Nazarov cyclisation

Cyclopenta-l,4-dioxanes 95 are formed in high yields through the acid-catalysed rearrangement of the dioxolanes 94 in which electrocyclisation of a hydroxypentadienyl carbocation, akin to a Nazarov cyclisation, is involved (Scheme 62) <00CEJ4021>. 

The Robinson annelation is by no means the only ionic reaction that makes six-membered rings. Six-membered rings form easily so trapping a Nazarov intermediate (chapter 35) makes good sense. The Friedel-Crafts-like disconnection 18 suggests a most unlikely cation 19 until we realise that it would be formed in the Nazarov cyclisation of the dienone 20 whose synthesis is discussed in the workbook. 

These container molecules exhibit large openings on each triangle face. That is why different exchange processes can potentially take place. In the literature various applications are described such as encapsulation of neutral molecules or cations [44-74]. Reactive or unstable species could also be stabilised [63, 67, 75-78]. The cages can serve as a catalyst, e.g. for the Aza Cope rearrangement [54, 66, 79-81] and for the hydrolysis of several compounds [82-85]. They have also been used for C-H bond activation [54, 57, 61, 66, 69] or Nazarov cyclisation [86],... 

Both a base and an Ir catalyst 6 are necessary to effect diastereoselective sequential Nazarov cyclisation and Michael addition between a pyran-based alkylidene (3-ketoester and a nitrostyrene. The reaction is diastereoselective, leading to substituted cyclopenta[b]pyrans with three stereocentres <06JA5312>. 

The cyclopenta[c]pyran system 6 is formed when allenyl propynyl ethers are heated in CO in the presence of Co/Rh nanoparticles a Pauson-Khand reaction is involved <07SL453>. An enantioselective Bronsted acid-catalysed Nazarov cyclisation of a dihydropyran-based divinylketone affords cyclopenta[/>]pyrans 7 <07AG(E)2097> and Sc and In triflates catalyse a similar reaction of 6-alkenoyl derivatives of both dihydropyran and thiopyran <07S1733>. 

A Nazarov cyclisation of l-(3,4-dihydro-2//-pyran-6-yl)-3-phenylpropenones affords cyclopenta[Z)]pyranones (Scheme 9) <03OL4931> and the conjugated ethoxytriene 7 derived from tetrahydropyran-2-one also yields a fused cyclopentenone <03JOC9728>. 

The photo-Nazarov cyclisation of l-cyclohexenyl phenyl ketone (285) yields the hexahydrofluorenone (286). Schaffner s group has examined the mechanism of this reaction and have found evidence for some novel intermediates. They propose that the excited state of (285) decays by cis-trans isomerisation of the cyclohexenyl double bond the tx-ans-cyclohexenyl derivative (287) cyclises to the oxallyl species (288) which collapses to the relatively stable enol (289) or reacts with accumulated (289) to give the isolable enol dimer (290). When the ketone derived from (290) is photolysed it gives back (289) along with (286). The enol (290) and its corresponding ketone were both isolated and characterised, while (287) and (288) were trappable with cyclopentadiene. The enol (289) was observable by H-NMR before it ketonised and gave the isolated product (286). 

Oppolzer,18 who wanted this cyclopentenone for the synthesis of modhephene 75 followed this strategy and found that the Friedel-Crafts went well with A1C13 as catalyst and the Nazarov cyclisation with another Lewis acid, SnCl4. You will notice the position of the double bond in the final product there are no protons on one side of the cation 73 so one must be lost from the other side. In cases where there is a choice, the more substituted alkene results, as here. The product is ideally functionalised for development into modhephene 75. 

Another silicon-assisted kind of torquoselectivity is in the allylsilane-type of Nazarov cyclisation. Now there is chirality, and there is a high level of torquoselectivity in the sense shown by the allylsilane 6.507, determined by the chirality.957... 

Phosphorodithioic adds have been prepared according to an improved synthesis of 3,3 -disubstituted BINOL derivatives (226-231). In preliminary experiments, these new Bronsted adds were tested as organocatalysts in three reactions. They promoted the Nazarov cyclisation with mixed selec-tivities, the Mannich reaction with good enantioselectivity and they catalyzed efficiently the alkylation of iV-acyliminium with enol silyl ether. ... 

One of the first industrial muscone syntheses stems from work at BASF. [182] Analogous to the synthesis of exaltone, cyclododecanone is converted, by reaction with but-3-yn-2-ol, into a diol, which is further transformed by a Meyer-Schuster rearrangement and Nazarov cyclisation into a methyl-substituted bicycle. A very short route to the same product was described by Mitsui Petrochemical Industries a few years later this involved the direct conversion of cy-clododecene with crotonic acid in the presence of polyphosphoric acid, and resulted in a remarkable yield of 54 %. [183]... 

A catal34ic asymmetric Nazarov cyclisation of fully-substituted die-nones (297) that provided cyclopentenone derivatives (298) with vicinal quaternary stereocenters in high optical purity and as single diastereo-isomers, has been carried out in the presence ofiV-triflyl phosphoramide (299) (Scheme 80). ... 

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