Nickel-Catalyzed Cycloadditions

Transcription

1 ckel-catalyzed Cycloadditions Tristan ambert MacMillan Group eting January 31, 001 Properties of nickel Introduction to metal-catalyzed cycloadditions ckel-catalyzed cycloadditions eview of metal-catalyzed cycloadditions: autens, Chem. ev., 1996, 96, 49. ysical Properties of ckel Across the first row of transition metals, there is a trend towards decreased stability of higher oxidation states such that only (II) occurs in the normal chemistry of the element Sc Ti V Cr Mn Fe Co Cu n decreased stability of higher oxidation states Cotton, Advanced Inorganic Chemistry, 6th ed.; p. 835 The vast majority of (II) complexes are square planar Tetrahedral complexes are important with bulky (i.e. phosphine) ligands d x -y "Free ion" d xy d z Tetrahedral ctahedral Square planar configuration avoids occupation of high energy anitbonding orbital Tetragonal distortion Square planar d xz, d yz Greenwood, Chemistry of the elements; p. 1347

2 Introduction to tal-catalyzed Cycloadditions Definition of Cycloaddition: -A reaction of two separate! systems in which a ring is formed with two more " bonds and two fewer! bonds than the reactants cycloaddition cyclization ote: As an exception to the above definition, in certain cases one of the! systems can be a reactive " bond Cycloadditions have been promoted by heat, light, ewis acids, high pressure, and sonication Many of these conditions require the presence of polarized functional groups in the substrate to facilitate the transformation. In general reaction of unactivated olefins, acetylenes, or dienes is notoriously poor and extreme conditions are necessary to achieve good yields of cycloadducts tal catalysts provide new opportunities for highly selective cycloaddition reactions since complexation of a metal to a reactant significantly modifies its reactivity, thus allowing for improved reactivity and novel chemistry It should be emphasized that while the products of these reactions are clearly cycloadducts, most if not all reactions proceed in a stepwise fashion and probably involve a cyclization as a key event autens, Chem. ev., 1996, 96, 49. [ 1] Cycloadditions: (II) Catalyzed Cyclopropanations of lectron Deficient lefins C tal-stabilized Alkyl Carbenes 10 mol% Br 0.6 eq ai, 0.8 eq n 0.5 eq C Br, 0 o C, 4h C ield (with respect to C Br ) 9% C 10 mol% Br 1.0 eq ai, 0.8 eq n 0.5 eq C Br, 0 o C, 4h C 90% 10 mol% Br 1.0 eq ai, 0.8 eq n 0.5 eq C Br, 0 o C, 96h 97% Kanai, Chem. ett., 1979, Kanai, Bull. Chem. Soc. Jpn., 1983, 53, 105. General eactivity Trends with Various Catalysts catalyst reactive olefins h (Ac) 4 styrene, enol ethers Cu(acac), CuP() 3 enamines, alkyl substituted olefins Cu(Tf), Cu(Tf), Cu(BF 4 ) Pd(Ac), Pd, Pd(P 3 ) 4 (CD), (P 3 ) 4, ai/n and Br terminal olefins styrene, strained, conjugated terminal olefins; #,$-unsaturated carbonyl compounds #,$-unsaturated carbonyl compounds, acrylonitrile

3 Catalytic Cycle of (II) Catalyzed Cyclopropanation Catalytic Cycle Br n otes: Differences with the Simmons-Smith reaction 0 nbr C Br 1. lectron deficient olefins are more reactive than electron rich olefins. Dibromomethane is more suitable than diiodomethane 3. o cyclopropanation occurs in diethyl ether (reactions performed in TF) Br C Br 10-0 mol% nbr or Al 3 additive dramatically increases yields. >50 mol% dramatically decreases yields. xcess ai (4 eq) is also beneficical. The role of ewis acids and solvent has not been n or 0 clarified nbr or II = C, C, C, C Kanai, Bull. Chem. Soc. Jpn., 1983, 53, 105. [ 1] Cycloadditions: ckel Carbenes From ighly Strained ydrocarbons Bicyclo[1.1.0]butane: strain energy 66 kcal/mol C (CD) 0 o C 9% C chanism: oyori, Tetrahedron ett., 1974, (0) n eaction is stereospecific with respect to the starting olefin ature of bonding in -carbene n C 1-1 C C Carbenoids involving metals with high backbonding capacity have considerable ylide character ckel has low electronegativity carbenenoid carbon nucleophilic oyori, Tetrahedron ett., 1973, 1691.

