Furyllithium

Furyllithium reacts rapidly with trialkylborons though the furylborons 91 believed to be formed are not actually isolated. Treated with an electrophile (iodine or A-chlorosuccinimide), they transfer one alkyl residue to the furan ring and eject the boron residue in a reaction well known in other series (Scheme 46). The 2-alkylfurans are indeed produced in excellent yields and the method is better than many other syntheses.236... 

In the presence of zinc iodide, 2-furyllithium undergoes stereoselective addition to afford the anti adduct 10 with high selectivity. This adduct can be transformed into D-ribulose through standard sequences (6). 

Treating 2-furyllithium (derived from deprotonation of furan with n-BuLi) with ZnCl2 gave 2-furylzinc chloride, which then was coupled with 1,3-dibromobenzene to furnish bis-furylbenzene 12 [20, 21]. In addition, 2-furylzinc chloride was coupled with 4-iodobenzoic acid to give adduct 13. The Negishi reaction conditions were compatible with the carboxylic acid [22]. 

Addition of 2-furyllithium to the reagent afforded a 2 3 anti/syn ratio on addition of various zinc halides, this very modest si facial preference was overturned, resulting in an almost exclusive re-face addition. The resulting anti-addition product was parlayed into D-ribulose in four steps (eq 3). ... 

A synthesis of (+)-KDO has been reported by Martin and Zinke [118], which relies on the highly stereoselective addition of 2-furyllithium to 2,3-O-isopropylidene-D-glyceraldehyde R)-24. 

Table Effect of Additive on the Stereoselective Reaction of 2-Furyllithium with (13) ...

Older methods of preparing furanthiols and their derivatives have been overshadowed by lithiation techniques in which the metallated furan is treated with sulfur and alkylated to give the desired alkylthiofurans.198,199 Phosphoryl thioesters are obtained in the same way, as are their selenium equivalents.200 2-Furyllithium affords lithium furan-2-selenite when treated with selenium dioxide.201... 

The reaction of di(2-furyl)sulfoxide with 2-furyllithium did not give any ligand coupling product over a wide range of temperatures. 101... 

While successful couplings with a-haloacetals are rare (elimination of HBr and/or alcohol usually is the main reaction), satisfactory yields of alkylation products have been obtained from the reactions of 2-furyllithium and of 2-thienyllithium with BrCH2CH(OEt)2 in THF [43]. This haloacetal is less reactive than simple primary alkyl bromides. Addition of HMPT, in order to give higher rates of conversion, had an adverse effect due to promotion of the elimination reaction [9]. With phenyl-lithium, which is more strongly basic than the heteroaryllithiums, elimination predominated, even in the absence of HMPT [9]. 

Such side reactions can be avoided by inverse addition using a large excess of the chloroformate. We have described some very successful reactions with lithium acetylides [6, 7]. Addition of solutions of 2-furyllithium and of 2-thienyllithium to a large excess of methyl chloroformate also gave good results, but a low yield of methyl benzoate was obtained with the stronger base phenyllithium [9]. 

With the less basic 2-thienyllithium, mainly the dithioester, 2-thienyl-C(S)SCH3 (resulting from carbophilic attack and subsequent methylation), was obtained. 2-Furyllithium also mainly gave the dithioester. By using the Grignard derivatives, the pure dithioesters were obtained in excellent yields [55] ... 

Whereas interaction between 2-thienyllithium and 2-furyllithium and carbon disulfide in THF affords the corresponding dithioates RCSSLi as the predominant products, aryllithium compounds seem to attack mainly on sulfur with formation of arenethiolates and tarry products [9]. If during the addition of carbon disulfide copper bromide is present in the solution, however, the desired formation of Ar—CSSLi does take place and subsequent addition of methyl iodide affords the dithioesters in good yields. Good results are also obtained when using less than stoichiometric amounts of CuBr. We therefore presume that carbon disulfide reacts more easily with the arylcopper intermediate than with aryllithium copper is subsequently transmitted from the copper dithioate to aryllithium. 

Auf analoge Weise wird mit 2-Furyllithium 2-(2-Furyl-2-imino-l,1,1-trimethoxy-ethan (R = 2-Furyl 31 %) erhalten. 

The stereoselective addition of 2-furyllithium to aldehydes 167 or 893 in the presence of excess zinc bromide in THF at —20 °C proceeds with 98% stereoselectivity to provide either 170 or 894. In both cases the i -geometry of the carbinol is obtained. 

T. Mukaiyama, Y. Yuki, and K. Suzuki, The stereoselective synthesis of L-tagatose An application of Zn (II) mediated highly stereoselective addition of 2-furyllithium to polyoxygenated aldehyde, Chem. Lett., 1169 (1982). 

Recently, we described a general approach to the synthesis of 6-amino-6-deoxy-uloses [34, 35]. The applied methodology involved diastereoselective addition of 2-furyllithium (60) to N,N-diprotected a-amino aldehydes. The application of N,N-diprotected D-alaninals 67a, 67b, and 67c to this reaction afforded adducts 68 with high diastereoselectivity (Scheme 15). 

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