Aldehyde (Prepared in-house)

Tris(trimethylsilyl)silane [(TMS)₃SiH] (Sigma-Aldrich)

Azobis(isobutyronitrile) (AIBN)

Benzene (Distilled from sodium-benzophenone ketyl)

To a solution of the aldehyde (80 mg, 0.25 mmol, 1 equiv.) in benzene (4 mL) were added (TMS)₃SiH (117 μL, 0.38 mmol, 1.5 equiv.) and AIBN (4 mg, 0.02 mmol, 0.08 equiv.). The solution was sparged by bubbling argon through the solution for 30 minutes after which the solution was maintained under an atmosphere of argon and heated at reflux for 4 hours. After cooling and removal of the solvent in vacuo the remaining residue was purified by flash column chromatography (silica gel, EtOAc-hexane, 1:20) to yield the cyclopentane (134 mg, 94%) as a mixture of four diastereoisomers. Integration of the methyl ether (OMe) signals between 3.2-3.4 ppm in the ¹H NMR spectrum established the diastereoisomeric ratio to be 35:25:20:20.

The radical reducing agent (TMS)₃SiH has been used as a less toxic substitute for Bu₃SnH and in many situations shows similar reactivity to the more commonly used tin-based reagent (see Other References 1). In this example (TMS)₃SiH is able to replace Bu₃SnH in a ketyl radical cyclization (Page 735), however, the stronger silicon-oxygen bond that is formed results in the protection of the new secondary alcohol as a silyl ether. Overall, the reaction produces a new 5-membered ring, two contiguous asymmetric centres (secondary alcohol and protected tertiary alcohol) with in situ protection of the secondary alcohol.
Note 1. The (TMS)₃Si (sisyl) group has been shown to be a photolabile protecting group, being cleaved by exposure to UV light (254 nm), and also hydrolytically labile as is the case for other silyl ethers (see Other References 2). This provides an orthogonal protection strategy even in the presence of a TBS ether.

GC-MS: t_R = 38.65, 38.88 (2 diastereoisomers), 39.01 min

HRMS (ESI): calcd for C₂₄H₅₆O₅Si₅Na [M + Na⁺] 587.2866, found 587.2881

 

Hong, L. P. T.; Chak, C.; Donner, C. D. Org. Biomol. Chem., 2013, 11, 6186-6194.

1. Chatgilialoglu, C. Acc. Chem. Res., 1992, 25, 188-194; Chatgilialoglu, C. Chem. Eur. J., 2008, 14, 2310-2320.

2. Brook, M. A.; Balduzzi, S.; Mohamed, M.; Gottardo, C. Tetrahedron, 1999, 55, 10027-10040.