Anionic domino processes

Anionic domino processes are the most often encountered domino reactions in the chemical literature. The well-known Robinson annulation, double Michael reaction, Pictet-Spengler cyclization, reductive amination, etc., all fall into this category. The primary step in this process is the attack of either an anion (e. g., a carban-ion, an enolate, or an alkoxide) or a pseudo anion as an uncharged nucleophile (e. g., an amine, or an alcohol) onto an electrophilic center. A bond formation takes place with the creation of a new real or pseudo-anionic functionality, which can undergo further transformations. The sequence can then be terminated either by the addition of a proton or by the elimination of an X group. 

Besides the numerous examples of anionic/anionic processes, anionic/pericydic 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. 

The group of Molina and Fresneda employed even two different types of anionic domino processes in their total synthesis of the novel marine alkaloid variolin B (2-295) (Scheme 2.67) [150]. It is generally accepted that marine organisms are among... 

In the following section, anionic/anionic domino processes will be discussed which are, to date, much less common, although important structural elements may... 

Taylor and coworkers also developed similar twofold intramolecular Li-mediated carboadditions [193]. In contrast to the aforementioned sequences, they were able to utilize functionalized triple bonds and to trap the intermediate lithiated species such as 2-352 with other electrophiles besides a proton. Such a 2.2.2 process will be discussed in the following section, which relates to threefold anionic domino processes. 

Leaving the (retro-)aldol addition-initiated threefold anionic domino processes, we are now describing sequences which are initiated by a SN-type transformation. In particular, domino reactions based on SN/1,4-Brook rearrangement/SN reactions are well known. For example, the group of Schaumann obtained functionalized cyclopentanols of type 2-461 by addition of lithiated silyldithioacetals 2-458 to epoxy-homoallyl tosylates 2-459 in 41-75% yield (Scheme 2.106) [248]. 

The following example completes the section of threefold anionic domino processes initiated by a SN-type reaction. As discussed earlier in Section 2.2, the reaction of a five-membered cyclic phosphonium ylide with enones, a, 3-unsaturated esters, and a, 3-unsaturated thioesters provides cycloheptene or hydroazulene derivatives in a domino Michael/intramolecular Wittig reaction. This sequence... 

The final group of threefold anionic domino processes described here includes transformations with an initiating elimination step which is either followed by two Michael additions or by substitutions. Thus, reaction of protected nitro alcohol 2-... 

A fourfold anionic domino process consistingofadominoMichael/aldol/Michael/ aldol process was used by Koo and coworkers for the synthesis of bicyclo[3.3.1]non-anes. They employed 2 equiv. of inexpensive ethyl acetoacetate and 1 equiv. of a simple a, 3-unsaturated aldehyde [290]. Differently substituted dihydroquinolines were assembled in a Michael/aldol/elimination/Friedel-Crafts-type alkylation protocol by the Wessel group [291]. An impressive approach in this field, namely the construction of the indole moiety 2-557, which represents the middle core of the man-zamines, has been published by Marko and coworkers [292]. Manzamine A (2-555) and B (2-556) are members of this unique family of indole alkaloids which were isolated from sponges of the genus Haliclona and Pelina (Scheme 2.126) [293]. 

Another elimination triggered tetrafold anionic domino process has been reported by Risch and coworkers [301]. These authors synthesized polycyclic bipyridine scaffolds as 2-585 (Scheme 2.132) which are potentially useful as ligands for host-guest systems or interesting building blocks for supramolecular applications [302]. The process combines an amine elimination from 2-584 and a Michael addi-... 

As the last example of a fourfold anionic domino process, the synthesis of a new analogue 2-592 of the antibacterially active quinoline derivative A-57,207 (2-593) [304] by the group of Kim will be described (Scheme 2.134) [305]. 

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-... 

Oxidative or Reductive/Anionic/Anionic Domino Processes... 

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