Chapter 23 Organocobalt and Organomercury Compounds

Transcription

1 Chapter 23 rganocobalt and rganomercury Compounds I. rganocobalt Compounds A. eaction Mechanism B. pimerization C. Addition eactions D. adical Cyclization II. rganomercury Compounds III. Summary IV. eferences Co 2 = C P 1 Figure 1. The structure of coenzyme B 12 (5'-adenosylcobalamin) I. rganocobalt Compounds An organometallic complex that contains a carbon cobalt bond can function as a radical precursor because such a bond is easily broken homolytically. Facile cleavage occurs because carbon cobalt bonds are significantly weaker than most covalent bonds: 1,2 in fact, the C Co bond in coenzyme B 12 (1, Figure 1) is one of the weakest covalent bonds known (BD = 31.5 kcal mol -1 ). 3 nzymatic reaction, mild heating, and photolysis with visible light all cause homolysis of C Co

2 516 Chapter 23 bonds. Adding to the usefulness of organocobalt complexes as radical precursors is the fact that, despite their considerable reactivity, many of these complexes can be handled in the laboratory. Although C Co bond homolysis takes place at relatively low temperatures, photolysis is the method of choice for radical formation in reactions conducted outside biological settings. 4 9 The reason for this choice is that C Co bond fragmentation occurs with low-energy (visible) light at temperatures that avoid possible side reactions from even mild heating of complex, cobalt-containing compounds. 2 2 C 2 enzyme C 2 + Co II ( 1 ) [ ] and [ Co II ] are general formulas for cobalt complexes in different oxidation states. In this reaction these symbols represent the portion of coenzyme B 12 (see Figure 1) that does not include an adenosyl group. Coenzyme B 12 (1, Figure 1) provided the original stimulus for using carbon cobalt bond homolysis to form carbon-centered radicals The enzyme-induced homolysis of the C Co bond in 1 produced the 5-deoxyadenosyl radical 2 and the cobalt-containing radical 3 (eq 1). The discovery that carbon-centered radicals could be produced in this way led to interest in finding simpler molecules that would mimic such behavior. Co(dmg) 2 py = Co py Figure 2. General structure for a cobaloxime derivative Among the several types of organocobalt complexes found to be useful in generating carbon-centered radicals, cobaloximes [bis(dimethylglyoximato)cobalt complexes] (Figure 2) are the most widely used in carbohydrate chemistry Many reactions of cobalt-containing carbohydrates and much of the mechanistic information about reactions caused by C Co bond homolysis come from study of cobaloximes.

3 rganocobalt and rganomercury Compounds Co II ( 2 ) = carbohydrate moiety and Co II are cobalt complexes. I 4 aco I (dmg) 2 py C 3, - 10 o C py(dmg) (dmg) 2 py ( 3 ) 6 12% = Me 2 C 34% A. eaction Mechanism In the reactions of carbohydrates cobalt occurs in three oxidation states [Co(I), Co(II), and Co(III)]. Co(III) is the oxidation state for cobalt in neutral, organocobalt complexes. 2 Co(II), which exhibits radical behavior, is found in complexes produced by homolytic cleavage of a C Co bond (eq 2). Compounds with cobalt in the Co(I) oxidation state are nucleophilic and react with iodides, bromides, and sulfonates to produce Co(III) complexes. 11,16 Although a compound such as aco I (dmg) 2 py is nucleophile, simple displacement does not explain all the products formed when it reacts with a halogenated carbohydrate such as the iodide 4 (eq 3). 16 ucleophilic displacement of iodide ion from 4 should produce the organocobalt derivative 5 but not 6, which is, in fact, the major reaction product. Due to the weakness of the carbon cobalt bond, a possible explanation for the formation of 6 is that it is produced from 5 during reaction. This explanation seems unlikely, however, because although a gradual conversion of 5 into 6 does occur at 38 o C (Scheme 1), 16 this reaction is far too slow to explain the substantial amount of 5 that is formed in a short period of time in reactions conducted at -10 o C (eq 3). A better explanation for the formation of the cobalt complex 6 is proposed in the mechanism shown in Scheme 2. The first step in this process is electron transfer from aco I (dmg) 2 py to the iodide 4 to give Co II (dmg) 2 py and the radical anion 8. (lectron transfer of this type has been proposed in reactions of both carbohydrates 12,17,18 and noncarbohydrates 10.) xpulsion of iodide ion to form 7 and combination of this radical with Co II (dmg) 2 py can occur from either face of the furanoid ring to give the observed products 5 and Since interaction of the combining radicals should begin when they are well separated, steric effects in the early stages of reaction

