Organocatalysed Sigmatropic Rearrangement. Petri Pihko Group Literature Seminar, Nicolas Probst 08/03/2011

Transcription

1 rganocatalysed Sigmatropic earrangement Petri Pihko Group Literature Seminar, icolas Probst 08/03/2011

2 2010 Wiley-VC Verlag Gmb & Co. KGaA, Weinheim Chem. Eur. J. 2010, 16, rganocatalysis and sigmatropic rearrangement 2" Sigmatropic rearrangement : in most instances concerted process reactions governed by orbital symmetry powerful C-C and C-X bond-forming methodology cyclic and/or highly ordered transition states leading to high levels of stereoselectivity rganocatalysis mode of activation : nucleophilic catalysis enamine catalysis (1 paper of [2,3]!) iminium catalysis, hydrogen-bonding catalysis (1 paper of [3,3]!) DI: /chem Asymmetric rganocatalytic earrangement eactions Albert Moyano,* [a] iama El-amdouni, [a, b] and Ahmed Atlamsani [b] Dedicated to Professor Josep M. ibó on the occasion of his 70th birthday è 1 mini-review about the subject 5260 Woodward,. B.; offmann,. J. Am. Chem. Soc. 1965, 87, Moyano, A.; El-amdouni,.; Atlamsani, A. Chem. Eur. J. 2010, 16,

3 Shaw, S. A.; Aleman, P.; Kampf, J. W.; Va, P.; Vedejs, E. J. Am. Chem. Soc. 2006, 128, Steglich and related [1,3] rearrangements ucleophilic catalysis 3" 1 (1 mol%) t-amyl alcohol 0 C, 12 h 95% yield 91% ee 1 (10 mol%) C 2 2, T 24h A + B A/B: 3:2 >95% conv. 91% ee [A] 1 (1 mol%) Et 2, T 92% yield 92% ee C 2 1 (1 mol%) Et 2, T 35 d C 2 >95% conv. 55% ee 3 C Ac 2 1 st generation Vedejs catalyst 1

4 Steglich and related [1,3] rearrangements ucleophilic catalysis 4" 2 (10 mol%) AcEt, 0 C 2 h 94% yield 92% ee C 2 C 2 Ac t-bu 2 2 nd generation Vedejs catalyst 2 3 (10 mol%) C 2 2!50 C, 16 h 68% yield 94% ee S 3 Duffey, T. A.; Shaw, S. A.; Vedejs, E. J. Am. Chem. Soc. 2009, 131, Joannesse, C.; Johnston, C. P.; Concellon, C.; Simal, C.; ilp, D.; Smith, A. D. Angew. Chem. Int. Ed. 2009, 48,

5 Kobbelgaard, S.; Brandes, S.; Jørgensen, K.A. Chem. Eur. J. 2008, 14, " Asymmetric rganocatalysed [1,3]-sigmatropic rearrangement C 3 [1,3] C 3 [3,3] C 3 1 EWG 2 1 EWG 2 verman earrangement 1 EWG 2 Access to β-amino acids C 3 C 3 DQD 1 DQD earrangement of imidate to amide C 2 1 (10 mol%) dioxane 0.5 h, 40 C C 2 77% yield 90% ee DQD = C EWG 3 C 3 C S 2'! S 2' 1 EWG EWG

6 6" Asymmetric rganocatalysed [1,3]-sigmatropic rearrangement DQD = r the rearrangement of carbamates to amine : Ts C 2 t-bu 2 (20 mol%) C 2 2,!35 C, 43 h Ts C 2 t-bu 43% yield 71% ee DQD DQD 2 PG 1 EWG 2 3 -C 2 S 2' PG 1 EWG S 2' 1 PG! EWG

7 Mcally, A.; Evans, B.; Gaunt, M. J. Angewandte Int. Ed. 2006, 45, " Enamine catalysis activation: Development of a [2,3] Wittig earrangement through Secondary Amine Catalysis Conventional [2,3] Wittig earrangement Z Strong Base Low Temperature Z Z Mild condition First and only one to date of enamine activation Favouring syn diastereomers rganocatalysed version (20 mol%) (0.5 M)!5 C, 24 h dr (syn/anti) 6.5:1 84% yield

