Cyclization/fragmentation

Comparable cyclization-fragmentation sequences have been developed for acyclic and heterocyclic systems. 

Scheme 3.19. Domino radical cyclization/fragmentation procedure in the synthesis of...

Scheme 3.79. Domino radical cyclization/fragmentation/electrocyclization for the synthesis of a dihydroindene.

This annulation has invariably been made by reaction of 3-amino-1,2,4-triazole derivatives with three-carbon cyclizing fragments. The three-carbon fragments may be incorporated in one step or in two consecutive steps as schematically represented in Schemes 26 and 27, respectively. 

It is highly probable that most of the conformational exploration of the BR s occurs while they are triplets. Ultimately, the triplets will convert to singlets which probably react (by cyclization, fragmentation, or reverse hydrogen transfer to the parent molecule) before significant conformational change occurs. 

M. E. Jung and S. W. T. Choe, Stereospecific intramolecular formyl transfer via radical cyclization-fragmentation—preparation of alkyl 2-deoxy-2-ot-formylglucopyranosides and similar compounds, Tetrahedron Lett. 34 6247 (1993). 

Pattenden and Schulz have reported that treatment of the acetylene derivative 43 with (TMS)3SiH leads, in one pot, to the bicyclic compound 44 in 70% yield (equation 71)". The proposed mechanism involves (TMS)3Si radical addition to the triple bond to form a vinyl radical followed by a remarkable cascade of radical cyclization-fragmentation-transannulation-ring expansion and termination via ejection of the (TMS Si radical to afford the bicyclic product. 

Schell and coworkers have reported the cyclization-fragmentation chemistry of related vinylogous imides as a function of tether length (Scheme 14)32. Irradiation of the vinylogous imide 50 produced the crossed photoadduct 51, in which the iV-acetyl group... 

The same workers reported the application of this cyclization-fragmentation sequence to substrates 79 and 81, which led to the formation of retro-Mannich fragmentation products 80 and 82, respectively, in good yield (Scheme 19)40. 

Treatment of the ketenethioacetals 100 with BusSnH under radical forming conditions (AIBN, PhH, reflux) directly affords benzothiophene 101. The reaction involves a radical centered tandem cyclization-fragmentation sequence (Scheme 23) <1995TL2861>. 

A laser flash study of the photoreactions of hexan-2-one and 5-methylhexan-2-one has provided evidence for the existence of the triplet 1,4-biradicals produced by the y-hydrogen abstraction typical of Norrish Type II reactivity. The photochemical behaviour of the alkanone, nonan-5-one, in urea inclusion compounds has been studied. In solution, irradiation of nonan-5-one yields hexan-2-one, propylene, and two cyclobutanols. In the clathrate, the fragmentation products were essentially the same but only one cyclobutanol was observed. The cyclization fragmentation ratio was established as 0.67, compared with 0.32 in methanol. The authors suggest that the CIS-cyclobutanol has less stringent rotational requirements and that it is this isomer (43) which is formed in the clathrate. 

The mitomycins (191) have attracted much attention as a result of their interesting structure and potent anticancer properties [43]. One approach to these materials is illustrated in Eq. 36 [44]. A key intermediate in the implementation of this plan is azocinone (193), a substance that proved accessible in high yield via the novel mediated A-tosyl group cleavage-cyclization-fragmentation of 194. Here, ascorbic acid behaves as a proton donor and a reductant in combination with anthracene (Scheme 17). 

Ring expansions of methylenecyclobutanes through a cyclization-fragmentation sequence is similar to previously discussed ring expansion of cyclobutanones (see Scheme 10) [16]. Compared to its ketone counterpart, the alkene system gives higher yields of ring expansion products (Scheme 22) [29]. 

Our own efforts began with failure. Inspired by the radical addition-atom transfer-cyclization-fragmentation sequence reported by Heiba (Eq. 1) [5], we attempted the... 

Danishefsky and Panek have reported a synthesis of an erythrina alkaloid that revolves around a cyclization-fragmentation sequence to establish the B-ring while retaining useful functionality in the A-ring (Eq. 21) [46]. Thus, ff-amino selenide 70 (10 steps from A-Boc-3,4-dimethyoxy-2-phenethylamine) was treated with TBTH to give enol acetate 71 in 65% yield. A simple oxidation sequence completed the synthesis of 3-demethoxyerythratidinone. 

A sequence consisting of three steps, i.e. radical cyclization/fragmentation/ electrocyclization, recently reported by Parsons [75], allows for the construction of a fused ring system in one synthetic operation starting from an appropriately substituted furan. 

On elaboration of l,5-hexadiene-3,4-diol through a 1,3-dioxolane derivative, the RCM delivers a precursor of either exo-brevicomin or endo-brevicomin. A route to (+)-malyngolide also exploits the RCM process. A successful cyclization-fragmentation approach to medium-sized rings is based on the RCM reaction of 2-hydroxycycloalkanones that are substituted with proper alkenyl groups at both a- and a -positions.- ... 

A process involving cyclization-fragmentation of 2-(( )-bromoalkyl)-l,l-dicyanocy-clopropanes is a radical alternative to the Thorpe-Ziegler reaction of dinitriles. Thus,... 

An extremely interesting example of cascade radical reactions has been reported recently <93TL5653>. The initial radical generation from the 3-bromothiophene (565) is brought about by tributyltin hydride. This is then followed by cyclization, fragmentation, recyclization by the 5-exotrig mode and a final fragmentation. After all this, the product (566) is obtained in 74% yield (Scheme 120). 

Treatment of the ketenethioacetals (73) with BujSnH under radical forming conditions (AIBN, PhH, reflux) directly affords thiophenes (79) and/or (80) (Scheme 21) <93TL5653>. The reaction involves a radical centered tandem cyclization-fragmentation sequence for example, cyclization (74)- (75), fragmentation (75)- (76), cyclization (76)- (77), fragmentation (77)- (79). Application of this procedure to some other annelated thiophenes was also described. 

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