Progress on the synthesis of 1,2,3,5,9-cyclodecapentaen-7-yne and supporting studies Citation Yang, Maximillian Y. (1992) Progress on the synthesis of 1,2,3,5,9-cyclodecapentaen-7-yne and supporting studies. Master's thesis, California Institute of Technology. doi:10.7907/bfhp-k953. https://resolver.caltech.edu/CaltechTHESIS:10042011-102102178 Abstract Progress on the synthesis of 1,2,3,5,9-cyclodecapentaen-7-yne (1), a compound structurally related to both (Z)-1,2,4-heptatrien-6-yne and the activated core of neocarzinostatin chromophore, is reported. The novel compound 1 is of theoretical interest as an example of a monocyclic 10-membered ring that fulfills the aromaticity requirements of Hückel's rule. The alcohol 24, envisioned to serve as a possible precursor to 1, has been synthesized. In related, collaborative studies, 1-bromo-4-trimethylsilylnaphthalene, 1-bromo-5-trimethylsilylnaphthalene, 2-bromo-7-trimethylsilylnaphthalene, 1-chloro- 4-trimethylsilylnaphthalene, 1-chloro-5-trimethylsilylnaphthalene, and 2-chloro-7- trimethylsilylnaphthalene have been synthesized. These compounds will be used in gas-phase studies as precursors to the corresponding naphthalene biradicals. These studies will determine the heat of formation of each corresponding naphthalene biradical. Item Type: Thesis (Master's thesis) Subject Keywords: Chemistry Degree Grantor: California Institute of Technology Division: Chemistry and Chemical Engineering Major Option: Chemistry Thesis Availability: Public (worldwide access) Research Advisor(s): Myers, Andrew G. Thesis Committee: Unknown, Unknown Defense Date: 1 November 1991 Record Number: CaltechTHESIS:10042011-102102178 Persistent URL: https://resolver.caltech.edu/CaltechTHESIS:10042011-102102178 DOI: 10.7907/bfhp-k953 Default Usage Policy: No commercial reproduction, distribution, display or performance rights in this work are provided. ID Code: 6704 Collection: CaltechTHESIS Deposited By: INVALID USER Deposited On: 04 Oct 2011 17:58 Last Modified: 09 Nov 2022 19:20 Thesis Files PDF - Final Version See Usage Policy. 8MB Repository Staff Only: item control page

Progress on the Synthesis of 1,2,3,5 ,9-cyclodecapentaen-7 -yne and Supporting Studies Maximillian Y. Yang In partial fulfillment of the requirements for the degree of Master of Science California Institute of Technology Pasadena, California November 1991 Abstract - Progress on the synthesis of 1,2,3,5,9-cyclodecapentaen-7-yne (1), a compound structurally related to both (Z)-1,2,4-heptatrien-6-yne and the activated core of neocarzinostatin chromophore, is reported. The novel compound 1 is of theoretical interest as an example of a monocyclic lO-membered ring that fulfills the aromaticity requirements of Ruckel's rule. The alcohol 24, envisioned to serve as a possible precursor to 1, has been synthesized. In related, collaborative studies, l-bromo-4-trimethylsilylnaphthalene, 1bromo-5-trimethylsilylnaphthalene, 2-bromo-7-trimethylsilylnaphthalene, l-chloro4-trimethylsilylnaphthalene, l-chloro-5-trimethylsilylnaphthalene, and 2-chloro-7trimethylsilylnaphtha1ene have been synthesized. These compounds will be used in gas-phase studies as precursors to the corresponding naphthalene biradicals. These studies will determine the heat of formation of each corresponding naph thalene biradical. 1 24 Table of Abbreyjatjons Bu . butyl CSA camphorsulfonic acid eq DMSO equivalents EtOAc ethyl acetate EtOH Et3N ethanol triethylamine h hour(s) IR infrared methyl Me MeOH dimethylsulfoxide methanol min minute(s) n normal NMR nuclear magnetic resonance Ph phenyl t Tf20 tertiary trifluoromethanesulfonic acid anhydride (triflic anhydride) THF tetrahydrofuran THP 1LC tetrahydropyran thin layer chromatography TMS trimethylsilyl Table of Contents Acknowledgments 1 Introduction 2 Synthesis of 24 Synthesis of Naphthalene Derivatives 5 8 References 10 Experimental for 24 12 Spectra 24 Experimental for Naphthalene Derivatives 33 Spectra 43 AckDQwled~eDts; I would like to thank the following people for their help and support throughout the course of my graduate studies at Caltech: Elaine KUQ for much needed moral support, technical advice, and explanations. Pete Dragovich for technical help and advice, for help in proofreading my thesis, and for well-appreciated loans of glassware and equipment during my first few months in lab. Katherine Widdowson for late night talk and company in lab, and for help in proofreading my thesis. My roommates and friends, Jack, Jerome, and Gary, for moral support and encouragement throughout. Yonchu Jenkins for lots of moral support and words of encouragement. And finally , I would like to thank Prof. Andrew Myers for his guidance and patience throughout 2 Introduction Within the last several years a new class of antitumor antibiotics has been defined on the basis of the proposed ability of these compounds to form highly reactive. DNA-bound biradical intermediates. These biradical intermediates have been implicated in the biological activity of these compounds. Examples include calichemicin and esperamicin 1 which are proposed to form a l,4-dehydrobenzene derivative via a Bergman-like rearrangement. 2 Similarly. studies carried out by the Myers lab on the neocarzinostatin (NeS) chromophore (2) indicate the formation of a 3.7-dehydroindene derivative3 (4) via a reactive cumulene intermediate (3) (Scheme I): Scheme I OH OH o ( 0 .. ·· CH 3 • CH 3 o o OCH3J:): o ,.,\ NHCH 3 CH 3 OH ,,\ O CoH J ) NHCH CH 3 OH OH OH 3 2 CH 3 OCH 3 4 3 3 Further studies carried out to elucidate the mechanistic aspects of the NCS biradical fomiation have included the synthesis and thermal rearrangement of (Z)-l,2,4-heptatrien-6'yne4 (Scheme II). Scheme II • • 6 The goal of the research presented here is the synthesis of l,2,3,5,9-cyclodecapentaen-7yne (I) , a monocyclic structure similar to both 3 and 5. This novel cumulene system contains the essential structural features of reactivity of both 3 and 5, but is nonetheless quite different in that' a symmetric resonance delocalized structure can be drawn for it. The classical Kekul6 structure for 1 is unsatisfactory since it does not show the symmetric nature of the molecule. 