COMMUNICATIONS 12: A solution o f 4 (71 mg, 0.08 mmol) in benzene (10 mL) was treated with CNlBu (9 pL, 0.08 mmol) and stirred for 1 h at room temperature. The solvent was removed. the residue repeatedly washed with acetone and dried in vacuum. An orange-red solid was isolated which was stable in air for short periods: yield 56 mg (98%); m.p. 2 2 2 - C (decomp). 13: A solution of 4 (87 mg, 0.10 mmol) in T H F ( I S mL) was treated with NaC,H, (44 mg, 0.50 mmol) and stirred for 1 h at room temperature. The solvent was removed, the residue was extracted with pentane/benzene (1: 1; 3 mL), and the sohtion chromatographed on A1,0, (see 4). Withether a violet fraction was eluted from which after evaporation of the solvent and recrystallization from ether/pentane violet needles were isolated; yield 53 mg (80%); m.p. 208 'C (decomp). Compound 14 was prepared analogously; yield 78%: m.p. 132 'C (decamp). Received: July 31, 1993 [Z 6251 IE] German version: Angrw. Chen?. 1994. 106, 82 1 ) U. Weber. L. Zsolnai, G . Huttner, 1 Orgunomet. Chem. 1984,260,281-291; b) G . Huttner, U. Weber, 9. Sigwarth, 0. Scheidsteger, H . Lang. L. Zsolnai, ibid. 1985, 282, 331 -348. a) A. R. Barron, A. M. Cowley, R. A. Jones, C. M. Nunn, D. L. Westmoreland, Polyhedron 1988. 7,77- 78; b) A. L. Balch. V. J. Catalano. M. A. Chatfield. J. K. Nagle, M. M. Olmstedd. P. E. Reedy, Jr., J. Am. Chrm. Soc. 1991, 113, 12521258. a) W. Levason. C. A. McAuliffe, Phosphine, Arsine und Stibine Complr.\-esoJ [he Trunsitiun Elrmrnts, Elsevier. Amsterdam, 1977: b) W. Levason, C. A. McAuliffe, Acc. Chrm. Res. 1978, 11. 363-368: c) N . R. Champness, W. Levason, M. Webster. Coord. Chem. Rev., in press. P. Schwab, N . Mahr, J. Wolf, H. Werner, Angew. Chem. 1993, 105, 1498-1500; Angeiv. Chem. Inr. Ed. Engl. 1993, 32. 1480- 1482. Crystals from THF/S-propanol: crystal size 0.3 x 0.2 x 0.2 mm: orthorhomhic, space group Pnmu (no. 62), Z = 4; u =17.730(7). b =13.008(1), r = 14.919(1) A; Y = 3441.0(7) A'. pcalEd =1.660 g ~ m - ~max. : 2 8 = 54" (Mo,,, 2 = 0.70930 .&.graphite monochromator. w/28-Scan, T = 293 K); 4264 reflec> 3 O(Fa)]. Lorentzian tions measured. 4028 independent, 2777 observed polarization correction ( p = 19.0 cm- '), direct methods (SHELXS-86). refinement with program package SDP (Enraf-Nonius), position of hydrogen atoms calculated according to ideal geometry (C-H distance 0.95 A), refined with the riding model; R = 0.027, R , = 0.033; reflexiparameter ratio 13.16; residual electron density f0.7381-0.554 e k ' . Further details of the X-ray structure analysis are available on request from the Fachinformationszentrum Karlsruhe. D-76344 Eggenstein-Leopoldshafen (FRG), on quoting the depository number CSD-57659. the names of the authors. and the journal citation. T. Yamamoto, A. R. Garber, J. R. Wilkinson. C. 9 . Boss, W. E. Streib, L. J. Todd. J. Chew. Soc. Chem. Commun. 1974, 354-356. H. Ueda. Y. Kai. N. Yasuoka, N. Kasai, Bull. Chem. Suc. Jpn. 1977,50.2250-2254. P. Hong. N . Nishii, K. Sonogashira. N. Hagihara, 1 Chem. Suc. Chem. C u m mun. 1972, 993. [c3 compounds, which include 9, carry a labile tertiary hydroxyl group to the C1 carbonyl group. This inherent lability is one of the reasons that, with the exception of the biomimetically oriented urdamycin-B synthesis of Yamaguchi et al.,['I no total synthesis of angucyclins is known. We now present the first synthesis of racemic rabelomycin (rac-9), in which the synthetic problem is solved in a simple and productive manner with the help of a Diels-Alder reaction and a new type of photooxygenation of a nonfunctionalized C-atom. Previously, only model