Cycloadditions of nitrosobenzenes

Diels-Alder reactions. The cycloaddition of nitrosobenzene with 1 has been used for synthesis of an amino sugar (4).1... 

Cycloadditions of nitrosobenzenes with simple carbocyclic 1,3-dienes have been known for many years.Ib 4 In a recent investigation, Kresze et al. have added p-chloronitrosobenzene to some 5,6-difunctionalized 1,3-cyclohexadienes (Scheme 3-VI).15 In the first example shown, only one cycloadduct was produced, although it is not obvious why this is the case. Also puzzling is the stereochemical result of the second example shown in the scheme. Based on Hart s work (Scheme 3-IV), one might have expected the sy/i-hydroxyl isomer to be the major product of this reaction. 

Cycloaddition of nitrosobenzenes to pyrido[l,2- ]pyrazines 261, followed by Dimroth rearrangement of the initial cycloadduct, leads to l-oxa-2,4-diazine intermediates that ate trapped in solution using (CO)4Mo(norbornadiene) to produce the complexes 262 (R = Aryl R =alkyl, Aryl) (Equation 64) <1999JHC627>. 

Details for the high yield preparation of 5-imino-2-pyrroIidone derivatives and their 5-atkylimino analogues have been provided by Koberda and Lange (Scheme 70). 1,2-Oxazine and its N-substituted derivatives e.g. (181) are elusive and have not knowingly been prepared. An attempted synthesis of these compounds by the cycloaddition of nitrosobenzene to a-pyrone gave instead azoxybenzene and a 2 1 adduct (182) in 24% yield, (Scheme 71). ... 

Diels-Alder and hetero [4 -I- 2] cycloadditions of l-(l,3-butadien-l-yl)benzotriazole (638) with N-phenylmaleimide, maleic anhydride, ethyl acrylate, Eschenmoser salt, and nitrosobenzene give a... 

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). 

Cycloadditions of nitroso compounds and 1,3-dienes lead to 3,6-dihydro-2//- 1,2-oxazines this is a well tried and documented procedure (B-67MI22700), a comparatively modern example of which is the regiospecific synthesis of 2,3,4-trisubstituted derivatives (155) from the addition of nitrosobenzenes to 1,2-disubstituted dienes (154) (78T697). 

The [4+2] cycloaddition of 2-substituted-l,2-dihydropyridines 109 with heterodienophile nitrosobenzene gives unstable cycloadducts 110 as single diastereomers in 98% ee. Adducts 110 can be reduced with alane to give 3-aminosubstituted-l,2,3,6-tetrahydropyridines 111 with a /razw-relationship between the 2-substituent and 3-amino group (Scheme 30) <2005JOC2368>. 

The Regioselectivity ofHetero Diels-Alder Reactions. In a few cases, carbonyl, nitrosyl, cyano, and other double bonds with one or more electronegative heteroatoms have acted as dienophiles in Diels-Alder reactions. The carbonyl group has a HOMO and a LUMO as shown in Fig. 1.51. The energies of both orbitals are relatively low, and most of their Diels-Alder reactions will therefore be guided by the interaction between the HOMO of the diene and the LUMO of the carbonyl compound. This explains the regioselectivity in the cycloaddition of dimethylbutadiene 6.176 and formaldehyde, and between 1-substitituted butadienes 6.177 and nitrosobenzenes. 

When acylnitroso derivatives are employed as dienophiles in the cycloaddition, the re-gioselectivity of the reaction is inverted with respect to the mode of addition of nitrosobenzene. Thus l,2-dihydro-A -methoxycarbonylpyridine. by reaction with V-acylhydroxylamines in the presence of tetraalkylammonium periodate at 78 r C in dichloromethane, leads to the corresponding 2-oxa-3,5-diazabicyclo[2.2.2]oct-7-enes in good yield. The regiochemistry of the cycloaddition product 2 was determined by 13C NMR84-86. 