8 8" Enamine catalysis activation: Development of a [2,3] Wittig earrangement through Secondary Amine Catalysis ydrogen bond participation of in TS Via syn TS Via trans TS [2,3]

9 9" Enamine catalysis activation: Development of a [2,3] Wittig earrangement through Secondary Amine Catalysis The complete transfer of chirality suggests the rearrangement proceeds via a concerted mechanism (as oppose to a stepwise ionic pathway) Enantioselective version developed Acid cocatalyst under study (4-CF 3 ) 94% ee (20 mol%) (0.5 M)!5 C, 24 h (4-CF 3 ) 86% yield dr (syn/anti) 6.5:1 92% ee rganocatalytic enantioselective rearrangement (4-CF 3 ) (20mol%) (0.5 M) T, 5 days 75% yield 60% ee dr (syn/anti) 2:1 (4-CF 3 )

10 + Enamine catalysis activation: 2,5-diphenylpyrrolidine-catalyzed α-chlorination of aldehydes CS Up to 97% ee [1,3]-sigmatropic rearrangement vs. direct addition to enamine ighest electronic density on nitrogen (DFT calculation) Via ammoniumchloride intermediate o secondary isotope effect o influence of chlorine source Absence of nonlinear effect [1,3] DS ! CS 2 10" alland,.; Lie, M. A.; Kjærsgaard, A.; Marigo, M.; Schiøtt, B.; Jørgensen, K. A. Chem. Eur. J. 2005, 11,

11 Enamine catalysis activation 11" [1,3]-sigmatropic rearrangement pathway conceivable? MacMillan suggests for his α- chlorination a protonated enamine pathway rganocatalytic α-fluorination + S S F FSI (20 mol%).dca TF + 10% i-pr!10 C, 12h n-ex + F 1.2 equiv. 98% conv. 98% ee (5 mol%).tfa C 3 (0.5 M)!30 C, 8 h n-ex via a protonated enamine n-ex 91% conv. 92% ee F S S via a protonated enamine Brochu, M. P.; Brown, S. P.; MacMillan, D. W. C. J. Am. Chem. Soc. 2004, 126, Beeson, T. D.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, Kwiatkowski, P.; Beeson, T. D.; Conrad, J. C.; MacMillan, D. W. C. J. Am. Chem. Soc. 2011, 133,

12 ueping, M.; Antonchick, A. P. Angew. Chem. Int. Ed. 2008, 47, Aminoallylation of aldehydes Catalytic Enantioselective [3,3] Aza-Cope earrangement 12" Aminoallylation of nonenolisable aldehyde (aromatic aldehyde or cinnamaldehyde) bearing either EWG or EDG + Condensation 2 Ar Ar P [3,3] Access to homoallylic amine, precursors for β-amino acids, aminoalcohols, aminoepoxides, pyrrolidines and piperidines 2 Ar Ar P Ar Ar P! Ar + 2 (10mol%) P MTBE, 3-Å MS, 50 C 48 h Ar 61-81% 90:10 to 97:3!

13 Iminium catalysis activation Aza-Petasis-Ferrier earrangement 13" Catalysed by chiral Brønsted acid on concerted rearrangement via a iminium catalysis Efficient entry to β-amino acids ' PG '' A* A* ' Bn A PG ' PG '' Boc Bn isomerization of double bond Boc Bn 1. Ar P Ar AcEt, 30 C 1,5 h 2. ab 4 / i-pr Ar = (2 mol%) i-pr i-pr anti Boc Bn + syn Boc Z/E > 99:1, anti/syn 98:2, 95% yield, ee (anti/syn) 93/32 Z/E > 1:99, anti/syn 23:77, 94% yield, ee (anti/syn) 17/88, Bn Terada, M.; Toda, Y. J. Am. Chem. Soc., 2009, 131,

14 Enantioselective semipinacol rearrangement Iminium catalysis activation 14" 1,2-sigmatropic migration in the semipinacol rearrangement cat. (20 mol%) BLP (40 mol%) C % yield 77% ee BLP = -Boc-L-phenylglycine Zhang, E.; Fan, C.-A.; Tu, Y.-Q.; Zhang, F.-M.; Song, Y.-L. J. Am. Chem. Soc. 2009, 131,

