Bistrimethylsilylpropargylic Ether: A Versatile Ambident Synthon to Access Substituted Allenyne Ethers and r-Substituted Bispropargylic Alcohols Maude Brossat,† Marie-Pierre Heck,*,† and Charles Mioskowski†,‡,§ CEA-Saclay, iBiTec-S, SerVice de Chimie Bioorganique et de Marquage, Baˆ t 547, F-91191 Gif sur YVette cedex, France, and Laboratoire de Synthe` se Bio-organique, Faculte´ de Pharmacie, UniVersite´ Louis Pasteur, 74 route du Rhin, BP24, 67401 Illkirch, France
[email protected] ReceiVed May 15, 2007
The reactivity of 1,5-bis(trimethylsilyl)propargylic ethers 3 toward bases and electrophiles was investigated. Bispropargylic ethers 4, substituted allenyne ethers 6-8, and R-substituted bispropargylic ethers 9 were prepared in good yields, respectively, by protodesilylation, isomerization, or metalation/alkylation of bispropargylic protected alcohol 3. The ambident behavior of metalated synthon 3 was discussed and rationalized. Removal of the protecting groups of 9 easily afforded useful R-substituted bispropargylic alcohol. Although propargylic alcohols and propargylic ethers are well-known as versatile building blocks in organic synthesis, there are only a few reports concerning their bispropargylic homologues.1 Our interest in the development of fatty acids bearing polyalkyne functionalities led us to investigate the chemistry of bispropargylic alcohols 1 and 2 and bispropargylic ethers 3 (Figure 1). To our knowledge, the rare reactivities of penta-1,4-diyn-3ol 12 reported in the literature are its transformation into ketone,3 metallabenzenes,4 dienynes, and vinylallenes.5 The corresponding silylated 1,4-diyn-3-ol6 2 is relatively more documented: alcohol 2 oxidized into ketone can generate chalcogenapyra†
Service de Chimie Bioorganique et de Marquage. Universite´ Louis Pasteur. § In memory of Dr. Charles Mioskowski “Miko”, our exceptional supervisor and friend who died on June 2nd, 2007. ‡
(1) (a) Migliorese, K. G.; Tanaka, Y.; Miller, S. I. J. Org. Chem. 1974, 39, 739-747. (b) Auffant, A.; Diederich, F.; Boudon, C.; Gisselbrecht, J.P.; Gross, M. HelV. Chim. Acta 2004, 87, 3085-3105. (c) Convertino, V.; Manini, P.; Schweizer, W. B.; Diederich, F. Org. Biomol. Chem. 2006, 4, 1206-1208. (2) Jones, E. R. H.; Lee, H. H.; Whiting, M. C. J. Chem. Soc. 1960, 3483-3489. (3) Wille, F.; Strasser R. Chem. Ber. 1961, 1606-1611. (4) (a) Xia, H.; He, G.; Zhang, H.; Wen, T. B.; Sung, H. H. Y.; Williams, I. D.; Jia, G. J. Am. Chem. Soc. 2004, 126, 6862-6863. (b) Zhang, H.; Xia, H.; He, G.; Wen, T. B.; Gong, L.; Jia, G. Angew. Chem., Int. Ed. 2006, 45, 2920-2923. (5) Maurer, H.; Hopf, H. Eur. J. Org. Chem. 2005, 2702-2707.
FIGURE 1. 1,5-Bispropargylic synthons.
