February 2022

Here we present our work on a Kiyooka aldol protocol for the stereoselective synthesis of tertiary alcohols. In the obtained products, three oxygenated carbon atoms that could further be differentiated flank the chiral tertiary alcohol. This methodology can be applied to simple aromatic or aliphatic aldehydes and more complex substrates bearing a chiral center in the α- and/or β-position. For complex substrates, an unexpected dependency between stereoselectivity and double-bond geometry of the ketene acetal was observed. Furthermore, applications in or towards the synthesis of natural products are presented.1 Introduction2 Scope of the Reaction3 Synthetic Applications4 Conclusion

Unsymmetrical 1,1,2-triacylalkenes were conveniently prepared by the oxidative coupling of 1,3-keto esters with terminal alkynes by employing 4.0 equivalents of inexpensive ceric ammonium nitrate (CAN) as the oxidant in acetonitrile as the solvent at 0 °C. The method is milder than previously reported methods and can be conducted under air, thereby demonstrating its practicality and versatility for preparing these useful building blocks. The reaction is believed to occur by a single-electron-transfer process of the 1,3-keto ester substrate initiated by CAN to generate an α-radical species that quickly adds to the terminal alkyne partner in the reaction. Subsequent oxidation of the resulting vinyl radical by air and CAN then leads to the formation of the triacylalkene product as a mixture of E- and Z-isomers. The reaction was shown to be general, with 27 illustrative examples of the formation of the desired products in up to quantitative yield and with moderate to excellent alkene geometrical selectivities.

A mild and convenient method for the synthesis of 2,2-dihaloketones and gem-dihalolactols has been developed. For the synthesis of 2,2-dihaloketones, alkynes were employed as substrates to react with halogenating agents, Cl2 or ClBr, that were generated in situ from aqueous HCl and NCS or NBS, respectively. On the other hand, gem-dihalolactols could be prepared from alkynol substrates by using the same reaction conditions. This method could be applied to a broad range of substrates to give the corresponding products in low to good yields.