Nitroso Nitrostyrene

Inter [4+2]/inter [3+2] The tandem intermolecular [4+2]/intermolecular [3+2] cycloadditions create bicyclic nitroso acetals with up to six stereogenic centers, which can be controlled by the choice of the stereochemistry of each component and the Lewis acids. The nitronate derived from 2-nitrostyrene and 1-trimethylsilyloxycyclohexene reacts with methyl acrylate to give the nitroso acetal in good yield and high diastereoselectivity (Eq. 8.107).154... 

Al-Nitrosodiethanolamine, 2 449, 450 Nitroso dyes, 9 263-264 Nitro soluble dyes, 7 373t Nitroso soluble dyes, 7 373t Nitrosomonas, use in recirculating aquaculture biofiltration, 3 196 P-Nitrostyrenes, preparation by nitration of styrenes, 16 581 Nitrosyl chloride, 20 634 Nitrosyl complexes, osmium, 19 642 Nitrosyl perchlorate, 18 279 Nitrosyl tetrafluoroborate, 4 144t n-Nitrotoluene, 17 263... 

The reaction of 1,4-diphenylbuta-l,3-diene (2) with trithiazyl trichloride (3) yields a bi(thiadiazole) (4), an isothiazoloisothiazole (5), a dithiazolothiazine (6), and two thiazin-odithiatriazepines (7) and (8) by 1,2-, 1,3-, and 1,4-cycloaddition reactions (Scheme 2). The bridged-mode (/3-tether) tandem inter-[4 -E 2]/intra-[3 -E 2] cycloaddition of (ii)-2-methyl-2-nitrostyrene (9) with 1-butoxypenta-1,4-diene (10) produces stable tricyclic nitroso acetals (11) which afford, after reduction and protection, highly functionalized aminocyclopentanedimethanol triacetates (12) (Scheme 3). ... 

This pressure effect was also observed in the tandem cycloaddition nitroalkene. Combination of methyl acrylate with 2-nitrostyrene and ethyl vinyl ether proceeds at 15 kbar over 1 h to produce a mixmre of diastereomeric nitroso acetals (Eq. 2.24) (83,235,236). 

Nitrosamines, 1074, 1076 Nitrosobenzene, 629, 630 Nitroso compounds, table of, 1085 p-Nitroso derivatives, 660 N-Nitrosodiethylamine, 426 N-Nitrosodimethylamine, 426 p-Nitrosodimetlivlaniline, 562,573 N-Nitrosoethylaniline, 570 N-Nitrosomethylaniline, 562. 563, 570 p-Nitroso-N-methylanOine, 563, 574 Nitrosomethylurea. 968, 969 a-Nitroso-(3-naphthol, 958 (3-Nitrostyrene, 709, 717 a(3-Nonenoic acid, 405, 468 -Nonoic acid. 487... 

The reduction of an a, i3-unsaturated nitro compound [29], such as /3-nitrostyrene (V), occurs in two steps. The first reduction of (V) is a four-electron reaction that yields phenylacetaldoxime (VI) the reaction has been formulated as a reduction of the nitro group followed by a rearrangement of the unsaturated hydroxylamine (VII), but might also be regarded as a 1,4-reduction of the intermediate unsaturated nitroso compound. There is no conclusive evidence for either route, but the former has been chosen here, as the protonation of the heteroatom would be expected to be faster than protonation of the carbon atom ... 

A four-component [4 + 2]/[4 + 2]/[3 + 2] cycloaddition reaction, reported by Scheeren et is another application of multicomponent reactions. The interaction of 2-methoxy-l,3-butadiene (92) (1 equiv.) with p-nitrostyrene (81a) (3 equiv.) at 1.5 GPa led to a mixture of nitroso-acetals 93-95. In this reaction, p-nitrostyrene (81a) first reacts as a dienophile in the normal electron-demand Diels-Alder reaction, it then reacts as a heterodiene in the inverse electron-demand hetero-Diels-Alder reaction and, finally, it acts as a dipolarophile in the [3 + 2] cycloaddition (Scheme 7.23). 

