Cycloaddition reactions nitroso compounds

DFT studies of the intramolecular ene-like (or the so-called 1,3-dipolar ene) reaction between nitrile oxides and alkenes show that this reaction is a three-step process involving a stepwise carbenoid addition of nitrile oxide to form a bicyclic nitroso compound, followed by a retro-ene reaction of the nitrosocyclopropane intermediate. The competitive reactions, either the intramolecular [3 + 2] cycloaddition between nitrile oxides and alkenes or the intermolecular dimerization of nitrile oxides to form furoxans, can overwhelm the intramolecular 1,3-dipolar ene reaction if the tether joining the nitrile oxide and alkene is elongated, or if substituents such as trimethylsilyl are absent (425). 

Aliphatic and aromatic nitroso compounds are powerful dienophiles and react with a variety of acyclic, cychc and heterocyclic 1,3-dienes producing cyclic hydroxylamines. The reaction proceeds with a high regioselectivity at room temperature (equation 99 291-293 Asymmetric variation of the reaction with chiral copper-BINAP catalyst has been reported ". The cycloaddition is reversible and some amounts of diene and nitroso components may be observed in reaction products. 

The meso-ionic 1,3-oxazol-S-ones show an incredible array of cycloaddition reactions. Reference has already been made to the cycloaddition reactions of the derivative 50, which are interpreted as involving cycloaddition to the valence tautomer 51. In addition, an extremely comprehensive study of the 1,3-dipolar cycloaddition reactions of meso-ionic l,3-oxazol-5-ones (66) has been undertaken by Huisgen and his co-workers. The 1,3-dipolarophiles that have been examined include alkenes, alkynes, aldehydes, a-keto esters, a-diketones, thiobenzophenone, thiono esters, carbon oxysulfide, carbon disulfide, nitriles, nitro-, nitroso-, and azo-compounds, and cyclopropane and cyclobutene derivatives. In these reactions the l,3-oxazol-5-ones (66)... 

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

Similarly, the formation of the pyrrolinone (4) from the reaction of nitrosobenzene and a-pyrone may also involve the 2H- 1,2-oxazine (3), which then traps a second molecule of the nitroso compound in a [4+2] cycloaddition step (Scheme 2) (76JOC2496). 

In the light of the foregoing discussion it may be expected that fluoroalkenes participate in cycloaddition reactions with unsaturated systems containing heteroatoms [260], e.g. nitroso compounds [261], sulphur trioxide [262], sulphur dioxide [263], nitriles [264] and so on (Figure 7.78). 

Nitrene generation from nitroso and nitro compounds with triethyl phosphite can also be used. For example, (304 R = NO) and TEP give (305) in 98% yield (63JCS42). The pyrrole (309) and TEP, refluxed in xylene (7 d), give the mesomerically stabilized heteropen-talene derivative (310) which undergoes cycloaddition reactions (Scheme 91) (79JOC622). 

Cycloaddition Reactions. Chiral acrylamides derived from pyrrolidines (2) or (3) undergo stereoselective [4 + 2] cycloaddition reactions with a variety of cyclic dienes. Similarly, nitroso compounds derivatized with pyrrolidine (2) and generated in situ give cycloadducts with a high degree of stereoselectivity (eq 6). Intramolecular [2 + 2] cycloadditions involving pyrrolidine-derived keteniminium salts have been shown to produce chiral cyclobutanones. ... 

A unified picture of the mechanism of this cycloaddition for various structural types of nitroso dienophiles is not available. Depending upon the electronic and steric nature of the particular nitroso compound, the reaction apparently may vary from a concerted pericyclic process to one involving discrete dipolar intermediates. The net result of this mechanistic diversity is a few anomalous regiochemi-cal results in the cycloaddition. 

Readily available a-chloro nitroso compounds have been used on a number of occasions as hetero-dienophiles since the first report appeared in 1947. The initial adduct of this reaction is unstable and if alcohol solvent is used a dihydrooxazine hydrochloride (89) is produced (equation 33). The cycloadditions proceed under very mild conditions with most 1,3-dienes and, as outlined in Scheme 13, Ae regio-selectivity is excellent. - ... 

The use of acyl nitroso compounds as dienophiles was first described by Kirby. The primary method for generating these highly reactive, unstable species is by periodate oxidation of hydroxamic acids. The acyl nitroso compounds can be trapped in a Diels-Alder reaction with 9,10-dimethylanthracene to give adduct (95) (equation 36) which can act as an alternative source of the dienophile, since retro [4 + 2] cycloaddition occurs under mild thermal conditions. 

Vinyl nitroso compounds have proven to be rather interesting species since they can act as either lit or 4ir components in Diels-Alder cycloadditions. The particular reaction which occurs is dependent upon the structure of the vinyl nitroso compound and the diene which are used. For example, vinyl nitroso compound (112), prepared from oxime (111), reacts as a dienophile (equation 44). On the other hand, nitroso compound (113) (equation 45) reacts with cyclopentadiene to give oxazine (114). Not enough data are presently available to interpret these results satisfactorily. 

Methods for the reductive cleavage of the N—O bond in hydroxylamines have assumed increasing importance in synthesis because it is a key step in routes based on cycloaddition of nitrones and nitroso compounds. Inter- and intra-molecular cycloadditions of nitrones lead to the formation of tetrahydroisox-azoles (Scheme 25) these compounds are then converted into amino alcohols by reductive cleavage of the N—-O bonds. This type of reaction sequence has been exploited in the synthesis of a number of alkaloids.Nitroso compounds, particularly those activated by electron-withdrawing substituents, act as dienophiles in the Diels-Alder reaction (Scheme 26) and the cycloadducts can be used as synthetic intermediates by cleaving the N—O bonds. 

Aryl nitroso compounds, which are readily available synthetic intermediates, react regioselectively with most 1,3-dienes. Scheme 12 shows two examples of cycloadditions with unsymmetrical dienes, affording single isomeric 3,6-dihydro-1,2-oxazines in each case. Kresze and coworkers have examined the cycloaddition of aromatic nitroso compounds in some detail and have rationalized the orientational results of this process. It appears that, depending upon the specific nitroso compound used, the reaction transition state varies fiom nonpolar to dipolar. ... 

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