7876
J . Org. C h e m . 1994,59, 7876-7888
Enediyne- and Tributyltin Hydride-MediatedAryl Radical Additions onto Various Radical Acceptors J a n e t Wisniewski Grissom,* Detlef Klingberg, Sabine Meyenburg, and Brenda L. Stallman Department of Chemistry, University of Utah, Salt Lake City, Utah 84112 Received July I , 1994@
Tandem enediyne-radical cyclizations were carried out on substrates that contain nitrile and ketone radical acceptors. The products of these cyclizations and the previously reported tandem enediyneradical cyclizations containing aldehyde and oxime ether radical acceptors were compared with tributyltin hydride-mediated aryl radical addition reactions with 1-bromonaphthalene derivatives containing aldehyde, oxime ether, nitrile, and ketone radical acceptors, since these substrates go through similar initial radical intermediates. Although many of the same products were observed using either method of aryl radical generation, there were distinct differences in the product composition and identity depending on which method was used. These differences can probably be primarily attributed to the temperature difference of the two modes of radical generation. We have recently developed a new method of ring formation, in which a radical generated from an enediyne cyclization1 undergoes a subsequent radical cyclization with a pendant olefin.2 To expand the scope and utility of this tandem enediyne-radical cyclization, we have also investigated aldehydes and oxime ethers as radical acceptor^.^ Although there had been reports about alkyl radical cyclizations using aldehydes4 and oxime ethers5 as radical acceptors, these reactions3 constituted the first examples of the addition of aryl radicals onto aldehyde and oxime ether radical acceptors. In order to investigate the impact of the specific reaction conditions, naphthyl bromides 4-7 were subjected to standard tributyltin hydride-mediated radical reaction conditions and the products were compared to those obtained from the previously reported tandem enediyne-radical cyclization of enediynes 30,31,38, and 39.3 To further explore the differences between these two methods of aryl radical generation, ketones and nitriles were also employed in both the tandem enediyne-radical cyclization (substrates 17,18,21, and 22)and the tributyltin hydride-mediated radical cyclization (substrates 9- 12). Synthesis of Naphthalene Precursors. Aldehydes 4 and 5, as well as oxime ethers 6 and 7,were readily available from 1-bromo-2-methylnaphthalene (1)(Scheme Abstract published in Advance ACS Abstracts, November 1,1994. (1) (a) Jones, R. R.; Bergman, R. G. J . Am. Chem. SOC.1972,94, 660.(b) Bergman, R.G. Acc. Chem. Res. 1973,6, 25. (c) Lockhart, T. P.; Mallon, C. B.; Bergman, R. G. J. Am. Chem. SOC.1980,102,5976. (d) Lockhart, T.P.; Comita, P. B.; Bergman, R. G. J. Am. Chem. SOC. 1981,103, 4082. (e) Lockhart, T. P.; Bergman, R. G. J. Am. Chem. (DBharucha, K. N.; Marsh, R. M.; Minto, R. E.; SOC.1981,103,4091. Bergman, R. G. J . Am. Chem. SOC.1992,114,3120. (2)(a) Grissom, J. W.; Calkins, T. L. Tetrahedron Lett. 1992,33, 2315.(b) Grissom, J.W.; Calkins, T. L. J . Org. Chem. 1993,58,5422. (c) Grissom, J. W.; Calkins, T. L., McMillen, H. A. J . Org. Chem. 1993, 58, 6556.(d) Grissom, J. W.; Calkins, T. L., Egan, M. J . Am. Chem. SOC.1993,115,11744.(e) Grissom, J. W.; Huang, D.; Calkins, T. L.; McMillen, H. A. Tetrahedron 1994,50,4635. (3)Grissom, J. W., Klingberg, D. J . Org. Chem. 1993,58,6559. (4)(a)Beckwith, A. L. J.; Raner, K. D. J. Org. Chem. 1992,57,4954. (b) Beckwith, A. L. J.; Hay, B. P. J . Am. Chem. SOC.1989,111,2674. (c) Fraser-Reid, B.; Walton, R. J . Am. Chem. SOC.1991,113, 5791. (5)(a) Marco-Contelles, J.;Pozuelo, C.; Jimeno, M. L.; Martinez, L.; Martinez-Grau, A. J. Org. Chem. 1992,57,2625. (b) Enholm, E. J.; Burroff, J. A.; Jaramillo, L. M. Tetrahedron Lett. 1990,31, 3727.(c) Parker, K.A.; Spero, D. M.; Van Epp, J . J. Org.Chem. 1988,53,4628. (d) Bartlett, P.A.; McLaren, K. L.; Ting, P. C. J.Am. Chem. SOC.1988, 110,1633.(e) Hart, D. J.; Seely, F. L. J . Am. Chem. SOC.1988,110, 1631.(0 Corey, E. J.; F'yne, S. G. Tetrahedron Lett. 1983,24,2821. @
0022-326319411959-7876$04.5010
c R --
a=
1:R-H
4:fl-1
2: R Br 3: CH2CH-CH2
5:n-2
6:n-1 rfl-2
a (a) NBS, benzoyl peroxide, CC4, A (67%); (b) allylmagnesium bromide, EbO, rt, 2 d (84%);(c) 0 3 , CHzClfleOH (97/3),-78 "C (74%); (d) (i) 9-BBN, THF, rt; (ii) EtOH, NaOH, H202 (61%); (e) 1.2equiv of PCC, CHzClz (68%);(0 BnONH3C1, pyridine, CHzClz (97% for 6;92% for 7).
