Nazarov interrupted reactions

This reactivity proved to be a general process, providing the unique products in moderate yields following cyclopropanation and immediate treatment with silver tetrafluoroborate. These structures revealed that a cascade sequence was proceeding stereoselectively in every case to furnish a single product as the result of conrotatory 4jt electrocyclization, electrophilic aromatic substitution at the least hindered position on the arene moiety (para to the MeO) in favor of six-membered ring formation, and desilylation with protonation from the exo face of the bicyclic product. Dehydrochlorination to form a second cationic intermediate did not occur in this case, due to structural restrictions imposed by the bridged architecture of 81. 

The cascade sequences presented herein demonstrate unprecedented modes of reactivity in Nazarov chemistry that are initiated by the silver(I)-promoted ring opening of halocyclopropanes. The ease with which the gem-dichlorocyclopropanes can be prepared, the relatively mild reaction conditions, and the efficiency of these processes make these substrates attractive intermediates for an application in natural product synthesis. 

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A stereochemical study of the synthesis of unsaturated 1,4-aminoalcohols via the reaction of unsaturated 1,4-alkoxyalcohols with chorosulfonyl isocyanate revealed a competition between an retentive mechanism and an SnI racemization mechanism, with the latter having a greater proportion with systems where the carbocation intermediate is more stable.254 An interrupted Nazarov reaction was observed, in which a nonconjugated alkene held near the dienone nucleus undergoes intramolecular trapping of the Nazarov cyclopentenyl cation intermediate.255 Cholesterol couples to 6-chloropurine under the conditions of the Mitsunobu reaction the stereochemistry and structural diversity of the products indicate that a homoallylic carbocation derived from cholesterol is the key intermediate.256 l-Siloxy-l,5-diynes undergo a Brpnsted acid-promoted 5-endo-dig cyclization with a ketenium ion and a vinyl cation proposed as intermediates.257... 

Figure 4.9. Silver(I)-mediated interrupted Nazarov reactions.

In an effort to provide experimental evidence for the formation of a second oxyallyl cationic intermediate, a gem-dichlorocyclopropane substrate was envisaged with two internal nucleophiles one to participate in the initial interrupted Nazarov reaction, and the other to capture the second cationic species. Surprisingly, when the carefully designed substrate 80 was subjected to the optimized reaction conditions, an alternate mode of trapping occurred to generate the intriguing bridged bicyclic product 81 (Scheme 4.25). 

Zuev, D., Paquette, L. A. First examples of the interrupted Nazarov reaction. Chemtracts 1999, 12, 1019-1025. 

Nazarov cyclization (in presence of Ets SiH) and the interrupted Nazarov reaction (in presence of pendant olefin, eq 60). ... 

It should be pointed out that this reaction has been carried out photochemically (i.e., the photo-Nazarov cyclization Fi2) or under near-critical water conditions. More importantly, it has been improved to occur in a controllable fashion, through a directed Nazarov cyclization or an interrupted Nazarov reaction. It is worth noting that two practically directed Nazarov cyclizations have been developed, one by Denmark by using the jS-cation stabilizing effect and electrofuge of silicon (Scheme 2),2 > 2tt,6,i3 and the other from Ichikawa by application of a /3-cation destabilizing effect and the... 

Q -electron-donating effect of fluorine to control the regiochemistry (Scheme 3). Analogous to silicon, tin is also used to direct the Nazarov cyclization. " The interrupted Nazarov reaction has been developed by West et al. to extend the reaction of the cationic endocyclic intermediate with carbon nucleophiles. Furthermore, this reaction has been extended to imino-Nazarov cyclization of vinyl allenyl imine. ... 

A novel approach to the synthesis of bicyclic lactones via an interrupted Nazarov reaction of gcm-divinyl dihydrofurans. 

Grant, T. N., West, F. G. (2007). Interrupted Nazarov reactions using dichlorocyclo-propanes A novel mode of arene trapping. Organic Letters, 9,3789-3792. 

In 1998, the first deliberate attempt to trap the oxyallyl cation with a nucleophile during a thermal Nazarov reaction was reported by West and coworkers [23]. Coining the term interrupted Nazarov reaction, they described the interception of the oxyallyl intermediate of a Nazarov reaction by a tethered alkene (Scheme 3.20). Upon submission of divinyl ketones 87 to the LA, a conrotatory ring closure generates the oxyallyl cation intermediate 89. The alkene moiety adds selectively to the oxyallyl cation intermediate to form bicycle 90. The stabilized tertiary carbocation is then trapped by the enolate oxygen to give intermediate 91, which, under acidic aqueous conditions, is converted to the final hemiketal product 88. The reaction provides an efficient and stereoselective method to prepare tricychc compounds 88 in yields ranging from 42 to 89% [24]. 

Scheme 3.20 Stereoselective interrupted Nazarov reaction and trapping of the oxyallyl cation intermediate...

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