nones,5 enynylcarbene tungsten complexes,7 tetraethynylethenes,8 and tetraethynylallenes.9 Because bispropargylic alcohol 1 is known to be difficult to handle,10 we have prepared and studied the corresponding 1,5-bis(trimethylsilyl)propargylic ether 3. To our surprise, when 3 was submitted to bases and subsequent addition of electrophiles, either substituted allenyne ethers 6-8 and/or R-substituted bispropargylic derivatives 9 and/or bispropargylic ethers 4 were isolated (Figure 1). Although many synthetic approaches to allenes11 (basecatalyzed isomerization of propargyl derivatives,12 Mitsunobu displacement of propargyl alcohols13), to 1,2-dien-4-ynes,14 to substituted alkoxyallenes,15 and to silyloxyallenes16 have been described, to date to our knowledge, no method has been reported for the preparation of substituted allenyne ethers 6-8. Moreover, removal of the protecting groups of 9 could give (6) Detty, M. R.; Luss, H. R. Organometallics 1992, 11, 2157-2162. (7) Cosset, C.; Del Rio, I.; Pe´ron, V.; Windmu¨ller, B.; Le Bozec, H. Synlett 1996, 435-436. (8) Anthony, J.; Boldi, A. M.; Rubin, Y.; Hobi, M.; Gramlich, V.; Knobler, C. B.; Seiler, P.; Diederich, F. HelV. Chim. Acta 1995, 78, 1344. (9) Lange, T.; van Loon, J.-D.; Tykwinski, R. R.; Schreiber, M.; Diederich, F. Synthesis 1996, 537-550. (10) We thank Prof. Jia (see ref 4) for his helpful and warning comments: a violent explosion may take place during the vacuum distillation of crude 1 if the bath temperature is over 90 oC or if the viscosity of the residue is too high to permit the diffusion of heat. In that case, distillation should be stopped immediately to avoid accident. (11) (a) Krause, N.; Hashmi, S. K. Modern Allene Chemistry; WileyVCH: New York, 2004; Vol. 1. (b) Bruneau, C.; Dixneuf, P. H. In ComprehensiVe Organic Functional Group Transformations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.; Pergamon: New York; 1995; Vol. 2, pp 953-996. (c) Ma, S. Chem. ReV. 2005, 105, 2829-2871. (12) (a) Pourcelot, G.; Cadiot, P. Bull. Soc. Chem. Fr. 1966, 30163021. (b) Hoff, S.; Bransdma, L.; Arens, J.-F. Recl. TraV. Chim. Pays-Bas 1968, 87, 916-924. (c) Hausherr, A.; Orschel, B.; Scherer, S.; Reissig, H.-U. Synthesis 2001, 9, 1377-1385. (d) Mereyala, H. B.; Gurraka, S. R.; Mohan, S. K. Tetrahedron 1999, 55, 11331-11342. (13) Myers, A. G.; Zheng, B. J. Am. Chem. Soc. 1996, 118, 4492-4493. (14) For preparation of allenynes catalyzed by Pd, see: (a) Markl, G.; Attenberger, P.; Kellner, J. Tetrahedron Lett. 1988, 29, 3651-3654. (b) Mandai, M.; Nakata, T.; Murayama, H.; Yamaoki, H.; Ogawa, M.; Kawada, M.; Tsuji, J. Tetrahedron Lett. 1990, 31, 7179-7180. (c) Alami, M.; Linstrumelle, G. Tetrahedron Lett. 1991, 32, 6109-6112. (d) CondonGueugnot, S.; Linstrumelle, G. Tetrahedron 2000, 56, 1851-1857. (15) (a) Zimmer, R. Synthesis 1993, 165-178. (b) For reverse Brook rearrangement, see: Tokeshi, B. K.; Tius, M. A. Synthesis 2004, 5, 786790. (c) Sakaguchi, K.; Fujita, M.; Suzuki, H.; Higashino, M.; Ohfune, Y. Tetrahedron Lett. 2000, 41, 6589-6592. (16) (a) Kuwajima, I.; Kato, M. Tetrahedron Lett. 1980, 21, 623-626. (b) Kruithof, K. J. H.; Klumpp, G. W. Tetrahedron Lett. 1982, 23, 31013102. (c) Reich, H. J.; Eisenhart, E. K.; Olson, R. E.; Kelly, M. J. J. Am. Chem. Soc. 1986, 108, 7791-7800. 10.1021/jo0709753 CCC: $37.00 © 2007 American Chemical Society
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J. Org. Chem. 2007, 72, 5938-5941
Published on Web 06/28/2007
SCHEME 1.