compounds lacking the tertiary hydroxyl group could be prepared with the Diels- Alder reaction.". Retrosynthetic analysis yielded a diene (OH instead of %,Me, in 6 , see Scheme 2) which, as preliminary experiments indicated, is probably extremely labile and, furthermore, not easily accessible. We therefore had the idea of replacing the hydroxyl group in the diene with a substituent that is a poorer leaving group. Our original intention was to use the dimethylphenylsilyl group, which could be replaced by a hydroxyl group in a later step." However, to study the Michael addition of lithiated silanes to Michael acceptors such as 3-methylcyclohexenone, the cheaper trimethylsilyllithium was chosen. This reagent is prepared by Still by treatment of hexamethyldisilane (1) with methyllithium in hexamethylphosphoric triamide (HMPT).However, on carrying out the reaction on a larger scale, it was discovered that the C-Si bond and not the Si-Si bond in 1 is broken, leading to the formation of pentamethyldisilyllithium (2, Scheme 1). This result is in agreement with an observation of H ~ d r l i k [ ' ~and " ] was recently confirmed for cyclic silanes by Allred et al.[13b1 Under the conditions described in the Experimental Section the cleavage of the C-Si bond in hexamethyldisilane by alkyllithium compounds to afford 2 is a general reaction which takes place not only with methyllithium in ether, but also, for example, with n-butyllithium. Obviously, the negative charge on the silicon is stabilized by the second silicon atom in the t( position. This effective stabilization is also noticeable in the reactivity of the species. The "soft" anion adds to the a,fl-unsaturated carbonyl compounds cyclohexenone (3 a), 3-methylcyclohexenone (3b), and 3,4-dimethylcyclohexenone (3c) to give exclusively the 1,4 addition products (Scheme l).[14=]The adducts 4a-4c that are formed are chiral, and further evidence for the presence of a SiMe,SiMe, unit is provided by the splitting of the signal of the diastereotopic methyl groups in the SiMe, group in both the 'H and 13CNMR spectra (see Experimental for 4b). + First Total Synthesis of ( )-Rabelomycin ** Karsten Krohn * and Karamali Khanbabaee Dedicated to Professor Ulrich Wannagat on the occasion of his 70th birthday Rabelomycin (9), known since 1970,['] is a structurally simple member of the rapidly expanding class of angucyclin antibiotics.[*]The name angucyclins was given to the class on the basis of the analogy with the anthracyclins and the angular benz[a]anthracene framew~rk.[~I In particular, angucyclin antibiotics are characterized by antif~ngal,[~] antiviral,[51enzyme inhibitory,[61and antitumor activity.['] Most of the biologically active [*I [**I Prof. K. Krohn, Dip1.-Chem. K. Khanbabaee Fachbereich Chemie und Chemietechnik der Universitit-Gesamthochschule Warburger Strasse 100, D-33098 Paderborn (FRG) Telefax: Int. code + (5251)60-3245 Synthetic Angucyclins, Part 2. This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. Part 1 : K. Krohn. F. Ballwanz, W. Baltus, Liehigs Ann. Chem. 1993, 991-913. Angen. Chem. 1111. Ed. E n d . 