Anion pericyclic reactions

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. 

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]. 

The novel [6+2] annulation approach developed by the Takeda group has also been included in a threefold anionic/pericyclic process (Scheme 2.149) [340]. The reaction leads to functionalized eight-membered rings 2-659 in a highly stereoselective manner, starting from acylsilanes 2-656 and 3-(trimethylsilyl)vinyl-lithium (2-657). After 1,2-addition and 1,2-Brook rearrangement, the cyclobutane 2-... 

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-... 

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]. 

An efficient and also elegant synthesis of the active anti-influenza A virus indole alkaloid hirsu-tine 67 is performed by an inter-intermolecular anionic-pericyclic three- component domino reaction followed by solvolysis and hydrogenation (scheme 13).[261 The synthetic sequence developed by us contains first a Knoevenagel condensation of enantiopure 61 and 62 with the formation of the... 

An elegant approach to polyquinanes has recently been described by Paquette et aL1281 By means of an anionic-pericyclic domino reaction four new C-C bonds are formed in one process. First, a two-fold addition of a vinyl lithium reagent, e.g. cyclopentyl lithium to diisopropyl squarate takes... 

An interesting pericyclic-anionic-pericyclic domino reaction showing a high stereoselectivity is the cycloaddition-aldol-retro-ene process depicted in scheme 20.1581 The procedure presumably starts with a [4+2]-cycloaddition of diene 98 and S02 in presence of a Lewis acid. After opening of the formed adduct reaction with (Z)-silyl vinyl ether 99 leads to a mixture of alk-2-enesulfinic acids 101. It follows a retro-ene reaction which affords a 7 3 mixture of the products 102 and 103. The reaction described by Vogel et al is a nice example for the efficient generation of polypropionate chains with the stereoselective formation of three stereogenic centers and one (0-double bond in a three-component domino reaction in its strict definition. 

Dithiolanes and 1,3-dithiolenes, formation in pericyclic reactions of alkenes and acetylenes with anions of dithiocarboxylic acids 91PS(58)255. 

Most of the reactions presented in previous chapters involved nucleophiles and electrophiles and occurred in several steps involving cationic, anionic, or, in the last chapter, radical intermediates. In this chapter a group of concerted (one-step) reactions, called pericyclic reactions, that involve none of these intermediates is discussed. The mechanisms of these reactions are exceedingly simple because they consist of a single step. Yet, as we shall see, pericyclic reactions are amazingly selective, both in terms of when they occur and also in their stereochemical requirements. 

Among ions, the opening of a cyclopropyl anion is exemplified by the reactions of the trans and cis aziridines 6.55 and 6.58, which are isoelectronic with the cyclopropyl anion. They open in the conrotatory sense to give the W- and sickle-shaped ylids 6.56 and 6.59, respectively, which are isoelectronic with the corresponding allyl anions. This step is an unfavourable equilibrium, which can be detected by the 1,3-dipolar cycloaddition of the ylids to dimethyl acetylenedicarboxylate, which takes place suprafacially on both components to give the cis and trans dihydropyrroles 6.57 and 6.60. The conrotatory closing of a pentadienyl cation can be followed in the NMR spectra of the ions 6.61 and 6.62, and the disrotatory closing of a pentadienyl anion can be seen in what is probably the oldest known pericyclic reaction, the formation of amarine 6.64 from the anion 6.63. 

There are, however, also many examples of mixed domino processes , such as the synthesis of daphnilactone (see Scheme 0.6), where two anionic processes are followed by two pericyclic reactions. As can be seen from the information in Table 0.1, by counting only two steps we have 64 categories, yet by including a further step the number increases to 512. However, many of these categories are not - or only scarcely - occupied. Therefore, only the first number of the different chapter correlates with our mechanistic classification. The second number only corresponds to a consecutive numbering to avoid empty chapters. Thus, for example in Chapters 4 and 6, which describe pericyclic and transition metal-catalyzed reactions, respectively, the second number corresponds to the frequency of the different processes. 

Besides the numerous examples of anionic/anionic processes, anionic/pericyclic domino reactions have become increasingly important and present the second largest group of anionically induced sequences. In contrast, there are only a few examples of anionic/radical, anionic/transition metal-mediated, as well as anionic/re-ductive or anionic/oxidative domino reactions. Anionic/photochemically induced and anionic/enzyme-mediated domino sequences have not been found in the literature during the past few decades. It should be noted that, as a consequence of our definition, anionic/cationic domino processes are not listed, as already stated for cationic/anionic domino processes. Thus, these reactions would require an oxidative and reductive step, respectively, which would be discussed under oxidative or reductive processes. 

One very fascinating domino reaction is the fivefold anionic/pericyclic sequence developed by Heathcock and coworkers for the total synthesis of alkaloids ofthe Daphniphyllum family [351], of which one example was presented in the Introduction. Another example is the synthesis of secodaphniphylline (2-692) [352]. As depicted in Scheme 2.154, a twofold condensation of methylamine with the dialdehyde 2-686 led to the formation of the dihydropyridinium ion 2-687 which underwent an intramolecular hetero-Diels-Alder reaction to give the unsaturated iminium ion 2-688. This cyclized, providing carbocation 2-689. Subsequent 1,5-hydride shift afforded the iminium ion 2-690 which, upon aqueous work-up, is hydrolyzed to give the final product 2-691 in a remarkable yield of about 75 %. In a similar way, dihydrosqualene dialdehyde was transformed into the corresponding polycyclic compound [353]. 

Although the synthetic utility of radical anion pericyclic processes is still to be explored, the recently disclosed intermediacy of radical anions in metathesis reactions with Grubb s catalyst [360] should ignite the search for further examples of this interesting class of reactions. 

Pericyclic Reactions of Anion Radicals General aspects of anion radical pericyclic additions... 

Perhaps the most interesting reaction of all of the possible anion radical pericyclic reactions, a Diels-Alder cycloaddition, has not been definitively exemplified, but one potential example of such a reaction has been proposed [127],... 

This section covers the formation of cyclopropanes via cyclization of reactive allylic intermediates (cations, anions, radicals). Included are those transformations of allylic functional derivatives (e.g. allylic halides, alcohols, aldehydes, ketones, acids, esters, boronates, Grignard reagents) to cyclopropyl derivatives that do not actually proceed via allylic reactive intermediates, but which are not covered by other sections of this volume. Additionally, this section will cover methods for the formation of cyclopropanes by pericyclic reactions. 

The oxy-Cope rearrangement can be thermally induced (equation 223, path a) but this process competes with an other well-established, concerted pericyclic reaction, i.e. the /1-hydroxyolefin retro-ene cleavage (path h)-- -. However, it was found that the oxy-Cope rearrangement can be accelerated under base-catalysis conditions (e.g. in the presence of potassium alkoxides) by a factor of I O - (the so-called anionic oxy-Cope rearrangement , path This base-induced acceleration is attributable to a dramatic decrease in the... 

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