4 518 Chapter 23 should be small and a mixture of products expected. Stereoselective formation of 6 is consistent with the β face of the radical 7 being less hindered than the α face. Scheme 1 Co II (dmg) 2 py Me 2 C + Me 2 C (dmg) 2 py or Me 2 C or 6 7 (dmg) 2 py time (min) 5 62% 0 38% 74% % 89% 96% % 4% data for thermal interconversion at 38 o C Scheme 2 I Co I (dmg) 2 py - Co II (dmg) 2 py I - I = Me 2 C Co II (dmg) 2 py (dmg) 2 py 6 + py(dmg) 2 5 adicals such as Co(dmg) 2 py are responsible for a type of reactivity known as the persistent-radical effect. This effect causes a reaction that generates a persistent radical 1 [e.g.,

5 rganocobalt and rganomercury Compounds 519 Co(dmg) 2 py] and a transient radical 2 (typically a carbon-centered one) in equal amounts to give a higher yield of the cross-coupling product ( 1 2 ) than would be expected from random radical coupling. This effect, which is discussed in Section II.B.1.c (p 35) of Chapter 3 in Volume I, is responsible for only cross-coupling products (5 and 6) being detected in the reaction shown in Scheme 1. Scheme 3 AcC 2 Ac Ac Ac - Co II (dmg) 2 py Co II (dmg) 2 py AcC 2 Ac Ac Ac 9 (dmg) 2 py Co II (dmg) 2 py - Co II (dmg) 2 py Ac Ac AcC 2 Ac (dmg) 2 py 10 B. pimerization Because the carbon cobalt bond is extremely weak, thermal epimerization is observable in organocobalt complexes when cobalt is bonded to a chiral carbon atom; for example, in a reaction already encountered, interconversion between cobaloximes 5 and 6 takes place at 38 o C (Scheme 1). 16 Similar reaction also occurs when the anomeric cobaloximes 9 and 10 are heated or photolyzed (Scheme 3). 16 In each case radicals are proposed as the intermediates responsible for the epimerization process. C. Addition eactions If carbon cobalt bond homolysis generates a nucleophilic, carbon-centered radical ( ) in the presence a compound with an electron-deficient multiple bond, radical addition to the unsaturated compound takes place (Scheme 4). 10 adicals produced in this way are known to add to acrylonitrile (and its derivatives), styrene, 19a maleic anhydride, 19b and derivatives of methyl acrylate. 20 Because the adduct radical 11 (Scheme 4) is less nucleophilic than the initially formed radical, reaction of 11 with another substrate molecule is usually too slow to compete with radical combination to give the organocobalt complex 12. Although formation of 12 completes the

6 520 Chapter 23 radical phase of the reaction, further transformation does take place. Compound 12 either undergoes β-elimination to generate an unsaturated carbohydrate or substitution that replaces the cobalt-containing substituent with a proton. 10 xamples of these two types of reaction are found in eq 4 14 and eq 5, 12 respectively. Scheme Co II Co II 11 - Co II Co II - 12 = an electron-withdrawing substituent S S = a proton donor - = an organocobalt compound C 2 Co(dmg) 2 py C 2 C=CC Bn C 2 =CC 6 5 t + Co(dmg) 2 py Bn ( 4 ) 63% C 2 Ac C 2 Ac Ac Ac + C 2 =CC Ac Co(dmg) 2 py C 6 6 C 3 D Ac Ac Ac C 2 CC 56% D ( 5 ) adical addition initiated by photolysis of organocobalt complexes can be used to prepare nitrogen-containing compounds other than those derived from acrylonitrile and its derivatives Irradiation of the cobaloxime 13, for example, produces a primary radical that adds to a deprotonated nitro compound to form a nitrogen-containing, carbon-linked disaccharide (Scheme 5). 22 eaction of the cobaloxime 14 with nitric oxide produces an oxime (eq 6). 24 Carbohydrate-substituted pyridines also can be prepared by radical addition (eq 7). 21