1994, 33. No. 1 0 VCH - RZ R' R2 R' MeLl MegSiSiMeg LiSiMepSiMeg HMPTITHF + Scheme 1 Thus, the reagent is already sufficiently selective towards 1,4addition that the formation of silylcuprates, through the addition of copper salts to the reagent (cf. ref. [ll]), is not necessary. The reagent even adds smoothly to sterically hindered enones. The easily accessible pentamethyldisilyllithium (2) is a new synthetic reagent, whose usefulness in the synthesis of tertiary alcohols is demonstrated by this first synthesis of rabelomycin. The first advantage of having a silyl group on the tertiary carbon atom is shown in the next step of the synthesis. Chain Verlagsgesellschaft mbH, 0-69451 Weinheim.1994 0S70-0833/94/0101-0099 $10.00+ .25N 99 COMMUNICATIONS extension of the b-silylketone 4b to the unsaturated ester 5 in a Wittig-Horner reaction with triethylphosphonoacetate can be carried out without the risk of a base-catalyzed fl elimination in 95 % yield. The presence of two signals in the 29Si N M R spectrum at S = - 7.63 (SiMe,) and at 6 = - 19.51 (SiMe,) confirms that the Si-Si bond survives the transformation intact." The silyl group provides a further benefit in the next step through its property of destabilizing anions in the /l position to the silicon atom. Theoretically, two regioisomeric dienolates can be formed by the deprotonation of 5 with lithium diisopropylamine (LDA). Our plan assumed, however, that proton abstraction ct to the tertiary carbon atom in 5 would be suppressed by a combination of the steric shielding afforded by the methyl and silyl groups and the p-effect of the silicon. This expectation was completely fulfilled, and after selective enolate formation with LDA and trapping with trimethylsilyl chloride only the desired regioisomer of the diene 6 (76%) could be isolated. The subsequent Diels- Alder reaction proceeded regiospecifically to give a 1 :1 mixture of the phenol 8 a (32 YO) and the ethyl ether 8 b (33 YO)(Scheme 2). However, the formation of 4b 0 0 "Si,Me5 :;::kAoEt 0 - 1 LDA, -78 "C Me,SiO J,,.,.,=15Hz;1H,2-H,).3.04(d.J,,,,=15Hr;1H.2-H,),3.0~(s;2H,4-H,),6.9 ( s : 1 H, 5-H). 7.25 (dd. J9, ,, = 2.0.Jg,," =7.3 Hz: 1 H. 9-H). 7.65 (dd, J9, I I = 2.0. J,,,=7.3H~.1H.Il-H).7.67(t,J~,,~=J,,,=7.3Hz;1H,10-H),1I.65(~;1H, -OH). 12.30(s: 1 H. OH): I3C N M R : 6 = 30.05 (prim.), 44.26 (sec.), 53.89 (sec.), 76.95 (quat.). 115.03 (quat.). 116.83 (quat.), 120.10 (tert.), 122.04 (tert.), 124.02 (tert.). 128.04(quat.). 135.46(quat.), 137.82(tert.), 138.06(quat.), 150.63 (quat.). 162.06 (quat.). 163.77 (quat.), 183.19 (quat.), 192.57 (quat.), 196.05 (quat.). MS (160 C ) ??I;= (Yo): 338 (13)[ M i ] ,321 (25).320 (100)[ M t - H,O], 310 (54) 305 (15).295 (21). 292 (25). 281 (23), 280 (94). 2 MeSSEI EtO Experimental Section Preparation of 2 and Michael addition to 3 b to form 4 b: A solution of hexamethyldisilane (50.0 mL. 0.34mol) in HMPT (200mL) was cooled to 0 -C and treated with a 5 % solution of methyllithium in ether (88mL. 0.2 mol) under nitrogen. After 15 min dry T H F (0.5 L) was added over 10 min. the reaction mixture cooled to -78'C. followed by treatment with a solution of 3 b (16.5g, 0.15mol) in dry T H F (100 mL). After 15 min the reaction was quenched by the addition of dry methanol (20mL), and the mixture then warmed to 0 ° C . The product was extracted with n-pentane (I L), the pentane solution washed twice with water (a total of 1 L) and dried over magnesium sulfate. The solution was concentrated under vacuum, and the residue fractionally distilled under oil pump vacuum; yield 21.2g (58%) (9599 C: 1.3Torr). colorless oil. ' H N M R (200 MHr. CDCI,): 6 = - 0.07 (s; 3H. SiMe,). 0.08 (s: 3 H , SiMe2).0.00(s: 9 H . SiMe,). 0.86(s: 3 H , CH,), 1.39-1.47(m; I H ) . 1.61-1.80(dt: I H ) , 1.84-1.94 (m: 3H). 2.14-2.35 (m: 3 H ) : l 3 C N M R (50MHz. CDCI,): 6 = - 5.57 (prim.). -5.42 (prim.). -0.94 (3 x prim.). 20.46 (prim.). 