Synthesis of Bispropargylic Ethers 3a-fa
a Reaction conditions: (a) PCl, DMAP (3a-d); (b) DHP, PPh .HBr (3e); 3 (c) EtMgBr, DMPMBr (3f).
SCHEME 2.
SCHEME 3.
Protodesilylation of 3d-f
Reaction of 3d-f with Bases or TBAF
access to R-substituted bispropargylic alcohols which could be useful partners in acetylene chemistry to afford new polyalkynylated species and oligodiacetylenes.17 Herein we report our results concerning the synthesis and the reactivity of bispropargylic ethers toward bases and electrophiles. Starting from the easily available 1,5-bis(trimethylsilyl)propargylic alcohol 2,6,8 trimethylsilyl ether 3a, triethylsilyl ether 3b, tert-butyldimethylsilyl ether 3c, tert-butyldiphenylsilyl ether 3d, tetrahydropyranyl ether 3e, and 1,3-dimethoxybenzyl ether 3f were prepared following classical procedures (Scheme 1). When protected propargylic ethers 3a-c were submitted to the protodesilylation reaction (methanolic K2CO3 or KOH), only material loss upon treatment or degradation products were observed. However, the TMS deprotection of 3d, 3e, and 3f yielded the corresponding bispropargylic ethers 4d (64%), 4e (70%), and 4f (65%) (Scheme 2). Monoprotected bispropargylic ethers 5d-f were not obtained under these reaction conditions.18 The cleavage of the TMS protective groups of bispropargylic ethers 3d-f was investigated with t-BuOK19 and TBAF.20 Surprisingly, the reaction did not afford the corresponding deprotected bispropargylic ethers 4d-f or 5d-f, but yielded the allenyne ethers 6d, 7d, and 8d (Scheme 3). These interesting results encouraged us to explore the formation of such allenyne ethers with a variety of basic conditions. The results are reported in Table 1. First, we (17) Leibrock, B.; Vostrowsky, O.; Hirsch, A. Eur. J. Org. Chem. 2001, 4401-4409. (18) (a) Whatever conditions used (time, temperature, equivalent of base), 3d-f yielded mostly 4d-f compared to 5d-f. (b) 5d was successfully prepared from 4d with BuLi/TMSCl (43% yield); see Supporting Information for details. (19) Alayrac, C. Ph.D. Thesis, University of Strasbourg, France, 1993. (20) TBAF treatment was employed for 3e,f.
TABLE 1. Reaction of Alkynes 3d-f, 5d with Bases or TBAF entry
substrate
conditionsa
6d
7d
8d-f
1 2 3 4 5 6 7 8 9
3d 3d 3d 3d 3d 3e 3f 3e 5d
t-BuOK, 0.2 equiv t-BuOK, 0.5 equiv t-BuOK, 1 equiv BuLi, 1 equiv LDA, 1 equiv, -78 °C t-BuOK, 1 equiv t-BuOK, 1 equiv TBAF, 1 equiv t-BuOK, 0.5 equiv
49%
18% 70%
b 8d: 20% 8d: 84%
83% 75%
14% 10%
36%
8e: 65% 8f: 59% 8e: 58% c
All of the reactions were run in THF at 0 °C for 5 min (except for entry 5); see Experimental Section for details. b 3d was recovered (30% yield). c 5d was recovered (60% yield). a
investigated the reactivity of silylated bispropargylic ether 3d with different amounts of t-BuOK (entries 1-3). When 3d was submitted to t-BuOK (0.2 equiv, entry 1) for 5 min, two differently substituted propargylic allenes 6d (49% yield) and 7d (18% yield) were identified. Use of 0.5 equiv of t-BuOK under identical conditions afforded 7d (70% yield) and totally deprotected allenyne ether 8d (20% yield) (entry 2). As expected, the treatment of 3d with 1 equiv of t-BuOK yielded allenyne ether 8d as a single product (84%, entry 3). These results