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The methodology has been successfully extended with modifications to both the bis(nucleophile) and the bis(electrophile) components, as shown in the Table.5
1. Department of Chemistry, Harvard University, Cambridge, MA 02138.
2. Department of Chemistry, Stanford University, Stanford, CA 94305.
3. (a) Clark, R. D.; Heathcock, C. H. Synthesis 1974, 47\ (b) Clark, R. D.; Heathcock, C. H. J. Org. Chem. 1976, 41, 636.
4. (a) McDermott, J. X.; White, J. F.; Whitesides, G. M. J. Am. Chem. Soc. 1976, 98, 6521; (b) McDermott, J. X.; Wilson, M. E.; Whitesides, G. M. J. Am. Chem. Soc. 1976, 98, 6529; (c) West, R.; Rochow, E. G. J. Org. Chem. 1953, 18, 1739.
5. (a) Wender, P. A.; White, A. W. J. Am. Chem. Soc. 1988, 110, 2218; (b) Wender, P. A.; Eck, S. L. Tetrahedron Lett. 1977, 1245.
6. For example, see (a) Sato, N.; Ishiyama, T.; Miyaura, N.; Suzuki, A. Bull. Soc. Chem. Jpn. 1987, 60, 3471; Kienzle, F.; Minder, R. E. Helv. Chim. Acta 1987, 70, 1537.
7. Stork, G.; Danheiser, R. L.; Ganem, B. J. Am. Chem. Soc. 1973, 95, 3414.
Reagent M = CuSPh
SPIROANNELATION USING ORGANOBIS(CUPRATES) Equiv. Substrate Product
Yields in parentheses woro Uutuimlmid by Internal standard gas chromatographic analysis
Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)
9.9-Dimethylspiro[4.5]decan-7-one: Sprio[4.5]decan-7-one, 9,9-dimethyl- (10); (63858-64-0)
3-Chloro-5,5-dimethylcyclohex-2-en-1-one: 2-Cyclohexen-1-one, 3-chloro-5,5-dimethyl- (8,9); (17530-69-7)
Dimedone: 1,3-Cyclohexanedione, 5,5-dimethyl- (8,9); (126-81-8)
Oxalyl chloride (8); Ethanedioyl dichloride (9); (79-37-8)
1.4-Dilithiobutane: Lithium, ц-tetramethylenedi- (8); ц-1,4-butanediyldi-(9); (2123-72-0)
Lithium (8,9); (7439-93-2)
1.4-Dichlorobutane: Butane, 1,4-dichloro- (8,9); (110-56-5) sec-Butyl alcohol: 2-Butanol, (±)- (8,9); (15892-23-6)
1.10-Phenanthroline (8,9); (66-71-7)
Copper(1) thiophenoxide: Benzenethiol, copper(1+) salt (8,9); (1192-40-1)
ALKYNYL(PHENYL)IODONIUM TOSYLATES: PREPARATION AND STEREOSPECIFIC COUPLING WITH VINYLCOPPER REAGENTS. FORMATION OF CONJUGATED ENYNES. 1-HEXYNYL(PHENYL)I0D0NIUM TOSYLATE AND (E)-5-PHENYLDODEC-5-EN-7-YNE (Iodine, 1-hexynyl(4-methylbenzenesulfonato-0)phenyl-) and (Benzene, (1-butyl-1-octen-3-ynyl)-, (E)-)
C4H9U. THF -70°C -> -20°C
-70°C -> reflux
B. C4H9C=CSi(CH3)3 + Phio B1^El2°:C„HCl3 - aq25°aLOTS
0°C -» 25°C
0 C^HgBr Mg CuBr ■ SMe2> C6H5C=CH^ C4HQC—C-I+-C6H5 p-CH3CgH4S03
Submitted by Peter J. Stang and Tsugio Kitamura.1 Checked by Kazuaki Ishihara and Hisashi Yamamoto.
A. 1-Trimethylsilyl-1-hexyne (Note 1). A dry, 500-mL, three-necked, round-bottomed flask (equipped with a magnetic stirrer system) is fitted with one 50-mL and one 125-mL pressure-equalizing addition funnel and a reflux condenser. The top of
the condenser is mounted with a T-piece connected at one end to an argon outlet and at the other end to an oil bubbler. The apparatus is purged with dry argon and the reaction is carried out under an argon atmosphere. The flask is charged with 16.4 g (0.20 mol) of 1-hexyne (Note 2) and 200 mL of tetrahydrofuran (THF, Note 3), and the mixture is cooled to approximately -70°C with a dry ice-2-propanol slush bath. The 125-mL dropping funnel is filled with 80 mL (0.20 mol) of 1.63 M butyllithium in hexane (Note 4) which is added over a period of 30 min to the stirred, cold (-70°C) 1-hexyne in THF. After addition is complete the flask is gradually warmed over a 3-hr period to -20°C, then recooled to -70°C with the dry ice-2-propanol slush bath. Chlorotrimethylsilane (Note 5), 25.3 mL (0.20 mol), is placed in the 50-mL dropping funnel and added over a period of 15 min to the stirred, cooled reaction mixture. After the addition is complete the slush bath is removed and the mixture is first stirred at room temperature for 16 hr, then heated under reflux for 1 hr (Note 6). The mixture is cooled to 0°C with an ice-water bath and then 50 mL of water is carefully added. The entire reaction mixture is transferred to a 1-L separatory funnel and extracted with 200 mL of pentane. The organic phase is separated, washed successively with three 100-mL portions of water followed by 100 mL of saturated sodium chloride solution and then dried over anhydrous magnesium sulfate. After filtration the solvent is distilled off through a 15-cm Vigreux column. The pale yellow residue is transferred to a 100-mL round-bottomed flask and distilled through a 15-cm Vigreux column to give 25.0-27.5 g (81-89%) of 1-trimethylsilyl-1-hexyne as a clear, colorless liquid, bp 149-156°C, that can be used as is in the subsequent step.