1). Bromination of 1 with N-bromosuccinimide ( N B W and subsequent reaction with allylmagnesium bromide7 yielded olefin 3 in 56% overall yield, which, upon ozonolysis, gave aldehyde 4 in 74% yield. Attempts to synthesize aldehyde 5 in the same manner as aldehyde 4 by using homoallylmagnesium bromide instead of allylmagnesium bromide resulted in very low yields of the homologous substitution product, which proved difficult to purify. Alternatively, 5 could be obtained from 3 via hydroboration with 9-borabicyclo[3.3.1lnonane(9BBN), followed by a n oxidative workup (61%) and subsequent oxidation with pyridinium chlorochromate (PCC, 68%). Oxime ethers 6 and 7 could be obtained in excellent yields from aldehydes 4 and 5, respectively, by condensing each with 0-benzylhydroxylamine (Scheme 1, 97% for 6,92% for 7). Ketone 9 and nitrile 10 were both readily available from l-bromo-2-(bromomethyl)naphthalene(2)(Scheme 2). Conversion into the alcohol by treating 2 with calcium carbonate in a 1 : l mixture of 1,Qdioxane and water and subsequent PCC-oxidation gave rise to l-bromonaphthalene-2-carb~xaldehyde~ (8)in 65%yield over two steps. Treatment of 8 under Wittig reaction conditions with acetonyl triphenylphosphorane in refluxing toluene followed by catalytic hydrogenation of the resulting enone gave ketone 9 in 61% overall yield. Nitrile 10 could be obtained via a Horner-Emmons reaction of 8 with ~
~
~~~~~~
~
(6)Newman, M. S.;Kosak, A. I. J. Org. Chem. 1949,14, 375. (7)Abeywickrema, A. N.;Beckwith, A. L. J.; Gerba, S. J . Org.Chem. 1987,52,4072. (8)Smith, J. G.;Dibble, P. W.; Sandbom, R. E. J . Org. Chem. 1986, 51,3762.
0 1994 American Chemical Society
J. Org. Chem., Vol. 59, No. 25, 1994 7877
Enediyne- and n-Bu3SnH-Mediated Aryl Radical Additions
Scheme 4
Scheme 2 Br
Br
Br
2
I
Q
9
Br 0
16:n - 2
15:n-2 16:n=3
a (a) 1.5 equiv of 3-butynol or 4-pentynol or 5-hexynol, 0.03 equiv of (Ph3P)zPdCl~,O.lequiv of CUI, 3.0 equiv of NEt3, THF (58% for 1456% for 15/48% for 16);(b) 1.2 equiv of (trimethylsilyl)acetylene, same as (a) (96% for 1494% for 15/94% for 16); (c) KzCO3, MeOH (97%); (d) TsC1, pyridine, CHzClz (81% for 17/88% for 18); (e) NaCN, DMSO,(77% for 17/91% for 18).
8
Scheme 5 10
(a) CaC03, 1,4-dioxane/HzO, A, 10 h (67%); (b) 1.2 equiv of PCC, CHzClz (97%); (c) Ph3P=CHCOCH3, toluene, A (95%); (d) Hz, P d C , EtOAc (64%); (e) (EtO)zP(O)CHzCN, (CH&COK, THF (98%); (0 1.5 equiv of NaBH4, i-PrOH, A, 36 h (75%).
Scheme 3
4' 4: a.b
\\
15:n-1 l6:n-2
SiMe3
