Tandem pericyclic

Tandem pericyclic processes offer the opportunity to synthesize complex highly substituted cyclic molecules in a completely stereocontrolled fashion in a few consecutive steps. As a consequence, tandem processes have been studied extensively. Some tandem processes involving Diels-Alder reactions have recently been reviewed38,40,107. 

Tandem pericyclic reactions are a powerful strategy for construction of complex, polycyclic compounds. In recent years tandem [4 + 2]/[3 + 2] chemistry of nitro-alkenes and nitronates has been developed by Denmark et al. as a general approach to functionalized pyrrolidine-containing structures [118]. Within the subclass of inter [4 -I- 2]/intra [3 + 2] cycloadditions, they have documented the fused mode (/3-tether, Eq. 77), spiro mode (a-tether, Eq. 78), and bridged mode (a-tether, Eq. 79 or /3-tether, Eq. 80) constructions. These are highly stereoselective processes in the presence of Lewis acid such as SnCU and are amenable to asymmetric modification by use of chiral vinyl ethers. Finally, the nitroso acetals are readily transformed, by hydroge-nolysis, into polycyclic, a-hydroxypyrrolidinones, 4-aminocyclohexanones, and cyclo-pentylamines. 

The retrosynthesis of Aara-e-viniferin (445) by Thomas et al. indicated that the y-butyrolactone (823) was a key intermediate, which later converted from the corresponding stilbene by manganese triacetate-mediated oxidative lactonization (Scheme 18) [407]. In subsequent papers, they described the FeCb-promoted tandem pericyclic synthesis of catechol analogs of restrytisol C. 3,4-Dimethoxy-12-acetoxy stilbene (824), which was synthesized by Heck coupling, was treated with FeCb to give the unnatural stilbene dimers 585 and 586 (Scheme 19) [288]. 

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... 

The following transformations involve two or more pericyclic reactions occurring in tandem during the process. Suggest a plausible sequence of reactions that can lead to the observed product. 

In a series of publications over the past few years, the group of Barriault has reported on microwave-assisted tandem oxy-Cope/Claisen/ene and closely related reactions [175-178], These pericyclic transformations typically proceed in a highly stereoselective fashion and can be exploited for the synthesis of complex natural products possessing decalin skeletons, such as the abietane diterpene wiedamannic... 

A remarkable example is the combination of three pericyclic reactions for the synthesis of decalin frameworks with quaternary centers by a tandem oxy-Cope-ene-Claisen reaction shown in 163 [539] (Scheme 1.72). 

It has been established that the course of the sequential pericyclic reaction of cyclopentadienones with acyclic conjugated alkadienes depends on the reaction temperature, thermal treatment at low temperatures affording 3a,4,7,7a-tetrahydroinden-l-one derivatives by way of a Cope rearrangement (see Scheme 38). Roman et al have developed an efficient stereoselective synthesis of enantiomerically pure i-nitrotricyclo[5.2.2.0 ]undeca-3,8-dienes via a tandem consecutive asymmetric Diels-Alder-Cope rearrangement (see Scheme 39). Adducts... 

Norrish reaction Pericyclic elimination Tandem cationic cyclization Bergmann cycloaromatization... 

It is less common to find two pericyclic reactions of the same kind coupled together but the Alder ene reaction and the oxo ene reaction can both be catalysed by Lewis acids under the same conditions. A simple example is the combination of the exocyclic alkene 157 with acrolein. The intermediate unsaturated aldehyde 158 cyclises stereoselectively to form a new carbocyclic ring 159. The intermediate 158 is perfectly stable so the tandem sequence is convenient rather than necessary.22... 

We left compound 35 as the product of a tandem conjugate addition/alkylation and promised further chemistry later in the chapter. In fact, 35 was used in another more remarkable tandem sequence involving two pericyclic reactions and the creation of a polycyclic Daphniphyllum alkaloid. The first few steps are straightforward and give diol 173 in good yield.8... 

As we move from pericyclic reactions to other processes, we can consider a tandem metallation route to the same basic skeleton, that of ellipticine 205, the basis of some important drugs. The selectivity problem here is to relate the position of the two nitrogen atoms. 

According to DFT calculations, the mechanism of this reaction is stepwise [73] and consists of a tandem [2+2] cycloaddition-cycloreversion sequence (Scheme 2.2). Both processes take place via supra-supra mechanisms that are thermally allowed because of the interplay between tt fx and lone pair localized orbitals. The corresponding transition structures TSl and TS2 are nonaromatic as indicated by the low negative values of the nucleus-independent chemical shifts (NICS), thus discarding true pericyclic processes [74,75]. In one special case, a highly hindered 1,3,2-/l -oxaphosphazetidine INT (Scheme 2.2) reaction intermediate was charac-... 

J.B. Feltenberger, R. Hayashl, Y. Tang, E.S.C. Babiash, R.P. Hsung, Enamide-benzyne-[2-H2] cycloaddilion stereoselective tandem [2+2]-pericyclic ring-opening-intramolecular N-Tethered [4+2] cycloadditions, Org. Lett. 11 (2009) 3666-3669. 

The overall result of this process is the formation of two new CT-bonds in addition to the generation of a new stereocaiter adjacent to the heteroatom, thereby constituting a tandem anionic—pericyclic ring-closure sequence. It can be considered formally an equivalent of a [3+3] cycloaddition in which the three carbons of aldehyde 2 have been added to the two carbons and one oxygen atom of pyrone 1 [3a,b,4,13,14]. The term [3+3] cycloaddition was adapted by us from Seebach s work describing a Stork-type carbo-[3+3] cycloaddition reaction between nitroalkenes and enamines [14]. 

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