Oxyallyl cation intermediate

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). 

If a suitable (1,3-di-f-butyl) allene is epoxidized with m-CPBA the unstable allene oxide can actually be isolated. On heating, this epoxide gives a stable fra s-di-f-butylcycl6propanone. It is very difficult to see how this reaction could happen except via the oxyallyl cation intermediate. 

While cyclopropanone has been shown to possess the closed structure by microwave spectroscopy, many of its reactions appear to proceed by way of the zwitterionic oxyallyl cation intermediate C. The addition of 2,2-dimethylcyclopropanone to furan is analogous to the [4+2]-cycloaddition just described, and yields a product consistent with this rationalization ... 

It is worth noting that the putative occurrence of an ojq allylic cation (or its protonated form) in the Favorskii process has broad implications beyond the rearrangement itself. For exanple, oxyallylic cation intermediates are important players in several other reactions, such as the synthetically valuable (4+3)-cycloaddition reaction. 

A one-step Lewis acid-catalysed intermolecular 4- -3-cycloaddition of aromatic a,)3-unsaturated aldehyde and ketones (105) with epoxides (106) formed seven-membered oxacycles (107) under mild conditions (Scheme 34).The effect of oxygen-, sulfur-, and halogen-substituents on the reactivity of nitrogen-stabilized oxyallyl cations in 4- -3-cycloaddition reactions has been extensively investigated. Aza-oxyallyl cationic intermediates react with cyclopentadiene and furan via an aza-4 -I- 3-cycloaddition reaction to form bicyclic cycloadducts in moderate yields. The intramolecular formal 4- -4-cycloaddition of conjugated enynes with an e-deflcient cyclobutene (108) yielded a strained six-membered cyclic allene (109) that isomerized to a 1,3-cyclohexadiene (110). This intermediate underwent a thermal or acid-promoted six-electron electrocyclic ring opening to yield a 2,4,6-cyclooctatrienone (111) (Scheme 35). ... 

It was observed that enones 6, possessing an electron-donating group (EDG) at the a-position, undergo facile Nazarov cyclization in the presence of an LA or Bronsted acid (Scheme 3.3). To rationalize this peculiar reactivity, one can suggest the EDG increases the electron density at the terminal carbon of the pentadienyl cation 7. As a result, it lowers the activation barrier for the cyclization. In addition, the EDG stabilizes the oxyallyl cation intermediate 8 and leads to highly regiose-lective ehmination. 

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...

Prior to these reports, a-haloketones had been used directly in [4+3] cycloadditions to generate oxyallyl cation intermediates in situ, via enolate formation under basic conditions or reducing conditions (Scheme 18.7) [5,16]. Under these conditions, the precise counterion and its... 

Jeffrey CS, Barnes KL, Eickhoff JA, Carson CR. Generation of aza-oxyallyl cationic intermediates aza [4+3] cycloaddition reactions for heterocycle synthesis. J. Am. Chem. Soc. 2011 133 7688-7691. 

The Ga(III)-catalysed three-component 4 -I- 3-cycloaddition reactions of indoles (128), ketones (129), and cyclohexadienes (130) produced cyclohepta[h]indole derivatives (131) in a single step at room temperature (Scheme 40). The 4-i-3-cycloaddition reactions of pyrroles with stabilized 2-(silyloxy)allyl cations formed tropinones in high yields (85%)4 The intramolecular 4-t-3-cycloaddition reaction of diaza-oxyallyl cationic intermediates and cyclic dienes yielded bicyclic ureas in good to excellent yields. ... 

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