ion formation/aza-Cope/ imino aldol (Mannich) process, which has often been used in organic synthesis, especially to construct the pyrrolidine framework. The group of Brummond [450] has recently used this approach to synthesize the core structure 2-885 of the immunosuppressant FR 901483 (2-886) [451] (Scheme 2.197). The process is most likely initiated by the acid-catalyzed formation of the iminium ion 2-882. There follows an aza-Cope rearrangement to produce 2-883, which cyclizes under formation of the aldehyde 2-884. As this compound is rather unstable, it was transformed into the stable acetal 2-885. The proposed intermediate 2-880 is quite unusual as it does not obey Bredf s rule. Recently, this approach was used successfully for a formal total synthesis of FR 901483 2-886 [452]. 

The connection of radical and pericyclic transformations in one and the same reaction sequence seems to be on the fringe within the field of domino processes. Here, we describe two examples, both of which are highly interesting from a mechanistic viewpoint. The first example addresses the synthesis of dihydroindene 3-326 by Parsons and coworkers, starting from the furan 3-321 (Scheme 3.79) [128]. Reaction of 3-321 with tributyltin hydride and AIBN in refluxing toluene led to the 1,3,5-hexatriene 3-324 via the radicals 3-322 and 3-323. 3-324 then underwent an elec-trocyclization to yield the hexadiene 3-325 which, under the reaction conditions, aromatized to afford 3-326 in 51 % yield. 

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. 

The second largest group of pericyclic domino reactions starts with a sigmatropic rearrangement, which is most often a Claisen or an oxa- and aza-Cope rearrangement however, some processes also exist with a 2,3-sigmatropic rearrangement as the second step. 

Since the number of domino processes which start with a Diels-Alder reaction is rather large, we have subdivided this section of the chapter according to the second step, which might be a second Diels-Alder reaction, a 1,3-dipolar cycloaddition, or a sigmatropic rearrangement. However, there are also several examples where the following reaction is not a pericyclic but rather is an aldol reaction these examples will be discussed under the term Mixed Transformations . 

Baldwin and coworkers described an interesting and high-yielding pericyclic domino process, consisting of a Cope and a Diels-Alder reaction, which on thermal treatment of the tetraene 4-253 led to tricyclic compound 4-254 (Scheme 4.54) [89]. 

Barriault developed a new pericyclic domino process for the synthesis of the bioactive diterpenoid vinigrol (4-262), which was isolated from Vtrgaria nigra [92]. The natural product possesses antihypertensive and anti-platelet-aggregating properties. 4-262 contains a unique tricyclo [4.4.4.04a8a]tetradecane framework, which could be obtained by a combination of an oxy-Cope, a Claisen and an ene reaction... 

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