Cycloaddition Events

It is instructive to note that the intramolecular [2+2] cycloaddition process should benefit from the presence of the cis C1-C2 double bond in 14. Indeed, the cis C1-C2 double bond is expected to facilitate the key [2+2] cycloaddition event by bringing into proximity the reactive ketene moiety and the C5-C6 olefin and by... 

Formation of the ester cyclization precursor 92 was readily achieved as a 1 1 mixture of diastereoisomers and, upon irradiation, afforded a 1 1 mixture of cyclobutanes 93 differing only in the stereochemistry of the silyloxy substituent. The tether had therefore controlled both the regio- and stereoselectivity of the cycloaddition event. Subsequent manipulations afforded the desired natural product (Scheme 10-30). 

The reaction is surmised to occur via the formation of an enamine intermediate, followed by azide addition to generate a zwitterionic intermediate primed for the 1,3-dipolar-cycloaddition event (Scheme 5.46). Syn-elimination regenerates the catalyst, where proline s carhojg late group plays an important role in the elimination step, driven hy rearomatisation of the triazole product. 

Especially when combining two or more pericyclic reactions with each other, the outcome is highly efficient and could be almost qualified as miraculous, as each cycloaddition event could introduce a new ring, two new covalent bonds, and up to four new contiguous asymmetric centers in one step. Moreover, great progress has been achieved in the intramolecular and asymmetric pericyclic reactions recently, which provide highly effective approaches for the rapid elaboration of complex polycyclic systems. Some prominent total syntheses achieved based on pericyclic MBFTs will be exemplified below. 

Thermal or Ni(0)-catalyzed [2+2] cyclodimerization reactions of higher [ ]cumulenes give access to radialenes bearing cumulenic ir-systems ( extended radialenes, compare Scheme 4.13, Section 4.2.2, and Chapter 9). However, the success and the regioselectivity of the cycloaddition event depend strongly on the steric demand of the substituents at both ends of the cumulene [7, 8, 51]. Thus, a thermally induced cyclodimerization of a [4]cumulene furnished radialene 77... 

The tandem intermolecular-[4 + 2]/intermolecular-[3 + 2] cycloadditions create bicyclic nitroso acetals with up to six stereogenic centers in a predictable fashion (Scheme 16.53). Because both cycloadditions are usually conceited and the geometry of the components is preserved, the relationship between those substituents in the nitroso acetal will also be preserved. For example, in Scheme 16.53 the substituents A and B, as well as E and F in nitroso acetal 237 will take up a cis relationship to each other. However, the relationships B/C, C/D, and D/E are established by the topicity of the cycloaddition events as described below. Upon hydrogenol-ysis, those stereocenters in product 239 are also preserved unless further reactions follow, the most important of which is the loss of the C(6) stereogenic center during reductive alkylation when substituent F is an alkoxy group. 

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