J. Org. C h e m . 1993,58, 6217-6223
6217
Ligand, Solvent, and Deuterium Isotope Effects in Mn(II1)-Based Oxidative Free-Radical Cyclizations Barry B. Snider’ and Bridget A. McCarthy Department of Chemistry, Brandeis University, Waltham, Massachusetts 02254-9110 Received April 19, 1993.
Oxidation of @-ketoester 1 with Mn(pic)3and Cu(0Ac)z affords bicycloalkane 8, not the expected alkene 7, which is formed in high yield with Mn(OAc)3and Cu(0Ac)z. A series of control experiments established that the most likely explanation for this observation is that Mn(pic)z, but not Mn(OAc)z, reacts with the bicyclic radical 5 more rapidly than Cu(0Ac)z does. These studies also indicate the potential for improved yields from oxidative free-radical cyclization of deuterated substrates. For instance, reaction of @-ketoester 1-d with 2 equiv of Mn(0Ac)s and no Cu(0Ac)z affords 65% of 8, whereas @-ketoester 1 provides only 22% of 8 under the same conditions. Large kinetic isotope effects change the nature of the termination step and prevent the formation of acyclic radical 3 by intermolecular hydrogen transfer. Solvent and ligand effects on the oxidation of @-ketoester 1, malonate 14, and acetylenic @-ketoester 25 are described.
Introduction We have recently developed an efficient oxidative freeradical cyclization procedure using Mn(0Ac)a to oxidize an unsaturated &keto ester, l,bdiketone, or 1,3-diester to an a-keto radical that cyclizes.1g2 The reaction is terminated by oxidation of the cyclic radical with Mnor Cu(0Ac)z. Mono, tandem, and triple cyclizations (OAC)~ have been carried out in high yield. The conversion of b-keto ester 1 to methylenebicyclo[3.2.lloctane 7 shown in Scheme I is a typical example of this reaction. Reaction of 1 with 2 equiv of Mn(0Ac)s and 1 equiv of Cu(0Ac)z in AcOH at rt for 14 h affords 86 % of 7.1bf The slow step in this process is the formation of Mn(II1) enolate 2, which rapidly loses Mn(I1) to give the acyclic manganese-free free radical 3.1Ca Cyclization of radical 3 affords tertiary monocyclic radical 4, which undergoesa second cyclization to give primary bicyclic radical 5 as a -2.5:l mixture of ezo and endo isomers. Primary radical 5 is not oxidized by Mn(II1) but reacts rapidly with Cu(I1) to afford the Cu(II1)intermediate 6, which rapidly loses AcOH and Cu(OAc) providing alkene 7. Mn(II1) rapidly oxidized Cu(1) to Cu(I1) so that 2 equiv of Mn(II1) and only a catalytic amount of Cu(I1) are required. Mn(II1) oxidizes tertiary radicals rapidly, but is much less effective at oxidizing primary and secondary radicals. Oxidation of @-ketoester 1 with 2 equiv of Mn(0Ac)a in AcOH without Cu(0Ac)z as a cooxidant affords only 14% of alkene 7. The major pathway is abstraction of a hydrogen atom from solvent or another molecule of 1 to afford alkanes 8a (7%) and 8b (17%).If (1) For previous papers in this series see: (a) Snider, B. B.; Mohan,
R. M.; Kates, S. A. J. Org. Chem. 1986, 50, 3569. (b) Snider, B. B.; Dombrcaki,M. A. J. Org. Chem. 1987,52,5487. (c) Snider,B. B.;Patricia,
J. J.; Kates, S. A. J. Org. Chem. 1988,53,2137. (d) Snider,B. B.; Patricia, J. J. J. Org. Chem. 1989, 54, 38. (e) Katee, S. A.; Dombrcaki, M. A.; Snider, B. B. J. Org.Chem. 1990,55,2427. (0Dombrcaki, M. A.; Kates, S. A.; Snider, B. B. J. Am. Chem. SOC.1990,112,2759. (8) Curran, D. P.; Morgan, T.M.; Schwartz, C. E.; Snider, B. B.; Dombroeki, M. A. J. Am. Chem. SOC.1991, 119, 6607. (h) Snider, B. B.; Merritt, J. E.; Dombroeki, M. A.; Buckman, B. 0. J. Org. Chem. 1991, 56, 5544. (i) Snider, B. B.; Buckman, B. 0. J. Org. Chem. 1992,57, 322. (2) For reviews of Mn(0Ac)sas an oxidant see: (a) de Klein, W. J. In Organic Syntheeis by Oxidation with Metal Compounds;Mijs, W. J., de Jonge, C. R. H., Eds.; Plenum Press: New York, 1986, pp 261-314. (b) Badanyan, Sh. 0.; Melikyan, G. G.; Mkrtchyan, D. A. Rues. Chem. Rev. 1989,58, 286; Uepekhi Khimii 1989,58,475.