led us to suppose that t-BuOK should promote the isomerization21 of bispropargylic ether 3d into allenyne ether 6d, which after subsequent TMS cleavages should generate allenes 7d and/or 8d. The reaction of 3d was examined with BuLi22 or LDA (entries 4 and 5): interestingly, allene 6d was obtained in 83 and 75% yield, respectively, and 7d in 14 and 10% yield, respectively. Next, the reaction was extended to compounds 3e and 3f (entries 6-8). As expected, t-BuOK promoted the isomerization of 3e and 3f and the TMS removal to afford allenyne ethers 8e and 8f in 65 and 59% yield, respectively (entries 6 and 7). Similarly, TBAF generated the transformation of 3e into 8e (65%) (entry 8). Finally, the treatment of mono-TMS-protected alkyne 5d18b with t-BuOK gave allenyne ether 7d (36% yield, entry 9), which allowed us to conclude that t-BuOK should first induce the isomerization of the triple bond into the corresponding allene. These results revealed the ability of silylated bispropargylic ethers 3 to provide allenyne ethers 6-8. At this stage, we were interested in the preparation of substituted allenyne ethers 6. Therefore, the metalation and the subsequent trapping of bispropargylic ethers 3d-f were examined. Unexpectedly, the reaction of 3d-f with BuLi followed by the addition of TMSCl did not afford the corresponding trisubstituted allene 6, but the R-substituted bispropargylic ether 9a was isolated as a single product (Scheme 4). The reaction of bispropargylic ethers 3d-f was therefore undertaken with a variety of electrophiles. The results are summarized in Table 2. As indicated in entry 1, the reaction of 3d with BuLi (1 equiv) and TMSCl (1 equiv) yielded R-trimethylsilyl bispropargylic ether 9a (39%). Similarly, the metalation of 3d followed by the alkylation with allyliodide gave the corresponding R-allylbispropargylic ether 9b (entry 2, 45% yield).23 The reaction of 3d with BuLi followed by an aqueous workup afforded the substituted allenyne ether 6d (entry 3, 80% yield). Interestingly, trapping of the lithiated bispropargylic ether 3d with Me3SnCl (21) Base-catalyzed isomerization of alkynes has precedent in the literature: Hopf, H. Chem. Ber. 1971, 104, 3087-3095; see also ref 12. (22) n-BuLi was used for all of the reactions. s-BuLi gave the same results (products and yields). (23) Addition of the electrophile prior to addition of BuLi (internal quench) gave the same alkylation results.
J. Org. Chem, Vol. 72, No. 15, 2007 5939
SCHEME 4.
SCHEME 6. Access to r-Substituted Bispropargylic Alcohol 11
Alkylation of 3d-f
TABLE 2. Results of the Metalation/Alkylation entry
substrate
electrophilea
productb
1 2 3 4 5 6 7 8 9 10 11
3d 3d 3d 3d 3e 3e 3e 3e 3f 6d 8d
TMSCl H2CdCHCH2I H2O Me3SnCl TMSCl H2CdCHCH2I CH3I (CH3)2SO4 DMPMBr TMSCl TMSCl
9a: 39% 9b: 45% 6d: 80% 6e: 55% 9c: 79% 9d: 81% 9e: 60% 9e: 55% 9f: 40% 9a: 30% 9a: 24%
a Reaction conditions: BuLi (1 equiv), electrophile (1 equiv), THF, -78 °C, 10 min. b Isolated yields 3d: P ) TBDPS, 3e: P ) THP, 3f: P ) DMPM, 9a: P ) TBDPS, E ) TMS, 9b: P ) TBDPS, E ) H2CdCHCH2I, 9c: P ) THP, E ) TMS, 9d: P ) THP, E ) H2CdCH-CH2I, 9e: P ) THP, E ) Me, 9f: P ) DMPM, E ) DMPM; 6d: P ) TBDPS, E ) TMS, 6e: P ) TBDPS, E ) SnMe3.
SCHEME 5.
