Cycloaddition-cycloreversion

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 ... 

The bicyclic system 5 can also be used to prepare annulated systems by cycloaddition-cycloreversion processes. With 2//-pyran-2-one (6) a mixture of cycloadducts is formed on... 

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. 

Dicyclohexyl ether [Brpnsted acid promoted ketone reduction, symmetrical ether], 123 Diels-Alder cycloaddition-cycloreversion pathway, alkene to alkane reductions, trisubstituted alkenes, 39-40 3,5-Dimethyl-1 -cyclohexen-1 -yl... 

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. 

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. 

Acetylene dicarboxylic esters and (less easily) acetylene monocarboxylic esters replace nitriles from the 4,5-positions of 1,2,4,3-triazaphosphole rings (92) to give carboxyl derivatives of 1,2,3-diazaphospholes, presumably by a cycloaddition/cycloreversion mechanism, R/R = Me/Ph, SiMej/NMCj <83ZN(B)1484>. 

In 1984, a facile synthesis of pyrrolo[3,4-/7]indole (5) as a stable indole-2,3-quinodimethane analogue using an intramolecular azide-alkene cycloaddition-cycloreversion strategy was reported (Scheme 9.2) (3). Treatment of bromo compound 3 with NaNs in aqueous tetrahydrofuran (THF) produced the triazoline 4 via an intramolecular 1,3-dipolar cycloaddition of an intermediate azide. Treatment of the triazoline 4 with p-toluenesulfonic acid (p-TSA) effected 1,3-dipolar cycloreversion of 4 to give pyrroloindole 5 in 82% yield along with diethyl diazomalonate. 

Three new syntheses of fro-condensed heteroaromatic pyrroles and their derivatives were described <1995T193, 2003T1477> using retro-malonate addition and/or 1,3-dipolar cycloaddition-cycloreversion methods. 

The mechanism of the cycloaddition appears to be concerted for various reagents however, for several cases, radical cation cycloaddition-cycloreversions have a stepwise component. For example, CIDNP effects observed during the PET induced dimerization of spiro[2.4]heptadiene (97) identify a dimer radical cation with spin density only on two carbons of the dienophile fragment this intermediate must be a doubly linked radical cation ( 99 + 282,283 pulsed laser experiment at high concentrations of 97 supports a second dimer radical cation at high... 

Ozonation of alkenes involves a cycloaddition-cycloreversion sequence. A synthetically significant differentiation of an alkene is shown below [246]. 

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... 

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 previous chapter in CHEC-II(1996) reported on the stability and derived thermochemical data for the isomerization of /3-sultones, the cycloreversion of 1,2-oxathietanes, the relative stability of 1,2- and 1,3-oxathietanes, the isomerization of 1,2-oxathietes, as well as aspects related to stereoisomerization <1996CHEC-II(1B)1083>. Unfortunately, no new studies or information has been presented over the last decade. The only experimental observation worthy of mention is that an equilibrium mixture of the thioketone 27 along with the 6-oxa-7-thiabicy-clo[3.1.1]heptane 28 was isolated in 48% yield from the thermal decomposition of a precursor dithiirane oxide <1997BCJ509>. This indicated that the activation barrier for cycloaddition-cycloreversion is low at ambient temperature. 

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>. 

Highly substituted 4-dimethylamino-4/7-thiopyrans result from a cycloaddition-cycloreversion-cycloaddition sequence commencing with the heterodiyne 417 and dimethyl acetylenedicarboxylate (DMAD) <1996J(P2)2623, 1997MI2185>. Activated alkynes cycloadd to 3-aryl-2-cyanothioacrylamides yielding 4-aryl-477-thiopyrans 418 (Scheme 127) <1994J(P1)989>. 

Pyridazine dienes behave similarly to pyrimidines inasmuch they as well tend to undergo a cycloaddition-cycloreversion sequence involving the extrusion of nitrogen in the latter step. Condensed pyridazines have been employed... 

Further recent work on cycloaddition chemistry of nitrogen heterocycles deals with 1,2,4-triazines. These cyclic dienes undergo a cycloaddition-cycloreversion series as well in this case, nitrogen is evolved and thus a pyridine derivative is generated as final product. Snyder et al. efficiently constructed the canthine skeleton by heating the indolyl-tethered 1,2,4-triazine 3-85 which yielded the tetracyclic product 3-86 (Fig. 3-25) [325,326]. 

BTMSBD reacts with a variety of nucleophiles to give novel heterocycles such as selenophen tellurophen and pyrazoles. It has also been used 1n [2+4] cycloaddition/cycloreversion sequences to prepare ethynyl-substituted Pyridazlnes and furans. ... 

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. 

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

Whereas a [2 + 2] pericyclic reaction is essentially forbidden in the ground state, a [2+1] open-shell reaction is feasible. In this respect, the radical cations detected in this context represent distinct stages of pericyclic, radical-cation catalyzed cycloaddi-tions/cycloreversions. In Fig. 7.11, three distinct stages, a tight (cyclobutane-like), an extended (bis ethene), and a trapezoid, of a hole- (or radical-cation) catalyzed cycloaddition/cycloreversion are presented in a schematic way. °... 

For pagodane-related carbon skeletons 4C/3e radical cations with tight and extended geometries could be established by spectroscopy (predominately EPR) and quantum chemical calculations at the DFT level of theory. Such structures resemble frozen stages of cycloadditions/cycloreversions on the hyper energy surface of the hole-catalyzed cyclobutane formation. 

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