0022-3263/93/1958-6217$04.00/0
Scheme I 0 -c
1
‘ 2
3
I
1.
F02Me
P
Narasaka has recently reported that Mn(II1) picolinate [Mn(pic)al in DMF is a useful reagent for the oxidation of @-keto acids to radicals, the oxidative cleavage of cyclopropanolsto give @-ketoradicals, and the oxidation of nitroalkanes to cation radical^.^ In particular, he noted that @-ketoacids afford different mixtures of products with Mn(pic)3 and Mn(0Ac)s. As part of a surveyof other Mn(II1) reagenta and suitable solvents, we examined the oxidative cyclization of 1 with Mn(pi~)3.~ To our surprise, we found that oxidation of 1 with 2 equivof Mn(pic)sand 1 equiv of Cu(0Ac)z in AcOH (3) (a) N a r d , K.; Miyoehi, N.; Iwakura, K.; Okauchi, T.Chem. Lett. 1989,2169. (b) Narasaka,K.;Iwakura,K.; Okauchi, T.Chem.Lett. 1991,423. (c) Iwaaawa, N.;Hayakawa, S.;Isobe, K.; N a r d , K. Chem. Lett. 1991,1193. (d) Iwaeawa, N.; Hayakawa, S.;Funahashi,M.; Isobe, K.; Narasaka, K. Bull. Chem. SOC.Jpn. 1993,66,819. (e) Iwasawa, N.; Funahashi, M.; Hayakawa, S.; Narasaka, K. Chem. Lett. 1993,545. (4) For the preparation of Mn(pic)z and Mn(pic)a see: (a) Gmelin Handbook of Znorganic Chemistry,Mn Main VolumeD4,8thed.; Springer Verlag: Berlin, 1985; pp 308-312. (b) Kleinstain, A.; Webb, G. A. J. Znorg. Nucl. Chem. 1971,33,405. (c)Yamaguchi,H.; Sawyer,D. T .Znorg. Chem. 1986,24,971. (d) Richert,S.; Tsang, P. K. S.;Sawyer,D. T.Znorg. Chem. 1988,27, 1814 and 1989,2%,2471.
0 1993 American Chemical Society
6218 J. Org. Chem., Vol. 58, No.23, 1993
Snider and McCarthy
Table I. Ligand and Deuterium Isotope Effects on the Oxidative Free-Radical Cyclization of &Keto Eater 1 with Mn(II1) and Cu(I1) in EtOH and AcOH Mn(1II)a Cu(1I)b equiv of Mn(II1) entry solvent substrate oxidant oxidant additives consumedc 7(%) a(%) 1 AcOH 1 Mn(0Ac)s Cu(OAc)2 2 86 0 2 AcOH 1 Mn(0Ac)s none 14 24 1 Mn(pith CU(OAC)~ 0.3 0 15 3 AcOH 4 EtOH 1 fi(OAC)s CU(OAC)~ 2 71 4 5 EtOH 1 Mn(0Ac)s none 0.3 2 24 EtOH 1 Mn(pic)s CU(OAC)~ 0.22 0 22 6 AcOH 1 Mn(0Ac)s Cu(pic)2 2 76 4 7 8 EtOH 1 Mn(0Ac)s Cu(pic)s 38 14 9 AcOH 1 Mn(0Ac)s Cu(OAc)2 picHd 2 70 5 AcOH 1 Mn(0Ac)s CU(OAC)~ picHe 9 18 10 11 AcOH 1 Mn(0Ac)S Cu(0Ac)z PPf 2 80 0 12 AcOD-dr 1 Mn(0Ac)s none 5 2447 AcOD-dr 1 Mn(pic)s CU(OAC)~
