Brominations and Non-Halogens. Evans Group Seminar p November 23, 2009 Pascal Bindschädler

Transcription

1 lefin Addition Reactions II: ominations and Non-alogens Evans Group Seminar p November 23, 2009 Pascal Bindschädler

2 Presentation utline 1. omination: The verall Process a) verall Process / istory b) omonium-ion ( -Complex): Formation and Structure c) -Complex: Formation and Structure d) verall chanism (calculated) 2. omination: Reactions a) Substituent Effects / Regioselectivity b) Towards Enantioselective ominations c) omolactonization / omocyclizations 3. xymercuration a) verall Process b) Reactions 4. Reactions of Tl(III) with lefins 5. Electrophilic Selenation of lefins

3 Selected References

4 omination: verall Reaction chanism

5 istory of the omonium Ion : Postulation of bromonium ion as origin of anti (trans) selectivity Roberts, I. J. Am. Chem. Soc. 1937,, 59,, : NMR spectra of bromonium ions in SbF 5 -S 2 lah, G.A. J. Am. Chem. Soc. 1967, 89, 4744; lah, G.A. J. Am. Chem. Soc. 1969, 91, : First bromonium salt (no X-ray) Wynberg,. J. Chem. Soc., Chem. Commun D 1967, 907.

6 omonium Ion Crystal Structure own, R.S. J. Am. Chem. Soc. 1985, 107, 4504.

7 Calculated omonium Ion Structures

8 omonium Ion vs. 2-omocarbocation Calculations of bromonium ions and 2-bromocarbocations: 2-bromoethylcation ("cis") 1-bromoethylcation ("trans") Calculations of bromonium ions and 1-bromocarbocations: "trans" "cis" Benzylic 2-bromocarbocation: Influence of aryl substituent (Y) on dihedral angles of lowest energy conformation: Y Y= p Vacuum 99.4 N CCl DMS Y F B3LYP/6-31+G(d,p); LANL2DZ. CN N Ar B3LYP/6-31+G(d) Schaefer,.F. III, J. Am. Chem. Soc. 1990, 112, 8260: DZ+d ClSD Damrauer, R.; adad, C.M. J. rg. Chem. 1998, 63, 9476: MP2/BB2//MP2/SB Sigalas, M.P. Tetrahedron 2003, 59, 9476: MP2/6-311G(d,p) & B3LYP/ G(d,p) Barrier for rotation ( ): G = 6kcal/mol (Y=) (vacuum) Sauers, R.R. Tetrahedron 2005, 61, 8358

9 Reversibility of omonium Ion Formation

10 Evidence for π-complex Tetraneopentylethylene: Reaction stops at the stage of -complex -Ratioof1 and 2 is dependent on the bromine concentration - Existence of stable -complexes formed in equilibrium with reagents in DCE was deduced from concentration-dependant UV spectra Angew.Chem.Int.Ed.Engl.1997, 36, ther sterically congested alkenes: free 2 2 adds syntothisolefin: J. Am. Chem. Soc. 1990, 102, Does not react with 2 at all: Chem. Ber. 1984, 117, 277. Reaction with 2 yields addition-elimination products: J. Am. Chem. Soc. 1990, 112, Reviews: Acc. Chem. Res. 1997, 30, 131; Chem.Eur.J.2003, 9, 1036.

11 Calculated π-complexes Geometries and complexation energies (both at MP2/6-311+G**) corrected for ZPE and BSSE of 1:1 2 complexes of acetylene, ethylene, and allene. (Data in parantheses at B3LYP G** level) Bianchini, R.; Lenoir, D.; Goldberg, N. Chem.Eur.J.1999, 5, 1570; Chiappe, C.; Lenoir, D.; Schleyer, P. v. R. Chem.Eur.J.2002, 8, 967; Review: Lenoir, D.; Chiappe, C. Chem.Eur.J.2003, 9, 1036.