Formation of 6d, 6e, and 9a-f
yielded the stannylated allenyne ether 6e (entry 4, 55%). Then the reaction was extended to substrates 3e and 3f and to various electrophiles (entries 5-9). The reaction of the lithiated bispropargylic ether 3e with TMSCl, allyliodide, methyliodide, or dimethylsulfate yielded the corresponding R-substituted alkynyl ethers 9c-e in good yields (55-81%). The alkylation of 3f with BuLi and 1,3-dimethoxybenzylbromide afforded 9f (40% yield). Furthermore, alkylations were directly carried out on allenes 6d and 8d (entries 10 and 11): metalation of allenes 6d and 8d with BuLi, followed by trapping with TMSCl, produced R-trimethylsilyl bispropargylic ether 9a as a single product in 30 and 24% yield, respectively.24 All of our attempts to extend this reaction to aldehydes and ketones gave complex mixtures where allenes or acetylenic products were not identified. The results reported in Table 2 suggested that the regioselectivity of the alkylation is depending on the nature of the electrophile. Presumably, the reaction of 3d-f with BuLi is occurring via a mesomeric ambident carbanion able to react either under its allenyllithiated form A or under its bispropargyllithiated form B (Scheme 5). Addition of water or Me3SnCl provides allenyne ether 6d and 6e, respectively (Table 2, entries 5940 J. Org. Chem., Vol. 72, No. 15, 2007
3 and 4), whereas other electrophiles (TMSCl, MeI, allyliodide) generate R-substituted alkynyl ethers 9a-f (Table 2, entries 1, 2, and 5-11). The observed results can be explained according to the hard/ soft acid/base principle (HSAB):25 the bispropargylic anion B is characterized as soft, while the allenyl anion A is classified as hard. The regioselectivities observed with water, Me3SnCl (hard electrophiles, Table 2, entries 3 and 4), MeI, dimethylsulfate, allyliodide, and dimethoxybenzylbromide (soft electrophiles, Table 2, entries 2 and 6-9) may be understood in terms of HSAB theory favoring a “soft-soft” or a “hard-hard” combination. However, to our surprise, chlorotrimethylsilane, classified as a hard electrophile, afforded exclusively R-TMS alkynyl ethers 9a and 9c (Table 2, entries 1, 5, 10, and 11). In light of this result, we propose that the charge distribution and the stability of the bispropargylic species B versus the allenic species A are very important factors and could outweigh the HSAB theory.26 Finally, we attempted to generate R-allylbispropargylic alcohol 11 from R-allylbispropargylic ether 9d. Removal of the THP group was achieved with PPTS in EtOH to produce alcohol 10 (89% yield), which after protodesilylation with K2CO3 yielded R-allylbispropargylic alcohol 12 (65%) (Scheme 6). This successful preparation of alcohol 11 from 9d is an alternative method of the known addition of a metalate species to corresponding bispropargylic ketones27 and should allow access to a broad range of substituted alcohols 11 that are useful in transition-metal-catalyzed cyclizations. In conclusion, we have reported the reaction of 1,5-bis(trimethylsilyl)propargylic ethers 3 toward bases (t-BuOK, LDA, BuLi) and TBAF, generating allenyne ethers 6-8 in good yields. Interestingly, the lithiation of 3 followed by the trapping with Me3SnCl afforded stannylated allene 6e. These substituted allenes represent versatile and useful building blocks in organic synthesis since they can be transformed into olefins, R,βunsaturated carbonyl compounds, and propargylation products. Moreover, we have developed an access to R-substituted bispropargylic alcohols 9a-f by lithiation of the bisacetylenic synthon 3 followed by the subsequent addition of an electrophile. This methodology is an alternative method to the reported addition of a metalate species to a functionalized bispropargylic ketone. Finally, this study confirms the ambident behavior of metalated synthon 3 yielding either acetylenic compounds or allenic compounds. Further studies concerning the application of our methodology in organic synthesis are ongoing in our laboratory. (24) These low yields are due to the instabilities of 6d and 8d. (25) (a) Pearson, R. G.; Songstad, J. J. Am. Chem. Soc. 1967, 89, 18271836. (b) Ho, T.-S. Chem. ReV. 1975, 75, 1-20. (26) HSAB rationalization and inconsistent reactivity were previously reported for lithiated allenes: (a) Creary, X. J. Am. Chem. Soc. 1977, 99, 7632-7639. (b) Leroux, Y.; Roman, C. Tetrahedron Lett. 1973, 28, 25852586. (c) Grovenstein, E., Jr.; Chiu, K.-W.; Patil, B. B. J. Am. Chem. Soc. 1980, 102, 5848-5859. (d) Langer, P.; Do¨ring M.; Seyferth, D.; Go¨rls, H. Chem.sEur. J. 2001, 7, 573-584. (27) Livingston, R.; Cox, L. R.; Odermatt, S.; Diederich, F. HelV. Chim. Acta 2002, 85, 3052-3077.
