Non-Metathesis Ruthenium-Catalyzed Reactions for Organic Synthesis

Transcription

1 on-tathesis thenium-catalyzed eactions for rganic Synthesis Tristan Lambert MacMillan Group eting May 23, 2002 I. Properties of thenium II. eductions III. xidations IV. Isomerizations V. C-C bond forming reactions Murahashi, Chem. ev., 1998, Trost, Toste, Chem. ev., 2001, 2067.

2 Properties of thenium thenium has the widest range of accessible oxidation states of any element in the periodic table (C) 2-4 4d 7 5s 1 4 -II 0 VIII thenium complexes of each oxidation state can assume several coordination geometries xidation state 0 II Coordination number Geometry Examples trigonal bipy. (C) 5 trigonal bipy. Cl(P 3 ) 3 octahedral Cl 2 C(P 3 ) 3 complexes are generally characterized as having high electron transfer ability, high Lewis acidity, low redox potentials, and the ability to stabilize reactive species such as oxometals, metallacycles, and metal carbene complexes. III 6 octahedral [( 3 ) 5 Cl] 2 VI 4 tetrahedral 4 2- The wide range of oxidation states, coordination VII VIII 4 4 tetrahedral - 4 tetrahedral 4 geometries, and tunable properties result in the ability of complexes to catalyze a remarkable range of chemical transformations Cotton, 5th Ed.

3 egioselective eduction of Unsymmetrical Cyclic Anhydrides reducing agent A B reducing agent yield % A : B LiAl : 19 2 mol% Cl 2 (P 3 ) : 1 2 Morand and Kayser, J.C.S., Chem. Comm., 1976, Cl 4 (dppb) 3 2 (15 atm), 160 o C 88% Ikariya, Tetrahedron Lett., 1986, 365.

4 Asymmetric ydrogenation of Prochiral lefins C 2 cat. (Ac) 2 [(S)-BIAP] 2 (135 atm) C 2 oyori, J. rg. Chem., 1987, (S)-naproxen 97% ee 0.1 mol% {Cl[(S)-BIAP] (benzene)} Cl 1 mol % (Ac) 2 [()-BIAP] 2 (100 atm) Et 3 Takaya, J. C. S., Chem. Comm., 1992, % ee C 2 (4 atm) 0.5 mol% (CCF 3 ) 2 [()-BIAP] 2 (20 atm) 95% ee LiAl 4 Bruneau and Dixneuf, J. rg. Chem., 1996, ()-laudanosine >99.5% ee oyori, JACS, 1986, 7117.

5 Enantioselective eduction of Ketones 0.5 mol% Cl 2 [()-BIAP] 2 (93 atm) 100% yield 92% ee 2 oyori, JACS, 1988, mol% (Ac) 2 [(S)-BIAP] 2 (50 atm) 72% yield 96% ee 2 Ts Ts 5 mol% (Ac) 2 [(S)-BIAP] 80% yield 84% ee Charette, Tetrahedron Lett., 1996, mol % { 2 [()-BIAP] 2 Cl 4 }Et 3 2 (80 atm) oyori, JACS, 1988, % yield 99% ee Cl P P favored P = ()-BIAP P 0.05 mol % Cl 2 [()-BIAP] 2 (100 atm) oyori, JACS, 1987, % yield 99% ee S P P Cl unfavored

6 Dynamic Kinetic esolution of!-keto Esters 3 2 -BIAP 3 C 0.5 mol% Br 2 [()-BIAP] 2 (100 atm) C acyclic syn-favored 99 : 1 syn : anti 98% ee 3 2 -BIAP 3 cyclic anti-favored 0.1 mol% Cl(C 6 6 ) - [()-BIAP]Cl 2 (100 atm) oyori, JACS, 1989, : 99 syn : anti 93% ee If equilibration is faster than hydrogenation, high ee's can be obtained 0.2 mol% Br 2 [()-BIAP] 2 (100 atm) Boc Boc > 99 : 1 syn : anti 4-Substituted!"keto-esters can be used as well 99% ee P P P P oyori, Tetrahedron Lett., 1988, 6327.

