Asymmetric Pentenylation of Aldehydes: A New Benchmark for the Preparation of Ethyl-Substituted Homoallylic Alcohol

Abstract

A highly diastereo- and enantioselective boron-mediated pentenylation reaction is presented. The chiral pentenylborane ­reagents, which are derived from pinene, undergo addition to various aldehydes to afford ethyl-substituted homoallylic alcohols in good yield and high stereoselectivity. The latter are then easily converted into the corresponding α,β-unsaturated δ-lactones using an acylation/ring-closing metathesis sequence. The relative and absolute stereochemistry is exclusively controlled by the reagent.

Key words

asymmetric pentenylation - α,β-unsaturated lactone - ring-closing metathesis

References and Notes

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9

It is noteworthy that optically active ethyl-substituted homoallylic alcohols are exclusively accessed through aldol chemistry.

10

General Procedure for the syn- Selective Boron-Mediated Pentenylation Reaction: To a stirred suspension of t-BuOK (1.1 equiv) and (Z)-2-pentene (2.2 equiv) in THF at -78 ˚C was added n-BuLi (1.1 equiv) dropwise. After complete addition, the reaction mixture was stirred for 5 min at
-50 ˚C. The resulting orange solution was then cooled
to -78 ˚C and to it, was added dropwise a solution of (+)-methoxydiisopinocampheylborane in Et₂O (1.35 equiv, 0.5 M in Et₂O). After stirring for 30 min at -78 ˚C, boron trifluoride diethyl etherate (1.5 equiv) was added followed by the aldehyde (1 equiv). The reaction mixture was then stirred for an extra 5 h at the same temperature before it was treated with a 3 M solution of NaOH and H₂O₂ and refluxed for 1 h. The reaction mixture was then extracted with EtOAc, washed with brine, dried over MgSO₄ and concentrated under reduced pressure. The crude residue was purified by flash column chromatography on silica gel using a gradient of eluents to afford the corresponding homoallylic alcohol.

13

Same procedure as previously employed except that the temperature was not raised to -50 ˚C after the addition of n-BuLi.