Cycloaddition reactions on activated exo-glycals

Cycloaddition reactions of activated exo-glycals and nitrones proceeded only under microwave activation, with excellent facial selectivities on furanoglycosylidenes and good stereocontrol on the nitrone producing only two diastereomeric spiroisoxazolidines. α/β-Spiro sugar-isoxazolidines are obtained from pyrano exo-glycals. The cycloaddition reaction with nitrile oxide proceeds at room temperature and gives open-chain isoxazoles due to facile β-elimination of the sugar ring oxygen on the intermediate isoxazoline ring system. All the heterocycles obtained this way can be regarded as nucleoside analogues.

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Methyl (3R,4R,5S,7S,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC20H33NO8[α]D25=-159.1 (c 1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4R,5S,7S,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC20H33NO8[α]D26=-70.1 (c 1.1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (4R,5S,7S,8R,9R)-8,9-isopropylidenedioxy-2-benzyl-7-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC23H31NO8[α]D26=-91.2 (c 2.0, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3R,4S,5S,7S,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-phenyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC23H31NO8[α]D25=+1.8 (c 1.1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4S,5S,7S,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-phenyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC23H31NO8[α]D26=-50.1 (c 0.4, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4S,5S,7S,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC20H33NO8[α]D25=+3.5 (c 1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (4S,5S,7S,8R,9R)-8,9-isopropylidenedioxy-2-benzyl-7-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC23H31NO8[α]D26=+25.5 (c 1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4R,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(methoxymethoxy)methyl]-3-phenyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC21H29NO8[α]D25=-127.3 (c 1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3R,4R,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(methoxymethoxy)methyl]-3-phenyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC21H29NO8[α]D25=-9.0 (c 1.1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3R,4R,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(methoxymethoxy)methyl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC18H31NO8[α]D25=-89.9 (c 0.9, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4R,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(methoxymethoxy)methyl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC18H31NO8[α]D25=-45.7 (c 1.4, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3R,4R,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-benzyl-7-[(methoxymethoxy)methyl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC24H35NO8[α]D26=-199.6 (c 1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4R,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-benzyl-7-[(methoxymethoxy)methyl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC24H35NO8[α]D26=-27.0 (c 1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (4R,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-benzyl-7-[(methoxymethoxy)methyl]-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC21H29NO8[α]D26=-80.6 (c 1.3, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3R,4S,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(methoxymethoxy)methyl]-3-phenyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC21H29NO8[α]D25=-11.8 (c 1.1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4S,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(methoxymethoxy)methyl]-3-phenyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC21H29NO8[α]D25=-169.7 (c 1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4S,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(methoxymethoxy)methyl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC18H31NO8[α]D25=-9.3 (c 1.1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3R,4S,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-methyl-7-[(methoxymethoxy)methyl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC18H31NO8[α]D25=-131.7 (c 0.9, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4S,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-benzyl-7-[(methoxymethoxy)methyl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC24H35NO8[α]D25=-40.3 (c 1.1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3R,4S,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-benzyl-7-[(methoxymethoxy)methyl]-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC24H35NO8[α]D25=-97.4 (c 0.9, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (4S,5S,7R,8R,9R)-8,9-isopropylidenedioxy-2-benzyl-7-[(methoxymethoxy)methyl]-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC21H29NO8[α]D26=-44.7 (c 0.8, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4R,5R,7R,8R,9S,10R)-8,9,10-tris(benzyloxy)-7-[(benzyloxy)methyl]-2-methyl-3-phenyl-1,6-dioxa-2-azaspiro[4.5]decane-4-carboxylateC45H47NO8[α]D25=+18.0 (c 1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3R,4R,5R,7R,8R,9S,10R)-8,9,10-tris(benzyloxy)-7-[(benzyloxy)methyl]-2-methyl-3-phenyl-1,6-dioxa-2-azaspiro[4.5]decane-4-carboxylateC45H47NO8[α]D25=+38.6 (c 0.4, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4S,5S,7R,8R,9S,10R)-8,9,10-tris(benzyloxy)-7-[(benzyloxy)methyl]-2-methyl-3-phenyl-1,6-dioxa-2-azaspiro[4.5]decane-4-carboxylateC45H47NO8[α]D26=+16.6 (c 2.5, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4S,5S,7R,8R,9S,10R)-8,9,10-tris(benzyloxy)-7-[(benzyloxy)methyl]-2-methyl-3-propyl-1,6-dioxa-2-azaspiro[4.5]decane-4-carboxylateC42H49NO8[α]D25=+13.0 (c 0.5, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3S,4R,5R,7R,8R,9S,10R)-8,9,10-tris(benzyloxy)-7-[(benzyloxy)methyl]-2-methyl-3-propyl-1,6-dioxa-2-azaspiro[4.5]decane-4-carboxylateC42H49NO8[α]D25=+31.8 (c 1.1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (3R,4S,5S,7R,8R,9S,10R)-8,9,10-tris(benzyloxy)-7-[(benzyloxy)methyl]-2-methyl-3-propyl-1,6-dioxa-2-azaspiro[4.5]decane-4-carboxylateC42H49NO8[α]D25=+12.4 (c 0.4, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (4R,5R,7R,8R,9S,10R)-8,9,10-tris(benzyloxy)-7-[(benzyloxy)methyl]-2-benzyl-1,6-dioxa-2-azaspiro[4.5]decane-4-carboxylateC45H47NO8[α]D26=+35.0 (c 1, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (4R,5R,7R,8R,9S,10R)-8,9,10-tris(methoxymethoxy)-7-[(methoxymethoxy)methyl]-2-benzyl-1,6-dioxa-2-azaspiro[4.5]decane-4-carboxylateC25H39NO12[α]D25=+27 (c 0.9, CHCl3)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (1′R,2′R,3′S,4′R)-3-phenyl-5[(1′,2′-4′,5′-diisopropylidenedioxy, 3′-hydroxy)pentyl]-isoxazole-4-carboxylateC22H27NO8[α]D25=+26.2 (c 0.9, CHCl3)Source of chirality: natural and nitrile oxide–olefin cycloaddition

Methyl (1′R,2′S,3′R,4′R)-3-phenyl-5-[4′-hydroxy-1′,2′,3′,5′-tetra(benzyloxy)pentyl]-isoxazole-4-carboxylateC44H43NO8[α]D25=+38.7 (c 0.6, CHCl3)Source of chirality: natural and nitrile oxide–olefin cycloaddition

Methyl (3S,4R,5S,7S,8R,9R)-8,9-dihydroxy-7-[(1′R)-1′,2′-dihydroxyethyl]-2-methyl-3-propyl-1,6-dioxa-2-azaspiro[4.4]nonane-4-carboxylateC14H25NO8[α]D25=-21.2 (c 1.0, CH3OH)Source of chirality: natural and nitrone–olefin cycloaddition

Methyl (1′R,2′R,3′S,4′R)-3-phenyl-5[(1′,2′,3′,4′,5′-hydroxy)pentyl]-isoxazole-4-carboxylateC16H19NO8[α]D25=+13.2 (c 0.8, CH3OH)Source of chirality: natural and nitrile oxide–olefin cycloaddition