4 [ 1] Cycloadditions: Vinyl Carbenes (CD) 73% C A C 60% C B C 3% A Cis maleate undergoes -catalyzed isomerization leading to small amounts of trans product chanism: n-1 n-1 n n-1 not observed n-1 n-1 Binger, Chem. Ber., 117, 1984, [ ] Cycloadditions: Catalysis of Thermally Forbidden Processes Dimerization of orbornadiene arly xamples, Fe, or Co cat. Dimerization of 1,3-butadiene Vallerino, J. Chem. Soc., 1957, 87. (CD) P(-o-bi) 3 97%.4% eimbach, ACI, 1967, 6, 800.

5 [ ] Cycloadditions: Strained Alkenes and lectron Deficient lefins 50 mol% cat o C neat 7-10 h A ield B A : B cat. = (CD) or (A) A = acrylonitrile = C = C 55% 7% 63:37 78: Certain strained or highly reactive enophiles undergo exclusive [ ] pathway oyori, Bull. Chem. Soc. Jpn., 55, 198, 85. (0) catalyzed reaction of electron deficient olefins with norbornadienes usually gives [ ] homo-diels-alder adducts 5 mol% (CD) 5.5 mol% P 3, r.t., 4 h ote: Pd(0) results in [3 ] cycloaddition oyori, J. Am. Chem. Soc., 1973, 95, % origins of endo selectivity mol% (CD) 43 mol% P 3 = C 49% exo only When = electron donating endo products observed (5-1 : 1) autens, J. Am. Chem. Soc., 117, 1995, [ ] Cycloadditions: lectron-deficient Allenes Thermal [ ] with allenes gives mixture of regioisomers heat etc. ckel-catalyzed reaction is highly selective cat o C to rt 30 min to 3h 33-81% single isomer = n-c 6 F 13, C 6 F 5, C t, C(), Ct, C, S Catalytic cycle 0 amamoto, J. Am. Chem. Soc., 000, 1,

6 [3! " ] Cycloadditions: tallocyclobutanes D D (A) (A) = bisacrylonitrile D D D D A B 87% 13% D D A B D D C D 61% 5% 4% 30% chanism: n n n Indicated bond in SM has one of the highest strain energies known (47.4 kcal/mol) #-hydride elimination [3! " ] Cycloadditions: thylenecyclopropane oyori, J. Am. Chem. Soc., 96, 1974, D 0.08D D D D D t C C t (an), 60 o C 1.34D 1.34D t C C t D D C t C t 38 6 Two possible pathways oyori, Tetrahedron ett., 1978, distal attack proximal attack M M "aked" nickel catalysts such as (CD) favor proximal ring opening osphine ligands result in a preference for distal ring opening Palladium reacts exclusively at the distal position chanism (proximal attack): Binger, Top. Curr. Chem., 1987, 135, 77. n 1 3 n 1 3 n 3 1 Binger, Top. Curr. Chem., 1983, 116, 1.

7 Intramolecular [ 3! " ] Cycloadditions With thylenecyclopropanes Synthesis of 13-Acetoxymodhephane C M C C Ac 13-Acetoxymodhephane catalyst (0 mol%) temp. yield (CD), P 3 (P 3 ) Pd, DIBA 110 o C 130 o C 74% 98% akamura, J.Chem. Soc., Chem. Comm., 1988, 111. Selection of metal catalyst governs regiochemical product Pd 10 mol% Pd (dba) 3 40 mol% (ipr) 3 P, 110 o C C C C 59% C C C 40 mol% (CD), 0 o C C C C 50% Motherwell, Tetrahedron ett., 1989, [ " " " ] Cycloadditions: Alkyne Cyclotrimerizations Although in principle thermal [ ] cycloadditions are symmetry allowed, the entropic barriers associated with bringing three reaction partners together and enthalpic activation energy contributions mitigate against such processes The use of a transition metal catalyst enables entropic constraints to be circumvented by coordination of the reaction partners to the metal complex in a stepwise process metal catalyst (, Co, Pd, Cr, h, Fe, or Ta) 5, 6 1, 3, 4 Intermolecular reaction suffers from chemo- and regioselectivity problems complex product mixture ( ) n 1 metal catalyst (, h, or Co) n = -5 ( ) n 1 Partially intramolecular cyclotrimerization has become a very useful synthetic procedure

8 [!!! ] Cyclotrimerizations: chanism and Scope General chanism: Modifications of Cyclotrimerization M n M n- M n C Mn M n C C C 3 1 n- 1 5 M autens,chem. ev., 96, 1996, 49. [!!! ] Cycloadditions: Semi-Intramolecular Alkyne Cyclotrimerizations Asymmetric Synthesis of Isoindoline and Isoquinoline Derivatives TMS Tr 8 mol% (CD) 0 mol% * TF, 3 o C TMS * Tr TMS TMS * ield ee (S, S)-BPPM 9% 60% ()-(S)-BPPFA 5% 73% P tbu P (S, S)-BPPM Fe P P ()-(S)-BPPFA Tr 8 mol% (CD) 40 mol% * TF, 3 o C * Tr * ield ee (S, S)-BPPM 4% 6% (S)--MP 6% 54% P (S)--MP Mori, J. rg. Chem., 59, 1994, 6133.