Experimental Section (3-(tert-Butyldiphenylsilanyloxy)penta-1,4-diyne-1,5-diyl)bistrimethylsilane (3d). To a stirred solution of bistrimethylsilyl propargylic alcohol 26,8 (100 mg, 0.44 mmol) in CH2Cl2 (7 mL) were added tert-butyldiphenylsilyl chloride (0.12 mL, 0.48 mmol) and DMAP (0.48 mmol), and the reaction was stirred at room temperature for 3 h. The mixture was concentrated, diluted with Et2O (15 mL), and washed with brine (10 mL). The organic layer was separated, dried over anhydrous MgSO4, and concentrated under vacuum. The crude product was purified by flash chromatography on silica gel (pentane/Et2O: 98/2) to afford 3d (177 mg, 90%) as a white solid: 1H NMR (CDCl3) δ 7.78 (d, J ) 7.1 Hz, 4H), 7.46-7.40 (m, 6H), 5.11 (s, 1H), 1.11 (s, 9H), 0.18 (s, 18H); 13C NMR (CDCl ) δ 135.8, 132.8, 129.7, 127.5, 102.2, 88.9, 54.7, 3 26.6, 19.2, -0.5; IR (neat, cm-1) 2959, 2181, 1592, 1062, 848; mp 71 °C; MS (TOF) m/z (M + Na+) ) 485; HRMS calcd for C27H38OSi3Na [M + Na+] ) 485.2128, found ) 485.2111. tert-Butyl-(1-ethynylprop-2-ynyloxy)diphenylsilane (4d). To a stirred solution of bispropargylic ether 3d (115 mg, 0.25 mmol) in MeOH (6 mL) was added K2CO3 (35 mg, 0.25 mmol). The reaction mixture was stirred at room temperature for 1 h and then was quenched with saturated ammonium chloride (10 mL) and extracted with Et2O (3 × 10 mL). The organic layer was separated, washed with H2O and brine, dried over anhydrous MgSO4, filtered, and concentrated under vacuum. The crude residue was purified by silica gel flash chromatography (pentane/CH2Cl2: 98/2) to afford 4d (48 mg, 60%) as a colorless oil: 1H NMR (CDCl3) δ 7.76 (d, J ) 6.5 Hz, 4H), 7.48-7.39 (m, 6H), 5.08 (t, J ) 2.2 Hz, 1H), 2.49 (d, J ) 2.2 Hz, 2H), 1.11 (s, 9H); 13C NMR (CDCl3) δ 135.8, 132.4, 130.0, 127.7, 80.9, 72.4, 53.5, 26.6, 19.2; IR (neat, cm-1) 3292, 2126, 1428, 1111, 703; MS (TOF) m/z (M + K+) ) 357. 3-(tert-Butyldiphenylsilanyloxy)-1,5-bistrimethylsilanylpenta1,2-dien-4-yne (6d). To a stirred solution of 3d (100 mg, 0.22 mmol) in THF (5 mL) at rt was added dropwise n-BuLi (0.22 mL, 1.6 M in hexane, 0.22 mmol). After 5 min of stirring, the reaction was quenched with saturated ammonium chloride and extracted with Et2O. The organic layer was separated, washed with H2O and brine, dried over magnesium sulfate, and concentrated under vacuum. Purification of the crude by flash chromatography with pentane afforded 6d as a brown oil (84 mg, 80%): 1H NMR (CDCl3) δ 7.75-7.73 (m, 4H), 7.42-7.37 (m, 6H), 5.48 (s, 1H), 1.09 (s, 9H), 0.11 (s, 9H), -0.06 (s, 9H); 13C NMR (CDCl3) δ 212.3, 135.8, 132.8, 129.7, 127.5, 110.2, 101.7, 100.3, 98.9, 26.6, 19.2, -0.4, -1.5; IR (neat, cm-1) 2957, 2148, 1922, 1472, 1313, 1112, 838, 698; MS (TOF) m/z (M + Na+) ) 881; HRMS calcd for C57H74OSi3 ) 858.5047, found ) 858.5060. 