Rhodium Carbenoids and C-H Insertion

Transcription

1 hodium Carbenoids and C- Insertion Literature Talk Uttam K. Tambar March 1, pm, oyes 147 h h h h h h irreversible reversible carbenoid 2 h2l4 1 h2l4 or h2l4 2 utline I. What is a Carbene? II. What is a Carbenoid? III. Carbenoid Formation from iazo Compounds IV. C- Insertion with hodium Carbenoids V. Enantioselective C- Insertion with hodium Carbenoids Michael P. oyle (University of rizona) General eferences: Modern Catalytic Methods for rganic Synthesis with iazo Compounds: From Cyclopropanes to lides (oyle) Chem ev. 1986, 86, 919 (oyle) Chem ev. 2003, 103, 2861 (avies) dvanced rganic Chemistry: eactions and Mechanisms (ernard Miller) Carey & Sundberg, Part, Chapter 10 uw M. L. avies (University at uffalo - SU) 1

2 I. What is a Carbene: Structure Carbenes are neutral molecules containing divalent carbon atoms with 2 unshared electrons: C: 2 possible electronic structures: singlet and triplet 100 : singlet resembles carbocation and carbanion united on same carbon "sp 2 " filled orbital with empty "p" oribtal many groups (with unshared electrons) can stabilize singlet more than triplet triplet resembles diradical groups in "sp" orbital, 2 partially filled orthogonal "p" oribtals usually more stable than singlet form (und's rule) I. What is a Carbene: Formation from iazo ecomposition! or hƒ C riving force for decomposition of diazo compounds: formation of activation energy for diazoalkane decomposition = 30 kcal/mol (thermal or photochemical energy) Usually it is difficult to know if a "carbene" reaction in solution involves a free carbene or some pseudo-carbene species that behaves like a carbene 2

3 Free carbenes undergo insertion reactions I. What is a Carbene: eactivity singlet carbene irect (one-step) insertion into C- bonds, which leads to retention of stereochemistry at carbon o selectivity between different types of C- bonds in intermolecular reactions (only some selectivity in intramolecular reactions) (a) C 2 JCS 1956, 78, : (statistical mixture) 6 (b) photolysis of diazomethane in heptane: JCS 1961, 83, 1934 C 2 hf 38% 25% 24% 13% "methylene must be classified as the most indiscriminate reagent known in organic chemistry." (JCS 1956, 78, 3224) Free carbenes undergo insertion reactions I. What is a Carbene: eactivity triplet carbene Multi-step process (involving radical pairs), which can lead to scrambling of stereochemistry hƒ triplet -Me C 2 radical pair JCS 1969, 91, 4549 &

4 II. What is a Carbenoid: Structure and Formation Carbenoid is a vague term used for a molecule in which all carbons are tetravalent but still has properties resembling those of a carbene (usually the carbene-like carbon has multiple bonds with a metal) C ML n Carbenoids can be formed by reacting salts of transition metals (eg. Cu, Pd, h) with diazo compounds Initially the transition metal complexes used to decompose diazo compounds were heterogenous Cu complexes (JCS 1906, 89, 179) Et Copper dust Et Et Et Et Et II. What is a Carbenoid: Structure and Formation Then homogeneous Cu complexes were utilized Cu! TL 1966, 59 Et () 3 PCuCl C 2 Et C 2 Et JCS 1969, 91, 1135 & 1141 In 1952 ates postulated that the reaction of transition metal complexes with diazo compounds led to the generation of transient electrophilic metal carbenes: "reaction of C: (or of the CC:-copper complex) probably involves an attack by the unshared pair of electrons on oxygen, nitrogen or sulfur at the electron-deficient methine carbon followed by a prototropic shift" (JCS 1952, 74, 5376) Cu complexed with Cu - =, S, 2 Electrophile ucleophile 4

5 III. Carbenoid Formation from iazo Compounds: Lewis cid Promoted ecomposition of iazo Compounds iazo compounds are unstable to acid promoted decomposition: 3 C 2 C Site of protonation: 2 C 2 C 3 C kinetic product thermodynamic product This instability of diazo compounds towards acids models their reactivity with lewis acidic transition metal complexes: L 2 C L 2 C III. Carbenoid Formation from iazo Compounds: Mechanism of Transition Metal Promoted ecomposition of iazo Compounds Lewis acidic transition metal complexes, like h(ii) complexes, are effective catalysts for diazo decomposition. ctivity of transition metal complexes depends on coordinative unsaturation at metal center, which allows them to react as "electrophiles" for diazo compound: JCS 1996, 118, 8162 h h reversible h h irreversible carbenoid h h Some eccentric metal mediated diazo decomposition reactions do not yield carbenoids, and these reactions are often catalyzed by non-transition metal lewis acids as well: ' Cu(Tf) 2 or ' F 3 Et 2 Cu: J. rganomet. Chem. 1975, 88, 15 ' F 3 : JC 1980, 45, 3657 ' ML n ML n 5

