A diastereoselective Co2(CO)8-mediated Pauson–Khand reaction (PKR) of siloxy-tethered 1,7-enynes for the synthesis of cyclopentaoxasilinones has been developed. This transformation can be performed on a multigram scale and is characterized by a broad substrate scope, functional group compatibility, and high chemo- and diastereoselectivity. Oxidation of the resulting cyclopenta­oxasilinones delivers stereoenriched β-alkylated cyclopentenones, which are inaccessible by intermolecular PKRs. This research provides a practical solution to the challenges associated with the classical intermolecular PKR.

A diastereoselective Co₂(CO)₈-mediated Pauson-Khand reaction (PKR) of siloxy-tethered 1,7-enynes for the synthesis of cyclopentaoxasilinones has been developed. This transformation can be performed on a multi-gram scale and is characterized by broad substrate scope, functional group compatibility, and high chemo- and diastereoselectivity. Oxidation of the resulting cyclopentaoxasilinones delivers stereoenriched β-alkylated cyclopentenones, which are inaccessible by intermolecular PKRs. This research provides a practical solution to the challenges associated with the classical intermolecular PKR.

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Propargyl alcohols S23 -S25 purchased commercial sources and used as is without further purification. B. 1,7-Siloxy-Tethered Enynes General Procedure 1: 1,7-Siloxy-Tethered Enyne SynthesisA flame dried round-bottom flask equipped with a magnetic stir-bar was sequentially charged with dry CH 2 Cl 2 (0.5 M with respect to the propargyl alcohol), allyldiisopropylchlorosilane S21 29 (1.2 equiv), DMAP (0.2 equiv), and NEt 3 (2.0 equiv) under an inert atmosphere (N 2 ). The reaction mixture was cooled to 0 °C. In a separate flame-dried pear-shaped flask, the propargyl alcohol (S1 -S20 and S23 -S25; 1.0 equiv) was dissolved in CH 2 Cl 2 (1.0 M) and added dropwise to the 0 °C reaction mixture via syringe. This was followed by rinsing the pear-shaped flask with an additional portion of CH 2 Cl 2 (0.3 mL). The cooling bath was removed, and the reaction mixture allowed to stir at room temperature (25 o C) for 18 h. Upon consumption of the propargyl alcohol, as noted by TLC analysis, the reaction mixture was quenched with sat. aq. NH 4 Cl. The aqueous phase was extracted with CH 2 Cl 2 (3x 20 mL), and the combined organic phases were washed with brine, dried with MgSO 4 , filtered, and concentrated under reduced pressure. Flash chromatography (hexanes -0.25% Et 2 O/hexanes) yielded enynes 1a-j and 5a-k as colorless oils.

Propargyl alcohols S23 -S25 purchased commercial sources and used as is without further purification. B. 1,7-Siloxy-Tethered Enynes General Procedure 1: 1,7-Siloxy-Tethered Enyne SynthesisA flame dried round-bottom flask equipped with a magnetic stir-bar was sequentially charged with dry CH 2 Cl 2 (0.5 M with respect to the propargyl alcohol), allyldiisopropylchlorosilane S21 29 (1.2 equiv), DMAP (0.2 equiv), and NEt 3 (2.0 equiv) under an inert atmosphere (N 2 ). The reaction mixture was cooled to 0 °C. In a separate flame-dried pear-shaped flask, the propargyl alcohol (S1 -S20 and S23 -S25; 1.0 equiv) was dissolved in CH 2 Cl 2 (1.0 M) and added dropwise to the 0 °C reaction mixture via syringe. This was followed by rinsing the pear-shaped flask with an additional portion of CH 2 Cl 2 (0.3 mL). The cooling bath was removed, and the reaction mixture allowed to stir at room temperature (25 o C) for 18 h. Upon consumption of the propargyl alcohol, as noted by TLC analysis, the reaction mixture was quenched with sat. aq. NH 4 Cl. The aqueous phase was extracted with CH 2 Cl 2 (3x 20 mL), and the combined organic phases were washed with brine, dried with MgSO 4 , filtered, and concentrated under reduced pressure. Flash chromatography (hexanes -0.25% Et 2 O/hexanes) yielded enynes 1a-j and 5a-k as colorless oils.