2-Lithiofuran addition

Martin and co-workers have utilized 1-lithiofuran addition as a key carbon-carbon bond-forming step for construction of 8,8a-di-ep/-castanospermine. Intermediate furan aduct 233 is elaborated to 234 via furan oxidation and thence to the castanospermine analogue 235 (Scheme 41). 

Transformation of chiral nitrones into enantiomer enriched a-chiral N -hydroxylamines and their derivatives, has been successfully employed in the enantioselective synthesis of (+ )-(R)- and (—)-(S)-zileuton (216). An expeditious synthesis of thymine polyoxin C (347), based on the stereocontrolled addition of 2-lithiofuran (a masked carboxylate group) to the A-benzyl nitrone derived from methyl 2,3-O-isopropylidene-dialdo-D-ribofuranoside, is described (Scheme 2.151) (194). 

Danishefsky et al. have to separate a mixture of diastereomeric alcohols after addition of 2-bro-mo-5-lithiofuran to their aldehyde 22 (Scheme 3), obtaining the desired diastereomer in a yield of 57 %. 22 was synthesized in an interesting pathway via the ring opening of the cyclobutanone 21. 

The aminohomologation of (/ )-24 via nitronate 53 can use the addition of 2-lithiofuran instead of 2-lithiothiazole. The furyl moiety can then be oxidized to the corresponding 2-aminoaldonic acids [67b]. Alternatively, the nucleophilic addition of alkoxy-methyllithium derivatives to nitrones of type 53 are either syn or anti selective in the absence or the presence of Et2AlCl, respectively. The adducts thus obtained were converted into C-4 building blocks and (3-hydroxy-a-aminoacids [67c]. 

Martin has made ample use of this strategy for the synthesis of various polyketide natural products. Furan 164, prepared by addition of lithiofuran to a lactaldehyde derivative, gave the bridged ketal 165 upon oxidation and acid catalyzed dehydration <99T3561>. The bicyclic architecture allowed highly diastereoselective reactions which led to 166, a key intermediate for... 

Steps KDO synthesis from furan presented Martin et al. [150]. The reaction started from addition of 2-lithiofuran to isopropylidene-D-glyceraldehyde (Scheme 59). 

When the desired aryllithium or heteroaryllithium species is not accessible using directed proton abstraction, then halogen-lithium exchange provides an efficient method for its formation. Bromine-lithium exchange is particularly popular and allows a regiospecific formation of the desired organolithium compound, which can then be used for subsequent carbon-carbon bond formation. For example, 3-lithiofuran can be obtained by treatment of 3-bromofiiran with n-butyllithium addition of an aldehyde gives the 3-substituted furan product (1.123). 

Trisubst. ethylene derivs. A soln. of (Z)-2-(l-butyl-l-hexenyl)-l,3,2-dioxaborinane in dry ether at —78° treated dropwise with a soln. of 2-lithiofuran (prepared from ethereal furan and -butyllithium at 0° for 0.5 h), stirred at -78° for 0.5 h and 0° for 1 h, solvent removed, methanol added at 0° followed by slow addition of a soln. of iodine in methanol with vigorous stirring at - 78°, 3 h later the mixture warmed to room temp, 3 M NaOH added, and worked up after 15 min 5-(2-furanyl)-(Z)-5-decene. Y 80%. This is part of a multistep regio- and geo-specific synthesis of ethylene from acetylene derivs., and is especially notable in that the product may contain 3 different groups on the unsaturation. F.e.s. H.C. Brown, N.G. Bhat, J. Org. Chem. 53, 6009-13 (1988). 

The rare sugar D-ribulose has been prepared from the chiral aldehyde (18) as shown in Scheme 2. An important feature of this synthesis is the first step in which 2-lithiofuran can be added with very high specificity (>95%) to (19) in the presence of zinc iodide, whereas in its absence little specificity is observed. It is therefore presumed that addition actually takes place to a zinc chelate of (18). 

Homologation of olefins by four carbon atoms is achieved by reaction of the derived borane (265) with buta-1,3-diene monoxide in the presence of catalytic amounts of oxygen. Trialkylboranes are also converted into the 4,4-dialkyl-c/j-but-2-ene-l,4-diols (266) in good yields by addition to a-lithiofuran and oxidation of the intermediate boroxarocyclohexenes (267) with hydrogen peroxide. ... 

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