1 A framework molecular model of 1 shows the compound to be planar and to have very little bond or angle strain. This is significant since the 10 It electron containing compound would then fulfill the requirements for aromaticity under Hiickel's rule. This interesting possibility has been the motivation behind various unsuccessful attempts to the synthesize 1 and closely related lO-membered rings. 5 . 6 The parent [lOJ-annulene 7 is not aromatic since the strong steric interaction of the hydrogen atoms on the inside of the ring force the molecule out of planarity. This problem is not encountered in compound 1. On the other hand, the in-plane It electrons of 1 may interact, perhaps facilitating the formation of the biradical intermediate 8 analogous to that of 4 and 6. 4 • • 1 8 A successful synthesis of 1 would not only solve a synthetic problem that has been in the literature for over 40 years, it would also be of great theoretical interest. A successful synthesis of 1 would allow physical studies of this unusual molecule and perhaps bring new understanding to the current theories of aromaticity. The similarity of compound 1 to 3 and 5 and its hypothetical cyclization to the reactive biradical intermediate 8 would make it an interesting compound for further studies in biradical formation. In related, collaborative studies with the Squires lab, a series of naphthalene derivatives (Figure 1) were synthesized to be used as gas-phase precursors to the respective naphthalene biradicals. 7 In particular, l-chloro-5-trimethylsilylnaphthalene was synthesized as a precursor to 1,5-dehydronaphthalene (8) , a potential product from the thermal cyclization of 1. These gasphase studies may provide reliable, and otherwise elusive, thermodynamic data for each respective biradical. Figure 1 ~ Vy Br ¢o:S~ # # ~ ¢o:S~ 12 ~ # # 11 10 CI I ~ Br 9 Vy TMS"CVBr # # CI 13 14 5 Discussion The alcohol 24, envisioned to serve as a synthetic precursor to the hydrocarbon 1, was synthesized by the convergent multistep route outlined in Scheme IV and discussed in the following pages. This syn thesis featured the use of the same starting material, propiolic acid, and a common synthetic route to the two fragments 19 and 21. Scheme IV ( H 0 OH HI, Cui I~OH • o °C 25 °C 0 51-71% I~OMe CH2N2, ether, 0 95-100% 15 17 16 LiAIH4, ether, -78°C Et3N, ether, 25°C 63·67% 55 -75% 19 18 dihydropyran , CSA, CH2CI2 TMS----"==:----,, ~OTHP • a °C 83-90% H---=~---" NaOH, MeOH, 25 °C ~OTHP • 65-85% 20 TMS 19 ~OH pyridine, Tf 20 21 TMS • CH2CI2, -22 ° -78 °C 22 ~OTf TMS H n·BuLi, THF , -78 °C 21 \OTHP • ~ 23-36% 23 ) OTHP 6 Scheme IV (cont.) TMS CI3CCOOH, ~O CH3CN, 25°C '1 50-74% NaOH, MaOH, 25°C ~OH 62-67% 24 H )=s. H CH,oH 2S The alcohol 18 was synthesized from propiolic acid (15) by a slight modification of the procedure of Moss et aI. 8 Treatment of 15 with CuI and HI formed the acid 16. A small amount of trans product was produced, but it was easily removed by recrystallization. Diazomethane was used for methylation of the acid 16 (Moss et aI. used methanol-sulfuric acid). Reduction of the ester 17 with lithium aluminum hydride gave the aIcohol18. Small amounts of trans isomer were produced (less than 5% by NMR) by this procedure, but were not removed until the next step. The alcohol 19 was prepared by coupling 18 and (trimethylsilyl)acetylene using CuI, Et3N, and Pd catalyst. Flash chromatography was used to separate the cis and trans isomers of 19. The pure cis isomer of 19 was then converted to the tetrahydropyranyl ether 20 by treatment with dihydropyran and catalytic amounts of camphorsulfonic acid. Treatment of 20 with NaOH afforded 21. The triflate 22 was prepared by the procedure of Vedejs.9 The best yields were obtained when 22 was filtered, and stored in crude form at -78 °C under inen atmosphere immediately before the subsequent coupling reaction; no attempt was made to purify 22. The coupled product 23 was synthesized by a nucleophilic displacement of the triflate 22 by the lithium acetyl ide derived from 21. Purification of 23 by chromatography was complicated by the similarity in polarity of the starring material 21 and the desired product 23. Improved yields were obtained by using the impure 23 for the next step. Deprotection of 23 with trichloroacetic acid gave the alcohol 24. The deprotection of 24, which was briefly explored with NaOH, not only removed 7 the trimethylsilyl group, but unfonunately isomerized the expected tenninal acetylene 26 to give the allene 25. Evidence for the fonnation of 25 was seen in the IR and NMR spectra (IR absorption of 1930 cm-! corresponding to the C=C=C stretch, and J = 6.6 Hz for the CH2=C=CH coupling). This isomerization, rationalized to be caused by deprotonation of the relatively acidic methylene protons under the basic conditions, may be avoided by use of more acidic approaches to remove the trimethylsilyl group. Many alternatives are available, such as treatment with HF·Et3N or KF, and future studies would have to explore the options for the deprotection of 24 to avoid the presumed deprotonation and subsequent isomerization to the allene 25 that is experienced with NaOH. Once the deprotection is achieved, 26 could be oxidized to the aldehyde 27, which is expected to allow closure to the 10-membered ring by an intramolecular acetylide-aldehyde addition of 27. Elimination of water from the resulting alcohol 28 is then projected to fonn the target compound 1 (Scheme V). Scheme V H--===--"""~L"""":----' • ~ CHO 27 26 H ---."