Synthesis of 2-chromanol by hydroformylation of 2-hydroxystyrene derivatives

2-Benzyloxy- and 2-tosyloxystyrene were hydroformylated under different reaction conditions with the aim to obtain the corresponding linear aldehydes, valuable intermediates to 2-chromanol, a structural moiety present in several interesting therapeutically active molecules. The best results were obtained by using the catalytic precursor Pt(Xantphos)Cl₂ in toluene or the water-soluble catalytic system Rh(CO)₂acac/Xantphos(SO₃Na)₂ in the biphasic medium water/toluene. Rather good regioselectivities were also achieved employing the unmodified complex Rh₄(CO)₁₂ at high temperature and low pressure for very short reaction times: unfortunately the chemoselectivity of the process was not satisfactory, due to the extensive formation of the substrate hydrogenation product.