12 chanism for the Reaction of Ethene with 2 2 Most likely pathway for the reaction of ethylene with 2 2 at the G3MP2B3 level. For TS2 F, I2 F, and I3 F the G3MP2B3 energies were calculated using F/6-31G(d) optimized geometries. Reaction of with ethene propene isobutene fluoroethane chloroethane: Reaction of 2 with ethene, propene, isobutene, fluoroethane, chloroethane: Poirier, R.A. J. Phys. Chem. A, 2007, 111, 13218; Reaction of Adamantylideneadamantane (Ad=Ad) with 2 and 2 2 : Poirier, R.A. J. Phys. Chem. A, 2008, 112, 152;

13 omination Substituent Effects Alkene k rel Kinetics: Substitution effects on bromination rate ( 2 25 C) C 2 =C 2 1 C 3 C=C 2 85 EtCC=C iprc=c 2 80 tbuc=c 2 20 (C 3 ) 2 C=C C 2 7,960 (C 3 ) 2 C=CC 3 276,000 (C 3 ) 2 C=C(C 3 ) 2 3,025,000 - omination rate increases for more substituted alkenes; - omination rate decreases for sterically demandingdi alkyl l substituents t on the alkene. Ruasse, M.-F. Adv.Phys.rg.Chem.1993, 28, 207 (Review). Stereochemical outcome versus structure Alkene % anti addtion % anti addtion ( 2 in Ac@ 25 C) Ar ( 2 in C 2 Cl 25 C) 100% C % % syn addition increases with stabilization of 100% "benzylic carbocation" 4-()C % Ph Ph 73% 3,5-(CF 3 ) 2 C % 83% Dubois, J.E. J. Am. Chem. Soc. 1978, 100, 7645; Ruasse, M.-F. Adv.Phys.rg.Chem.1993, 28, 207 (Review).

14 omination: Regioselectivity omination of cyclohexene derivatives: Pasto, D.J. J. Am. Chem. Soc. 1970, 92, Trans-diaxial opening of bromonium ions may be viewed as an extension of the Fürst-Plattner Rule for epoxide opening (Fürst, A.; Plattner, P.A. elv. Chim. Acta 1949, 32, 275). 3 C - C Pry C 3 C 3 C 47% 53% 3 C Pry C 100% 3 C syn: unreactive + 3 C anti: reactive + Both bromonium ions are formed (equilibrium); however, for the syn isomer to react, ring opening must proceed against the polarization due to the methyl substituent and is not observed. nly the Markovnikov products are formed.

15 Enantioselective omination Palladium(II)-catalyzed asymmetric 1,2-dibromo synthesis: enry, P.M. rg. Lett. 2003, 5, 439. Ar L * -L * = (S)-BINAP s = solvent Ar = Ph, 4-C 6 4, 4-CNC 6 4 *L s *L s Pd Pd Li (0.2M), Cu 2 (2.5M) TF/ 2 Ar ee >95% * Ar = Ph, 4-C 6 4, 4-CNC Works also with 1,2-disubstituted alkenes. - owever, method has never been applied or reproduced; - source of Pd is not specified; - only limited supporting information Generation and trapping of enantiopure bromonium ions: addock, D.C. Chem. Commun. 2009, C % btained by kinetic resolution: Jacobsen, E.N. J. Am. Chem. Soc. 2002, 124, C C Ts Cl TiCl 4 C C C Ts TiCl 4 C C Same product ratio (3:4 = 6:1) was obtained for both, the reaction of 1 with TiCl 4 and 2 with TiCl 4. chanism via enantiopure bromonium ion. Cl

16 Towards Enantioselective omination

17 omolactonization

18 omocyclization

19 omocyclization: Cascades Example for bromonium-initiated epoxide-opening cascade: Key step in the total synthesis of ent-dioxepandehydrothyrsiferol NBS, FIP 4A MS + 0 C, 15min 3 36% (plus 36% C-3 epimer) Jamison, T.F. J. Am. Chem. Soc. 2009, 131, omonium-induced Polyene Cyclizations Key step in the total synthesis of 4-isocymobarbatol + MM BDSB C 3 N 2 MM -25 C, 5min 74% MM Et S BDSB SbCl 5 Et Snyder, S.A. Angew.Chem.Int.Ed.2009, 48, BDSB was found to be superior to TBC, NBS/PPh 3, 2 /AgBF 4 - BDSB: "Reagent for powerful electrophilic bromination. Finally enables direct formation of cation- cyclization products with essentially every class of standard terpene substrate with predictable stereochemistry. " - "..render this transformation asymmetric.. is the subject of current study." TBC

