Tandem reactions 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]. 

Fig. 7.9 Electrocyclic tandem reaction as generated by RAIN. Rearrangement of a benzocyclobutane 8 into a isochromanone lTvia intermediate compounds 9 and 10.

The corresponding reaction of 2-alkenyl-3-alkadienyM-nitropyrrole 1156 also leads to 3-nitroindoles 1158 (21-90%) via intermediate 1157, however, now together with 3-nitrotetrahydroindole derivatives 1159 (Scheme 225) <1998T1913>. The latter compounds are formed by a tandem 6jt-electrocyclization-intramolecular Diels-Alder reaction, and are the predominant (or only) products when nitrobenzene is replaced by triglyme (70-78% yield). 

Three enantiomerically pure starting materials ensure remote stereochemical control Tandem iminium ion formation and vinyl silane cyclisation Part IV - Tandem Pericyclic Reactions Electrocyclic Formation of a Diene for Diels-Alder Reaction Tandem Ene Reactions Tandem [3,3]-Sigmatropic Rearrangements Tandem Aza-Diels-Alder and Aza-Ene Reactions... 

A tandem reaction sequence involving electrocyclization, azide capture, and Schmidt rearrangement is observed when certain cross-conjugated dienones and alkyl azides are treated with BE3 OEt2. ... 

Keywords 2-Bromoamlines, isothiocyanates, sodium azide, copper acetate, potassium phosphate, 1,10-phenanthroline, DMF, EtsN, room temperature, sequential three-component reaction, tandem addition, electrocyclization, IV-arylation, l-substituted-2-azido-l//-benzo [iflimidazoles... 

Tandem sequences involving Knoevenagel condensation followed by electrocyclization have not been employed as extensively as other tandem reactions (such as the tandem Knoevenagel-Diels-Alder reaction), but have been used in a few cases with great success, rapidly constructing complex polycyclic cores. 

Some reactions of particular interest are some examples of tandem reactions such as (i) the Stille coupling/elimination sequence with a 1,1-dibromo-l-alkene in the preparation of Callipeltoside [89] or (ii) the Stille coupling/electrocyclization cascade in the synthesis of immunosuppressants (Scheme 6.12) [90] or (iii) distan-nylated reagents such as 1,2-vinylditin and 1,4-dienyltin used in double Stille reaction sequences [91] and peculiar cascade reactions [92]. 

This multicomponent reaction was used by the same group to prepare a ring-expanded analogue 114 of the marine sesquiterpenoid frondosin B through a remarkable reaction cascade [102]. An unprecedented tandem 1,7-hydrogen shift, 8 7r-electrocyclization converting 112 to 113 was proposed to explain the formation of this ring-expanded species (Scheme 8.47). 

According to RAIN, only one reaction pathway namely the electrocyclic tandem reaction8— 9—-10—-11 leads from 8 to II under the conditions given below. 

The cyclobutene ring first opens in an electrocyclic reaction 152. This must be conrotatory as it is a four electron process but there is no stereochemistry at this stage. Then an intramolecular Diels-Alder cycloaddition 153 closes the new six-membered ring. This is a particularly favourable reaction as the formation of the alkene completes a benzene ring. It would not be possible to prepare such an unstable diene so a tandem process is necessary. 

In the case of monosubstituted cyclobutenone 31, the adduct with lithiovinylsuofone 32 was reported to undergo an extraordinarily facile tandem 47r-67T electrocyclic process (33 34) at - 78 °C to give cyclohexenone 36 [70]. The photochemical process may oblige the opposite direction on a hydroxyl group to be oriented inwardly actually cyanohydrin 37 was reported to give butenolide 39 as a result of an intramolecular addition reaction of (Z)-hydroxyvinylketene 38 [71] (Scheme 6). 

Fig. 3 Examples of quinazolines prepared by tandem aza-Wittig/electrocyclization, heterocyclization, three-component reaction...

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