[53101-93-2] · C4H3LiO · 3-Lithiofuran · (MW 74.007)
(nucleophilic organolithium reagent useful for alkylation; addition to ketones, acid chlorides, aldehydes, amides, lactones, carbon dioxide, nitrones, epoxides, sulfinate esters, boronic esters, metal carbonyls, borates, metal halides; affords intermediates for organometallic coupling reactions)
Alternate Name: b-furyllithium.
Preparative Methods: metalation of Furan at the 3-position requires a metal-halogen1-7 or metal-metal exchange8 since deprotonation of furan occurs preferentially at the 2-position. 3-Lithiofuran (1) (eq 1)1-3 is prepared by the treatment of 3-iodofuran (2a) with n-Butyllithium in ether or THF (-78 °C);4,5 by the treatment of 3-bromofuran (2b) with n-butyllithium in THF (-78 °C);6,7 or by the reaction of 3-tri-n-butylstannylfuran (2c) with n-butyllithium in THF (-78 °C).8
Handling, Storage, and Precautions: the reagent is generated in situ, under anhydrous conditions in an inert atmosphere at low temperatures (<=-40 °C), and used shortly after preparation. The ability to store the reagent is not clear. As n-BuLi is employed, the precautions for preparation and use would mirror those of n-BuLi and related organometallic reagents. It has been demonstrated that good temperature control is important to the regiochemical integrity of the reagent. Temperatures exceeding -40 °C during the course of reagent generation and use permit isomerization of 3-lithiofuran to the more thermodynamically stable 2-lithiofuran (eq 2).7
3-Lithiofuran (1) reacts readily with allylic halides and primary alkyl halides, in the presence of Hexamethylphosphoric Triamide, to give 3-substituted furans (eq 3).7
3-Lithiofuran (1) adds to acid chlorides to give furyl ketones (eq 4),5 to aldehydes (eq 5),7,9,10 and to ketones (eq 6)11 to give carbinols. The reaction of 3-lithiofuran (1) with lactones affords the related lactols (eq 7).12 Carbon Dioxide reacts with 3-lithiofuran (1) to provide 3-furoic acid.8,13 Although 3-lithiofuran is considered to be relatively unreactive, it will add to amides to give amines via the reduction of an intermediate enamine (eq 8).14,15
Treatment of 3-lithiofuran (1) with CuBr.SMe2 (see Copper(I) Bromide) and 2-lithiofuran affords a higher order cuprate which adds to epoxides, giving carbinols (eq 9).16 3-Lithiofuran (1) affords branched hydroxylamines upon reaction with nitrones (eq 10).17 (-)-(S)-Menthyl p-toluenesulfinate,18 an optically pure boronic ester (see (-)-(1R,2S,5R)-Menthyl (S)-p-Toluenesulfinate),19 and Hexacarbonylchromium20 also react with 3-lithiofuran (1) to provide an optically pure furyl sulfoxide (eq 11), an optically pure borinic ester (eq 12), and a furyl-substituted chromium carbene (eq 13), respectively.
A variety of substituted 3-lithiofurans has been prepared by metal halogen exchange [(3),21 (4),22 (5),23 (6)24]. However, when blocking [(7),25 (8)26] and/or coordinating groups at the 4-position (9)27 are present, metalation reactions provide an effective path to 3-lithiofurans. 3-Lithiofurans (8) and (9) have undergone metal-metal exchange to afford the bromozinc26 and tin reagents,28 respectively. These reagents, as well as a boronic acid produced from (9),27 have been employed in palladium-catalyzed carbon-carbon bond forming reactions.
Mark A. Collins & Steven P. Tanis
The Upjohn Company, Kalamazoo, MI, USA