Multiple Metal-Carbon Bonds for Catalytic Metathesis Reactions. Nobel Lecture December 8, 2005

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1 Multiple tal-arbon Bonds for atalytic tathesis eactions obel Lecture December 8,

2 tal-carbon double and triple bonds in which the transition metal is in a "low oxidation state" were discovered by E.. Fischer. r δ - 3 δ + Br W "carbene" "carbyne" 2

3 Beta hydride elimination in an ethyl complex L 1 M L 3 L 1 M L 3 + L 2 L 2 3

4 Known Group 4 Peralkyl omplexes (M = Ti, Zr, f) in α β 2 α β Si 2 α β M Si 2 3 Si 2 M 2 Si M 2 3 All alkyls lack one or more hydrogen atoms on the atom β with respect to the metal. 4

5 The first relatively stable permethyl complex Wl Al 3 pentane W Ti V r Mn Fe Zr b Mo Tc u f Ta W e s A. J. Shortland and G. Wilkinson J. hem. Soc., Dalton Trans. 1973, 872. *ote added in proof. examethylrhenium (K. rtis and G. Wilkinson) and pentamethyl[t]antalum (. Schrock, DuPont, Wilmington, private communication) have recently been synthesized. Geoffrey Wilkinson, obel Lecture, December 11,

6 Synthesis of tantalum pentaalkyls Tal Zn 2 pentane 2 Li Ta 3 l Zn ether 2 (Juvinall) 3 Ta Decomposes above 0 bimolecularly Si 3 Tal Si 2 Mgl 1/2 3 Si 2 Ta Ta 2 Si 3 3 Si 2 2 Si 3 Si 3 "It is assumed that a penta-alkyl complex cannot exist for steric reasons." (Mowat, W.; Wilkinson, G. J. hem. Soc, Dalton Trans. 1973, 10, 1120.) 6

7 eopentyls yield a stable product of α hydrogen abstraction. 2 Li Ta( 2 3 ) 3 l 2 Ta J. Am. hem. Soc. 1974, 96, 6796 Distills in a good vacuum at 75. ( 2 ) 3 Ta α hydrogen activation 2 - δ+ ( 2 ) 3 Ta δ- δ- 2 - δ+ - 4 α hydrogen abstraction (deprotonation) δ + δ + δ - ( 2 ) 3 Ta 7

8 Alkylidenes can be deprotonated to yield tantalum-carbon triple bonds δ+ Ta δ- δ+ 3 LiButyl - Butyl 2 Li + - Ta Guggenberger, L. J.; Schrock,.. J. Am. hem. Soc. 1975, 97,

9 Alkylidenes decompose bimolecularly. 2 δ+ Ta δ- p 2 Ta 2 Tap 2 2 L Ta Ta L 18 electrons - + base L =, 2 4, P 3 [p 2 Ta 3 ] + Schrock,.. J. Am. hem. Soc. 1975, 97, Bimolecular decomposition of alkylidenes, especially methylenes, is difficult to prevent, especially in electron deficient species. 9

10 lefin metathesis and the hauvin mechanism (1971) 2 =' = + '=' + =' - '=' + =' - = M= M ' M=' M = Mo, W, or e 10

11 Alkyne metathesis and the metalacyclobutadiene mechanism 2 ' ' ' + M ' M M - M ' ' ' M = Mo, W (suggested by T. Katz; 1975) 11

12 eaction of tantalum alkylidenes with olefins. l l Ta - 2 = 2 l Ta 2 l + 4 olefins pl 2 Ta - 2 β = =- pl 2 Ta - β 2 = =- 2 12

13 Modification of b and Ta yields metathesis catalysts M(-)L 2 l = M = b or Ta 4 products of rearrangement of metallacyclobutanes L = P 3 M(-)(-) 2 l(p 3 ) + olefins also metathesis products (~35 turnovers for cis-2-pentene) Alkoxides "prevent reduction" and "promote metathesis." J. Molec. atal. 1980, 8, 73; J. Am. hem. Soc. 1981, 103,

14 An oxo neopentylidene complex of tungsten l L Ta L l l + W - - l Ta l L W l L L = a phosphine, e.g. PEt 3 L = L l L W l - = l L W l (All 3 cat) Even = 14

