Development of Chiral Phosphine Olefin Ligands and Their Use in Asymmetric Catalysis

Transcription

1 Development of Chiral osphine lefin Ligands and Their Use in Asymmetric Catalysis 2 Wei-Liang Duan July 31, 2007 Research Works in Hayashi Group, Kyoto University (ct, 2003 Mar, 2007)

2 Conventional Chiral Ligands in Asymmetric Catalysis 1, N, N, N diene 2 2 R N N R 2 N R binap bisoxazoline phox -bod (R)-Binap and (R,R)--bod in the odium-catalyzed 1,4-Addition of enylboronic to Cyclohexenone [Cl(C 2 H 4 ) 2 ] 2 /L (3 mol % ) L/ = B(H) equiv KH (0.5 equiv) dioxane/h 2 (10/1) 30-35ºC,1h 2 2 (R )-binap: 96% yield, 99% ee (R,R )--bod: 97% yield, 96% ee Hayashi, T.; Takahashi, M.; Takaya, Y.; gasawara, M. J. Am. Chem. Soc. 2002, tomaru, Y.; kamoto, K.; Shintani.; Hayashi, T. J. rg. Chem. 2005, 70, 2503

3 Chiral Environment of tal Ligand Complexes 2 C 2 -Symmetric Bisphosphine Ligand M Determining factor: orientation of two phenyl groups (R)-binap C 2 -Symmetric Diene Ligand Determining factor: H H (R,R)--bod H M H size difference of two substituents

4 Chiral Diene Ligands vs Binap in Asymmetric Catalysis 3 + [Cl(C 2 H 4 ) 2 ] 2 /L (3 mol % ) L/ = 1.1 Na(3mol%) toluene, 60 C, 22 h Sn Sn 3 (R)-binap <10% yield (R,R)-Bn-nbd 80% yield, 95% ee Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, Cl N Ts H + (B) 3 [Cl(C 2 H 4 ) 2 ] 2 /L (3 mol % ) L/ = 1.1) KH (0.2 equiv) H 2 (3.6equiv) dioxane, 60 C, 6 h Cl HN Ts 2 2 (R )-binap 28% yield, 31% ee (R,R )--bod 96% yield, 98% ee Tokunaga, N.; tomaru, Y.; kamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126,

5 Feature of Chiral Diene Design of Novel Chiral osphine lefin Ligands 4 combination R M R good chiral environment low coordination ability R good chiral environment M R R high coordination ability R R R M R high coordination ability R R R ur Target Structure For the first example of chiral phosphine olefin ligand: Maire,.; Deblon, S.; Breher, F.; Geier, J.; Böhler, C.; Rüegger, H.; Schönberg, H.; Grützmacher, H. Chem. Eur. J. 2004, 10, 4198.

6 reparation of osphine lefin Ligands (±)- 7 Br 2 H (CCl) 2,DMS Et 3 N, CH 2 Cl 2 96% yield Br cat. TsH HCH 2 CH 2 H (±)- (±)- 94% yield Br 5 (i) t-buli, THF; then Cl 2 (ii) H 2 2 aq, acetone 2 1 N HClaq THF 2 LDA, THF; then yntf % (over two steps) (iii) chiral HLC resolution (D-H) 99% yield 89% yield Tf cat. dcl 2 (dppf) MgBr, Et 2 2 HSiCl 3,Et 3 N C 6 H % yield 84% yield 1 (7S)--ol 2 2 CF Shintani, R.; Duan, W.-L.; Nagano, T.; kada, A.; Hayashi, T. Angew. Chem., Int. Ed. 2005, 44, 4611.

7 Structure of a odium/(7s)--ol Complex 6 3 [(H)(cod)] = C 6 H 6 50 C, 5 h 70% yield H C 3 symmetrical complex (2) (2) (1) (2) (1) (1) (3) (3)

8 Structural Feature of /-ol Trimeric Complex bidentate ligand the axis of C 3 symmetry the same side of (1) (2) (3) triangular plane 7 (2) (3) (1) (1) (2) (3) (1) C C C C (2) C C /(7S)--ol trimeric complex C C C C C C

9 Comparison of Selected Bond Distances and Angles Å 2.13 Å 1.43 Å 2.09 Å side view top view /(7S)--ol trimeric complex 1.50 Å 2.13 Å 1.41 Å 2.10 Å side view top view [Cl((R,R )--bod)] 2

10 Comparison of Selected Bond Distances and Angles side view top view /(7S)--ol trimeric complex side view top view [Cl((R,R )--bod)] 2