A [4 + 2]/[4 + 2]/[3 + 2] cycloaddition using four different components has also been investigated.The interaction of p-nitrostyrene (81a), diene 92, styrene (96) and A-phenylmaleimide (97) under 1.5 GPa pressure in dichloromethane solution for 16h at room temperature (Scheme 7.24) afforded a mixture of diastereomeric nitroso-acetals 98 and 99. In this case, 92 reacted as a diene, A-phenylmaleimide as a dienophile, p-nitrostyrene as the heterodiene and styrene as a dipolarophile. 

The first example of the successful application of high pressure in the one-pot [4 + 2]/[3 + 2] cycloaddition is the reaction of ethyl vinyl ether (10), yff-nitrostyrene (11) and methyl acrylate (12) (Scheme 9.5). At ambient pressure nitroso acetal (13) was obtained in 43 % yield, after stirring for 20 days using 30 equiv. of enol ether... 

First, the reactivity of nitrostyrenes (15a and 15b) in combination with methyl acrylate and styrene as the dipolarophile was investigated (Scheme 9.6). With methyl acrylate as the dipolarophile, nitroso acetals (17 and 18) were obtained after 18 h at 15 kbar and room temperature (RT) in 95 and 78 % yield, respectively. Both nitroso acetals (17 and 18) were isolated as a mixture of three diastereomers. The products were formed from a completely regioselective 1,3-dipolar cycloaddition, which is in agreement with reported literature data on related cycloadditions of mono-substituted acrylates with nitrones and nitronates [22]... 

Dihydrofuran (21) reacted with nitrostyrene (15a) and methyl acrylate yielding the tricyclic nitroso acetal (23) in 88 % yield as a mixture of three diastereomers (15 kbar, RT, 16 h. Scheme 9.7). The use of methyl-substituted nitrostyrene (15b) resulted in the formation of nitroso acetal (24) as a mixture of five diastereomers in 84 % yield (15 kbar, 50 °C, 18 h). The formation of five diaster-eomeric products indicated a non-selective [4 - - 2] cycloaddition exo and mdo). The loss of endo-selectivity in the [4 -I- 2] cycloaddition was also observed when 3,4-dihydropyran (22) was used. Tricyclic nitroso acetal (25) was produced in 37 % yield (15 kbar, 50 °C, 92 h) as a mixture of diastereomers resulting from exo and mdo [4 -h 2] cydoadditions and syn/anti exo and endo 1,3-dipolar cydoadditions [7]. It is known that 3,4-dihydropyran (22) reacts much more slowly than the five-membered 2,3-dihydrofuran (21), mainly due to the lower ring strain. This is reflected in the moderate yield of 25 and the lack of reactivity of 3,4-dihydropyran... 

A nice demonstration of the powerful effect of high pressure is the one-pot formation of nitroso acetals from stericaUy-hindered and low-activated dipolarophiles such as )ff-tra s-substituted a, -unsaturated esters. The di-substituted acrylates 42 and 44 reacted with enol ether (14) and nitrostyrene (15b) at 15 kbar and 50 °C in 18 h, producing nitroso acetals 43 and 45 as diastereomeric mixtures in yields of 82 and 74 %, respectively (Scheme 9.14). Seebach and coworkers previously reported that, although some modifications of the acrylate are tolerated (e.g. a-substitution), -substituted a,yS-unsaturated esters did not react with nitronates in refluxing toluene [24]. 

In contrast to the complete regioselectivity observed in the 1,3-dipolar cycloaddition of nitronate 16b and methyl crotonate 42 or methyl cinnamate 44 shown in Scheme 9.14, the [3 -t 2] cycloaddition of yS-nitrostyrene (15a) and nitronate intermediate 16a was not completely regioselective. Regio-isomers 46 and 47 were formed in 83 % yield, as mixtures of diastereomers, in a 7 3 ratio after the high pressure-promoted domino cycloaddition of enol ether 14 with 2 equiv. fi-nitrostyrene (15a) (15 kbar, RT, 18 h, Scheme 9.15). The formation of regio-isomer 46 as major product was rather unexpected, since comparable 1,3-dipolar cycloadditions of nitrones and nitroalkenes [25] showed the opposite regio-isomer to be formed predominantly. This nitroso acetal (46) was converted to )S-lactam (48) via a base-catalyzed rearrangement (Scheme 9.16). This conversion appeared applicable to different hi- and tricyclic nitroso acetals and led to the formation of a novel class of bi- and tricyclic yS-lactams [26]. 