6 III. Carbenoid Formation from iazo Compounds: Effect of Lewis ases SC 2 S: n electron rich substrate (S:) can react with the electrophilic metal carbenoid, which results in the regeneration of the transition metal complex (important for catalysis) Sometimes the reaction between the electrophilic carbenoid and a Lewis basic substrate (S:) is desirable L n M L n M C 2 L - n M C 2 2 ut sometimes a Lewis base (:) substrate can associate with the coordinatively usaturated transition metal complex and inhibits diazo decomposition: ML n -: ML n 2 C : - 2 C L n M C 2 Effective inhibitors for diazo decomposition: amines, sulfides, nitriles, (sometimes alkenes, aromatics) (Inorg. Chem. 1982, 21, 2196) Ineffective inhibitors for diazo decomposition: halogenated hydrocarbons, eg. CM, CE (great solvents for diazo decomposition) III. Carbenoid Formation from iazo Compounds: h(ii) Catalysts Carbene C- insertions are highly non-selective Carbenoid C- insertions are much more selective because of the reduced reactivity of carbenoids h Carbenoids (generated from h(ii) dimer complexes) have become the most common catalysts for C- insertion reactions because of their selectivity and the ease with which ligands are modified irhodium (II) carboxylates: First example of h carbenoid generation from diazo decomposition: (TL 1973, 2233) Et h 2 (c) 4 2 Et = Et, i-pr, t-u,, Me 4h symmetry with 4 bridging acetate ligands and 1 vacant coordinate site per metal atom presents an octahedral geometry resembling a circular wall with an electron rich circumference and electron deficient core: h h! -! - h!! - Complexes are air stable and easy to work with! - 6

7 III. Carbenoid Formation from iazo Compounds: h(ii) Catalysts Electron-withdrawing capabilities of carboxylate ligands affect properties of the catalyst (eg. h 2 (c) 4 does not form olefin complexes in solution, but h 2 (TF) 4 does form olefin complexes in solution) Inorg. Chem. 1984, 23, 3684 ther ligands used in dirhodium (II) complexes: carboxamidates h h h Inorg. Chem. 1986, 25, 260 phosphates and orthometallated phosphines r r P h h r porphoryns r h r C TL 1992, 33, 5983 TL 1992, 33, 5987 r TL 1980, 21, 3489 h 2 (C) 16 TL 1981, 22, 1783 III. Carbenoid Formation from iazo Compounds: Stability of h carbenoid complexes The use of dirhodium (II) catalysts for intramolecular C- insertion of diazo carbonyls has developed into a significant synthetic achievement because of the stability of these intermediates increasing stability Z Z, Z =,, = alkyl, aryl, increasing reactivity stable dirhodium tetracarboxylate carbenoid was isolated recently by Padwa: JCS 2001, 123, h 2 (t-uc) 4 h h 7

8 ifferent Types of Insertion eactions: IV. C- Insertion with h Carbenoids: Introduction h (II) complexes are used for C-, Si-, and eteratom- insertion reactions C- and Si- insertions are unique because of the low polarity of the bonds, so their mechanisms are distinct from eteroatom- insertions C- Insertion via Metal Carbenoids vs. C- ctivation via xidative ddition: In metal carbenoid induced C- activation the metal atom is not thought to interact directly with the alkane C- bond (this is different than most other C- activation reactions, which involve oxidative addition of the metal across the alkane C- bond): C ML n C vs. C ML n C ML n C- Insertion via Metal Carbenoids C ML n C- ctivation via xidative ddition IV. C- Insertion with h Carbenoids: Mechanism of C- Insertion h 2 L 4 h 2 L 4 1 or h 2 L 4 2 Carbenoid's empty p-orbital overlaps with the!-orbital of the C- bond C-C and C- bond formation with carbenoid carbon proceeds as ligated metal dissociates (1) Taber prefers a transition state in which there is a more pronounced interaction/transfer of hydrogen to rhodium (2), followed by a reductive elimination (JCS 1996, 118, 547) 8