11 osphine lefin (7S)--ol vs (R,R)--bod in the odium-catalyzed Asymmetric 1,4-Addition 9 + ArB(H) equiv [Cl(ligand)] 2 (5 mol % ) KH (0.5 equiv) dioxane /H 2 (10/1) 50 C, 3 h (7S )--ol vs (R,R )--bod: similar trend in chiral induction 2 Ar 89 98% yield (7S)--ol (R,R )--bod stereocontrol by olefin chirality in (7S )--ol F 3 C 98% ee 99% ee 98% ee 98% ee 95% ee 96% ee 98% ee 96% ee n-ent 93% ee 96% ee 97% ee 95% ee 72% ee 83% ee

12 Ligand Effect in the odium-catalyzed Asymmetric 1,4-Addition of enylboronic Acid to 1-Benzylmaleimide 10 N /ligand (5 mol % ) + B(H) 2 KH (0.5 equiv) 3.0 equiv dioxane/h 2 (10/1) 50 C, 3 h N 2 2 NEt 2 2 (R )-binap (S )-phosphoramidite-net 2 (R,R)--bod (7S )--ol 70% yield, 58% ee 100% yield, 45% ee 18% yield, 91% ee 98% yield, 93% ee high yield high ee

13 osphine vs lefin: Ligand Substituent Effect in the odium-catalyzed Asymmetric 1,4-Addition 11 N /ligand (5 mol % ) + B(H) 2 KH (0.5 equiv) 3.0 equiv dioxane/h 2 (10/1) 50 C, 3 h N 2 CF 3 2 substituents on phosphorus small influence on the enantioselectivity 94% ee 95% ee 93% ee substituents on olefin significant impact on the enantioselectivity 93% ee 84% ee 91% ee

14 roposed Catalytic Cycle 12 transmetalation B(H) 3 insertion B(H) 2 H H 2 hydrolysis = 2

15 roposed Stereochemical athway 13 αre face (R)-isomer αsi face

16 Structural Insight of enyl odium Species 14 + intermediate in proposed stereochemical pathway H + B(H) equiv to 3 C 6 H 6 50 C, 10 min J =339Hz J =27.1Hz : 1 trans cis H + B(H) equiv to () 3 dioxane 50 C, 20 min J =507Hz J =44.4Hz () 3 + () 3 >15 : 1 trans cis

17 bservation of Reaction Intermediates in Catalytic Cycle by 31 NMR 15 in dioxane at 50 C 3 major 3 minor t -Bu 1 h oxa-π-allylrhodium 3 t -Bu H 2 1 h trimer H B(H) 2 10 min 3 major 3 minor 3

18 Summary for Experimental Results 16 + ArB(H) 2 /(7S)--ol (5 mol %) Ar 93 98% ee (R) 2 (7S)--ol In charge of stereoselection How about its catalytic activity? 2 hybrid ligand phosphine vs olefin, whichis the determining factor for its catalytic activity?

19 Kinetic Studies on the 1,4-Addition Reaction Catalyzed by /(7S)--ol Using a Reaction Calorimeter A pertinent review: Blackmond, D. G. Angew. Chem., Int. Ed. 2005, 44, B(H) 2 + catalyst dioxane/h 2 (10/1) 30 C + B(H) 3 Heat = Reaction rate conv. = [ q ] 0 t [ q ] 0 t(end) heat flow (mw) [ q ] 0 t [ q ] 0 t(end) heat flow (mw) conversion t(0) t time (min) t(end) time (min)

20 Quantitative Analysis Using the Graph of Rate vs [B(H) 2 ] 18 B(H) 2 + catalyst dioxane/h 2 (10/1) 30 C + B(H) 3 heat = reaction rate reaction progress heat flow (mw) rate (mm/sec) time (min) [B(H) 2 (6)] (M) Time = 100% conv. Time = 0

21 revious Works: Comparison of Catalytic Activity between /cod and /binap 19 [] (1.3 mm) B(H) 2 + dioxane/h 2 =10/1 MVK B(H) 3 (530 mm), (69 mm) (100 mm) 50 C catalytic activity: [(H)(cod)] 2 >> [(H)(binap)] 2 50% conv. 3 min 54 min Kina, A.; Iwamura, H.; Hayashi, T. J. Am. Chem. Soc. 2006, 128, Kina, A.; Yasuhara, Y.; Nishimura, T.; Iwamura, H.; Hayashi, T. Chem. Asian J. 2006, 1, 707.