15 6 protein modific,xtion has been used to identie key amino-acid residues [ 14-l 61, and several competitive inhibitors and alternative substrates have been synthesized obtained on several naturally occurring chorismate mutates, and on mtibody 1 F7. X-ray crystal structures of the enzyme from Ba~i//ns rrfbtilir [J-C,] and of antibody 15" aisen earrangement acceleration by -bonds Chemistry Chorismate mutases catalyse [3,3]-sigmatropic rearrangement of chorismate to prephenate Key hydrogen-bond donating residues in the active site of & Biology Vol 2 o 4 the1995,enzyme Fig. 1. The rearrangement of chorismic acid (7) to prephenic acid (2). The presumed transition state is shown, together with the transition state analog inhibitor (3) used in (b)x-ray crystallographic. studies. This [3,3[-pericyclic process is formally analogous to a aisen rearrangement. Argll 0 Current Biology Ltd ISS Ser84 I Glu52 Fig. 2. The active site of E. co/i chorismate m&se. (a) A space-filling model of the active site of the chorismate mutase domain of the E. co/i P-protein complexed with transition-state analog inhibitor 3 as defined by a 2.2 p\ resolution X-ray diffraction analysis [42]. (b) Schematic diagram of the hydrogen bonding and electrostatic interactions of the transition-state inhibitor 3 with the relevant side Lee, A. Y.; Stewart, J. D.; ardy, J.; Ganem, B Chem. Biol. 1995, 2, Active site of E. coli chorismate mutase : (a) X-ray structure in complex with intermediate 3 (b) Schematic representation,the enzyme forms 2 bonds with 7 195

16 aisen earrangement acceleration by -bonds 16" n-π* conjugation : a lone pair of electrons from oxygen brought into conjugation with the double bond. Conjugation lowers the overall energy Disruption of n-π* conjugation : raise the energy of the reactant and reduce the activation enthalpy for rearrangement Solvent Solvent-

17 aisen earrangement acceleration by -bonds 17" Jorgensen : model for the aqueous acceleration of the aisen rearrangement of allyl vinyl ether by quantum mechanical calculations Enhanced hydrogen bonding in the TS Severance, D. L.; Jorgensen, W. L. J. Am. Chem. Soc. 1992, 114,

18 Kirsten, M.; ehbein, J.; iersemann, M.; Strassner, T. J. rg. Chem. 2007, 72, aisen earrangement acceleration by -bonds 18" (thio)urea : potential organocatalysts by DFT calculation, but slight reproductible rate accelerating effect Solvent effect with CF 3 C 2 S Ar Ar C 2 -ipr 5 Solvent, T, t C 2 -ipr Ar = 2,5-(CF 3 )C 6 3 entry thiourea mol % solvent a T [ C] t conv. b [%] Ar Ar S Ar S Ar 1 C d 10 2 CF 3 C d 41 3 CF 3 C h 41 4 DCE 25 5 d C d CF 3 C d C h CF 3 C h DCE 25 5 d 14 Proposed transition state a DCE) 1,2-dichloroethane. b For entries 5-8, 0.1 mmol of 7 was dissolved in 2 ml of the indicated solvent. Conversion was determined by M. For experimental details see the Experimental Section.

19 Uyeda, C.; Jacobsen, E.. J. Am. Chem. Soc. 2008, 130, Uyeda, C.; ötheli, A..; Jacobsen, E.. Angew. Chem. Int. Ed. 2010, 49, aisen earrangement of -allyl α- and β-keto esters ydrogen-bond mediated asymmetric catalysis 19" Et Et Cat. (20mol%) C, 5-14 d exane 89% yield dr > 20:1 ee 82% Et 36h, 40 C Toluene (0.2M) Cat. (5mol%) Et 98% conversion 11:1 d.r. eal catalysis enhancement achieved An approach to quaternary stereogenic centers Preference for the chair-like transition state igh degree of charge separation with guanidinium salt CF 3 2 Cat.! B CF

20 20" aisen earrangement acceleration by -bonds "ydrogen bonding by a simple chiral alcohol to a carbonyl group can accomplish what has previously been considered to be the domain of enzymes, catalytic antibodies and metal-based Lewis acids. These studies indicate the broad potential for hydrogen- bond catalysis in asymmetric synthesis" V.. awal Yong uang, Aditya K. Unni, Avinash. Thadani, Viresh. awal ature 2003, 424, 146.

21 21" Thank you for your attention.. Made in apple