9 IV. C- Insertion with h Carbenoids: General Characteristics of a Good h Complex for C- Insertion Proficient C- insertion requires an appropriate level of electrophilic character at the metal center If the metal center is too electrophilic catalyst displays poor selectivity because of high reactivity, and it is susceptible to undesired competing reactions If the metal center is not electrophilic enough catalyst is not reactive enough to insert C- bond Solutions: Electron-withdrawing groups on metal or adjacent to carbenoid carbon increase the electrophilicity of the carbenoid intermediate The best metal complexes bind to the carbenoid carbon through strong!-donation and weak "-back donation, which stabilizes the carbenoid carbon somewhat but still ensures electrophilicity IV. C- Insertion with h Carbenoids: Trends in Selectivity for Intermolecular C- Insertion Intermolecular C- insertion has mechanistic value, but it is not always synthetically useful (because of low selectivity) Et h 2 (c) 4 Et k = x 10-4 s -1 (reaction is first order in ethyl diazoacetate) Tetrahedron 1989, 45, 69 9

10 IV. C- Insertion with h Carbenoids: Trends in Selectivity for Intramolecular C- Insertion C- insertion occurs preferably at a carbon that can stabilize positive charge (electronic effects) tertiary carbon > secondary carbon > primary carbon (because of the availability of the electron density in the C- bond) 3 e E h 2 (c) 4 E E 2 e JCS 1986, 108, alkoxy groups activate adjacent C- bonds: h 2 (c) 4 n n 30% 0% n Tetrahedron 1991, 47, 1765 IV. C- Insertion with h Carbenoids: Trends in Selectivity for Intramolecular C- Insertion electron-withdrawing groups (eg. C 2 Me) inhibit adjacent C- bonds (TL 1988, 29, 2283) h 2 (c) 4 C 2 Me C 2 Me C 2 Me h 2 (c) 4 h 2 (c) 4 64% C 2 Me 0% 0% C 2 Me C 2 Me Sometimes electronic effects are outweighed by steric or conformational factors 5 membered rings > 6 membered rings E h 2 (c) 4 E E not observed 10

11 IV. C- Insertion with h Carbenoids: iastereoselectivity in Intramolecular C- Insertion C 2 Me h 2 (ct) 4 C 2 Me C 2 Cl 2 91% Me h 2 (ct) 4 C 2 Cl 2 85% C 2 Me C 2 Me 2 S Me h 2 (ct) 4 C 2 Cl 2 60% S 2 me Model for explaining diastereoselectivity: pseudo-chair transition state (JCS 1996, 118, 547 & Tetrahedron 1996, 52, 3879) equitorial C 2Me Me h 2L 4 Me C 2 Me V. Enantioselective C- Insertion with h Carbenoids: Classification of Carbenoid Intermediates lthough dirhodium (II) catalysts provide the highest levels of asymmetric induction for C- insertion, there is no one class of chiral rhodium (II) complex that is effective for all C- insertion reactions This is because different types of carbenoid intermediates display very different reactivities 3 main categories of carbenoids: acceptor substituted carbenoid L n M acceptor/acceptor substituted carbenoid L n M donor/acceptor substituted carbenoid L n M EG 11

12 V. Enantioselective C- Insertion with h Carbenoids: cceptor Substitutd Carbenoids acceptor substituted carbenoid L n M Example of a catalyst for enantioselective intramolecular C- activation: % ield % ee Me 2 C h catalyst C 2 Cl 2 Me Et n h 4 JCS 1991, 113, 8982 catalyst 30% yield, 76% ee 3 C C 3 C 2 Cl 2 3 C V. Enantioselective C- Insertion with h Carbenoids: cceptor/cceptor Substitutd Carbenoids acceptor/acceptor substituted carbenoid L n M Example of a catalyst for enantioselective intramolecular C- activation: TL 1990, 31, 5173 h h 4 C 2 Me catalyst C 2 Cl 2 C 2 Me aq. MS 120 C % ield % ee Me n-pn C 2 =C

13 V. Enantioselective C- Insertion with h Carbenoids: onor/cceptor Substitutd Carbenoids donor/acceptor substituted carbenoid L n M EG Example of a catalyst for enantioselective intermolecular C- activation: catalyst 81 C Me 2 C Me 2 C S 2 r h h 4 JCS 1997, 119, 9075 % ield % ee Me Cl utlook for the Future h (II) carbenoids have become the most widely used catalysts for selective C- insertion reactions oth the catalyst design and carbenoid structure can affect reactivity and selectivity (chemoselectivity, regioselectivity, diastereoselectivity, and enantioselectivity) C- insertion with h carbenoids is now becoming a powerful and widely applicable synthetic strategy for total synthesis (avoidance of functional group manipulations) major area of future research will be to broaden the range of carbenoid systems that can undergo selective C- insertion reactions ecent computational studies to study the mechanism may help make the design of future systems more rational and predictable 13