Diphenyl nitrones

The major adduct from C,iV-diphenyl nitrone (265) and 1 could not be isolated, as the 5-spirocyclopropaneisoxazolidine 266 underwent rearrangement under the reaction conditions, also affording the uncommon rearrangement product benzazocine 269 (Scheme 43) [66],... 

C, A-diphenyl nitrones (p-XC6H4CHN(0)Ph, X = NO2, Cl, H, Me and MeO) with N-phenylmaleimide to form 2,3,6-triaryl derivatives of l-oxa-2,6-diazabicyclo[3.3.0]octane-5,7-dione. No enthalpy of formation data are available for A-phenylmaleimide or for maleimide itself. However, it is available for the corresponding A-methyhnaleimide along with some other imides. The gas phase enthalpy of hydrogenation of this species (derived as the difference between its enthalpy of formation and that of N-methylsucc-inimide ) is 133.7 2.2 kJmoC. This value is essentially the same as for ethylene (derived as the difference between its enthalpy of formation and that of ethane) of 136.3 0.4 kJmoH. Therefore, let us assume the reaction of the above parent nitrone with ethylene to form the diphenylated isoxazolidine, shown in equation 12, has very much the same exothermicity as with A-phenylmaleimide, namely ca 82 kJmol . If so, the enthalpy of formation of 2,3-diphenylisoxazolidine would be 233 kJmol . Now, is this value plausible ... 

Cyclopentyl isoxazolidine cycloadduct 324 was prepared by intramolecular nitrone cycloaddition by Baldwin et al. (280,281,352,353) as part of studies toward a total synthesis of pretazettine (Scheme 1.69). Related adducts have been prepared elsewhere (354—356) including fluorine-substituted carbocycles (357) and the adducts prepared by lOAC by Shipman and co-workers (333,334) who demonstrated their potential as a route to aminocyclopentitols (Scheme 1.66, Section 1.11.2). Such bicyclic structures have been prepared in rather unique intermolecular fashion by Chandrasekhar and co-workers (357a) from the cycloaddition of C,N-diphenyl nitrone to fulvene (325). 

Elsewhere, Faita et al. (438) bound the Evans chiral auxiliary to Wang or Merrifield resin for use as a dipolarophile in cycloadditions with C,N-diphenyl-nitrone. Yields on both resins are significantly reduced in comparison to the solution phase reaction (43-20% compared to 95%) but are unaffected by addition of magnesium perchlorate or scandium triflate catalyst. A one-pot process has been reported by Hinzen and Ley (439) that oxidizes secondary hydroxylamines to the... 

In all of the above reactions, a chiral center of the alkene was located in the allylic position. However, as shall be demonstrated next, more distant chiral centers may also lead to highly selective cycloadditions with 1,3-dipoles. In two recent papers, the use of exocyclic alkenes has been applied in reactions with C,N-diphenylnitrone (165,166). The optically active alkenes 109 obtained from (S)-methyl cysteine have been applied in reactions with nitrones, nitrile oxides, and azomethine ylides. The 1,3-dipolar cycloaddition of 109 (R=Ph) with C,N-diphenyl nitrone proceeded to give endOa-1 Q and exOa-110 in a ratio of 70 30 (Scheme 12.36). Both product isomers arose from attack of the nitrone 68 at the... 

The inverse-electron demand 1,3-dipolar cycloaddition has also been pursued with other Ti(IV) complexes (364). The cycloaddition reaction of C,Al-diphenyl nitrone to ferf-butyl vinyl ether catalyzed by different bidentate C2-symmetrical ligands gave moderate to good diastereoselectivity, and up to 41% ee was achieved. 

Benzofurazan-l-oxid reagiert mit C,N-Diphenyl-nitron unter Bildung von l-Hydroxy-2-phe-nyl-benzimidazol-3-oxid (80%)334 ... 

In 2005, the Kinugasa reaction performed on /V-propargyl nucleobases, such as adenine, uracil, and thymine derivatives, with diphenyl nitrone has been reported to produce cis- and trans-(3-lactam nucleosides (Scheme 63), [157]. 

Highly porous silica gel served as a support for the TADDOL moiety derived from inexpensive and readily available i-tartaric acid, which provided access to htanium-based Lewis acid catalysts (Heckel, 2000). Such entihes are employed successfully for enantioselective reactions. TADDOLs were covalently attached to the trimethyl-silyl-hydrophobized silica gel, controlled-pore glass (CPG) at about 300 m2 g-1, at a loading of 0.3-0.4 mmol gl (Heckel, 2002). In a carefully monitored mulh-step immobilization procedure, the TADDOLs were titanated to yield dichloro-, diisopropyl-, or ditosyl-TADDOLates. These catalysts were employed in dialkylzinc addihon to benzaldehydes and diphenyl nitrone addihon to 3-crotonyloxazolidinone, a [3+2] cycloaddition. 

