Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes
- Lucie Brulíková,
- Aidan Harrison,
- Marvin J. Miller and
- Jan Hlaváč
Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184
Graphical Abstract
Scheme 1: Nitroso hetero-Diels–Alder reaction.
Scheme 2: The hetero-Diels–Alder reaction between thebaine (4) and an acylnitroso dienophile 5.
Figure 1: Examples of nitroso dienophiles frequently used in hetero-Diels–Alder reaction studies.
Scheme 3: Synthesis of arylnitroso species by substitution of a trifluoroborate group [36].
Scheme 4: Synthesis of arylnitroso compounds by amine oxidation.
Scheme 5: Synthesis of arylnitroso compounds by hydroxylamine oxidation.
Scheme 6: Synthesis of chloronitroso compounds by the treatment of a nitronate anion with oxalyl chloride.
Scheme 7: Non-oxidative routes to acylnitroso species.
Figure 2: RB3LYP/6-31G* computed energies (in kcal·mol−1) and bond lengths for exo and endo-transition states...
Scheme 8: Hetero-Diels–Alder cycloadditions of diene 28 and nitroso dienophiles 29.
Figure 3: Relative reactivity (ΔE#) and regioselectivity (Δ) for hetero-Diels–Alder of 28 and nitroso dienoph...
Scheme 9: Reaction of chiral 1-phosphono-1,3-butadiene 31 with nitroso dienophiles 32.
Scheme 10: Hetero-Diels–Alder reactions of hydroxamic acids 35 with various dienes 37.
Scheme 11: General regioselectivity of the nitroso hetero-Diels–Alder reaction observed with unsymmetrical die...
Scheme 12: Effect of the nitroso species on the regioselectivity for weakly directing 2-substituted dienes.
Scheme 13: Regioselectivity of 1,4-disubstituted dienes 51.
Scheme 14: Nitroso hetero-Diels–Alder reaction between Boc-nitroso compound 54 and dienes 55.
Scheme 15: Nitroso hetero-Diels–Alder reaction between Wightman reagent 58 and dienes 59.
Scheme 16: Regioselective reaction of 3-dienyl-2-azetidinones 62 with nitrosobenzene (47).
Scheme 17: The regioselective reaction of 1,3-butadienes 65 with various nitroso heterodienophiles 66.
Scheme 18: Catalysis of the nitroso hetero-Diels–Alder reaction by vanadium in the presence of the oxidant CHP...
Figure 4: 1,2-Oxazines synthesized in solution with moderate to high regioselectivity, showing the favored re...
Figure 5: 1,2-Oxazines synthesized in the solid phase with moderate to high regioselectivity, showing the fav...
Scheme 19: Regioselectivity of solution-phase nitroso hetero-Diels–Alder reaction with acyl and aryl nitroso d...
Scheme 20: Favored regioisomeric outcome for the solution and solid-phase reactions, giving hetero-Diels–Alder...
Figure 6: Favored regioisomers and regioisomeric ratios for 1,2-oxazines synthesized in solid phase (91, 93, ...
Scheme 21: Regiocontrol of the reaction between 3-dienyl-2-azetidinones and nitrosobenzene due to change in a ...
Scheme 22: Regiocontrol of the reaction between diene 111 and 2-methyl-6-nitrosopyridine (112) due to metal co...
Scheme 23: Asymmetric hetero-Diels–Alder reactions reported by Vasella [56].
Scheme 24: Asymmetric hetero-Diels–Alder reaction of cyclohexa-1,3-diene (120) with acylnitroso dienophile 119....
Scheme 25: Asymmetric induction with L-proline derivatives 124–126.
Scheme 26: Asymmetric cycloaddition of the acylnitroso compound 136 to diene 135.
Scheme 27: Asymmetric induction with arylmenthol-based nitroso dienophiles 142.
Scheme 28: Cycloaddition of silyloxycyclohexadiene 145 to the acylnitroso dienophile derived from (+)-camphors...
Scheme 29: Asymmetric reaction of O-isopropylidene-protected cis-cyclohexa-3,5-diene-1,2-diol 147 with mannofu...