( > H 28 OH 1 8 Naphthalene Deriyatives The synthesis of the naphthalene derivatives is outlined in Scheme VI: Scheme VI 1.5 series ~u "" 'CQ I .# .# Br ~u AICI3, Br2, 25 °C • ,-Su 66-98% '-Bu 38-50% Br 29 Br 31 30 1) n-BuLi, THF, -78°C Cuet, (CIiJl2SQ, 180 °C 2) TMSCI 67-82% 47-69% • Br Ct 9 12 1.4 series TMS p-dioxane, Br2 25-29% 1) n-BuLi, THF, -78 °C • • 2) TMSCI 30-3B'Io Br 32 33 CuCt, (CIiJl2SQ, 180 °C 32-46% Ct 13 "" "" ¢o 1.# Br 10 .# 9 2.7 series H~OH VJ PhaP, Br 2 • Br~Br VV 250°C 1) n·BuLi,THF, ·78 °C • 2) TMSCI 23·32% 67% 34 .35 TMS~Br VJ CuCI, (CHa)2SQ , 190°C 50% • TMS~CI VJ 11 14 The individual dibromonaphthalene compounds were synthesized as follows: 1,5dibromonaphthalene was synthesized from 2,6-di-t-butyl-naphthalene by a literature procedure; 10 1,4-dibromonaphthalene was synthesized from naphthalene by treatment with p-dioxane and bromine;l1 and 2,7 dibromonaphthalene was synthesized from 2,7-dihydroxynaphthalene by treatment with triphenylphosphine and bromine in analogy to a procedure for the preparation of 2-bromonaphthalene. 12 Each dibromonaphthalene was purified by recrystallization. Flash chromatography (using petroleum ether as eluent) was sometimes used for small scale experiments and found to be much more efficient than recrystallization. The bromotrimethylsilylnaphthalene derivatives were then obtained from the selective metallation of each dibromide by treatment with n-BuLi in THF and subsequent addition of trimethylsilylchloride at -78 °C. \3 The purification of each bromotrimethylsilylnaphthalene derivative was achieved by careful chromatography. Petroleum ether as eluent afforded the best separation. Recrystallization was also required when working with larger amounts of compound (> 100 mg). The conversion of the bromide to the chloride was then achieved by refluxing each bromotrimethylsilylnaphthalene derivative with CuCl in DMSO.14 Purification of the chlorotrimethylsilylnaphthalene derivatives required a combination of chromatography and recrystallization. 10 References: . 1) a) Lee, M. D.; Dunne, T. S.; Siegel, M. M.; Chang, C. c.; Morton, G. 0.; Borders, D. B. 1. Am. Chem. Soc. 1987, 109, 3464. b) Lee, M. D.; Ellestad, G. A.; Siegel, M. M.; Chang, C. C.; Morton, G. 0.; Borders, D. B.; McGahren, W. J. 1. Am. Chem. Soc. 1987,109,3466. c) Golik, 1.; Clardy, J.; Dubay, G.; Groenewold, G.; Kawaguchi, H.; Konishi, M.; Krishnan, B.; Ohkuman, H.; Saitoh, K.; Doyle, T. W. 1. Am. Chem. Soc. 1987, 109,3461. d) Golik, J.; Dubay, G.; Groenewold, G.; Kawaguchi, H.; Konishi, M.; Krishnan, B.; Ohkuman, H.; Saitoh, K.; Doyle, T. W. 1. Am. Chem. Soc. 1987, 109, 3462. 2) a) Bergman, R. G.; Jones, R. R.I. Am. Chem. Soc. 1972,94,660. b) Bergman, R. G. Acc. Chem. Res. 1973,6,25. 3) a) Myers, A. G. Tetrahedron Lell. 1987,28,4493. b) Myers, A. G.; Proteau, P. J. 1. Am. Chem. Soc. 1989, 111, 1146. 4) a) Myers, A. G.; Kuo, E. Y.; Finney, N. S. 1. Am. Chem. Soc. 1989,111,8057. b) Myers, A. G.; Dragovich, P. S. 1. Am. Chem. Soc. 1989, 111,9130. 5) a) Sworski, T. J. 1. Chem. Phys. 1948,16,550. b) Alder, R. W.; Edley, D. T. 1. Chem. Soc.(C) 1971, 3485. c) Sondheimer, F.; Calder, I. c.; Elix, J. A.; Gaoni, U.; Garret, P. 1.; Grohmann, K.; Mayer, J.; Sargent, M. V.; Wolovsky, R. Chem. Soc. , Spec. Publ. 1967, No. 21, 75. 6) for attempts at the synthesis of close analogs see: a) Sondheimer, F.; Mitchell, R. H. Tetrahedron 1970,26,2141. b) Whitlock, Jr. H. W.; Reed, 1. K. 1. Org. Chem. 1969,34, 874. c) Reese, C. B.; Shaw, A. 1. C. S. Chem. Comm. 1972,331. 7) Squires, R. R.; Paulino, J. A.; Wenthold., P. G. 1. Am. Chem. Soc. 1991, 113,7414. 8) Moss, R. A.; Wilk, B.; Jespersen, K. K.; Westbrook, 1. D. 1. Am. Chem. Soc. 1989, 111,6729. 9) Vedejs, E.; Engler, D. A.; Mullins, M. 1.1. Org. Chem. 1977,42,3109. 11 10) Harvey; R. G. ; Pataki, J.; Conez, C.; Raddo, P. D.; Yang, C. X. J. Org. Chern ..· 1991 , 56, 1210. 11) Bayer, R. W.; O ' Reilly, E. 1. J . Org. Chern. 1958,23,31 1. 12) a) Concilio, C.; Porzi, G. J. Organornet. Chern. 1977,128,95. b) Schaefer, J. P. ; Higgins, 1. J. Org. Chern. 1967,32, 1607. 13) a) Concilio, c.; Porzi, G. J . Organornet. Chern . 1977,128, 95. b) Katz, T . 1.; Sudhaka, A. J. Arn. Chern. Soc. 1986,108, 179. 14) Bacon, R. G. R.; Hill, H. A. O. 1. Chern. Soc. 1964, 1097. 12 Experimental Section: NMR spectra were recorded on JEOL lNM-GX400, Bruker AM-SOO, or GE QE Plus (300 MHz) instruments. Chemical shifts for proton spectra were reported as 0 in units of parts per million (ppm) relative to residual chloroform (@ 7.26) or residual benzene (@ 7.15) serving as internal reference. Chemical shifts for carbon-l 3 spectra were reported as 0 in units of parts per million (ppm) relative to deuteriochloroform (77.0) as internal reference. Multiplicities were reported as follows : s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br s (broad singlet), dd (doublet of doublets), dt (doublet of triplets). FTIR spectra were recorded on a Perkin-Elmer 1600 Series FTIR instrument. Intensity of IR peaks were abbreviated as follows: vw = very weak, w = weak, m = medium, s = strong, vs = very strong, br = broad. Mass spectra (MS) and high-resolution mass spectra were obtained from the UC Riverside mass spectroscopy facility. Spectra were reported in units of mass to charge (m/e). Melting points were determined on a B iichi apparatus and are uncorrected. Analytical and preparative thin layer chromatography were performed on Merck precoated silica gel 60 F-2S4 plates (25 mm , glass-backed) and Aldrich pre-coated silica gel 60 A, (250 ~m, glass backed, fluorescent at 254 nm), Merck Silica Gel 60 (230-400 mesh ASTM), and IT Baker Silica Gel 40 ~m. Extrations and chromatography employed HPLC grade ethyl acetate and hexanes, used as recei ved. Tetrahydrofuran and ethyl ether were distilled from sodium and benzophenone. Benzene was distilled from sodium. Dimethylsulfoxide, acetonitrile, trimethylsily!chloride, triethylamine, and methylene chloride were distilled from calcium hydride. Cuprous chloride was purified by recrystallization from 6 M HC!. Triflic anhydride was prepared by distillation of triflic acid from phosphorus pentoxide. (Trimethylsilyl)acetylene (Farchan labs) was stored over molecular sieves (4 A) prior to use. Diazomethane was distilled as an ethereal solution from Diazald® and potassium hydroxide. Dihydropyran (Aldrich) was stored over molecular sieves (4 A) prior to use . All other reagents were used as received. temperature unless otherwise specified. All reactions were carried out at room 13 HI,Cul .. I~OH o 15 16 CZl-3-lodQPropenoic Acid 16 Cuprous iodide (7 .00 g, 0.037 mol, 0.19 eq) and 48% HI (38 mL, 57 g, 0.446 mol, 1.13 eq) were placed in a 250-mL round-bottom flask and stirred. The brownish suspension was cooled to 0 °C and 15 (13.3 g, 0.190 mol, 1 eq.) was added drop wise over twenty minutes. The mixture was stirred for 4.5 h and was then allowed to crystallize at -20 °C overnight. A tan precipitate was collected by filtration, triturated with approximately 200 mL of chloroform, and filtered to remove the copper residue. This was washed with 15-mL portions of water, 1 M sodium thiosulfate, and water. The resulting yellow solution was dried over sodium sulfate and concentrated under vacuum to give a yellow solid. The crude product was recrystallized from · hot hexane to yield 26.77 g (71 %) of pale yellow crystals. IH NMR (400 MHz, CDCI3): 11.3 (br s, lH, OH), 7.69 (d, lH, J = 8.4 Hz, vinyl), 6.99 (d, 1H, J = 8.4 Hz, vinyl). FTIR (neat film, cm- 1): 3060 (br), 1698 (s), 1599 (s), 730 (m). MS (EI): 198 (M+), 181 (M+-OH), 153 (M+-COOH), 71 (M+-D. Exact Mass: calcd: 197.9ll7 TLC (100% EtOAc): Rf=O.ll found: 197.9172 14 I~OH o ether, 25°C I~OMe o 17 16 Methyl-(2)-3-iodopropenoate 17 The acid 16 (13.85 g, 0.0700 mol, 1 eq) was placed in a 125-mL erlenmeyer flask, dissolved in approximately 40 mL of dry ether, and cooled to 0 °C with stirring. Diazomethane in ether solution (1 M) was added dropwise to the staning material via a fire-polished glass pipette. The addition was continued until gas evolution stopped and TLC monitoring showed that all starting material was consumed. The solution was then concentrated under vacuum to give a yellow oil (14.56 g, 98%): The product was used without further purification in the next experiment. lH NMR (500 MHz, CDCI3): 7.47 (d, IH, J = 9.0 Hz, vinyl), 6.91 (d, 1H, J = 9.0 Hz, vinyl), 3.78 (s, 3H, OCH3). FTIR (neat film, em-I): 3062 (m), 2950 (m), 1726 (s), 1598 (s), 1204 (s), 1164 (s). TLC (30% EtOAc-hexanes): Rf=0.75 IS I~OMe LiAIH4, ether, -78 °C I~OH o 18 17 (2)- 3-Iodopropenol 18 A 100-mL flask was flame-dried under vacuum and then flushed with argon. Dry ether (30 mL) was added and the solution was cooled to -78 °C. Lithium aluminum hydride (0.81 g, 0.021 mol, 0.75 eq) was added portionwise and the suspension was stirred. A solution of 17 (4.70 g, 0.028 mol, 1.0 eq) in 15 mL of dry ether was added dropwise to the supension over 30 minutes with vigorous stirring. The solution was then allowed to warm to room temperature. After 0.75 h the excess lithium aluminum hydride was carefully quenched with water, poured into approx imately 30 mL of cold 3 M sulfuric acid, and stirred for five minutes to give a greenish mixture. The layers were separated and the aqueous layer was extracted with five portions of ether. The combined ether extracts were washed with one portion of saturated sodium carbonate, one portion of I M sodium thiosulfate, and one portion of saturated sodium chloride solution. The combined organic layers were dried over sodium sulfate and concentrated under vacuum to give 3.78 g of an orange liquid. Purification by flash chromatography on silica gel (10-15% EtOAc-hexane) afforded 3.46 g (67 %) of yellow oi l. lH NMR (500 MHz, CDCI3): 6.50 (dt, IH, J = 7.6, 5.9 Hz, vinyl), 6.40 (dt, IH, J = 1.5 , 7.6 Hz, vinyl) , 4.25 (dt, 2H, J = 1.5, 5.9 Hz, allylic), 1.70 (br, I H, OH). FTIR (neat film, cm- l ): 3316 (brs ), 3068 (w), 2870 (w), 1608 (s) , 1279 (s). MS (EI): 184 (M+), 167 (M+-OH), 57 (M+-I). E xact Mass: calcd: 183 .9385 TLC (30% EtOAc-hexanes): Rf = 0.37 found: 183.9379 16 TMS __ H, Cui, PdCI2(PPha)2 TMS --;;~---" ~OH ElaN, ether, 25°C 19 18 5-TrimethylsilyHZ)-2-penten-4-ynol 19 The starting material 18 (3.46 g, 0.019 mol, 1 eq) was placed in flame-dried flask and dissolved in approximately 50 mL of dry ether. Bis(triphenylphosphine)palladium(ID chloride (1.32 g, 1.9 mmol, 0.1 eq) was added and the mixture was stirred at 0 °C. The reaction vessel was evacuated and flushed with argon several times. Cuprous iodide (36 g, 1.9 mmol, 0.1 eq) and 10 mL of dry ether were placed in another flask. This reaction vessel was evacuated and flushed with argon several times and treated with 20 mL of triethylamine. The vessel was then evacuated and flushed with argon several times again. The suspension was then treated with (trimethylsilyl)acetylene (2.9 mL, 0.021 mol, 1.1 eq) causing a cloudy white suspension to be formed which subsequently became slightly yellow and then slightly green. This suspension was transferred by cannula into the starting material solution which subsequently turned brownish and then dark green within the first five minutes of the reaction. After a few more minutes the color reverted to a pale brown color. After 3.5 h the mixture was poured into a solution of 75 mL of saturated potassium carbonate and 75 mL of saturated ammonium chloride, and was stirred vigorously for one hour. The aqueous phase became deep blue. The layers were separated and the aqueous layer was extracted with five portions of ether. The combined organic layers were then washed with two portions of saturated sodium chloride solution and dried over sodium sulfate. Concentration under vacuum and purification by flash chromatography (10% EtOAchexanes) yielded 2.22 g (75%) of yellow oil. IH NMR (400 MHz, CDCI3): 6.10 (dt, lH, J = 6.4, 11.0 Hz, H2), 5.61 (d, lH, J = 11.0 Hz, H3), 4.42 (d, 2H, J = 6.4 Hz, HI), 1.70 (br, IH, OH). 