9 [ ] Cycloadditions: Alkynyl none / Alkene Cyclotrimerizations Montgomery (w/ Jeongbeob Seo) or (CD) P 3 single stereoisomer from either or starting material (99% and 63% yields respectively) A eaction sets two rings and four contiguous stereocenters with complete stereoselectivity Unusual chemoselectivity for alkene over alkyne in [ ] cyclotrimerization Simple enones (CD) P 3 A 3% 75% (CD) P 3 68% combined 4 : 1 dr Montgomery, J. Am. Chem. Soc., 1999, 11, 477. [ ] Cycloadditions: Alkynyl none / Alkene Cyclotrimerizations chanism 1 3 (CD) P A (CD) P C B 4 Products to not isomerize or epimerize under standard catalytic reaction conditions Authors propose preequilibrium between nickel metallacycles and a kinetic preference for addition of B or C to the simple enone to explain lack of reaction stereospecificity Montgomery, J. Am. Chem. Soc., 1999, 11, 477.

10 [ 3 ] and [ 1 ] Cycloadditions: Diverse eaction Manifolds From a Common ckel tallocycle eaction conditions chemoselect for nickel enolate or vinyl nickel moiety = I, C, 1 [ 3 ] adduct = TMDA chanisms TMDA suppresses [ ] dimerization Montgomery, J. Am. Chem. Soc., 000, 1, [ 1 ] adduct First examples of omo-diels-alder reaction [!!! ] omo-diels-alder Cycloadditions 05 o C "small amount" Ullman,Chem. ind. (ondon)., 1958, C C C C Blomquist, J. Am. Chem. Soc., 1958, 81, 667. reflux C C C C 100% ess activated olefins result in greatly diminished yields acrylonitrile and norbornadiene (00 o C, 1h) gives only 1% yield ckel catalysts greatly broaden scope and efficiency of DA 10% (CD) 0% P 3 Temp. ield exo : endo C C C S S 80 o C r.t. 80 o C r.t. r.t. 99% 58% 8% 75% 73% >0 : 1 3 : 1 4 : 1 1 : 1 >19 : 1 a a: P() 3 used instead of P 3 autens, J. Am. Chem. Soc., 1995, 117, 1076.

11 orbornadienes: [ ] Vs. [ ] (CD) P 3 ighly electron-deficient olefins (e.g. -phenylmaleimide) undergo [ ] reaction More electron-rich olefins (e.g. methyl vinyl ketone) favor [ ] pathway eaction pathway appears to be dependent upon coordination ability of the dienophile [ ] adduct [ ] adduct autens, J. Am. Chem. Soc., 1995, 117, [!!! ] omo-diels-alder Cycloadditions : egio- and Stereoselectivity -Substituted orbornadienes C C 13 mol% (CD) 4 mol% P 3, 80 o C C (para) C 94% exo : endo =.3 : 1 18 mol% (CD) C 36 mol% P 3, 80 o C (ortho) C 54% (80% one isomer) C Si 3 15 mol% (CD) Si 3 30 mol% P() 3 47%, 80 o C (meta) C P 3 gives mixture of [ ] and [ ] adducts Diene and dienophile substituents as well as ligands shown to have dramatic effect on selectivities autens, J. Am. Chem. Soc., 1995, 117, 1076.

12 [!!! ] omo-diels-alder: Cyclic Vs. Acyclic Dienophiles Acyclic Dienophiles: exo-selective 10 mol% (CD) 0 mol% P 3, 80 o C C 99% >0 : 1 exo : endo endo disfavored exo favored Cyclic Dienophiles: endo selective 10 mol% (CD) 0 mol% P 3, 80 o C 56% endo only endo favored exo disfavored autens, J. Am. Chem. Soc., 1995, 117, [!!! ] omo-diels-alder: 7-Substituted orbornadienes 0 mol% (CD) 40 mol% P 3, 80 o C C A C B C C C C D n-hexyl ield 83% A : B : C : D anti : syn exo : endo 40 : 58 : 1.6 : : : 84% 54 : 45 : 0.8 : : : 1 60% 71 : 8 : 0.8 : 0. 7 : 8 99 : 1 C 97% 80 : 0 : 0 : 0 80 : : 0 TIPS 90% 90 : 9 : 1 : 0 91 : 9 99 : 1 MM 89% 88 : 9 : 3 : 0 91 : 9 97 : 3 tbu 95% 95 : 5 : 0 : 0 95 : : 0 Anti : syn selectivity increases as group electronegativity of 7-substituent increases Ab initio calculations indicate a shift of electron density from the anti-! olefin to the syn-! olefin as electronegativity increases autens, J. Am. Chem. Soc., 1995, 117, 6863.

