Formal [4 + 2] cycloaddition of donor-acceptor cyclobutanes and aldehydes: stereoselective access to substituted tetrahydropyrans.
A highly diastereoselective synthesis of 2,6-cis-disubstituted tetrahydropyrans (THPs) via Lewis acid-catalyzed formal [4 + 2] cycloaddition of donor-acceptor cyclobutanes and aldehydes has been developed. THP products are formed in up to 96% yield and 99:1 diastereoselectivity. Aromatic, cinnamyl, and aliphatic aldehydes are competent dipolarophiles in this system. This methodology was extended to a [[2 + 2] + 2] cycloaddition of 4-methoxystyrene, dimethyl methylidene malonate, and an aldehyde to furnish THPs directly without prior isolation of the cyclobutane.
Parsons
Andrew T
AT
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA.
Johnson
Jeffrey S
JS
D000447:Aldehydes / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D003500:Cyclization; D003503:Cyclobutanes / Q000138:chemical synthesis / Q000737:chemistry*; D008314:Malonates / Q000737:chemistry; D011714:Pyrans / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000447:Aldehydes; D000475:Alkenes; D003503:Cyclobutanes; D008314:Malonates; D011714:Pyrans