7 Directed ydrogenation of Allylic and omoallylic Alcohols lefins allylic to alcohols can be selectively and asymmetrically hydrogenated [(S)-BIAP] geraniol ()-citronellol nerol [()-BIAP] [(S)-BIAP] (30 atm 2 ) 98% ee, 97% yield 0.2 mol% cat. (S)-citronellol oyori, JACS, 1987, omoallylic alcohols similarly under slightly more forcing conditions homogeraniol 0.5 mol% [(S)-BIAP] (100 atm 2 ) ()-homocitronellol 96% yield 92% ee omo homoallylic alcohols and higher analogs are inert [()-BIAP] 0.5 mol% [(S)-BIAP] (100 atm 2 ) no rxn 2 P P 2 C 3 C 3

8 xidation of Diols to Lactones 2 mol% 2 (P 3 ) o C, acetone 99% yield 2 mol% 2 (P 3 ) o C, acetone Murahashi, JC, 1987, % yield 2 mol% 2 (P 3 ) o C, acetone 95% yield 2 mol% 2 (P 3 ) 4 20 o C, toluene 99.6% yield C=CCC 3 Saburi and Yoshikawa, JC, 1986, % yield 0.2 mol% [Cl((S)-BIAP)- (C 6 6 )]Cl C=CCC 3 60 o C, toluene 61% yield 23% ee 2 2 mol% 2 (P 3 ) o C, DME hydrogen acceptor 59% yield ozaki, JMC, 1994, 473, 253. Murahashi, SynLett, 1991, 693. eactions can be performed intermolecularly to form esters and amides

9

10 xidative Cleavage of lefins Ac Ac Ac Ac 0.2 mol% 2 ai 4, CCl % yield Ac Ac C 2 C C 2 Et 0.2 mol% 2 ai 4, CCl % yield C 2 C C 2 Et Torii, JC, 1985, xidative cleavage of aromatic rings 1. ai 4, Cl 3 C 3 C / CCl 4 / 2 2. C % yield reactions proceed through a cyclic ruthenium (VI) diester 1. ai 4, Cl 3 C 3 C / CCl 4 / 2 2. C % yield 2 C 2 C In reactions where carboxylic acids are generated, the addition of C 3 C has a dramatic effect on rate and efficiency due to the disruption of insoluble carboxylate species Ghatak, Synthesis, 1983, 746. Sharpless, JC, 1981, 3936.

11 xidation of Ethers, Amines, and Alkanes xidation of!-methylenes of ethers and amines 0.2 mol% 2, ai 4 C 3 C / CCl 4 / 2 85% yield Boc TBS cat. 2, ai 4 CCl 4 / 2 90% yield Boc TBS Schuda, Tetrahedron Lett., 1983, Tanaka, Chem. arm. Bull., 1986, Amides can be oxidized in a similar manner to imides xidation of unactivated alkanes 0.2 mol% Cl 3, ai 4 C 3 C / CCl 4 / 2 69% yield Waegell, Tetrahedron Lett., 1989, 5271 JC, 1992, Ac 20 mol% Cl 3 ai 4 C 3 C / CCl 4 / 2 71% yield Ac Ac 20 mol% Cl 3 ai 4 C 3 C / CCl 4 / 2 57% yield Ac Yamada, Chem. Lett., 1985, 1385.

12 Tetrapropylammonium Perruthenate (TPAP) xidations (n-pr 4 )( 4 ) M, 4Å mol sieves C 2 Cl 2, rt 4 ( VIII, d 0 ) is a powerful, nonselective oxidant. Perruthenate ion, [ 4 ] - ( VII, d 1 ) is a milder oxidant though it will still cleave some C=C bonds. Disproportionates in aqueous solution below p = 8. Salts of the anion with large, organic cations are soluble in organic solvents and are much milder and selective oxidants. The tetrapropylammonium salt is the easiest to prepare. Water retards catalyst turnover so mol sieves are required Although [ 4 ] - is an overall 3e - oxidant, studies suggest the oxidation process is of the 2e - type. (VII) 2e - 2(V) (VI) 2e - (V) (VI) (IV) (IV) Yield % Product (Swern) Product Yield % 70 (35) TBDPS Ac 93 MM 73 TMS (0) Boc 92 TBS C C 3 7 eview: Ley, Synthesis, 1994, 639 and ref. therein.