Scheme 30: Synthesis of synthon 152 from 2-methoxyphenol 150 and chiral auxiliary 151.
Scheme 31: Asymmetric nitroso hetero-Diels–Alder reaction with Wightman chloronitroso reagent 58.
Scheme 32: Asymmetric 1,2-oxazine synthesis using chiral cyclic diene 157 and the application of this reaction...
Scheme 33: Asymmetric 1,2-oxazine synthesis using a chiral diene reported by Jones et al. [75]. aRegioisomeric rat...
Scheme 34: The nitroso hetero-Diels–Alder reaction of acyclic oxazolidine-substituted diene 170 and chiral 1-s...
Scheme 35: The nitroso hetero-Diels–Alder reaction of acyclic lactam-substituted diene 176 with various acylni...
Scheme 36: The hetero-Diels–Alder reaction of acylnitroso dienophile.
Scheme 37: The hetero-Diels–Alder reaction of arylnitroso dienophiles using Lewis acids.
Scheme 38: Asymmetric hetero-Diels–Alder reactions of chiral alkyl N-dienylpyroglutamates.
Scheme 39: Catalytic asymmetric arylnitroso reaction between mono-substituted 1,3-cyclohexadiene 196 and disub...
Figure 7: Plausible chelate intermediate complexes formed during the hetero-Diels–Alder reaction to give 1,2-...
Scheme 40: Catalytic asymmetric nitroso hetero-Diels–Alder between cyclic dienes and 2-nitrosopyridine.
Scheme 41: The reason for the increased enantioselectivity of stereoisomer 212 compared with stereoisomer 213.
Scheme 42: The copper-catalyzed nitroso hetero-Diels–Alder reaction of 6-methyl-2-nitrosopyridine (199) with p...
Scheme 43: Asymmetric nitroso hetero-Diels–Alder reaction of nitrosoarenes with dienylcarbamates catalyzed by ...
Scheme 44: The enantioselective hetero-Diels–Alder reaction between nitrosobenzene and (E)-2,4-pentadien-1-ol (...
Scheme 45: Asymmetric nitroso hetero-Diels–Alder reaction using tartaric acid ester chelation of the diene and...
Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues
- Lucie Brulikova and
- Jan Hlavac
Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80
Graphical Abstract
Figure 1: Investigated derivatives.
Figure 2: Modifications of uracil ring.
Figure 3: 5-(3,3,3-Trifluoro-1-methoxypropyl)-2'-deoxyuridine (1).
Scheme 1: Synthesis of 5-(3,3,3-trifluoro-1-methoxypropyl)-2'-deoxyuridine (1) and 5-(3,3,3-trifluoro-1-(2-pr...
Scheme 2: Synthesis of 5-(3,3,3-trifluoro-1-methoxyprop-1-yl)-5,6-dihydro-2'-deoxyuridine (8).
Scheme 3: Synthesis of 5-(methoxy-2-haloethyl)-2'-deoxyuridines 12 and 13.
Scheme 4: Synthesis of 5-(1-methoxy-2-iodoethyl) nucleosides 28–30.
Figure 4: [125I] radiolabelled 5-(1-methoxy-2-iodoethyl)-2'-deoxyuridine 31.
Scheme 5: Synthesis of 5-(1-alkoxy-2-iodoethyl) 34–36 and 5-(1-ethoxy-2,2-diiodoethyl)-2'-deoxyuridine (33).
Scheme 6: Synthesis of 5-(1-methoxy-2-iodoethyl)-3',5'-di-O-acetyl-2'-deoxyuridine (38) and 5-(1-ethoxy-2-iod...
Figure 5: 5-(1-Hydroxy(or ethoxy)-2-haloethyl)-3',5'-di-O-acetyl-2'-deoxyuridines 43–46.
Scheme 7: 5-(1-Methoxy-2,2-dihaloethyl)-2'-deoxyuridines 47–49.
Scheme 8: Synthesis of 5-[1-(2-haloethyl(or nitro)ethoxy)-2-iodoethyl]-2'-deoxyuridines 50–54.