15 A sterically demanding diisopropylphenyl imido group might be a desirable "ancillary" ligand. X i-pr W - X = i-pr The group should be a sterically demanding tertiary alkoxide. 15

16 A sterically demanding diisopropylphenyl imido group might be a desirable "ancillary" ligand. i-pr (F 3 ) 2 (F 3 ) 2 W i-pr - exafluoro-t-butoxide was chosen as a highly electron withdrawing alkoxide. 16

17 Synthesis of a tungsten neopentylidyne complex l W l l + 6 lmg 2-2 W 2 2 Volatile yellow crystals. Thermally stable, distilling at 75 in a good vacuum. (1978) 17

18 Tungsten-carbon triple bonds and alkyne metathesis W l in dme l W l l 3 Li- W purple crystals The tri-t-butoxide compound is a powerful catalyst for the alkyne metathesis reaction. 2 ' ' ' + 18

19 tal-metal bonds and "metathesis" reactions. W - W W - - (1982) X 3 W WX X 3 W WX 3 X 3 W WX 3 19

20 Synthesis of a tungsten imido alkylidene complex Ar l W - l Et 3 catalyst l Ar W l 2 Li Ar W ("14 electron" species) = -, 2 (F 3 ), (F 3 ) 2, and various bulky phenoxides W(Ar)(-)() 2 species are "well-defined" catalysts for the metathesis of olefins and the activity can be varied systematically by varying. Ar = i-pr i-pr 20

21 Structure of syn-w(ar)(-)(-) Å Å

22 Tungstenacyclobutanes can be isolated, but can be too stable toward loss of olefin Molybdacyclobutane intermediates lose an olefin more readily. 22

23 Two isomers (anti and syn) are available in any system through rotation about the M= bond. ' ' M ' k a/s k s/a M ' anti syn (usually favored) 23

24 lefin metathesis variations M - 2 = 2 M/M + = 2 MP (ing-pening tathesis Polymerization) x ontrol! 24

25 Polymerization of bistrifluoromethylnorbornadiene via enantiomorphic site control. Ph Si Mo 3 Si Ph F 3 F 3 F 3 F 3 F 3 F 3 F 3 F 3 F 3 F 3 F 3 F 3 x all cis and isotactic through enantiomeric site control when = 3 When = ( 3 ) 2 the polymer structure has a relatively random (71% cis) structure. 25

26 Alkynes are polymerized to yield polyenes. Et 2 2 Et Et 2 2 Et 2 Et 2 Et head-to-tail tail-to-tail or Soluble, highly conjugated (purple), and relatively air-stable; both rings observed in polymer made with Mo(Ar)( F6 ) 2 catalyst. E E E E E E E E * * E E E E E E >95% 5-membered rings produced with Mo(Ar)(-) 2 catalyst. 26

27 ing-closing metathesis with Mo catalyst (4-5 mol%) (atalyst = Mo(Ar)( 2 Ph)[(F 3 ) 2 ] 2 ) Ph Ph - 2 butene Ph Ph 15 min, 92% 2 hr at 50, 81% Ph Ph min, 92% Ph - propylene 180 min, 93% Ph Fu, G..; Grubbs,.. J. Am.hem. Soc. 1992, 114, 5426;

28 Synthesis of Fluvirucin-B 1 Ac ()F 3 Ac Et Et Mo cat = 2 Et Ac Ac ()F 3 Et 92% yield Et 2 Et Fluvirucin-B 1 A. F. ouri, Z. M. Xu, D. A. ogan, A.. oveyda, J. Am. hem. Soc. 1995, 117,

29 Mo or W catalyzed alkyne metathesis reactions are useful in organic chemistry. W cat ydrog W cat = W( 3 )( 3 ) 3 ivetone (Fürstner) lefins do not appear to react with M- triple bonds. 29

30 ther examples of alkyne metathesis in organic synthesis S 2 Motuporamine PGE 2-1,15-lactone Epothilone W cat - 2-butyne 1. Ts 2. 9-I-9- BB 80% S-(+)-citreofuran 30

31 An enantiomerically pure Mo catalyst Alexander, J. B.; La, D. S.; efalo, D..; oveyda, A.; Schrock,.. J. Am. hem. Soc. 1998, 120,