22.95(sec.),27.02(quat.),32.12(sec..41.46(sec.).49.55(sec.)213.31 (quat.) (Assignments from DEPT). Photooxygenation of Sd to 9: A solution of S d (30 mg, 0.092 mmol) in dichloromethane (6 mL) was exposed to diffuse daylight for 10 hours in three N M R tubes. After plate chromatographic purification on silica gel (dich1oromethane:ether = 80:20) orange crystals of 9 were obtained from the fraction of medium polarity. (22 mg, 70%): M p. 192-C (decomp.): (ref. [I]for (+)-rabelomycin: M.p. 193 "C (decomp.). 'H NMR (400 MHr. CDCI,): 6 =1.49 (s; 3H. CH,). 2.95 (d, OEt Received: June 12, 1993 Revised: September I . 1993 [Z6138 IE] German version: Angew Cheni. 1994. 106. 100 7 9 Scheme 2. this mixture is not a disadvantage, since the ethyl ether can be quantitatively converted into the phenol by treatment with aluminum trichloride. Under these conditions the Si-Si bond is also cleaved, and after hydrolytic workup the silanol 8 c is obtained (76% over both steps). Alternatively, the Si-Si bond can be cleaved under mild conditions with bromine.['4b1Silyl groups with electronegative substituents can be oxidatively replaced with hydroxyl groups.["b1 In this way 8c could be converted into the tertiary alcohol I-deoxyrabelomycin (8d, 78 YO) by mild treatment with potassium fluoride and hydrogen peroxide." 61 Due to the initially mentioned instability of the tertiary alcohol, the introduction of the oxygen at C1 of 8d was carried out in the last step of the synthesis. The oxygenation of 8 d to give rabelomycin 9 was successfully carried out in a new type of photooxygenation, in which a dilute solution of 8 d was exposed to daylight (70 YO).This photochemical introduction of oxygen at the angular benzylic position at C1 to form labile P-hydroxyketones has already proved successful in the synthesis of angucyclin analogues.["1 This reaction will, in our opinion, be an important step in future angucyclin syntheses, because base-catalyzed oxygenation["] of compounds with tertiary hydroxyl groups such as 8 d invariably leads to decomposition. [ l ] W.-C. Liu. W. L. Parker. D. S. Slusarchyk. G. L. Greenwood. S . F. Graham, E. Meyers. J. Arifihiof. 1970. 23. 437-441.  J. Rohr. R. Thiericke, N u t . Prod. Rep. 1992, 9. 103-137.  H. Drautr. H. Zihner. J. Rohr. A. Zeeck, J. Antihiof. 1986. 39, 1657-1669.  T. Oki. 0. Tenmyo. M. Hirano. K. Tomatsu, H. Kamai, J. Antihiot. 1990. 43. 763 -770. [ 5 ] S. Kondo. S. Gomi. D. Ikeda, M. Hamada. T. Takeuchi, H. Iwai, J. Seki, H. Hoshino, J. Antihior. 1991. 44. 1228-1236.  K. Ohta, E. Mlzutd, H. Okazaki, T. Kishi, Cliern. Pharm. Bull. 1984,32,43504359.  J. H. Wilton. D. C. Cheney, G . C . Hokanson. J. C . French, H. Cun-heng, J. Clardy. J. Org. Cliem. 1985, 50. 3936- 3938. [XI M. Yamaguchi, T.Okuma. A. Horiguchi. C. Ikeura, T. Minami, J Og.C/iem. 1992. 57. 1647-1649.  a) A. Guingant, M. M. Barreto, Trtrahedron Lett. 1987, 28,3107-3110;b) K. Kim, J. Reihenspies. G . Sulikowski, J. Org. Chem. 1992, 55, 5557-5559. [I01 J. A. Vdlderrdma, R. Araya-Maturana, M. F. Gonaalez, R. Tapia, F. Fariiia. M. C. Pdredes. J. Chrm. So<. Prrkin Trans. I 1991, 555-559. 1111 a) D. J. Ager, I . Fleming, J. Chem. Soc. Chem. Commun. 1978. 177-178: h) I. Fleming, R. Henning. H. Plaud, ihid. 1984, 29-31. [I21 W. C.Still. J. Org. Chrm. 1976, 41. 3063 -3064. [I31 a) P. F.Hudrlik. M. A. Waugh, A. M.Hudrlik, J. Organornet. Chem. 1984,271, 69 -76;h) A. L.Allred, R. T. Smart. D. A. Van Beek, Orgunometallics 1992,11, 4225-4230.  a) K . Krohn. P. Ritzenhoff. unpublished: h) G. Pilcher, M. L. P. LeitHo, Y Meng-Yan, R. Walsh. J. CAem. Soc. Furaday Truns. 1991. 87.841 -846.  We thank Prof. H. Marsmdnn (Universitit-GesamthochschulePaderhorn), for recording the 29Si NMR spectra [I61 T. H. Chan. K. T. Nwe, J. Org. C/iem. 1992,57, 6107-6111. [I71 K. Krohn, F. Ballwanz. W. Baltus. Lrehigs Ann. Cliem. 1993, 911 -913.