0.20 (s, 9H, TMS). FTIR (neat film, em-I): 3346 (br m) , 2922 (s), 2851 (m), 1250 (m), 844 (s). MS (C1NH3): 172 (M+N~+), 155 (MH+), 139 (M+-OH). . Exact Mass: ca1cd: ·155.0892 found: 155.0893 17 TI.C (30% EtOAc-hexanes): Rf=0.49 18 TMS--;;=--~ 'LOH dihydropyran, CSA, CH2CI2 o °C TMS -'S!a---.. ~OTHP • 20 19 TetrahYdropyranyl Ether 20 The staning material 19 (1.745 g, 11.3 mmol, I eq) was placed in a flamed-dried flask, dissolved in approximately 10 mL of dry methylene chloride, and cooled to 0 °C, Dihydropyran (1.55 mL, 17 mol, 1.5 eq) and 0,130 g of CSA were added. The solution was stirred for 1.5 h, poured into 50 mL of water, and extracted with three portions of I: I EtOAc-hexanes. The combined organic layers were washed with two portions of saturated sodium bicarbonate and one portion of saturated sodium chloride. The solution was dried over sodium sulfate, concentrated under vacuum, and purified by flash chromatography (5-10% EtOAc-hexanes) to give a yellow oil (2.42 g, 90%). lH NMR (400 MHz, CDCI3): 6.10 (dt, IH, J = 11.0, 6.8 Hz, H2), 5.63 (d, IH, J = 11.0 Hz, H3), 4.66 (t, IH, J = 3.4 Hz, OCH(C)O), 4.46 (q, IH, J = 6.8, 13.2 Hz, HI), 4.32 (q, IH, J = 6.8, 13.2 Hz, HI), 3.90 (m, IH, THP), 3.53 (m, IH, THP), 1.56-1.82 (m, 6H, THP), 0.19 (s, 9H, TMS). FfIR (neat film, cm- I ): 3032 (w), 2955 (s), 1250 (s), 1201 (s), 1120 (s), 844 (s), 760 (s). MS (DCI, NH3): 256 (M+NI-4+), 239 (MH+). Exact Mass [M+NI-4+j: ca1cd: 256.1732 TLC (30% EtOAc-hexanes) Rf=0.8 found: 256.1735 19 TMS;-l_---. H:---.;=a----. NaOH, MeOH, 25 · C \OTHP \OTHP 21 20 Tetrahydropvranyl Ether 21 To a solution of starting material 20 (0.337 g, 1.41 mmol, 1 eq) dissolved in MeOH (approx. 10 mL) was added 6 drops of 50% NaOH. The solution was stirred for 1.5 h and then diluted with water and extracted with three portions of ether. The combined organic layers were then washed with three portions of saturated sodium chloride solution, dried over sodium sulfate and concentrated under vacuum. Purification by flash chromatography (5-10% EtOAc-hexanes) gave a colorless oil (0.197 g, 84%). IH NMR (400 MHz, CDCI3): 6.15 (dt, IH, J = 11.0,5.8 Hz, H2), 5.58 (dd, IH, J = 11.0, 2.3 Hz, H3), 4.64 (t, IH, J = 11.0 Hz, chiral H), 4.42-4.49 (m, IH, J = 5.8, 12.9Hz, HI), 4.27-4.34 (m, IH, J = 5.8, 12.9Hz, HI), 3.83-3.91 (m, IH, THP), 3.48-3.55 (m, IH, THP), 3.15 (d, IH, J = 2.3 Hz, H5), 1.49-1.86 (m, 6H, THP). FrIR (neat film, cm- l ): 3289 (m) , 2942 (s), 2870 (m), 1441 (w), 1386 (w), 1201 (m), 1120 (s), 1032 (s). MS (DCI NH3): 184 (M+NI-4+), 167 (MH+). Exact Mass: caJcd: 184.1337 TLC (30% EtOAc-hexanes): Rf= 0.69 found: 184.1345 20 TMS -!!!!5----. TMS-==----.. pyridine, Tf 20 'LOH CH2CI2, -22 ° -78 °C 19 22 LOTI H --::=!!--." 21 L n-BuLi, THF, -78°C OTHP TMS-=~---'~~....- , 23-36% 23 1 Coupled Acetylenic Product 23 A reaction flask was flame-dried under vacuum and filled with argon. Dry methylene chloride (3 mL) was added and cooled to -22 °C. Pyridine (0.052 mL, 0.65 mmol, 1.1 eq) and triflic anhydride (0.109 mL, 0.65 mmol, l.l eq) were added sequentially. A white precipitate was formed and the solution became slightly colored with a pink hue. The solution was funher cooled to -40°C. Staning material 19 (0.100 mL, 0.59 mmol, I eq) and, after 0.5 h, 3 mL of dry hexane was added, causing funher precipitation. The solution was cooled to -78°C and then quickly filtered cold through sintered glass under inen atmosphere. The filtered precipitate became dark purple on standing. The filtrate was slightly brownish in color. This solution was kept at -78°C until used as described below. In another flame-dried reaction flask the staning material 21 (0.132 g, 0.79 mmol, 1.3 eq) was added, cooled to -78°C, and dissolved with 5 mL of dry TIIF. n-BuLi (0.5 mL, 1.6 M in hexanes, 0.79 mmol, 1.3 eq) was slowly added and the solution turned slightly orange in color. After I h the triflate 22 solution was introduced by cannula. The color of the solution immediately darkened to an orange color. The mixture was stirred for 0.5 h and then poured into 60 mL of water. The aqueous layer was extracted with three ponions of \: I EtOAc-hexanes solution. The combined organic layers were washed with one ponion of saturated aqueous sodium bicarbonate solution and two ponions of saturated sodium chloride solution, .dried over sodium sulfate, and concentrated under vacuum. Purification by flash chromatography (8% EtOAc-hexanes) yielded 0.064 g (36%) of de sired 23. tH NMR (400 MHz, CDCI3): 6.01 (dt, IH , J = 10.7, 6.4 Hz, H2), 5.93 (dt, IH, J = 10.7, 6.8 Hz, H7), 5.55-5 .60 (~d, 2H, J = II Hz, H8+H3), 4.65 (d, I H, OCH(C)O), 4.43 (dd, IH, J = 6.4, 12.5 Hz, CH20), 4.27 (dd, I H, J = 6.4, 12.5 Hz, CH20), 3.89 (m, IH, THP), 0THP 21 3.52 (m, lH, THP), 3.38 (d, 2H, J = 6.8 Hz, H6), 1.54-1.82 (m, 6H, THP), 0.20 (s, 9H, TMS). FI1R (neat film, em-I): 2955 (s), 2152 (m), 1250 (s), 1119 (s), 844 (s). TLC (30% EtOAc-hexanes) Rf= 0.85 22 TMS TMS ~ ClaCCObH, HzO \ • ~ CHaCN , 25·C OTHP \ OH 24 23 10-Trimethylsilyl-CZ,z)-2,7-decadien-4,9-diynoI24 The starting material 23 (36 mg, 0,119 mmol, I eq) was dissolved in 6 mL of acetonitrile ·and was treated with water (approximately I mL) and trichloroacetic acid (0.107 g, 0.655 mmol, 5.5 eq). The