32 Asymmetric catalyst design; a modular approach Imido Groups Diolates TIP s i-pr i-pr Mo Mo Mo Mo Mo TIP s s Ph 2 l l Mo Mo Mo Mo Mo s Ph 2 24 catalysts! 32

33 Asymmetric ing-losing tathesis (AM) Mo Ph - propylene 2 mol % cat no solvent, 22, 5 min 99% ee, 93% i-pr = i-pr i-pr i-pr i-pr Mo Ph 2 Si - ethylene 2 mol % cat no solvent, 60, 4 h 2 Si >99% ee, 98% i-pr i-pr 33

34 ing-pening / ing-losing tathesis i-pr Mo i-pr Ph 5 mol % 6 6 >99% ee, 76% 34

35 ing-pening / ross tathesis MM i-pr Mo i-pr Ph 5 mol % MM + X 6 6 X =,, F 3 X 95% yield, >98% ee, >98% trans D. S. La; J. G. Ford; E. S. Sattely; P. J. Bonitatebus;.. Schrock; A.. oveyda J. Am. hem. Soc. 1999, 121,

36 itrogen-ontaining substrates 5 mol % Mo Ph Ph 22 Ph - ethylene 20 min = >98% ee, 90% yield 36

37 Enantioselective synthesis of a tertiary ether in a drug 5 mol % Mo Ph = i-pr 6 6, 50 95% ee, 95% yield S2 F 3 efalo, D..; Kiely, A. F.; Wuchrer, M.; Jamieson, J. Y.; Schrock,..; oveyda, A.. J. Am. hem. Soc. 2001, 123, tipranavir (IV protease inhibitor) 37

38 A bis amido alkylidene catalyst precursor. Ph 2 Ar Ph 2 Ar Ph 2 Ph 2 Mo Ph 2 Ph 2 Mo - Ph 2 In situ Amido ligands deactivate the metal toward metathesis reactions. In situ catalyst prepared with gives same ee (93-94%) as 5 mol% [Mo] 6 D 6, 22 o the isolated catalyst. 38

39 Dineopentyl species were examined as bisalkoxide catalyst precursors. Ar Ar Mo + Mo Ar = 2,6-i-Pr = (F 3 ) 2, Adamantyl, 3, or Ar Preliminary results suggest that monoalkoxides are at least as active as bisalkoxides! (Surprising since dineopentyl species are essentially inactive.) 39

40 "Well-defined" catalysts can be prepared on a silica surface. Ar Ar Mo 2 2 Ar = 2,6-i-Pr Si Silica (Si 2 ) - 4 Mo 2 Si Silica (Si 2 ) Bimolecular decomposition of alkylidenes is not possible. Frédéric Blanc, Anne Baudouin, hristophe opéret, Jean Thivolle-azat, Jean-Marie Basset, Anne Lesage, Lyndon Emsley, Amritanshu Sinha, ichard. Schrock, Angew. hem. Int. Ed., in press. 40

41 Well-defined catalysts can be prepared on a silica surface using other "clean" neopentyl sources. Ta Ta(V) M 2 2 M e 2 2 e(vii) M(VI) (M = Mo, W) óperet,.; habanas, M.; Saint-Arroman,. P.; Basset, J.-M. Angew. hem. Int. Ed. 2003, 42,

42 The principles of high oxidation state alkylidene and alkylidyne chemistry extend to e(vii) W e W(VI) e(vii) lefins react with the e= bond selectively, not the e - bond. These e species are active olefin metathesis catalysts. 42

43 Present and future challenges 1. Prevent catalyst decomposition completely and/or find ways to regenerate catalysts from decomposition products. 2. Find ways to generate and evaluate all catalysts in situ from one precursor. 3. Synthesize new catalysts and aim for additional selectivity and efficiency in metathesis reactions. 43

44 44

45 "Unsupported" M=M bonds are formed in bisalkoxide systems (F 3 ) 2 (F 3 ) 2 W - =Et (F 3 ) 2 (F 3 ) 2 W 2 (F 3 ) W 2(F 3 ) A W=W species (W=W = 2.49 Å) that does not contain bridging groups. 45