3-(tert-Butyldiphenylsilanyloxy)-1-(trimethylstannyl)-1,5-bistrimethylsilanylpenta-1,2-dien-4-yne (6e). To a stirred solution of 3d (100 mg, 0.22 mmol) in THF (5 mL) at -78 °C was added dropwise n-BuLi (0.22 mL, 1.6 M in hexane, 0.22 mmol). A solution of trimethyltin chloride (44 mg, 0.22 mmol) in THF (0.25 mL) was then added. After stirring for 30 min at -78 °C, the reaction was quenched with saturated ammonium chloride, warmed to rt, and extracted with Et2O. The organic layer was separated, washed with H2O and brine, dried over magnesium sulfate, and concentrated under vacuum. The crude was purified by Kugelrohr distillation to afford 6e (76 mg, 55%) as a yellow oil: 1H NMR (CDCl3) δ 7.78-7.76 (m, 4H), 7.40-7.35 (m, 6H), 1.03 (s, 9H), 0.11 (s, 9H), 0.10 (s, 9H), -0.06 (s, 9H); 13C NMR (CDCl3) δ 209.1, 135.8, 133.4, 129.4, 127.4, 107.6, 106.5, 104.2, 101.5, 26.5, 19.3, -0.4, -7.5; IR (neat, cm-1) 2959, 2151, 1956, 1589, 1250, 1112, 845; HRMS calcd for C30H46OSi3Sn ) 626.1878, found ) 626.1880. 3-(tert-Butyldiphenylsilanyloxy)-5-trimethylsilanylpenta-1,2dien-4-yne (7d). To a stirred solution of ether 3d (50 mg, 0.11 mmol) in THF (3 mL) was added t-BuOK (7 mg, 0.06 mmol). The resulting brown mixture was stirred at room temperature for 2 min and was then quenched with saturated ammonium chloride and
extracted with Et2O. The organic layer was separated, washed with H2O and brine, dried over magnesium sulfate, and concentrated under vacuum to yield 40 mg of a mixture of 7d (70%) and 8d (20%) unseparable by flash chromatography. 7d: 1H NMR (CDCl3) δ 7.74-7.71 (m, 4H), 7.44-7.36 (m, 6H), 5.02 (s, 2H), 1.09 (s, 9H), 0.12 (s, 9H); 13C NMR (CDCl3) δ 209.5, 135.7, 133.1, 129.6, 127.4, 112.6, 100.8, 97.8, 87.7, 26.5, 19.2, -0.13. tert-Butyl-(1-ethynylpropa-1,2-dienyloxy)diphenylsilane (8d). To a stirred solution of bistrimethylsilyl propargylic ether 3d (200 mg, 0.44 mmol) in THF (6 mL) was added t-BuOK (53.8 mg, 0.44 mmol). The resulting brown reaction was stirred at room temperature for 10 min. The solution was quenched with saturated ammonium chloride and extracted with Et2O. The organic layer was separated, washed with H2O and brine, dried over magnesium sulfate, and concentrated under vacuum. The crude was purified by flash chromatography (pentane/CH2Cl2: 98/2) to afford 8d as an unstable yellow oil (117 mg, 84%): 1H NMR (CDCl3) δ 7.747.71 (m, 4H), 7.45-7.37 (m, 6H), 4.92 (d, J ) 1.6 Hz, 2H), 3.27 (s, 1H), 1.08 (s, 9H); 13C NMR (CDCl3) δ 209.1, 135.6, 132.5, 129.7, 127.4, 111.9, 88.3, 82.3, 77.5, 26.5, 19.2; IR (neat, cm-1) 3308, 2930, 1944, 1109, 701. 