solution was stirred for 4.5 h and then poured into approximately 50 mL of water. The aqueous layer was extracted with four portions of I: I EtOAc-hexanes. The combined organic layers were washed with two portions of saturated sodium bicarbonate and with one portion of saturated sodium chloride solution, and dried over sodium sulfate. Concentration and purification by flash chromatography (10% EtOAc-hexanes) gave a yellow oil (20 mg, 74%). IH NMR (400 MHz, CDCI3): 6.04 (dt, IH, J = 6.1,10.7 Hz, H2), 5.94 (dt, IH, J = 10.7, 6.8 Hz, H7) , 5.57-5.6 (2d,2H, J = 10.7 Hz, H3+H8) , 4.39 (d, 2H, J = 6.1 Hz, HI), 3.38 (d, 2H, J = 6.8 Hz, H6), 0.20 (s, 9H, TMS). FfIR (neat film, cm- 1): 3332 (br), 2959 (m), 2153 (m), 1614 (w), 1250 (m), 842 (s). TLC (30% EtOAc-hexanes): Rf=0.52 23 >=. H H NaOH, MeOH, 25 °C • CH,oH 24 2S Allene 2S A solution of starting material 24 (0.019 g, 0.082 mmol, 1 eq) in 10 mL of MeOH was treated with five drops of 10% NaOH. The reaction mixture turned bright yellow-orange within a few seconds. After ten minutes the solution became dark orange. The reaction was stirred for I h and then poured into 25 mL water. The solution was extracted with four portions of ether. The combined organic layers were washed with two portions of saturated sodium bicarbonate solution, one portion of saturated sodium chloride solution, dried over sodium sulfate, and ' concentrated under vacuum. The black tarry residue was purified by flash chromatography (10% EtOAc-hexanes) to yield a yellow oil (8 mg, 67%). IH NMR (400 MHz, CDCI3): 6.44 (dd, IH, J = 10.7, 15.4 Hz, H7), 6.07 (dt, IH, J = 6.1, 10.7 Hz, H2), 5.90 (dt, IH, J = 6.6, 10.7 Hz, H7), 5.7 (d, IH, J = 10.7, H3) , 5.7 (d, IH, J = 15.4, H6), 5.00 (d, 2H, J = 6.6 Hz, C=C=CH2), 4.41 (d, 2H,J = 6.1 Hz, HI). FfIR (neat film, cm- 1): 3345 (br s), 3029 (m), 2925 (m), 2177 (m), 1930 (s),1225 (m), 849 (s). TLC (30% EtOAc-hex.anes): Rf= 0.44 I~OH o __________________~______~.~____ J~ i i , I 12 9 5 , ,I ,, i 2 93.91 IT 72.03~--~----~------r-----r-----~-----------r-----------,---------L--~ c.-t 500 1500 1000 2500 2000 3000 3!!O0 4000 i o '~OMe o _ _ _ __ _~~J'_' I , ~----~ ,~~ .. " "i. ......' '" ~ < ! - . ~ ~ 7B . n ~ / j 1~ ,I I, \ II \ l I, I ' I ~ 1 - • 00 3500 300 0 2'500 20 00 1500 ~ 1000 c . ... '~OH -- .- ,II L i 8 i 7 , , i 6 , , i 3 i • 90 . 88 IT 1.04~----r-----.------.-----.__----.------------.----- ______ 4000 3500 3000 2500 2000 1500 I 1000 - sa TMS ~OH ~----------~ , i i ' , " 9 ,t" I B [ , 7 , . i 6 5 ~ ~------------~ i i' • , " ""; , 2 [ , 1 87. 90 IT 72.a.~--~----~-----,-----'-----r-----------r----------~--------~-'4000 3500 3000 2500 2000 1500 1000 Cll- I 500 i o =- TMS ~OTHP \ I~ j-vV J "'" 6 1" i i ' 9 i" 9 , i 7 0 t lL-J ~ i ,... i i i i • 5 6 "'" ? B8 . 63- f,f-....."..,~N'"".- IT '"'\ - I i not a peek IpEAKS 'I 4 400 . 0 c ,.-I S .7 8 I 40 00 3500 I 300 0 ! 2500 - - -r - - - - 2000 ,-- , ! 50 0 !OOO H == ~OTHP I 62.88 1 , 4000 , . 3500 i I , , , 3000 . 2~OO 2000 1500 1000 c .... TMS--~~ == '( \.OTHP r J r / ~ r- i ' l 9 , i" , , , , ,, , i '- \..J , j i 5 6 UJ~ ''" i , .. ,I. , ~ J~ ~ t £\ , , , i i f' " , j , 2 3 ~7e1..- I~ , i i I J •I 'I'. I /' II I III' .. ; i 1"1' i 715 . 77 ! iPEAlCS I 700 . 2 i i Hi : e." -1 1 I'II . I' .. ii j -', i .! ~ 59 . 3S L-~ :-- - I" - .- --- -T - - -"-1" - - - , . - 4000 3500 3000 - 2500 2000 1 -- - - - - "1 - !SOO - - - - -- - ; -- r - - -- ----r' iCOO ca- I 50 0 ; i o f<)' == TMS ~L.....~""" I ,. ~OH I I I I )~~~JJJlll J , """ 1\ I I\ I II ' 6 ,, ( r ,I I , , _ _-- L , , I i 'I _A-L , • 9 ' 7 / / I , , • 5 ' , , ' , t [ \ ) 2 l~rJ~r\ . I , . I: , " ' ,;j I I'! I I i J t i t; I A (V, 1/ ' ' \ 1-.' \1 ' I l'l ! t, 'I h· r \ ~ ~ ~ 1:" !:' I t /1 , . , I I j. I I I!: i ,; \ I; j ;I~ I' ',I I' 'I':i II , ", I ' j J",I ; I .' AI :!1\ ' I' .\ , , :j !; h .:, 1I , I, 7!. ~.-,1 -T'-4000 -.,- -,-,--r, 3500 3000 2~O O ,-- , t 20 00 1!500 1000 ' I. o i PI=M, CH,oH I :1 Ii ,! I' _______-'' -_--' 'J ~' I 9 1\, \ i \ '.l~ '--.-I. , a o 2 I I 0 •• 32 • .J....--.-----.--- .,. - - -,....-- ,--·- - '4000 3500 3CCO 2'30 0 2COO - .---- -- -- -r' - - ~50 0 :. 000 Cal-I 500 33 Br t-8U~ AlCI3, Br2 • t-Bu~ ~t-BU ~t-8U Br 29 30 1.5-Djbromo-3.7 -di-tert-butylnaphthalene 30 A 500-mL flask was flame-dried under vacuum and filled with argon. The starting material 29 (24.11 g, 0.100 mol, 1 eq) was dissolved in approximately 200 mL of dry methylene chloride and treated with aluminum chloride (60 mg, 0.450 mmol, 0.005 eq). A solution of bromine (12 ml, 0.233 mol, 2.3 eq) in 100 mL of dry methylene chloride was added dropwise via addition funnel over approximately two hours. The mixture was stirred overnight, resulting in a red solution which was washed with two portions of water and two portions of saturated sodium . carbonate to give a light green solution. The organic layers were dried over sodium sulfate and concentrated under vacuum to yield a semi-crystalline solid. Recrystallization from benzeneethanol gave a white crystalline material (26.39 g, 66%). lH NMR (400 MHz, CDCI3): 8.10 (s, 2H, H4+H8), 7.88 (s, 2H, H2+H6), 1.41 (s, 18H, (butyl). FIlR (neat film, cm- l ): 2963 (s), 1594 (m), 1374 (m), 880 (s). TLC (hexanes): Rf=0.74 34 Br I-Bu AIC1a, 5 °C • I-Bu Br o Br Br 31 30 1.5-Dibromonal2hthalene 31 A 200-mL flask was flame-dried under vacuum and filled with argon. The starting material 30 (5.0 g, 12.6 mmol, 1 eq) was added and dissolved in approximately 100 mL of dry benzene. The solution was cooled to SoC, aluminum chloride was added (1.68 g, 12.6 mmol, 1 eq), and the solution was stirred for I h (close monitoring of the reaction is necessary since overreaction yields an intractable mixture composed of mostly naphthalene). The reaction mixture was then poured into SO g of ice and stirred for five minutes and extracted