Cycloaddition/cycloreversion reactions

Snyder and coworkers followed a completely different path to canthin-6-one (Fig. 23). Earlier they had shown that indole-substituted 1,24-triazine 66 could be heated in refluxing triisopropylbenzene (bp = 232 °C) to give /3-carboline 67 via an intramolecular cycloaddition/cycloreversion reaction [58]. Selective oxidation of 67 at C-6 was achieved through the use of triethylbenzylammonium permanganate [59]. Success of the reaction proved to be very sensitive to the solvent chosen. Heating 67 for 4 h at 70 °C in a 5 1 mixture of dichloromethane and acetic acid gave a 65% yield of 63, yet use of increasing amounts of dichloromethane slowed the reaction down (no reaction occurred in pure dichloromethane), while use of pure acetic acid led to an intractable mixture. 

DIFFERENT STAGES OF CYCLOADDITION/CYCLOREVERSION REACTIONS WITHIN CONFINED ENVIRONMENTS... 

Tetrazines are utilized as the key reagents (dipolarophiles) in synthetically useful cycloaddition-cycloreversion reactions. In such cases, the tetrazine first undergoes a [4+2] cycloaddition to the isolated double bond of a suitable Diels-Alder adduct. The so-formed dihydropyridazine intermediate undergoes aromatization via elimination of the pyridazine system. An example of a tetrazine-based cycloaddition-cycloreversion reaction cascade is the application... 

Synthesis of Trifluoromethyl Pyrroles by [4-I-2] Cycloaddition Cycloreversion Reactions... 

Dipolar cycloaddition—cycloreversion reactions involving iso-miinchnones sometimes lead to the formation of substituted 3-pyrrolin-2-ones as minor by-products (1994JOC2447, 1994TL7159, 1996T3247, 1998BMC1273). 

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. 

An interesting perspective for synthesis is offered by the reaction sequence cycloaddition/cycloreversion. It often does not lead to the initial reactants, but to a different pair of dipole and dipolarophile instead ... 

A similar transformation occurs as a critical step in the total synthesis of (+)-estrone by a Diels-Alder cycloaddition-cycloreversion pathway (Eq. 80).227 It is worth noting that in this reaction the conjugated double bond is stereoselectively reduced while both an isolated double bond and a ketone carbonyl are preserved. 

Many cycloadditions of nitrones86,172 174 and thiones give cycloaddition-cycloreversion equilibria. A-Methyl-C,C-diphenyl- and A-methyl-C-phenyl-nitrones, react with aliphatic thiones forming 1,4,2-oxathiazolidines, while 4 does not afford a cycloadduct.172 A-Methyl-C,C-2,2,4,4-tetramethyl-3-cyclo-butanonenitrone reacts with alicyclic thioketones to give 1,4,2-oxathiazolidines,174 while with 4 it enters into a metathesis reaction. 

Examples of sequential [2 + 2] cycloaddition and [2 + 2] cycloreversion reactions leading to the formation of stable carbene complexes are sketched in Figure 3.30. 

The consistently low yields in the cycloaddition of aryl azides to certain enamines have been attributed to an unfavorable equilibrium between cycloaddition and cycloreversion reactions.232 The reversibility of the cycloaddition has been demonstrated on the basis of spectroscopic (Section III) and chemical evidence (Scheme 55). The conditions for cycloaddition and cycloreversion have been examined, using MO calculations.72... 

Although the 1,4,2-oxathiazolidine derivatives 16 (X = O Y = S) are usually nonisolable intermediates of reactions between nitrones and thiocarbonyl compounds, in some instances a cycloaddition/cycloreversion equilibrium is established with steric hindrance influencing its position. This is the case for the kinetically stable... 

As an alternative to [3+2] cycloaddition, product 191 (X = Se) can be prepared in 90% yield using a [4+2] cycloreversion reaction of the six-membered heterocycle 206 in the presence of mesitonitrile oxide (Equation 22) <1999JA8811>. 

Selenoacylamidines also take part in Diels-Alder reactions yielding 4W-selenopyrans through a cycloaddition-cycloreversion-cycloaddition sequence (95TL237). 5,6-Dihydro-27/-selenopyrans have also been obtained by hetero-Diels-Alder protocol (95JA10922). 

The tandem [2+2] cycloaddition-cycloreversion pathway for the reaction of iV-phosphazenes and aldehydes, which includes the formation of the l,3,2As-oxazaphosphetidine intermediates, has been studied computationally, using density functional theory (DFT) methods, and experimentally <2006JOC2839, 2006JOC6020>. 

This cycloreversion reaction has been utilized to generate 34 and study its reactions with olefins in a FTICR spectrometer43. 34 has been found to react with various olefins essentially along two competing channels H atom abstraction leading to the immonium ion m/z 44 (Scheme 36) and regioselective cycloaddition-cycloreversion. The latter reaction opens up a new possible access to ionized primary enamines in the gas phase. 

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