Scheme 9: Synthesis of alkoxyuracil analogues 56–61.
Figure 6: 5-(Methoxy-2-haloethyl)uracils 62–64.
Scheme 10: Synthesis of perfluoro derivatives 70–74.
Scheme 11: Synthesis of 1-β-D-arabinofuranosyl-5-(1-methoxy-2-iodoethyl)uracil (79).
Scheme 12: Synthesis of 1-β-D-arabinofuranosyl-5-(2,2-dibromo-1-methoxyethyl)uracil 82 and uridine analogue 83....
Scheme 13: Synthesis of methoxy derivative 87.
Scheme 14: Synthesis of 5-(1-methoxy-2-azidoethyl)-2'-deoxyuridine (93).
Scheme 15: Synthesis of methoxyalkyl derivatives 96 and 97.
Scheme 16: Synthesis of 5-(1-methoxyethyl)-2'-deoxyuridine (100).
Scheme 17: Synthesis of 2'-deoxy-5-(1-methoxyethyl)-4'-thiouridine (104).
Figure 7: 5-(1-Butoxyethyl)uracil 105 and 5-(1-butoxyethyl)-2'-deoxyuridine (106).
Scheme 18: Synthesis of β- and α-anomer of 5-(1-ethoxy-2-methylprop-1-yl)-2'-deoxyuridine.
Scheme 19: Synthesis of 5-(1-acyloxyethyl)-1-(tetrahydrofuran-2-yl)uracils 117 and 118.
Scheme 20: Synthesis of 5-(1,2-diacetoxyethyl)-3',5'-di-O-acetyl-2'-deoxyuridine 120.
Scheme 21: Synthesis of 5-[alkoxy-(4-nitrophenyl)methyl]uracils 124.
Scheme 22: Synthesis of 5-[alkoxy-(4-nitrophenyl)methyl]uridines 126 and 127.
Scheme 23: Synthesis of phosphoramidite 134. Reaction conditions 1: (a) TBDMSCl, imidazole, pyridine, 33 h, 99...
Scheme 24: Synthesis of phosphoramidite 145. (a) B(OCH3)3, CH(OCH3)3, Na2CO3, MeOH, 150 °C; (b) I2, (0.6 equiv...
Figure 8: Oligonucleotide 146.
Scheme 25: Synthesis of phosphoramidite 150.
Figure 9: 2'-Deoxyuridine derivatives 151–154.
Scheme 26: Synthesis of 2'-deoxyuridine derivatives 151–152.
Scheme 27: Synthesis of 5-[3-(2'-deoxyuridin-5-yl)-1-methoxyprop-1-yl]-2'-deoxyuridine (163).
Scheme 28: Synthesis of “metallocenonucleosides” 164 and 167.
Scheme 29: Synthesis of 5-(2,4:3,5-di-O-benzylidene-D-pentahydroxypentyl)-2,4-di-tert-butoxy-pyrimidine 172 an...
Figure 10: α- and β-pseudouridine (174 and 175).
Figure 11: 5'-Modified pseudouridine 176 and secopseudouridines 177, 178.
Figure 12: Methoxy derivatives 12, 13 and 28.
Figure 13: 5-(1-Methoxy-2,2-dihaloethyl)-2'-deoxyuridines 47–49.
Figure 14: 5-(1-Methoxyethyl)-2'-deoxyuridine 100.
Figure 15: 2'-Deoxy-5-(1-methoxyethyl)-4'-thiouridine (104).
Figure 16: 5-(1-Methoxy-2-azidoethyl)-2'-deoxyuridine (93).
Figure 17: 5-[1-(2-Halo(or nitro)ethoxy-2-iodoethyl)]-2'-deoxyuridines 50–54.
Figure 18: 5-[Alkoxy-(4-nitrophenyl)-methyl] uracil analogues 124, 126 and 127.
Figure 19: Methoxyiodoethyl pyrimidine nucleoside 79.
Figure 20: 5-[alkoxy-(4-nitro-phenyl)-methyl]uridines 126 and 127.