22 Rate Equation in the /binap and /diene Systems 20 [(H)(binap)] 2 :rate [B(H) 2 ] 1 [MVK] 0 [] 0.5 [(H)(cod)] 2 :rate [B(H) 2 ] 1 [MVK] 0 [] 0.65 Catalytic Cycle for the /binap or /diene Systems slow B(H) 2 B(H) 3 k 1 [] H H [] K dimer [] H Sol [] Sol []: /binap or /cod k 2 fast H 2 + binap: K dimer = 8 x 10 2 M 1 ; k 1 = 0.5 M 1 s 1 at 50 ºC cod: K dimer = 3.8 x 10 2 M 1 ; k 1 = 6.7 M 1 s 1

23 Comparison of Catalytic Activity between /-ol and /cod 21 Conversion % conv. B(H) 2 + MVK (67 mm) (201 mm) /-ol [(H)(cod)] 2 catalyst (2.7 mm ) dioxane/h 2 (10/1) 30 C /-ol: H catalytic activity: /-ol > [(H)(cod)] min 8.5 min time (min)

24 Results of the Kinetic Experiments: 22 rate [B(H) 2 ] 1 [MVK] 0 [] 0.4 roposed Catalytic Cycle for the /-ol-catalyzed 1,4-Addition of enylboronic Acid to thyl Vinyl Ketone (MVK) slow B(H) 2 B(H) 3 k 1 K trimer [] H H [] [] [] Sol active inactive []: /-ol k 2 fast H 2 + [] Sol k rate = 1 [B(H) 2 ][] 1/3 total (3K trimer ) 1/3 (7S)--ol: K trimer = 9 x 10 5 M 2 k 1 = 5 M 1 s 1 (at 30 ºC) cod: K dimer = 3.8 x 10 2 M 1 k 1 = 1.3 M 1 s 1 (at 30 ºC) Duan, W.-L.; Iwamura, H.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2007, 129, 2130.

25 Defination of Excess in Kinetic Study /(7S )--ol (4) (2.7 mm ) B(H) 2 + dioxane/h 2 (10/1) 30 C [ Excess ] = [MVK] 0 [B(H) 2 ] 0 = [MVK] t [B(H) 2 ] t = Constant (7S )--ol Concentration (M) excess MVK roduct excess B(H) time (min)

26 The Same Excess Experiment: /(7S )--ol (4) (2.7 mm ) B(H) 2 + dioxane/h 2 (10/1) 30 C (7S )--ol 2 24 overlay: no catalyst deactivation or product inhibition a, --: [1] 0 = 67 mm, [2] 0 = 201 mm ([ excess ] = 134 mm). b, --: [1] 0 = 80 mm, [2] 0 = 214 mm ([ excess ] = 134 mm). The same reaction rate (a and b) a: [1] = 30 mm, [2] =164 mm [3] = 37 mm 0.03 M b: [1] = 30 mm, [2] =164 mm [3] = 50 mm cat 4: more turnovers [B(H) 2 (1)] (M)

27 The Different Excess Experiment: /(7S )--ol (4) (2.7 mm ) B(H) 2 + dioxane/h 2 (10/1) 30 C (7S )--ol a, --: [1] 0 = 67 mm, [2] 0 = 201 mm, ([ excess ] = 134 mm). c, --: [1] 0 = 67 mm, [2] 0 = 101 mm, ([ excess ] = 34 mm). 0.3 a, --: [1] 0 = 67 mm, [2] 0 = 201 mm, ([ excess ] = 134 mm). d, --: [1] 0 = 85 mm, [2] 0 = 201 mm, ([ excess ] = 116 mm). c 0.2 a 0.25 d rate (mm/sec) rate (mm/sec) a 0.05 overlay: v [MVK] overlay: v [B(H) 2 ] [B(H) 2 (1)] (M) [B(H) 2 (1)] (M)

28 rder in [] total /(7S )--ol (4) (2.7 mm ) B(H) 2 + dioxane/h 2 (10/1) 30 C (7S )--ol 2 26 a, --: [1] 0 = 67 mm, [2] 0 = 201 mm, [4] 0 = 2.7 mm. e, --: [1] 0 = 67 mm, [2] 0 = 201 mm, [4] 0 = 3.8 mm. overlay: v [] total 0.4 [B(H) 2 (1)] (M) [B(H) 2 (1)] (M) v [B(H) 2 ] 1 [] 0.4

29 roposed Catalytic Cycle for the /-ol-catalyzed 1,4-Addition of enylboronic Acid to thyl Vinyl Ketone slow B(H) 2 B(H) 3 1 k 1 27 K trimer [] H H [] [] [] [] 5 Sol 6 4 active inactive []: /-ol 3 fast k 2 H 2 + Sol 2 rate = k 2 [2][6] [] total = 3[4] + [5] + [6] k 2 [2] >> k 1 [1] rate = k 1 [1][5] [] total = 3[4] + [5] K trimer = [4] [5] 3 k rate = 1 A=1 [1][] 1/3 total rate = (3K trimer ) 1/3 [1][] 1/3 total k 1 (1 + A) 1/3 + (1 A) 1/3 (6K trimer ) 1/3 A = K trimer [] total 2 1/2

