Cycloaddition/rearrangement sequence

Dipolar cycloaddition occurred preferentially at the electron-rich double bond of 22 to give the unstable triazoline 23, which on thermolysis led to extrusion of nitrogen and rearrangement to give the cyclopentenoid compound 25. The 1,3-dipolar cycloaddition-rearrangement sequence was subsequently extended to ultrasonic conditions. 

J(P1)2797>. A similar cycloaddition-rearrangement sequence accounted for the formation of oxazolo[4,5-r/ [l,2,3]tri-azoles 203 as side products from the reaction between triazolium imides 201 and N-substituted benzaldimines, leading to the imidazo[4,5-t/ [l,2,3]triazole 204 (Equation 23) (see Section 10.05.10.3). The oxazolotriazoles 203 were presumed to arise as a consequence of hydrolysis of the imine to the parent aldehydes under the reaction conditions <2003ARK110>. 

Padwa A, Dimitroff M, Liu B (2000) Formal Synthesis of ( )-Dendrobine Use of the Amidofuran Cycloaddition/Rearrangement Sequence. Org Lett 2 3233... 

The synthetic merits of the cycloaddition-rearrangement sequence in the construction of multi-ring frameworks are further illustrated by a concise... 

In addition to the formation of the pyridine framework by de novo approaches (see section 8.1) or by the cycloaddition/cycloreversion sequence (see section 8.2), one can employ reactions that proceed through a rearrangement pathway. The Boekelheide reaction (see section 8.3.1) involves the rearrangement of an existing pyridine skeleton to a more functionalized scaffold, while the Ciamician-Dennstedt reaction (section 8.3.2) generates the pyridine nucleus by rearrangement of an alternative heterocycle. 

Scheme 1. Isomeric product distribution resulting from [3 + 2] cycloaddition of diazomethane or a substituted azide to C70, and extrusion-rearrangement sequence to the respective 6-6 closed or 6-5 open structures...

Boonsombat J, Zhang H et al (2008) A general synthetic entry to the pentacyclic strychnos alkaloid family, using a [4 + 2]-cycloaddition/rearrangement cascade sequence. J Org Chem 73 3539-3550... 

Scheme 7.40 Formal synthesis of spatol via a (4+3)-cycloaddition/quasi-Favorskii rearrangement sequence.

SCHEME 5.6. Microwave-assisted diastereoselective synthesis of a 4-spiro-pyrazolidin-3-one via a hydrazone formation/Wolff rearrangement/l,2-hydrogen shift/l,3-dipolar cycloaddition domino sequence. 

Adducts derived from cyclopropyl-TMM reactions are versatile synthetic intermediates. Alkylidenecyclopropanes have been proven useful in further Pd-cata-lyzed transformations [4], On the other hand, vinylcyclopropanes can undergo smooth thermal ring-expansion to cyclopentenes. Thus, a total synthesis of 11-hy-droxyjasionone (27) was achieved with the cyclopropyl-TMM cycloaddition as the crucial step, and the thermal rearrangement of the initial adduct (28) as an entry to the bicyclo[6.3.0]undecyl compound (29), a key intermediate in the synthetic sequence (Scheme 2.9) [19]. 

Subsequent, investigation showed that with prolonged reaction times the initially formed cycloadduct 22a then underwent [2+4+]-polar cycloaddition followed by a sequence of rearrangements to afford a novel benzo-fused tricyclic compound 42 (see Equation 11) <1996CC2185>. Various experiments were conducted in order to elucidate the mechanism of the formation of 42. 

The reaction of 1,2,3-triazolium-l-aminides 3 with propiolate esters led to fluorescent 2,5-dihydro-1,2,3-triazine derivatives 4 in one pot, involving a Huisgen cycloaddition followed by a sequence of rearrangements <06JOC5679 06TL1721>. These reactions can be carried out in acetone, in water, or under solvent-free conditions. 

Treatment of the propargylic alcohol 144, readily prepared from condensation between benzophenone (143) and the lithium acetylide 101, with thionyl chloride promoted a sequence of reactions with an initial formation of the chlorosulfite 145 followed by an SNi reaction to produce in situ the chlorinated and the benzannulated enyne-allene 146 (Scheme 20.30) [62], A spontaneous Schmittel cyclization then generated the biradical 147, which in turn underwent a radical-radical coupling to form the formal [4+ 2]-cycloaddition product 148 and subsequently, after a prototropic rearrangement, 149. The chloride 149 is prone to hydrolysis to give the corresponding 11 H-bcnzo h fluoren-ll-ol 150 in 85% overall yield from 144. Several other llff-benzo[fc]fluoren-ll-ols were likewise synthesized from benzophenone derivatives. 

Asymmetric induction is possible in the two-step [3-1-2] cycloaddition by starting the sequence with an asymmetric cyclopropanation (Scheme 14.15) [106]. The Rh2(S-DOSP)4-catalyzed reactions gave the desired vinylcyclopropanes 126 with high enan-tioselectivities [106]. Partial or complete racemization occurred in the vinylcyclopro-pane rearrangement of monocyclic vinylcyclopropanes, but the fused vinylcyclopropanes 128-133 rearrange to form 134-139 with virtually no racemization. 

In mechanistic terms, the most important of these processes involve either a ring open-ing/ring closure sequence, most commonly of the ANRORC type, or a cycloaddition reaction followed by decomposition/rearrangement of the cycloadduct. 

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