7 rganocobalt and rganomercury Compounds 521 Scheme 5 (dmg) 2 py + Co II (dmg) 2 py 13 Ac Ac Me Ac Ac Ac Me Ac Co II (dmg) 2 py - Co I (dmg) 2 py C 2 Bn = Bn Bn C 2 Ac Ac Me Ac C 2 Ac Me Ac + Ac Co(dmg) 2 py 14 DMF C 2 Ac Me Ac Ac 79% ( 6 ) C 3 C 3 -Co(dmg) 2 py C 2 + Ts 1) 2) neutralization 58-64% ( 7 ) Ac = Ac Ac Bn

8 522 Chapter Me 2 C I Bn 2 Co(salen) t a Me 2 C Bn ( 8 ) 1 = C 2, 2 = 44% 1 =, 2 = C 2 36% D. adical Cyclization A carbon-centered radical formed from halogen-atom abstraction by a cobalt-centered radical will cyclize to produce a new ring system, when the substrate has a properly positioned multiple bond. 25,26 The reaction shown in eq 8 is an example in which internal addition generates a radical with a new five-membered ring. The cyclized radical then reacts with a molecule of oxygen in route to formation of a hydroxyl group. 26 Scheme 6 C 2 Ac Me Ac - Acg Ac gac C 2 Ac Me C Ac 3 - C 2 Ac C 2 Ac Me Ac Ac 49% Ac C 2 Ac Ac Ac g + C 2 =CC ab 4 C 2 Ac Ac Ac 1 ( 9 ) C 3 C =, 2 =C 2 C 2 C 40% 1 =C 2 C 2 C, 2 = 20% II. rganomercury Compounds There are similarities between the reactivites of carbon cobalt and carbon mercury bonds. Both are strong enough to exist in stable structures that can be isolated and both readily cleave upon heating or photolysis. The result in each case is formation of a metal-centered and a carbon-centered radical. Carbon-centered radicals produced by carbon mercury bond homolysis undergo typical radical reactions, such as hydrogen-atom abstraction (Scheme 6 27 ), 27,28 addition to

9 rganocobalt and rganomercury Compounds 523 a multiple bond (eq 9), 29 and combination with molecular oxygen (eq ). 30,31 Although organomercury compounds can be effective sources of carbon-centered radicals, their use in this role is limited by toxicity and environmental concerns. C 2 gbr C 2 Bn Bn Bn Bn ab 4 DMF 2 Bn Bn Bn Bn ( 10 ) Scheme 7 mercury hydride formation gx + ab 4 g + ab 3 X X = Cl, Ac = carbohydrate moiety initiation phase g + In g + In g + g propagation phase + C 2 =CZ C 2 CZ C 2 CZ + g C 2 C 2 Z + g g + g Z = an electron-withdrawing group Two basic methods exist for generating radicals from organomercury compounds. The first, photochemical homolysis of a carbon mercury bond, is illustrated by the reaction shown in Scheme The second is more complicated and consists of initially converting an organomercury compound into the corresponding mercury hydride by reaction with ab 4 (Scheme 7). 32 The hydride then produces a carbon-centered radical capable of reactions such as the addition to acrylonitrile shown in eq Adventitious initiation is credited with beginning this reaction. III. Summary rganocobalt complexes are sources of free radicals because heating, photolysis, or enzymatic reaction cleaves a carbon cobalt bond homolytically to produce carbon-centered and co-

