One-pot Jeffery-Heck and Reduction Sequence: Synthesis of Alcohols and Applied to the Synthesis of Flavan Natural Products

An effective and practical sequential one-pot [Pd]-catalyzed Jeffery-Heck reaction followed by reduction protocol is designed for the direct synthesis of 1,3-diphenylpropan-1-ols and 3-phenylpropan-1-ols starting from allyl alcohols and iodoarenes. Interestingly, 1,3-diphenylpropan-1-ols are known to be the synthetic precursors of biologically active un-natural compounds. Moreover, the de-hydroxylated 1,3-diphenylpropan-1-ols, i. e., 1,3-diarylpropanes exist as core structure in griffithane natural products isolated from Combretum griffithii stems. In addition, these systems are potential synthetic precursors of flavans with diverse functionalities on aromatic rings. Significantly, the strategy was further extended to the synthesis of natural product 7-methoxy-3′,4′-methylenedioxy flavan, which has been isolated from plant of Ageratum conyzoides and the formal synthesis of the 4′-hydroxy-7-methoxy flavan, an anti-feedant compound isolated from Lycoris raliata species, from the corresponding 2'-bromo-1,3-diphenylpropan-1-ol precursors by using an effective copper-catalyzed intra-molecular Buchwald-Hartwig cross-coupling as a key transformation.