[129471-18-7] · C6H11LiO2 · 4-Ethylenedioxybutyllithium · (MW 122.093)
(reagent used as a bis homoenolate equivalent for the production of aldehydes and lactones)
Preparative Method: solutions of the title compound can be obtained by treatment of a solution of chlorobutyraldehyde ethylene acetal (commercially available) in THF under inert gas with a solution of 2.4 equiv of Lithium Naphthalenide in THF at -78 °C for 7 h. Solutions are used directly.
Handling, Storage, and Precautions: the reagent is purported to be stable at -78 °C.
This lithium reagent was reported for the first time in 1990 by Ramon and Yus1 using the aromatic radical anion electron transfer technique (1 -> 2).2 A variety of Grignard counterparts to the reagent are known and had seen extensive use prior to 1990. The advantage of the lithium reagent is its generation at low temperature because these reagents are quite basic and readily decompose at ambient temperatures.3 However, the corresponding magnesium chloride can be prepared in high yield at room temperature in THF if the Grignard is prepared in high concentration (ca. 5 M).4
The reagent (2) reacts with a variety of carbonyl-containing electrophiles at low temperature to provide adducts in moderate to good yield (eqs 2 and 3).
Reaction with aldehydes and ketones gives the corresponding alcohols while reaction with benzonitrile or the amides provides the protected keto aldehydes (eq 4). Reagent (2) also reacts with Phenyl Isothiocyanate and benzaldehyde phenylimine to give adducts. However, (2) does not react well with alkyl halides either by itself or in the presence of CuI salts. Further, reaction with nitriles and anhydrides results only in proton transfer, attesting to the basicity of the species.
Treatment of (2) with a catalytic amount of CuBr-dimethyl sulfide complex (see Copper(I) Bromide) allows conjugate addition to 2-cyclohexen-1-one to occur, resulting in the 1,4-adduct in 61% yield (eq 5).
Hydrolysis of the adducts of (2) and carbonyl compounds with acid affords cyclic hemiacetals. These can be oxidized with CrVI reagents to give d-lactones in 30-60% overall yield from chloroacetal (1) (eq 6).
Reaction of (2) with a-trimethylsilyloxy aldehydes and ketones leads after hydrolysis to 6,8-dioxabicyclo[3.2.1]octanes, substructures found in the frontalin/brevicomin metabolite class (eq 7).6
3-Butenyllithium (3)7 has been used as a masked aldehyde bishomoenolate equivalent. Due to the amount of unmasking involved, however, this is not preferable to (2).
Kim F. Albizati
University of California, San Diego, CA, USA