3-(tert-Butyldiphenylsilanyloxy)-1,3,5-tristrimethylsilanylpenta-1,4-diyne (9a). To a stirred solution of 3d (100 mg, 0.22 mmol) in THF (5 mL) at -78 °C were added dropwise n-BuLi (0.22 mL, 1.6 M in hexane, 0.22 mmol) and then a solution of TMSCl (26 µL, 0.22 mmol) in THF (1 mL). After stirring for 10 min at -78 °C, the reaction was quenched with saturated ammonium chloride, warmed to rt, and extracted with Et2O. The organic layer was separated, washed with H2O and brine, dried over magnesium sulfate, and concentrated under vacuum. Purification by flash chromatography (pentane) afforded 9a (46 mg, 39%) as a colorless oil: 1H NMR (CDCl3) δ 7.75 (d, J ) 6.8 Hz, 4H), 7.40-7.30 (m, 6H), 1.09 (s, 9H), 0.26 (s, 9H), 0.01 (s, 18H); 13C NMR (CDCl3) δ 136.7, 134.5, 129.1, 126.8, 103.9, 92.8, 61.2, 27.0, 19.3, -0.4, -4.5; IR (neat, cm-1) 2959, 2180, 1590, 1062, 845; MS (TOF) m/z (M + Na+) ) 557. 1-Trimethylsilanyl-3-trimethylsilanylethynylhex-5-en-1-yn-3ol (10). To a stirred solution of 9d (177 mg, 0.51 mmol) in EtOH (20 mL) was added PPTS (65 mg, 026 mmol). The reaction was stirred at 60 °C until completion (for about 2.5 h) and was quenched with H2O and diluted with Et2O. The organic layer was separated, washed with H2O and brine, dried over magnesium sulfate, and concentrated under vacuum. The crude was purified by flash chromatography (pentane/Et2O: 9/1) to afford 10 as a yellow oil (120 mg, 89%): 1H NMR (CDCl3) δ 5.99-5.92 (m, 1H), 5.265.21 (m, 2H), 2.67 (d, J ) 7.2 Hz, 2H), 0.19 (s, 18H); 13C NMR (CDCl3) δ 131.7, 119.9, 104.4, 88.5, 63.0, 48.2, -0.4; IR (neat, cm-1) 3447, 2961, 2175, 1251, 844, 760; MS (TOF) m/z (M + Na+) ) 287. 3-Ethynylhex-5-en-1-yn-3-ol (11). To a stirred solution of 10 (120 mg, 0.45 mmol) in MeOH (10 mL) was added K2CO3 (62 mg, 0.45 mmol). The reaction was stirred at room temperature for 1 h and was quenched with saturated ammonium chloride and diluted with Et2O. The organic layer was separated, washed with H2O and brine, dried over magnesium sulfate, and concentrated under vacuum. The crude was purified by flash chromatography (pentane/Et2O: 8/2) to afford 11 as a colorless oil (35 mg, 65%): 1H NMR (CDCl ) δ 6.03-5.93 (m, 1H), 5.29-5.25 (m, 2H), 2.71 3 (d, J ) 7.2 Hz, 2H), 2.60 (s, 2H); 13C NMR (CDCl3) δ 131.2, 120.5, 83.1, 72.3, 62.2, 47.7; IR (neat, cm-1) 3308, 2927, 2376, 1249, 840. Supporting Information Available: General information, experimental procedures, and characterization data for compounds 3a-c, 3e,f, 4e,f, 5d, 8e,f, and 9b-f, and copies of 1H and 13C NMR spectra for all compounds. This material is available free of charge via the Internet at http://pubs.acs.org. JO0709753
J. Org. Chem, Vol. 72, No. 15, 2007 5941