with three portions of 1:1 EtOAc-hexanes. The combined organic layers were washed with two portions of water, dried over sodium sulfate and concentrated. The solid residue was purified by recrystallization from EtOH to give a white solid (1.827 g, 50%). mp = 125-126 °C. lH NMR (400 MHz, CDCI3): 8.26 (d, 2H, J = 7.6 Hz, H4+H8), 7.83 (d, 2H, J = 7.2 Hz. H2+H6), 7.42 (t, 2H, J = 7.6 Hz, H3+H7). FTIR (neat film, em-I): 1192 (m), 1138 (m), 777 (vs). TLC (hexanes): Rf=0.70 35 TMS Br ('A ~ Br 1) f}-Suli, THF, -78 °C 2)TMSCI • c;6 Br 31 9 1-Bromo-5-trimethylsilylnaphthalene 9 A 250-mL flask was flame-dried under vacuum and filled with argon. The starting material 31 (1.67 g, 5.9 mmol, 1 eq) was added, dissolved with 100 mL of dry TIIF, and cooled to -78°C. Cooling caused some precipitation. n-BuLi (4.0 mL, 6.4 mmol, 1.1 eq) was added over 5 min, which caused the solution to become lime green and the precipitate to dissolve. After allowing the solution to stir for 10 min, trimethylsilylchloride (0.82 mL, 6.46 mmol, 1.1 eq) was added over a couple of minutes and the reaction mixture was allowed to stir for another fifteen minutes. The mixture was poured into water, extracted with three portions of ether, washed with two portions of saturated sodium bicarbonate and one ponion of saturated sodium chloride solution, dried over sodium sulfate, and concentrated under vacuum. Purification by flash chromatography (petroleum ether) yielded 0.785 g of clear liquid (48%). IH NMR (400 MHz, CDCI3): 8.31 (d, lH, J = 8.6 Hz, H4 or H8), 8.08 (d, IH, J = 8.6 Hz, H4 or H8), 7.80 (d, lH, J = 6.8 Hz, H2 or H6), 7.74 (d, lH, J = 6.8 Hz, H2 or H6), 7.56 (t, lH, J ~ 8 Hz, H3 or H7), 7.35 (t, lH, J = 8 Hz, H3 or H7), 0.47 (s, 9H, TMS). FfIR (neat film, cm- 1): 3075 (w), 2956 (s), 2897 (w), 1584 (m), 1557 (s), 1251 (vs), 998 (vs), 838 (vs), 756 (s). !3C NMR (400 MHz, CDC!3): !39.2, 138.5, 134.3, 132.3, 129.8, 129.0, 128.3, 126.8, 126.1, 124.2, 1.0. TLC (hexanes) Rf=0.70 MS (EI): 280 (MW). 36 TMS TMS Q) Cuel, (CH3l2S0, 160 · C 67-82% o CI Br 9 12 l-Chloro-5-trimethylsilylnaphthalene 12 A reaction flask was flame-dried under vacuum and ftlled with argon. Starting material 9 (0.530 g, 1.89 mmol, 1 eq) was added and dissolved in 10 mL of dry dimethylsulfoxide. Cuprous chloride (0.215 g, 2.17 mmol, 1.15 eq) was added and the mixture refluxed for one hour with stirring. The reaction mixture was allowed to cool to room temperature and was then poured into 50 mL of cold 6 N HC!. The mixture was extracted with three portions of ether. The combined organic layers were washed with two portions of water, dried over sodium sulfate, and concentrated under vacuum. Purification by flash chromatography (petroleum ether) gave a clear colorless oil of >90% purity by NMR (0.299 g, 67 %). Resubjecting the product mixture to the reaction conditions gave >97% purity. lH NMR (400 MHz, CDCI3): 8.34 (d, IH, J = 8.6 Hz, H4 or H8), 8.03 (d, lH, J = 8.6 Hz, H4 or H8), 7.76 (d, lH, J = 6.6 Hz, H6), 7.58 (m, 2H, H2+H3), 7.42 (t, IH, J = 7 Hz, H7), 0.046 (s, 9H, TMS). FTIR (neat film, cm- 1): 3075 (w), 2957 (m), 2897 (m), 1585 (m), 1560 (m), 1252 (s), 854 (s), 839 (s), 785 (s). 13C NMR (400 MHz, CDCI3): 139.1 , 138.3, 134.3, 133.1 , 131.1, 127.6, 126.5, 126.2, 126.0, 125.6, 1.0. MS (EI): Exact Mass: calcd: 234.0631 TLC (hexanes): ' Rf=0.70 found: 234.0629 37 p-dioxane. Br 2 • Br 32 33 1.4-Djbromonaphthalene 33 A reaction flask was flame-dried under vacuum and filled with argon. p-Dioxane (9.2 mL, 0.11 mol, 2.2 eq), and bromine (5.5 mL, O. I I mol, 2.2 eq) were added (exothermic) forming a deep red solution with yellow solids. Naphthalene (32, 6.4 g, 0.050 mol, 1 eq) was added to this solid complex, which dissolved and began to give off white fumes. The reaction flask was placed in a hot water bath (40 0c) for three hours and then allowed to stand at room temperature overnight. The solid was treated with 10% NaOH at 0 °C until mixture was basic by pH paper. Crystals were formed and collected by filtration. Recrystallization twice from 95% EtOH gave a white needle solid (4.08 g, 31 %). mp = 79-80 °C. lH NMR (400 MHz, CDCI3): 8.24 (q, 2H, J = 3 Hz. H8+H5), 7.65 (q, 2H, J = 3 Hz, H6+H7), 7.64 (s, 2H, H2 +H3). FTIR (neat film, cm- 1): 1183 (m), 1139 (m), 961 (s), 812 (s), 751 (vs). nc (hexanes): Rf=0.67 38 TMS 1) n-BuLi, THF, -78°C • 2) TMSCI . ¢o Br Br 10 33 1-Bromo-4-trimethylsilylnaphthalene 10 A reaction flask was flame-dried under vacuum and filled with argon. The starting material 33 (4.08 g, 0.014 mol, 1 eq) was added and dissolved in approximately 50 mL of dry THF and cooled to -78°C. n-BuLi (11.6 mL, 0.0185 mol, 1.3 eq) was then added over seven minutes giving a yellow solution. After 15 min, trimethylsilyIchloride (2.35 mL, 0.0185 mol, 1.3 eq) was added over five minutes. The solution became a light lime green color. The mixture was stirred for 0.5 h and then poured in 50 mL of water and extracted with three portions of ether. The combined organic layers were washed with two portions of saturated sodium chloride solution, dried over sodium sulfate, and concentrated under vacuum. Purification by flash chromatography (hexane) twice yielded a white solid which was then recrystallized twice from EtOH to give 1.16 g of desired 20 (30%). mp = 60_5-62 0C. IH NMR (400 MHz, CDCI3): 8.32 (d, lH, J = 8.2 Hz, H5 or H8), 8.09 (d, lH, J = 8.2 Hz, H5 or H8), 7.75 (d, lH, J = 7.3 Hz, H2 or H3), 7.52 -7.61 (m, 2H, H6+H7), 7.49 (d, IH, J = 7.3 Hz, H2 or H3), 0.48 (s, 9H, TMS). l3C NMR (400 MHz, CDCI3): 138.5, 138.2, 133.3, 131.9, 129.3, 128.6, 128.1, 126.7, 126.4, 125.2,0.2. FflR (neat film, em-I): 3073 (m), 2956 (m), 2896 (w), 1573 (w), 1557 (m), 1251 (s), 877 (vs), 838 (vs), 765 (vs). TLC (hexanes): Rf=0.67 MS (El): 280 (MH+). 