@ Pergamon Tetrahedrontitters, Vol. 38, No. 38, pp.6625-6626, 1997 01997 ElsevierScienceLtd All rightsrewved.Printedin OrsatBritain PII: SO040-4039(97)01534-7 Oo40-4039/97$17.00+ o.(l) A Novel Synthesis of the Fluorene Skeleton E. J. Corey,* Mihai D. Azitnioara and Axel K. Fischer DepartmentofCbemistrysnd ChemiealBiology,HarvardUniversity,Cambridge,Massachusetts02138 Summary: 1,4,6-Trimethyl-9-trifluoroacetyl’uorene I has been synthesized in one potfrom 2- chloro-p-qlene 2 and has been characterized by single-crystal X-ray diffraction. O 1997 Elsevier Science Ltd. Lithium piperidide in ether has been reported to be a better benzyne-producing reagent than phenyllithium, whereas the generated benzyne, given a choice, reacts preferentially with phenyllithium over piperidide.1 However, a 1 : 1mixture of the two reagents in tetrahydrofuran (’H-IF),when treated sequentially with 2-chloro-p xylenez (2) and then ethyl tri.fluoroacetate, afforded the substituted fluorene 1 in 8ZZ0 yield, rather than the expected 3,6-dimethyl-2-phenyl-a, ct,ct-trifluoroacetophenone3.3 This result can be rationalized by the series of reactions shown in Scheme 1. If competitive deprotonations take place at position 3 and at the benzylic position of 2, to yield 4 and 5, respectively, 4 can generate benzyne 6, which then reacts preferentially with 5, rather than with either phenyllithium or lithium piperidide. The other benzylic position of 2 is not deprotonated, since no 1,4,7-trirnethylfluot.eneisomer of 1 has been observed. This suggests that the formation of 5 is favored by complexation effects involving lithium and the ortho-chlorine atom, o CF3 & /\ /\ +/ 1 Scheme 1 0 %) I; CF’ 1: 3 c NLI +: cl 1; RLI -RH 2 CWC%tEt 1 + c1 1; LI 4 Li + cl 1; -lJcl w :1 6 5 -I-ICI & E&’ 9 6 6625