6036
J. Am. Chem. SOC.1986, 108, 6036-6038
NH), 7.74 (m,2 H, NH). Anal. Calcd for CSOH68N80i&32:C, 52.99; H, 6.05; N, 9.88. Found: C, 52.72; H, 6.04; N, 10.04. Preparation of 13. Iodine (0.99 g, 8.0 mmol) in methanol (1 50 mL) was added to a solution of 12 (900 mg, 0.80 mmol) in methanol (200 mL) during a 2.5-h period at room temperature. The reaction mixture was stirred at room temperature for 4 h and cooled to 0 OC. To this cold solution was added 1 N aqueous Na2S,0, until the solution became colorless. The solution was evaporated to dryness under reduced pressure below 35 "C, and the residue was triturated with water (15 mL), filtered, washed with water, and dried in vacuo over P205. The crude product, upon chromatography using CHCll/acetone (8:2) as eluant, gave 13: 700 mg (89%); [alzS0+58O (c 0.5, CHC13); 'H NMR (360 MHz, CDC13) 6 0.95 (m, 12 H, Val methyl), 1.42 (d, 6 H, Lac methyl), 2.20-2.30 (m, 2 H, Val methine), 2.75-2.90 (m.4 H, Cys methylene), 4.25 (d, 2 H), 4.50-4.70 (m, 4 H), 4.90-5.40 (m,8 H), 5.45-5.60 (m, 4 H), 6.85 (d, 2 H, NH), 7.35 (s, 10 H, phenyl), 8.48 (d, 2 H, NH). Anal. Calcd for C44H56N60i2S2: C, 53.42; H, 5.71; N, 8.49. Found: C, 53.25; H, 5.88; N, 8.47. [Lac2,Lac6]Des-N-tetramethyltriostinA (2). Octadepsipeptide 13 (550 mg, 0.59 mmol) was stirred with 30-32% HBr in AcOH (20 mL) at room temperature for 1 h and diluted with ether (200 mL). This mixture was kept inside the refrigerator overnight, filtered in a stream of N1, washed with ether, and dried in vacuo over P20s: yield 460 mg (94%); mp 230 OC (dec). The above HBr salt (100 mg, 0.1 1 mmol) was dissolved in dry DMF ( I O mL) and the resultant solution cooled to 0 OC under N2. To this cold, stirred solution was added triethylamine (24 mg, 0.24 mmol), followed by 2-quinoxalinecarbonyl chloride (30 mg). After 5 min, triethylamine (24 mg) and 2-quinoxalinecarbonyl chloride (30 mg) were added. Once again, triethylamine (24 mg) and 2-quinoxalinecarbony1chloride (30 mg) were added after 5 min. The reaction mixture was stirred at 0 OC for 3 h and at room temperature overnight. The solution was evaporated to dryness and the residue triturated well with ether. The solid was filtered and washed with ether and water, respectively. The solid was dried in vacuo over P 2 0 5 and purified by preparative circular TLC using CHC13/acetone(7:3) as eluant. Pure product, Rj0.38 [CHC13/acetone (7:3)], was crystallized from CHCl,/ethyl ether as a tine powder: yield 65 mg (56%);mp 263-265 OC; [a]15d-15.4O (c 0.5, MeOH); 'H NMR (360 MHz) see Tables I and 11. Anal. Calcd for C46H52N10014S2: C,
53.46; H, 5.07; N, 13.55. Found: C, 53.33; H, 5.17; N , 13.37
Footprinting Experiments Stock solutions of [Lac2,Lac6]TANDEMand deoxyribonuclease
I (DNase I) were prepared as previously d e s ~ r i b e d .Footprinting ~ experiments were conducted with the 160-base pair duplex TyrT DNA fragment labeled at one of its 3' ends by incubation with TP. reverse transcriptase and ( Y - [ ~ ~ P ] ~ or A T( YP - [ ~ ~ P ] ~ CAliquots (3 pL) of the labeled DNA (9 pmol in base pairs) were incubated with 5 p L of the ligand (10-40 pM) at 37 OC for 30 min and then digested with 2 pL DNase I (final concentration 0.05 unit/mL). Samples (3 pL) were removed from the mixture after I-, and 5-, and 30-min digestions, and the reaction was stopped by adding 2.5 pL of 80% formamide solution containing 0.1% bromophenol blue and 10 mM EDTA. These were heated at 100 OC for at least 2 min prior to electrophoresis. The products of digestion were fractionated on 8% (w/v) polyacrylamide gels (0.3 mm thick) containing Tris-borate-EDTA buffer and 7 M urea. Gels were fixed in 10% acetic acid, transferred to Whatman 3MM paper, dried under vacuum, and subjected to autoradiography at -70 "C with an intensifying screen. Final analysis of autoradiographs was accomplished using microdensitometer scans as previously described.