30 Nonlinear Effect Studies on the Asymmetric 1,4-Addition Catalyzed by /1a 28 Rationale enantiopure catalyst nonenantiopure catalyst (60% ee) S-catalyst 80% R-catalyst 20% SSS-trimer SSS-trimer RRR-trimer K triimer K trimer K trimer k R-product S-monomer k R-product S-monomer R-monomer k K trimer = [SSS-trimer] [S-monomer] 3 = [RRR-trimer] [R-monomer] 3 K hetero = 0 SSR or RRS-heterochiral trimer S-product [S-monomer] [R-monomer] < ee prod < ee cat [S-monomer] + [R-monomer] > [monomer] ν : faster 60% ee catalyst 100% ee catalyst

31 Experimental Results + B(H)2 /(7S )--ol (20 100% ee) dioxane/h 2 (10/1) 30 C (7S )--ol 2 29 ee prod vs ee cat v ee /v 100%ee vs ee cat ee prod v ee /v 100%ee ee cat ee cat

32 Simulation + B(H)2 /(7S )--ol (20 100% ee) dioxane/h 2 (10/1) 30 C (7S )--ol 2 29 ee prod vs ee cat v ee /v 100%ee vs ee cat K trimer 2 x x x x ee prod x K trimer 2 x x x 10 5 v ee /v 100%ee ee cat ee cat

33 Simulation + B(H)2 /(7S )--ol (20 100% ee) dioxane/h 2 (10/1) 30 C (7S )--ol 2 29 ee prod vs ee cat v ee /v 100%ee vs ee cat K trimer 9 x 10 5 ee prod K trimer 9 x 10 5 v ee /v 100%ee ee cat ee cat

34 Extracting the Value of k 1 /(7S )--ol (4) (2.7 mm ) B(H) 2 + dioxane/h 2 (10/1) 30 C (7S )--ol 2 30 k rate = 1 [1][] 1/3 total (3K trimer ) 1/3 K trimer = 9 x 10 5 M 2 k 1 = 5 M 1 s The best fitting with K trimer = 9 x 10 5 M 2 k 1 = 5 M 1 s 1 (7S)--ol: k 1 = 5 M 1 s 1 ; K trimer = 9 x 10 5 M 2 cod: k 1 = 1.3 M 1 s 1 ; K dimer = 3.8 x 10 2 M 1 rate (mm/sec) a e [B(H) 2 (1)] (M)

35 Summary for odium/osphine-lefin Chemistry 31 odium-catalyzed 1,4-Addition + ArB(H) 2 /(7S )--ol (5 mol %) Ar 93 98% ee (R) (7S )--ol

36 32 Kinetic Study slow B(H) 2 B(H) 3 k 1 K trimer [] H H [] [] [] Sol active inactive []: /-ol k 2 fast H 2 + [] Sol reaction rate [B(H) 2 ] 1 [MVK] 0 [] 0.4 K trimer = 9 x 10 5 M 2 k 1 = 5 M 1 s 1

37 π-allyl-d/chiral osphine lefin Complex 33 2 dcl 2 (7S )--ol, NH 4 F 6 CHCl 3, r.t. d((7s )--ol) (7S )--ol Å Å C(5) C(4) d(1) (1) C(3) C(1) C(2)

38 alladium/chiral osphine-lefin Catalyzed Asymmetric Allylic Alkylation 34 2 C C 2 (3.0 equiv) Ac (1.0 equiv) [dcl(η 3 -C 3 H 5 )] 2 (3 mol % d) ligand (3 mol %) KAc (6 mol %) BSA (3.0 equiv) CH 2 Cl 2, r.t., 14 h 2 C C 2 (7S )-Bn-ol: 96% yield, 81% ee (S ) (7S )--ol: 87% yield, 96% ee (S ) 2 2 Bn (7S )-Bn-ol (7S )--ol Shintani, R.; Duan, W.-L.; komoto, K.; Hayashi, T. Tetrahedron: Asymmetry 2005, 16, 3400.

39 π-allyl-d/chiral osphine-lefin Complex: 35 2 dcl 2 (7S )--ol, NH 4 F 6 EtH, r.t. d((7s )--ol) F 6 (7S )--ol Å Å C(5) d(1) (1) C(4) C(3) C(2) C(1)

40 36 roposed Stereochemical athway d Nu Nu (S )-product

41 Acknowledgement Advisor: rofessor Tamio Hayashi rofessor Ryo Shintani All members of Hayashi group