The same group was able to perform a similar cycloaddition reaction but with complete reversal of the regioselectivity (Scheme 11.45) [126]. They revealed that the O vs. N selectivity is dependent on the presence or absence of a weak hydrogen-bond donor in the catalyst (OH group), which apparentiy coordinates the oxygen atom of nitrosobenzene to facilitate the formation of iV-nitroso aldol products. Nucleophilic attack of the preformed enamine is postulated to occur from the Re face as described in Scheme 11.45. For steric reasons the subsequent intramolecular 0-Michael addition just occurs when R are CH3 groups. 

The gold-catalysed cyclization/oxidative 3+2-cycloadditions of 1,5-enynes (57) with nitrosobenzene produced substituted isoxazoles (59) with high stereocontrol. The nitrosobenzene also acts as an oxidizing agent in this reaction. Alkenylgold carbocations (58) are important intermediates in this reaction sequence (Scheme 16). ... 

Very recently, Pericas reported a new strategy to immobihze trans-4-hydroxypro-line onto an insoluble Merrifield-type polymer by exploiting Cu(I)-catalyzed 1,3-dipolar cycloaddition ( click chemistry ) [42]. The supported catalyst 25 was successfully employed in the a-aminoxylation of ketones and aldehydes (Scheme 8.13). Under the optimized reaction conditions (20mol%/cat, 2 equiv. ketone, DMF, 23 °C, 3 h), the reaction of cyclohexanone with nitrosobenzene catalyzed by 25 gave the product in 60% yield and 98% ee (Scheme 8.13 Equation a). It should be noted that the reaction rates of cyclic ketones with supported catalyst are faster than those reported with (S)-proline. The use of a supported catalyst allowed for a simplification of the work-up procedure, as the product could often be obtained after simple filtration of the catalyst and evaporation of the solvents. Furthermore, 25 was recycled up to three times without any decrease in either the chemical and/or stereochemical efficiency. 

The regiochemistry of the addition of a-chloronitroso compounds with unsymmetrical acyclic dienes has been probed, and some results are listed in Table 3-II.lb 3a 23 In general, orientational preferences are in accord with those observed for arylnitroso compounds (cf. Table 3-1). As noted above, a glaring exception is the case of isoprene, which gives the opposite selectivities with chloronitroso compounds and nitrosobenzene. It was suggested that steric factors become important in cycloadditions... 

Heterocyclic o-quinodimethanes are unstable and reactive dienes that must be generated in situ. In solution and in the pre.sence of a dienophile the -quinodimethanes can be intercepted in a Diels-Alder reaction, often in high yield. Most of the dienophiles investigated so far have been electron deficient A-phenylmaleiinide. acrylonitrile, methyl vinyl ketone, acrylate, ftimarate and acetylenedicarboxylic esters are typically used. However, since the objective of most of the work was simply to establish that the o-quinodimethane was being formed, the scope of the reaction has not been adequately explored. The pyridine derived o-quinodimethane 12 has recently been shown to undergo cycloaddition to ethyl vinyl ether (Scheme 2) and to dihydroftiran <96T11889>, and it is thus clear that the scope of the Diels-Alder reaction extends beyond electron deficient alkenes and alkynes. Heterodienophiles (azodicarbonyl compounds and nitrosobenzene) have been added to indole-2,3-quinodimethanes <91T192,S> and this type of hetero Diels-Alder reaction is also potentially of wider application. 

The iV-phenylmaleimide derivative (518), prepared in two steps from a-pyrone and nitrosobenzene, is a dienophile and yields the cycloaddition product (519) on reaction with cyclohexa-l,3-diene." ° The sealed-tube reaction of anthracene with excess l,2-dibromo-3,3-difluorocyclopropene at 120°C gave the crystalline adduct (520), presumably by way of intermediate (521) the mechanism is not known. A synthesis of the tricyclo[5,2,2,0 ]undecane skeleton related to isoeremolactone has been reported. The Diels-Alder adduct (522) was a key intermediate in this synthesis, being converted in two standard steps into an epimeric mixture of compounds... 

---