Diastereoselective annulation of 4-hydroxypyran-2H-ones with enantiopure 2,3-dideoxy-alpha,beta-unsaturated sugar aldehydes derived from respective glycals.
One-pot condensations of 4-hydroxypyran-2H-ones 1 and 2, respectively, with various enantiopure 2,3-dideoxy-alpha,beta-unsaturated carbohydrate enals in the presence of l-proline in EtOAc at room temperature generated pyrano-pyrones. It was observed that, while benzyl-protected carbohydrate enals on condensation with 1 or 2 under the above conditions produced an inseparable diastereomeric mixture in a ratio of 1:1, the acyl-protected carbohydrate enals on treatment with 1 or 2 under identical conditions yielded products with moderate to very high diastereoselectivity. A remarkable asymmetric induction was noticed from the C-4 stereogenic center of the acyl-protected carbohydrate enals. An almost complete diastereoselectivity was observed in those reactions that involved condensation of 1 with acetyl-protected enals 5 and 7. The reaction of 2 with 5 also proceeded diastereoselectively to furnish the corresponding annulated product. The reaction presumably took place by C-1,2-addition of the pyrone onto the iminium salt of the alpha,beta-unsaturated carbohydrate enal generated in situ, followed by beta-elimination and cyclization of the 1-oxatriene involving a 6pi-electron electrocyclic process to yield a 2H,5H-pyrano[3,2-c]pyran-5-one derivative.
Sagar
Ram
R
Division of Medicinal and Process Chemistry, Central Drug Research Institute (CDRI), Lucknow 226001, India.
Singh
Pushpa
P
Kumar
Rishi
R
Maulik
Prakas R
PR
Shaw
Arun K
AK
D000447:Aldehydes / Q000737:chemistry*; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011392:Proline / Q000737:chemistry*; D011714:Pyrans / Q000737:chemistry*; D013237:Stereoisomerism
D000447:Aldehydes; D002241:Carbohydrates; D011714:Pyrans; D011392:Proline