The stereochemical limits of this type of domino reaction were also studied [8j. When l-phenyl-2-nitropropene 15b was used, the only product isolated was nitronate (16b). Nitroalkene 15b failed to react as a dipolarophile in the second cycloaddition with nitronate 16b, under even more extreme conditions (15 kbar, 50 °C, 96 h, Scheme 9.17). However, nitronate 16b reacted with y -nitrostyrene (15a) at 15 kbar, RT within 72 h completely regio- and stereoselectively producing the bicyclic nitroso acetal 49. 

The cyclic a,/ -unsattirated ketone cyclohex-2-en-l-one (50) was used as building block in the one-pot domino cycloaddition of enol ether 14 and nitrostyrene 15a. At 15 kbar and 50 "C, nitroso acetal 51 was formed in 67 % yield, whereas nitroso acetal 54a was formed as a side product (Scheme 9.18). This result indicated that the 1,3-dipolar cycloaddition is still faster with the electron-poor substituted cyclohexenone 50 than with the electron-rich mono-substituted enol ether 14. The one-pot reaction of 52 with enol ether 14 and nitrostyrene 15a merely resulted in formation of nitroso acetal 54a instead of nitroso acetal 53. The unwanted side reaction was not observed in the one-pot three-component reaction with 14 and methyl-substituted nitrostyrene 15b and 52 (Scheme 9.19). The large difference in reactivity between the three components in both the Diels-Alder and the [3 + 2] cycloaddition resulted in the formation of 55 as the main product. The side reaction of 16b with 14 to form 54b was prevented, since 14 was completely consumed in the reaction with 15b to give nitronate 16b (15 kbar, 50 °C, 16 h). However, heating (50 °C) the reaction mixture for 76 h at 15 kbar was necessary to produce nitroso acetal 55, which was formed as a mixture of two major diastereomers (ratio 3 1) in 69 % yield. 

In the presence of 3 equivalents of ) -nitrostyrene (15a) 2-methoxy-l,3-butadiene (61) reacted to afford the nitroso acetals 64 and 65, and at 15 kbar and 50 °C the conversion of the starting compounds was complete within 18 h (Scheme 9.24). 

Nitrosative cyclization, 547 Nitroso compounds, 97-98 Nitrosolysis, 422 N-Ni tro so-N-methylurea, 159 /3-Nitrostyrene, 422 Nitrosyl chloride, 422-423 Nitrosyl tetrafluoroborate, 226 cr-Nitrotriphenylmethane, 272 Nitroxides, 455-456 Nitroxyl radicals, 110 Nonactic acid, 106,107 Nonactin, 106, 625... 

An excellent high-pressure domino reaction is shown by the four-component transformation of 2-methoxybuta-l,3-diene 172 with fS-nitrostyrene 174 and 2 equiv of N-phenyhnaleimide 173, as reported by Scheeren and coworkers (Scheme 12.71) [99]. The reaction was completed within 42 h at 15 kbar to give a mixture of the two diastereomeric nitroso acetals rac-175 and roc-176 in yields of 84%. The domino process consists of a [4+2]/[4+2]/[3- -2] cycloaddition and leads to the products 175/176 with the formation of six new bonds and eight stereogenic centers in good yield and high stereoselectivity just forming only the two diastereomers in a ratio of7 3. 

Attempted reactions of 7d with Ru3(CO)i2 in order to isolate a possible nitrene complex intermediately formed were unsuccessful [9], Thus, we can only speculate about the reaction mechanism. Formation of a nitrene complex analogous to compound 4 is a reasonable hypothesis. However, when the carbonylation of some organic nitro derivatives was conducted in c/.y-cyclooctene as solvent and with Ru3(CO)i2 as catalyst, nitrones have been detected among the products [14]. Under these conditions, the intermediate nitroso derivative reacts with the alkene solvent to yield the corresponding nitrone. The reaction of nitroso derivatives with alkenes is in fact one of the methods for the preparation of nitrones [28]. Thus it could be that in the case of the carbonylation of ortho-nitrostyrenes, the reaction follows the path depicted in Scheme 4 ... 

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