39 TMS TMS ¢o CuCl, (CHal2S0, 180 ·C • Br ~ I . "'" ~ CI 13 10 1 ChlorD-4-trimethylsilylnaphthalene 13 A reactlon flask was flame-dried under vacuum and filled with argon. The staning material 10 (1.02 g, 3.65 mmol, 1 eq) was added and dissolved in 20 mL of dry dimethyl sulfoxide. Cuprous chloride (0.397 g, 4.01 mmo1, 1.1 eq) was added and the reactlon mixture was refluxed for 1.25 h. The mixture was cooled down to room temperature and poured into 50 mL of cold 6 N HC!. The mixture was extracted with three portions of ether. The combined ethereal extracts were washed with three portions of water, dried over sodium sulfate, and concentrated under vacuum. The residue was purified by flash chromatography (pentane) yielding 0.465 g of semi-pure compound which was further purified by recrystallization from EtOH to give 0.400 g of white flaky crystals (46%). mp = 52.5-53.5 cC. IH NMR (400 MHz, CDCI3): 8.35 (d, 1H, J = 8.2 Hz, H5 or H8), 8.10 (d, lH J = 8.2 Hz, H5 or H8), 7.53-7.62 (m, 4H, H2+H3+H6+H7) 0.48 (5, 9H, TMS). l3C NMR (400 MHz, CDCI3): 138.5, 138.3, 134.2, 133.2, 131.0, 128.8, 126.7, 126.7. 125.8, 125.7,0.0. FTIR (neat film, cm- 1): 2958 (m), 1576 (w), 1250 (5), 898 (vs), 839 (vs), 765 (vs). MS (EI) : Exact Mass: calcd: 234.0631 TLC (hexanes): Rr = 0.67 found: 234.0637 40 HO~OH ~ Br~Br 250°C ~ 35 34 2.7-Dibromonaphthalene 3S A reaction flask was flame-dried under vacuum and filled with ' argon. Triphenylphosphine (6.92 g, 26.4 mmol, 2.2 eq) and 15 mL of dry acetonitrile were added, stirred, and cooled to 0 °C (partial solution). Bromine (1.36 mL, 26.4 mmol, 2.2 eq) was added dropwise via pipette, forming a solid orange mixture. The starting material 34 (1.91 g, 0.012 mol, 1 eq) was dissolved in 10 mL of dry acetonitrile and added to reaction mixture. The reaction mixture was refluxed for 50 min and then the acetonitrile was distilled off under water aspirator pressure. The reaction mixture was heated on a sand bath to 230°C for an additional hour. The black tarry gum formed in the reaction was transferred to a beaker while hot where it solidified upon cooling. The tarry solid was extracted with boiling petroleum ether and boiling hexane until the solid became a grey, almost granular solid. The extracts were washed with 10% NaOH, dried over sodium sulfate, and concentrated under vacuum. The resulting solid was purified by recrystallization from EtOH (95%) to give 1.09 g of slightly pink solid (32%). mp = 137 -138°C. IH NMR (400 MHz, CDCI3): 7.91 (d, 2H, J = 1.9 Hz, HI+H8), 7.68 (d, 2H, J = 9.4 Hz, H4+H5), 7,57 (AB q, 2H, J = 9.4, 1.9 Hz, H3+H6). FI1R (neat film, cm- 1) : 3056 (vw), 1567 (m), 906 (s), 870 (s), 838 (vs). TLC (hexanes): Rr = 0.59 41 Br'W~ Br 1) n-BuLi, THF, -78 °C TMS'CO~ Br I .• .&.& 2) TMSCI 3S I· .& .& 11 2-Bromo-7-trimethylsilylnaphthalene II A reaction flask was flame-dried under vacuum and filled with argon. Starting material 3S (1.05 g, 3.67 mmol, 1 eq) was added, dissolved in 25 mL of dry THF, and cooled to -78°C. n-BuLi (2.52 mL, 4.04 mmol, 1.1 eq) was added over 4 min giving a bright yellow solution. After 10 min, trimethylsily!chloride (0.6 mL, 4.72 mmol, 1.2 eq) was added causing solution to lose color and intensity. The mixture was stirred for 0.5 h, poured into 50 mL of water, and extracted with three portions of ether. The com bined organic layers were washed with two portions of saturated sodium chloride solution, dried over sodium sulfate, and concentrated under vacuum. Purification by flash chromatography (petroleum ether) gave a colorless oil (0.683 g, 67%). mp = 42 - 43°C. IH NMR (400 MHz, CDCI3): 8.01 (s, lH, H8), 7.90 (s, lH, HI), 7.78 (d, lH, J = 8.2 Hz, H4 or H5), 7.69 (d, IH, J = 8.2 Hz, H4 or H5), 7.61 (d, 1H, J = 8.2 Hz, H3 or H6), 7.54 (d, lH, J = 8.2, 1.4 Hz, H3 or H6), 0.35 (s, 9H, TMS). FfIR (neat film, cm- 1): 3048 (w), 2955 (m), 2898 (w), 1583 (m), 1495 (m), 1249 (s), 1090 (s), 1060 (s), 887 (vs), 832 (vs), 750 (s). 13C NMR (400 MHz, CDCI3): 139.7, 134.3, 133.1, 132.3, 130.6, 130.4, 129.9, 129.7, 127.1,120.0, -0.5. TLC (hexanes): Rr= 0.59 MS (EI): 278 (M+-H). 42 TMS~Br ~ . CuCl, (CH3)2S0, 190°C . TMS~CI . ~ 11 . 14 2-Chloro-7-trimethylsilylnaphthalene 14 A reaction flask was flame-dried under vacuum and filled with argon. The starting material 11 (0.363 g, l.30 mmol, 1 eq) was placed in a 50-mL flask and dissolved with 20 mL of dry dimethylsulfoxide. Cuprous chloride (0.154 g, 1.56 mmol, l.2 eq) was added and stirred, forming a cloudy yellow solution. The system was flushed with argon and heated to a temperature of 190 °C for two hours. The solution was allowed to cool to room temperature, poured into 50 mL of ice-cold 6 N HCl, and stirred for five minutes. The solution was extracted with four portions of ether. The combined ethereal extracts were washed with two portions of saturated sodium bicarbonate solution, dried over sodium sulfate, and concentrated under vacuum. Purification by flash chromatography (petroleum ether) followed by recrystallization from EtOH gave 0.15 g of desired (49%). lH NMR (300 MHz, CDCI3): 7.91 (s, lH, H8), 7.83 (d, IH, J = 1.7 Hz, HI), 7.80 (d, 1H, J = 7.8 Hz, H4 or H5), 7.76 (d, IH, J = 8.7 Hz, H4 or H5), 7.61 (d, IH,J = 7.8 Hz, H3 or H6), 7.33 (AB q, IH, J = 1.7, 8.7 Hz, H3 or H6), 0.35 (s, 9H, TMS). i3C NMR (300 MHz, CDCI3): 139.4, 132.8, 131.8, 131.4, 130.1, 129.3, 127.1 , 126.8, 126.7, -1.1. FTlR (neat film, em-I): 3044 (w), 2956 (s) , 1586 (m), 1249 (s), 899 (s), 834 (vs). MS (El): Exact Mass : ca\cd: 234.063 1 TLC (hexanes): Rr = 0.59 found: 234.0637 8' t.8ut~: . ~t.8ut 8' ,i 9 ,, ,i , ,i , • i 6 7 , ,i 5 ,, ,i , , i 3 , ,i , i I 2 , ,i , .... , ,, 0 n.89 IT 69 . 61.-L-------r------~------_,----------------,_--------------~----------~-- 3000 2500 2000 lS00 1000 ell'" I B , i q .t • ' ! ' b '! 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