13 [ 4 4!! ] Cycloadditions: ckel-catalyzed Diels-Alder eactions eversal of thermal reactivity 135 o C C C 60% (acac), P 3 90% t 3 Al, 40 o C C C : 1 Garratt, J. Chem. Soc., Chem. Comm, 1974, 51. chanism: 0 0 II II II - 0 Wender, J. Am. Chem. Soc., 1989, 111, 643. [ 4 4!! ] Cycloadditions: ckel-catalyzed Intramolecular Diels-Alder eactions Alkyne and Allene Dienophiles Alkynes are typically poor dienophiles in the Diels-Alder reaction TBS 10 mol% (CD) 30 mol% P(o-bi) 3 5 o C, 11h TBS TBS >99% :1 dr TMS 10 mol% (CD) 30 mol% P(o-bi) 3 5 o C, 11h TMS Transition metal catalysts make these processes facile and synthetically useful 98% >99:1 dr TMS Wender, J. Am. Chem. Soc., 1989, 111, 643. MM 0 mol% (CD) TMS 40 mol% P(iC 3 F 6 ) 3 C 6 1, 80 o C Allenes: Catalyst-controlled chemocomplementarity TBS 5 mol% [h(cd)] 48 mol% P(-o-Bi) 3 TBS MM TMS 3 steps Steroidal, Vitamin D derivatives 90% one diastereomer Wender, J. rg.chem., 1995, 60, mol% (CD) 30 mol% P(-o-Bi) 3 TBS TF, 45 o C TF, 5 o C Wender, J. Am. Chem. Soc., 1995, 117, 1843.

14 [!!!! ] Cycloadditions: Cyclooctatetraene Synthesis First example by eppe, has been used on an industrial scale 4 -Catalyst C(iPr) -Catalyst = Br / CaC, (acac), (CT) eppe, eibigs Ann. Chem., 1948, 560, 1. tom Dieck developed first method for regioselective cycloadditions with monosubstituted alkynes 4 cat. (dad) C(iPr) (dad) major product major product C C Tol C(C 3 ) C C [ 4 4! 4 4! ] Cycloadditions: Cyclooctadiene Synthesis Intermolecular Substituted butadiene dimerization tom Dieck, Chem. Ber., 1985, 118, mol% (CD) benzene, = Si 3 (18d), = C (4h) =, = C (7h) 90% 70% 33% Use of butadiene results in significant [ 4 ] adduct Waegell, Tetrahedron ett. 1983, 4, 385. chanism: n n " 1," 3 -anti bis-" 1 n n " 3 -bis syn bis-" 1 n 0 n n " 3 -bis anti bis-" 1 Conditions can be optimized to minimize vinylcyclohexene and divinylcyclobutane formation Wilke, ACI, 1988, 7, 185.

15 [ 4 4! 4 4! ] Cycloadditions: Intramolecular Cyclooctadiene Synthesis 3-atom tethers cis-fused t C t C 11 mol% (CD) 33 mol% 3 P, 60 o C t C t C 70% 19 : 1 cis : trans 4-atom tethers trans-fused C 1 : C (CD) : 3 P 8% 5 : 95 cis : trans ote: other substrates give much lower selectivities Type I Wender, J. Am. Chem. Soc., 1986, 108, C 10 mol% (CD) 0 mol% 3 P, 110 o C C 9% 3 : 97 cis : trans Type II TBS 0 mol% (CD) 40 mol% 3 P, 110 o C TBS 5% 1.3 : 1 dr Towards taxane skeleton Wender, Tetrahedron ett., 1987, 8, 1. [ 4 4! 4 4! ] Cycloadditions: nantioselective Total Synthesis of ()-Asteriscanolide C BrMg 57% 1. isobutyric anhydride. DA 68% ( steps) C 3. i 1. A. Swern 4. Swern 64% (4 steps) Darvon A red. 97% 98% ee ed-al Sn 3 83% Sn 3 Sn 3 n-bui (CD) C P 3, 90 o C 56% 67% ed-al B 3 TF CuBr PCC 74% 48% ()-Asteriscanolide Wender, J. Am. Chem. Soc., 1988, 110, 5904.

16 [ 1 ] Cycloadditions: Cyclopentenone Synthesis 3 SiC cat. (CD) /, 8h Si 3 = epresentative examples 60% 38% : 1 dr 40% 41% t C t C 70% 58% >98 : ckel-catalyzed "ipper Annulation" of Conjugated nynes Buchwald, J. rg. Chem., 1996, 61, cat. Pd 0 cat. 0, rt 5-89% = n-c 6 F 13, CF, n-c 6 13 CF amamoto, J. Am. Chem. Soc., 000, 1, Catalytic cycle or 0