Science of Synthesis

Takahashi, K.; Nozaki, K., Science of Synthesis: C-1 Building Blocks in Organic Synthesis, (2014) 2, 207.

General Introduction

β-Hydroxyaldehydes are important synthetic intermediates that are usually constructed by aldol reaction of aldehydes or their isolated enolate equivalents with carbonyl compounds. Recent advances in aldol reactions have achieved high chemo- and stereoselectivities, but they require the use of stoichiometric quantities of the reagents to prepare the metal enolates or enamines. Transition-metal-catalyzed hydroformylation of epoxides with gaseous hydrogen/carbon monoxide is an alternative synthetic pathway to β-hydroxyaldehydes which is advantageous in the sense that it gives no stoichiometric waste. The most studied substrates are oxirane (ethylene oxide) and 2-methyloxirane (propylene oxide), both of which are commercially available in large quantities. The hydroformylation of epoxides was first reported by Watanabe and co-workers in 1964,[‌1‌,‌2‌] and then intensively studied by the group at Shell for many years. In industry, a one-pot, two-step reaction, the hydroformylation/hydrogenation of epoxides, plays a more significant role, providing 1,3-diols as the hydrogenation product of the initial β-hydroxyaldehydes. Within this chapter, the reaction mechanism for the hydroformylation of epoxides will be first discussed and then examples of reported catalyst systems for the hydroformylation and hydroformylation/hydrogenation of oxirane and 2-methyloxirane will be described. Then, hydroformylation of 7-oxabicyclo[4.1.0]heptane (cyclohexene oxide) followed by aldehyde protection will be mentioned, and finally the silylformylation of various epoxides will be discussed.

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