10 524 Chapter 23 balt-centered radicals. Cleaving the carbon cobalt bond in this way changes the oxidation state of cobalt from Co(III) to Co(II). Complexes with cobalt in the Co(II) oxidation state exhibit radical reactivity. Cobalt containing carbohydrates easily undergo epimerization reactions because the radicals formed by bond fragmentation readily recombine. Carbon-centered radicals produced from organocobalt complexes also undergo the characteristic radical reactions of addition and cyclization. rganocobalt and organomercury compounds have a similarity in reactivity because each contains a carbon-metal bond that is easily cleaved by heating or photolysis. Carbon-centered radicals produced from organomercury compounds undergo hydrogen-atom abstraction and radical addition reactions. Concern about the toxicity of organomercury compounds reduces their usefulness as radical precursors. IV. eferences 1. Banerjee,. Chem. ev. 2003, 103, Xu, Y.; Grissom, C. B. In Comprehensive atural Products Chemistry; Barton, D.; akanishi, K; Meth-Cohn,.; Poulter, C. D., ds.; lsevier: ew York, 1999, pp Finke,. G.; ay, B. P. Inorg. Chem. 1984, 23, Duong, K.. V.; Gaudemer, A.; Johnson, M. D.; Quillivic,.; Zylber, J. Tetrahedron Lett. 1975, Joblin, K..; Johnson, A. W.; Lappert, M. F.; icholson, B. K. J. Chem. Soc., Chem. Commun. 1975, Gani, D.; ollaway, M..; Johnson, A. W.; Lappert, M. F.; Wallis,. C. J. Chem. es. (S) 1981, Johnson, A. W.; Shaw,. J. Chem. Soc. 1962, ogenkamp,. P. C. J. Biol. Chem. 1963, 238, Johnson, A. W.; ldfield, D.; odrigo,.; Shaw,. J. Chem. Soc. 1964, Pattenden, G. Chem. Soc. ev. 1988, 17, Branchaud, B. P.; Friestad, G. K. In ncyclopedia of eagents for rganic Synthesis; Paquette, L. A., d.; John Wiley & Sons: ew York, 1995, pp Ghosez, A.; Göbel, T.; Giese, B. Chem. Ber. 1988, 121, Branchaud, B. P.; Meier, M. S. Tetrahedron Lett. 1988, 29, Branchaud, B. P.; Meier, M. S. J. rg. Chem. 1989, 54, Giese, B. Pure Appl. Chem. 1988, 60, Yu, G.-X.; Tyler, D..; Branchaud, B. P. J. rg. Chem. 2001, 66, Slade,. M.; Branchaud, B. P. rganometallics 1996, 15, Branchaud, B. P.; Yu, G.-X. rganometallics 1991, 10, a) Branchaud, B. P.; Meier, M. S.; Choi, Y. Tetrahedron Lett. 1988, 29, 167; b) Slade,. M.; Branchaud, B. P. J. rg. Chem. 1998, 63, 3544.

11 rganocobalt and rganomercury Compounds Giese, B.; Carboni, B.; Göbel, T.; Muhn,.; Wetterich, F. Tetrahedron Lett. 1992, 33, Branchaud, B. P.; Choi, Y. L. J. rg. Chem. 1988, 53, Martin,..; Xie, F.; Kakarla,.; Benhamza,. Synlett 1993, Branchaud, B. P.; Yu, G.-X. Tetrahedron Lett. 1988, 29, Viet, A.; Giese, B. Synlett 1990, a) Désiré, J.; Prandi, J. Tetrahedron Lett. 1997, 38, 6189; b) Mayer, S.; Prandi, J.; Bamhaoud, T.; Bakkas, S.; Guillou,. Tetrahedron 1998, 54, Désiré, J.; Prandi, J. ur. J. rg. Chem. 2000, orton, D.; Tarelli, J. M.; Wander, J. D. Carbohydr. es. 1972, 23, emy, G.; Cottier, L.; Descotes, G. Can. J. Chem. 1983, 61, Giese, B.; Gröninger, K. Tetrahedron Lett. 1984, 25, Bernotas,. C.; Ganem, B. Tetrahedron Lett. 1985, Moutel, S.; Prandi, J. Tetrahedron Lett. 1994, 35, Giese, B.; orler,. Tetrahedron 1985, 41, 4025.