The Lewis acid ATPH 97 was effective both in rate enhancement and in control of the regiochemistry i n the cycloaddition reactions b etween C,A-diphenyl nitrone (94) and catalytic amount (10 mol%) of 97, the regiochemistry of the 1,3-DC of 94 and 92 was reversed and the isoxazolidine-4-carbaldehyde 95 was obtained as the major cycloadduct in high yield <02TL657>. 

Density functional theory (DFT) calculations have been used to investigate and rationahze the regio- and stereochemical outcome of 1,3-DC of (C-hetaryl)nitrones with methyl acrylate and vinyl acetate <07T1448>, diphenyl nitrone with captodative olefins 1-acetylvinyl carboxylates <07EJO2352> and diphenyl nitrone with acrolein in the presence of a Lewis acid catalyst <07T4464>. 

Trifluoromethyl-substituted alkynes can also react with nitrones, leading to rearranged cycloadducts. The cycloaddition of ethyl 4,4,4-trifluorobut-2-ynoate and hexafluorobut-2-yne " with C,A -diphenyl nitrone is a route to trifluoromethyl-substituted indoles. 

Synthetically useful amounts of endo selectivity have been observed in the intermolecular cycloaddition reactions of some acyclic nitrones. For example, the reaction between C,A/-diphenyl nitrone and dimethyl maleate leads to a 9 1 mixture of products, the major arising via the (Z)-nitrone and endo transition state (equation 17). The endo but not the exo transition state experiences an energy-lowering... 

Enantioselective cycloadditions of nitrones with alkylidene malonates were catalyzed by the complex of Go(ll) with trisoxazoline 528. The cycloaddition was reversible and the diastereoselectivity could be controlled by reaction temperature. For example, A, C-diphenyl nitrone and diethyl 2-benzylidenemalonate reacted at —40°C under kinetic control, affording mainly the m-adduct 530, but at 0°C the thermodynamically more stable /ra r-isomer 529 was the major product (Equation 85) <20040L1677>. 

The benzylic anion (175) generated from (174) reacted with N-a-diphenyl-nitrone (176) to give the phosphorate (177), characterized by P NMR, and subsequent protonolysis products. A similar reaction of the O-trans isomer of... 

Discussion on synthesis of selected examples in this section is arranged as follows most common methods for monocyclic, bi/tri/tetracyclic, spiral isoxazolidines and less common methods for all known isoxazolidines. Monocyclic isoxazolidine with a variety of substituents (273)-(281) are synthesized mostly from C,A-diphenyl nitrone (265) with the corresponding alkenes (266)-(272) via intermolecular 1,3-dipolar cycloaddition (Equations (47)-(53)). Monocyclic isoxazolidines are also... 

The benzazepinone (33) is the major product in the addition of C,iV-diphenyl-nitrone to allene it is formed from the primary adduct (32) by ring-opening followed by biradical aromatic substitution. ... 

The energies and coefficients of the LUMO and HOMO of diazepine (6) (Figure 1) have been determined by MNDO calculations and used to explain the preference for addition of iV,a-diphenyl-nitrone at the 4,5-positions of (6). Consideration of these factors indicates that interactions between the LUMO of the diazepine (6) and HOMO of the nitrone control the reaction but do not explain the regiochemistry of the addition <92H(34)497). However, the major formation of the C—O bond at position 5 is explained by examination of the electron densities of positions in (6). 

DC reactions of mcsitonitrile oxide and C, -diphenyl nitrone with the resin-bound chiral iV-crotonyl-oxazolidinone 49 in the presence of different amounts of Mg(II) cation were reported. The study showed that the isoxazoline and isoxazolidine adducts can be obtained on solid-phase, but with lower selectivity and yield than the corresponding product synthesised in solution <01T8313>. 

In addition to their work on DA reaction, Seebach et al. also studied polymeric titanium catalyst 82,83 (see Figure 7.7) in the [3 + 2] cycloaddition of 3-crotonoyloxazolidinone and diphenyl nitrone (Table 7.5). The use of soluble catalysts 81a,b,d (entries 1-3) and supported-titanium catalysts 83a,b,d (entries 4-6) afforded similar performances in terms of yield, dia-stereoselectivity and enantioselectivity in favour of adduct 89a. Interestingly, the enantioselectivity was better in heterogeneous conditions with polymeric TADDOL-titanium complex 83d (entry 6, 56% enantiomeric excess) than using soluble catalysts (entries 1-3). 

Zinc-trifiate complexes with a series of chiral bis(oxazoline) ligands, differing in the length of the chain connecting the chiral oxazoline subvmits and in the nature of the substituent at the chiral center, catalyze the reaction of A(-crotonyloxazolidinone with cyclopentadiene (320). Cycloaddition reactions of alkenoyl-oxazolidinones with both cyclopentadiene and diphenyl nitrone take place with up to 86% ee (321). 

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