13 xidation of 3 o Amines to Iminium Ions C 3 Br cat. Cl 2 (P 3 ) 3 tbu rt Demethylation of anilines Murahashi, JACS, 1988, C 2 tbu 1. 3 mol% Cl 2 (P 3 ) 3 tbu Iminium ion intermediate can be trapped Murahashi, JACS, 1988, Murahashi, SynLett, 1992, 835. Br % yield 1. 3 mol% Cl 2 (P 3 ) 3 tbu mol% Cl 2 (P 3 ) 3 tbu 2. TiCl 4, -78 o C =, = = C 3 7, = Cl 67% (2 steps) chanism: C 2 TiCl 4-78 o C () 3 mol% Si 3 Cl 2 (P 3 ) 3 tbu C = C 2 tbu 60% yield 71% yield

14 Isomerization of Allylic Alcohols, Amines, and Ethers Z Z - Z 0.1 mol% Cl 2 (P 3 ) o C 92% yield C Salomon, JC, 1977, mol% C 6 13 C 6 13 C Cl(P 3 ) 3 80 o C Stille, JC, 1980, C 80% yield all cis 2 (P 3 ) o C BF 3 Et 2 C % yield -78 o C C 95% yield Suzuki, Tetrahedron Lett., 1980, (P 3 ) 4 TMS TMS 150 o C 100% yield (E / Z = 45 / 55) n-c 5 11 Et 2 (P 3 ) 4 PBu 3,, reflux Suzuki, Tetrahedron Lett., 1979, n-c % yield Ma, Tetrahedron Lett., 1989, 843. Et

15 Coupling of Allenes and Vinyl Ketones to Form Dienes cat. co-catalyst 53-81% yield Trost, JACS, 1999, ole of cocatalyst unknown, possibly activates enone. Ac 10% Cp(CD)Cl 15% CeCl DMF, 60 o C 81% Ac Cl, 72% (2 steps) C 2

16 Coupling of Allenes and Vinyl Ketones: Formation of Cyclic Ethers and Amines u n u cat. co-catalyst n Trost, JACS, 1999, and 2000, % yields u = or n = 1, 2 u n u n Product Yield = 82% = Bn 73% u u n = 74% = Bn 67% n u n = 70% = Bn 62% 10% Cp(C 3 C) 3 PF 6 15% CeCl DMF, 60 o C 72% yield

17 Coupling of Alkenes and Alkynes: thenium Catalyzed Alder-Ene eaction cat. or co-catalyst or C 2 C 2 tbu or or 10% Cp(CD)Cl 20% 4 PF 6, reflux or 2 2 C 2 C 2 tbu 65% yield, 12.5 : 1 regioisomers Trost, JACS, 1993, 4361 and 1995, 615.

18 Intramolecular Coupling of Alkenes and Alkynes lefin geometry of substrate can dictate product distribution TMS 10% Cp(C 3 C) 3 PF 6 DMF, rt A TMS 56% yield 8 : 1 A : B 10% Cp(C 3 C) 3 PF 6 TMS DMF, rt Trost, JACS, 2000, 714. B TMS 58% yield 1 : 17 A : B thenium-catalyzed intramolecular Pauson-Khand reaction Et 2 C Et 2 C 2 mol% 3 (C) 12 Et 2 C DMAc, C (15 atm) 140 o C Et 2 C 78% yield Mitsudo, JACS, 1997, Et 2 C Et 2 C Ln substrate must be unable to undergo!-hydride elimination

19 Intramolecular [5 2] Cycloadditions 10% Cp(C 3 C) 3 PF 6 acetone, rt Cp Wender has reported the same reaction using rhodium. owever, is ~10 times cheaper than h. Cp Cp Ts TMS TBDPS 20 mol% Cp(C 3 C) 3 PF 6 acetone, 50 o C TMS TBDPS Cp Ts 87% yield 2 C 10% Cp(C 3 C) 3 PF 6 2 C 2 C acetone, rt 85% yield 2 C Trost, JACS, 2000, 2379.

20 Addition of Water to Alkynes: Formation of 1,5-Diketones catalyst 2 chanism: C Trost, JACS, 1997, C 2 C 5 mol% Cp(CD)Cl 4 PF 6, In(Tf) 3 DMF / 2 1 : 1, 100 o C C Intramolecular variant is also known 2 C 2 C C K 2 C 3 10 mol% 93% yield Cp(C 3 C) 3 PF 6 10% CSA, 2 2 C 2 C 75% yield 69% yield 2 : 1 dr one diastereomer Trost, JACS, 2000, 5877.