Acknowledgment. R.K.O., K.R., and K.L.B. express appreciation to the National Institutes of Health (Grant AI 15759) for financial support, the National Science Foundation (Grant CHE-8417529) for support of an N M R instrumental grant, the Colorado State University Regional N M R Center (funded by National Science Foundation Grant CHE-8208821) for providing high-field N M R data, and Professor Murray Goodman for suggesting consideration of an oxygen isosteric analogue of TANDEM. M.J.W. and C.M.L.L. thank the Medical Research Council, the Cancer Research Campaign, and the Royal Society for financial support.
Communications to the Editor Organoborane-CatalyzedHydroalumination of Olefins Keiji Maruoka, Hiromi Sano, Kiyotaka Shinoda, Shuichi Nakai, and Hisashi Yamamoto*
Department of Applied Chemistry, Nagoya University Chikusa, Nagoya 464, Japan Received February 26, 1986 Among various hydrometalation reactions of olefins, hydroboration is far superior in view of the efficiency and versatility of the reaction.' However, the resulting organoboranes (C-B bonds) are relatively stable and not readily functionalized compared to the corresponding organoaluminums (C-AI bonds) that possess more carbanion character and hence undergo facile intermolecular transfer reactions with a variety of organic and inorganic electrophiles under milder conditions. Accordingly, considerable interest has been directed toward the synthetic potential of hydroalumination reactions, although the ionic AI-H bond has a weak affinity for olefins in nature. Several successful examples have been recently reported which utilize the transition-metal catalysts to effect the smooth hydroalumination,2but ( 1 ) (a) Brown, H. C. Boranes in Organic Chemistry; Cornell University Press: Ithaca, NY, 1972. (b) Cragg, G. M . L. Organoboranes in Organic Synthesis; Dekker: New York, 1973. (c) Brown, H. C. Organic Synthesis via Boranes; Wiley-Interscience: New York, 1975. (d) Onak, T. Organoborane Chemistry; Academic Press: New York, 1975.
0002-7863/86/ 1508-6036$01.50/0
these systems are not always satisfactorily employable for subsequent functi~nalization.~In this context we have been intrigued for some time in the possibility of organoborane-catalyzed hydroalumination with consideration for the distinct advantage of hydroboration. Here we wish to disclose the realization of our expectation by combining use of catalytic organoborane and dichloroaluminum hydride (C1,AIH) as a hydrometalation agent. catalytic R - B i
>c=c
98% do PhCH; radicals were clearly implicated in this reaction since the addition of 5 equiv of Ph,CH resulted in the enhanced formation Of C ~ H S C H ( C~~ H ~ C H ~ : C , ~ H S C H ~ C=H5 :~l )C. ~NO H Sarene alkylation was observed when 1:l C6D6-CDC1, was used as the solvent. This indicated that for alkylation to occur it was necessary for the arene to be coordinated to the metal' as was likely to happen when the cationic species was generated in situ in an aromatic solvent. With IC-CH3CNthere was no evidence for the displacement of CH3CN by C6H6 in CDCI, solution. Thus, the alkyl group in the Pd-CH,Ph+ species behaved as an incipient carbocation in the presence of a coordinated arene but, in the absence of the latter, preferentially underwent M-C bond homolysis to generate a radical-an apparently unprecedented dual (5) Garrou, P. E.; Heck, R. F. J . Am. Chem. SOC.1976, 98, 41 15. ( 6 ) (a) Reference 2b,c. For a few recent examples from Pd(1l) chemistry, see: (b) Moravskiy, A,; Stille, J. K. J. Am. Chem. Soc. 1981, 103, 4182. (c) Loar, M. K.; Stille, J . K. J . Am. Chem. SOC.1981, 103, 4174. (d) Gillie, A.: Stille, J . K. 1980, 102, 4933. (e) Komiya, S . ; Akai, Y.; Tanaka, K.; Yamamoto, T.; Yamamoto, A. Organometallics 1985, 4 , 1130. (f) Ozawa, F.; Ito, T.: Nakamura, Y.; Yamamoto, A. Bull. Chem. SOC.Jpn. 1981, 54, 1868. (7) For an alternative synthesis of this class of compounds, see: Anderson, G. K. Organometallics 1983, 2, 665. (8) In this respect, the mechanism for eq 2 differed significantly from that invoked for Friedel-Crafts alkylation using the traditional Lewis acids: see: Roberts, R. M.; Khalaf, A. A. Friedel-Crafts Alkylation Chemistry; Marcel Dekker: New York, 1984; Chapter 3.
0 1986 American Chemical Society