20 xymercuration I The overall process: gx 2 g X R gx NaB R 4 R R' R' reduction R' R - rcury(ii) salts used: g(ac) Kinetics: alpern, X.Y. J. Am. Chem. Soc. 1967, 89, , g(tfa) Reduction: NaB 4 :Pasto,D.J.J. Am. Chem. Soc. 1969, 91, 719; 2, g(n 3 ) 2, g(ms) 2 Bu 3 Sn: Whitesides, G.M. J. Am. Chem. Soc. 1970, 92, anti addition to alkene verview: own, X.Y. J. rg. Chem. 1981, 46, Markovnikov products - complementary to hydroboration - reduction: nonstereoselective xy-mercuration and bromination follow identical pathways: radical chain process Pasto, D.J. J. Am. Chem. Soc. 1970, 92, 7480 omonium and mercurium ions: Differences g(ac) 2 g(ac) 2 gx syn addition, TF, 2 3 C TF, 2 no rearrangement 3 C gac exclusive products Pyr other 3 C CCl 4,0 C isomers via non-classical carbocation; product distribution obtained Pasto, D.J. J. Am. Chem. Soc. 1970, 92, 7480 Can. J. Chem. 1971, 49, 885.

21 xymercuration II Model for cyclic systems: Chamberlin, A.R.; ehre, W.J. J. Am. Chem. Soc. 1987, 109, 672. X X X + Example: tbu g(ac) 2 tbu syn Favored -complex (for X =,I) Favored -complex (favored onium ion) for X =,I,gAc) 2 gac J.Chem.Soc.B1970, Model for acyclic allylic alcohols: Giese, B. Tetrahedron Lett. 1985, 26, R g Ac 1. g(ac) 2, 2 /TF R 2. NaB 4,Na Nu R anti R R anti/syn syn C 2 5 3:1 ipr 4:1 tbu 49:1 Remote directing group: No selectivity for intramolecular halocyclization of (E)-alkenes: I 2 obtained as 1:1-mixture - (E) I I Chamberlin, A.R.; ehre, W.J. J. Am. Chem. Soc. 1987, 109, 672.

22 xymercuration III

23 Reactions of Tl(III) with lefins I

24 Reactions of Tl(III) with lefins II

25 Reaction of Electrophilic Selenium with lefins I The overall process: R1 SeX R 2 R Addition R Se R1 R SeR 1 Bu 3 Sn R AIBN R 2 toluene R 2 Seminal: Sharpless, K.B. J. r g. Chem. 1974,, 39,, 429. Reviews: Selenolactonization: Jayaraman, N. Tetrahedr on, 2004, 60, Selenium electrophiles: Wirth, T. Eur. J. rg. Chem. 2009, Chiral electrophilic Se-reagents: Wirth, T. Curr.rg.Chem.2006, 10, Example for selenolactonization: PhSe PhSeCl NEt 3,C 2 Cl 2 2 2,TF C 2 Et -78 C to rt 0 Ctort 85% 88% Example for the use of chiral Se-reagents: R*SeTf = N 3 Ph R*SeTf NaN 3 Ph N 3 N 3 SeR* C 3CN C C to r.t. C C C 3 7 SeR* dr 97:3 dr 95:5 S SeTf -Se + sources: PhSeCl, PhSePF 6 and others. - anti addition to alkenes, also in benzylic position! - Markovnikov products - reduction: nonstereoselective radical chain process - alternative to reduction: 2 2, selenoxidepyrolysis Jones, G.B. Tetrahedron 1993, 49, 369. Electrophilic Se-reagents were also used to effect asymmetric hydroxyselenation, methoxyselenation and cyclofunctionalization reactions. igh facial selectivity, it mild reaction conditions. Tiecco, M. Angew.Chem.Int.Ed.2003, 42, 3131.

26 Reaction of Electrophilic Selenium with lefins II