21 econstitutive Addition of Alkynes and Allylic Alcohols catalyst 3 P 3 P L L Cl P 3 L C 2 tbu 10 mol% Cp(P 3 ) 2 Cl 4 PF o C Trost, JACS, 1990, C 2 tbu 44% yield 10 mol% Cp(P 3 ) 2 Cl L L L C mol% In(Tf) 3 1 eq. TFA, toluene 90 o C 8 C 2 61% yield

22 Electrophilic Addition to!-allyl thenium Complexes!-allyl complexes can exhibit nucleophilic as well as electrophilic behavior This property is due to the fact that ruthenium can access a wide range of oxidation states 1 mol% 3 (C) 12, C Et 3, CCl 3, rt Ac 55 : 45 Watanabe, rganometallics, 1995, % yield L Ac C is essential to catalytic activity--no rxn under Argon Tertiary amine base crucial, dimethylaniline, pyridine, K 2 C 3 were ineffective (see mechanism) L L Ac Generally, only acetate as allylic group gives good yields 1 mol% 3 (C) 12, C Et 2 Ac - Et 3 Ac L Et 3, CCl 3, rt = Ac = Br 87% 38% = C 2 39% = 0% Watanabe, JMC, 1989, 369, C51.

23 Activation of Aromatic C- Bonds: chanism 1 [] or 2 or Murai, Pure Appl. Chem., 1997, 589 and JC, 2000, Deuterium labelling experiment shows C- / olefin insertions are reversible D D D D D 99% D C Si(Et) 3 3 (C) 12 C 3 C, 120 o C D D D D D 44% D Si(Et) 3 39% D 1 mmol 1 atm 1 mmol 94% recovered 57% recovered (40% theoretical D at each of 5 positions)

24 Activation of Aromatic C- Bonds: Scope 1 = () 2 (C)(P 3 ) 3 2 = 3 (C) 12 Si(Et) % yield Si(Et) 3 C Si(Et) % yield C Si(Et) 3 Si(Et) % yield Si(Et) 3 TMS 1 83% yield TMS C Si(Et) % yield C Si(Et) 3 2 Si(Et) % yield (Et) 3 Si 2 tbu Si(Et) % yield tbu Si(Et) 3 Br 2, ethylene, C 80% yield Br Trost, Chem. ev., 2001, 2067.

25 ydrometallation Initiated eactions Baylis-illman type reaction 3 C [] [] [] C 3 [] C mol% 2 (P 3 ) 4 ipr, 40 o C 83% yield Matsuda, JMC, 1989, 377, 347. [] Substrate scope is very limited, h more effective C 3 Cycloisomerization of ene-ynes C 2 Et 5 mol% Cl(C)(P 3 ) 3 toluene, 110 o C 81% yield C 2 Et TBS C 2 Et 44% yield 10 mol% Cl(C)(P 3 ) 3 toluene, 110 o C TBS Mori, JC, 1998, Mori, rg. Lett., 2000, C 2 Et

26 Cyclopropanation Using Diazo Esters 5 mol% catalyst yield A(%ee) : B(%ee) C 2 Et catalyst A C 2 Et Cl Cl 73% 91(89) : 8(78) ishiyama 2 Stereochemical rational with pybox ligand B C 2 Et 0.15 mol% C = 100% 95(91) : 5(27) Cl Cl C 2 A B 5 mol% Cl 45% 7(15) : 93(97) As expected, = tbu gives higher dr and ee than = Et Katsuki Trost, Chem. ev., 2001, 2067 and ref. therein.

27 Conclusions thenium catalyzes a tremendous range of organic transformations including hydrogenation of olefins, carbonyls, and imines; hydrogen transfer reactions; oxidation of olefins, alcohols, lactols, amines, amides, aromatics, and unactivated C- bonds; epoxidations; olefin isomerizations; heteroatom addition to alkynes and nitriles; C- activation; olefin metathesis and ene-yne metathesis; metallacycle formation; Pauson-Khand reactions; nucleophilic and electrophilic allylic substitutions; radical reactions; and cyclopropanations among others. The field is relatively new and rapidly developing, especially in the area of C-C bond forming reactions. 50% of the articles sited in Trost, Chem. ev., 2001, 2067 were published in 1997 or after. thenium catalyzed chemistry promises to be an area of continuing development through the investigation of catalyst structure and the recognition and utilization of mechanistic intermediates.