Enantioselective NHC-catalysed redox [4+2]-hetero-Diels-Alder reactions using α-aroyloxyaldehydes and unsaturated ketoesters. Issue 2 (15th February 2017)

• Record Type: Journal Article
• Authors: Taylor, James E.; Davies, Alyn T.; Douglas, James J.; Churchill, Gwydion; Smith, Andrew D.
• Is Part Of: Tetrahedron, asymmetry. Volume 28:Issue 2(2017)
• Page Start: 355
• Page End: 366
• Publication Date: 2017-02-15
• Subjects: Asymmetry (Chemistry) -- Periodicals; 547.005
• DOI: 10.1016/j.tetasy.2017.01.002
• Languages: English
• ISSNs: 0957-4166

Abstract

Graphical abstract: Abstract: N-Heterocyclic carbene (NHC)-catalysed redox [4+2]-hetero-Diels-Alder reactions of α-aroyloxyaldehydes with either β, γ-unsaturated α-ketoesters or α, β-unsaturated γ-ketoesters generates substituted syn -dihydropyranones in good yield with excellent enantioselectivity (up to >99:1 er). The product diastereoselectivity is markedly dependent upon the nature of the unsaturated enone substituent. The presence of either electron-neutral or electron-rich aryl substituents gives excellent diastereoselectivity (up to >99:5 dr), while electron-deficient aryl substituents give reduced diastereoselectivity. In these cases, the syn -dihydropyranone products are more susceptible to base-promoted epimerisation at the C(4)-position under the reaction conditions, accounting for the lower diastereoselectivity obtained. Abstract : (5a R, 10b S )-2-Mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride: C21 H22 ClN3 O dr >95:5 er >99:1 [ α ] D 20 = +135.1 ( c 1.00, EtOH) Source of chirality: (1 S, 2 R )-1-amino-2, 3-dihydro-1 H -inden-2-ol Absolute configuration: (5a R, 10b S ) Abstract : (3 S, 4 S )-Methyl 3-benzyl-2-oxo-4-phenyl-3, 4-dihydro-2 H -pyran-6-carboxylate: C20 H18 O4 dr >95:5 er >99:1 [ α ] D 20 = +398 ( c 0.23, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Methyl 3-butyl-2-oxo-4-phenyl-3, 4-dihydro-2 H -pyran-6-carboxylate: C17 H20 O4 dr >95:5 er 98:2 [ α ] D 20 = +156 ( c 0.15, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Methyl 3-isobutyl-2-oxo-4-phenyl-3, 4-dihydro-2 H -pyran-6-carboxylate: C17 H20 O4 dr >95:5 er >99:1 [ α ] D 20 = +279 ( c 0.14, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 3-benzyl-2-oxo-4-( p -tolyl)-3, 4-dihydro-2 H -pyran-6-carboxylate: C22 H22 O4 dr 94:6 er 96:4 [ α ] D 20 = +299.4 ( c 0.5, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Methyl 3-benzyl-4-(4-methoxyphenyl)-2-oxo-3, 4-dihydro-2 H -pyran-6-carboxylate: C21 H20 O5 dr 91:9 er >99:1 [ α ] D 20 = +277.3 ( c 0.5, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 3-butyl-2-oxo-4-( p -tolyl)-3, 4-dihydro-2 H -pyran-6-carboxylate: C19 H24 O4 dr 92:8 er >99:1 [ α ] D 20 = +249.2 ( c 0.5, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Methyl 3-butyl-4-(4-methoxyphenyl)-2-oxo-3, 4-dihydro-2 H -pyran-6-carboxylate: C18 H22 O5 dr 92:8 er >99:1 [ α ] D 20 = +245.1 ( c 0.5, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Methyl 4-(4-bromophenyl)-3-butyl-2-oxo-3, 4-dihydro-2 H -pyran-6-carboxylate: C17 H19 BrO4 dr 89:11 er 99:1 [ α ] D 20 = +205.3 ( c 0.5, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Methyl 3-butyl-4-(naphthalen-2-yl)-2-oxo-3, 4-dihydro-2 H -pyran-6-carboxylate: C21 H22 O4 dr 94:6 er >99:1 [ α ] D 20 = +297.0 ( c 0.5, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 3-butyl-2-oxo-6-phenyl-3, 4-dihydro-2 H -pyran-4-carboxylate: C18 H22 O4 dr >95:5 er >99:1 [ α ] D 20 = +185.5 ( c 0.5, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 3-benzyl-2-oxo-6-phenyl-3, 4-dihydro-2 H -pyran-4-carboxylate: C21 H20 O4 dr >95:5 er >99:1 [ α ] D 20 = +173.0 ( c 1.05, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 3-(2-(benzyloxy)ethyl)-2-oxo-6-phenyl-3, 4-dihydro-2 H -pyran-4-carboxylate: C23 H24 O5 dr 90:10 er >99:1 [ α ] D 20 = +169.1 ( c 0.55, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 3-benzyl-6-methyl-2-oxo-3, 4-dihydro-2 H -pyran-4-carboxylate: C16 H18 O4 mp 88–89 °C dr >95:5 er 98.5:1.5 [ α ] D 20 = +270.9 ( c 0.32, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 3-butyl-2-oxo-6-( p -tolyl)-3, 4-dihydro-2 H -pyran-4-carboxylate: C19 H24 O4 dr >95:5 er >99:1 [ α ] D 20 = +158.4 ( c 0.38, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 3-butyl-6-(4-methoxyphenyl)-2-oxo-3, 4-dihydro-2 H -pyran-4-carboxylate: C19 H24 O5 dr >95:5 er >99:1 [ α ] D 20 = +123.6 ( c 0.39, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 6-(4-chlorophenyl)-3-methyl-2-oxo-3, 4-dihydro-2 H -pyran-4-carboxylate: C15 H15 ClO4 dr 80:20 er >99:1 [ α ] D 20 = +248.5 ( c 0.27, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 3-benzyl-2-oxo-6-(4-(trifluoromethyl)phenyl)-3, 4-dihydro-2 H -pyran-4-carboxylate: C22 H19 F3 O4 dr 80:20 er >99:1 [ α ] D 20 = +172.9 ( c 0.31, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 S )-Ethyl 3-methyl-6-(naphthalen-2-yl)-2-oxo-3, 4-dihydro-2 H -pyran-4-carboxylate: C19 H18 O4 dr 50:50 er >99:1 [ α ] D 20 = +220.3 ( c 0.34, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 S ) Abstract : (3 S, 4 R )-Ethyl 3-methyl-6-(naphthalen-2-yl)-2-oxo-3, 4-dihydro-2 H -pyran-4-carboxylate: dr 50:50 er >99:1 [ α ] D 20 = −91.9 ( c 0.37, CHCl3 ) Source of chirality: (5a R, 10b S )-2-mesityl-5a, 10b-dihydro-4 H, 6 H -indeno[2, 1- b ][1, 2, 4]triazolo[4, 3- d ][1, 4]oxazin-2-ium chloride Absolute configuration: (3 S, 4 R )