O H Hydrogen bonding promotes H-atom transfer from C H bonds for C-alkylation of alcohols

Transcription

1 ydrogen bonding promotes -atom transfer from C bonds for C-alkylation of alcohols Jenna L. Jeffrey, Jack A. Terrett, David W. C. MacMillan Science 2015, 349, Raffaele Colombo 9/26/2015 Raffaele Wipf Group Page 1 of 26 12/29/2015

2 2 C- activation C- activation refers to reactions involving the cleavage of an unreactive C- bond of alkanes, arenes, or alkyl chains by transition metal complexes The intermolecular catalytic functionalization of C(sp3) bonds in a selective manner represents a longstanding challenge Early studies by Bergman: Ir hv - 2 Ir Me 3 P Me 3 P Janowicz, A..; Bergman, R. G. J. Am. Chem. Soc. 1982, 104, Raffaele Wipf Group Page 2 of 26 12/29/2015

3 C(sp3)- activation artwig: rhodium-catalyzed borylation of terminal methyl groups Rh 3 Cp*Rh(! 4 -C 6 Me 6 ) White: iron-catalyzed oxidation of 2 and 3 aliphatic C bonds Me Me Me Me Fe (S,S)-PDP 2 2, Ac Selective, predictable Me Me Me Me (SbF 6 ) 2 N N NCC 3 Fe N NCC 3 N Fe (S,S)-PDP Importance of catalyst structure for site selectivity! Raffaele Wipf Group Page 3 of 26 12/29/2015

4 ydrogen abstraction The rate of hydrogen abstraction from a C bond depends on: - the C bond dissociation enthalpy (BDE) - polar effects in the transition state In 1987, Roberts discovered that certain electrophilic radicals (e.g., t-butoxyl) preferentially abstract hydrogen from electron-rich bonds, while nucleophilic radicals (e.g., amine-boryl) selectively cleave electron-deficient C bonds. For examples and theory of polarity-reversal catalysis of hydrogen-atom abstraction reactions see: Chem. Soc. Rev. 1999, 28, Raffaele Wipf Group Page 4 of 26 12/29/2015

5 xy-anionic substituent effect An alkoxide functionality accelerates sigmatropic processes wherein a bond to the carbon bearing the alkoxy group is broken. R R Cope rearrangement [3,3] R R R = k (s -1 ) = R = k (s -1 ) = R = - K + k (s -1 ) = n alkoxide enhances homolitic hydrogen atom abstractions by highly electrophilic perfluoro radicals. R 1 R 2 CX Na SCF 2 CF 2 CF 2 CF 2 R 1 R 2 C X CF 3 C 2 - Na + k (M -1 s -1 ) = CF 3 C 2 k (M -1 s -1 ) = 80 (CF 3 ) 2 C - Na + k (M -1 s -1 ) = (CF 3 )C k (M -1 s -1 ) = 390 k rel = 960 k rel = 280 Evans et al. J. Am. Chem. Soc. 1979, 101, William R. Dolbier, Jr. et al. rg. Biomol. Chem. 2004, 2, Raffaele Wipf Group Page 5 of 26 12/29/2015

6 Effect of -bond on C - bond -Bonding in alcohols is reflected in the C - bond strength The strength of C - bond is reflected in the one-bond 13 C- 1 coupling constant ( 1 J C ). F 3 C CF 3 FIP N quinuclidine exafluoroisopropanpl (FIP) solutions (1 M) in the tertiary amine solvents or an equimolar FIP/amine solution in CCl 3 Enthalpy of -bond formation measured by Isothermal Titration Calorimetry V. E. Anderson et al. J. Am. Chem. Soc. 2000, 122, ; J. rg. Chem. 2006, 71, Raffaele Wipf Group Page 6 of 26 12/29/2015

7 This work Is it possible to achieve efficient and selective activation of alcohol C bonds by catalytic complexation with a suitable hydrogen-bond acceptor? 7 Raffaele Wipf Group Page 7 of 26 12/29/2015

8 Photocatalyst Three catalyst system AT catalyst -bond acceptor catalyst 8 1 mol% 10 mol% 25 mol% N + N - P Ir[dF(CF 3 )ppy] 2 (dtbbpy)pf 6 quinuclidine TBAP Raffaele Wipf Group Page 8 of 26 12/29/2015

9 Three catalyst system 9 Raffaele Wipf Group Page 9 of 26 12/29/2015

10 C 2 Me C exanol Preliminary results 25 mol% of Bu 4 NX 1 mol% of Ir cat., 10 mol% of quinuclidine C 3 CN, blue LEDs, 27 C, 24 h acid work-up C Me 10 Ir cat. = quinuclidine = N Raffaele Wipf Group Page 10 of 26 12/29/2015

11 11 Alcohol Reaction scope C 2 Me 25 mol% of Bu 4 NP mol% of Ir cat., 10 mol% of quinucidine Me C 3 CN, blue LEDs, 27 C, 24 h acid work-up R R 1 + Me Ir cat. = 61% 93% 79% Me 85% 76% 90% quiniclidine = C N 84% 80% 90% Raffaele Wipf Group Page 11 of 26 12/29/2015

12 Selectivity in C- activation 12 Can strong C- bonds be activated in the presence of weaker C- bonds? Raffaele Wipf Group Page 12 of 26 12/29/2015

13 Selectivity in C- activation Alcohol C 2 Me 25 mol% of Bu 4 NP mol% of Ir cat., 10 mol% of quinuclidine C 3 CN, blue LEDs, 27 C, 24 h acid work-up R R 1 13 Raffaele Wipf Group Page 13 of 26 12/29/2015

14 Selectivity in C- activation Alcohol C 2 Me 25 mol% of Bu 4 NP mol% of Ir cat., 10 mol% of quinuclidine C 3 CN, blue LEDs, 27 C, 24 h acid work-up R R 1 14 Raffaele Wipf Group Page 14 of 26 12/29/2015

15 Selectivity in C- activation vs 15 C eq. 2 eq. methyl acrylate 1 mol% of Ir cat., 10 mol% of quinucidine C 3 CN, blue LEDs, 27 C, 24 h acid work-up C 5 11 C 2 Me 42% 24% with BuNP 4 2 (25 mol%) 75% 1% Raffaele Wipf Group Page 15 of 26 12/29/2015

16 13 C-NMR in CDCl3 NMR experiments Chemical shift of C1 (ppm) 1 J C (z) 16 1-hexanol hexanol / quinicidine 1: hexanol / TBAP 1: Both quinuclidine and TBAP can induce bond weakening of the C1 of 1-hexanol via hydrogen bonding Raffaele Wipf Group Page 16 of 26 12/29/2015

17 17 Et Et D/ Kinetic isotope effect methyl acrylate 1 mol% of Ir cat., 10 mol% of quinucidine 25 mol% of Bu 4 NP 4 2 C 3 CN, blue LEDs, 27 C, 24 h acid work-up Et Et KIE = k / k D = 1 C /D abstraction from the alcohol does not occur during the turnover-limiting transition state (TLTS) Raffaele Wipf Group Page 17 of 26 12/29/2015

18 C 5 11 D Kinetic isotope effect methyl acrylate 1 mol% of Ir cat., 10 mol% of quinucidine 25 mol% of Bu 4 NP 4 2 C 3 CN, blue LEDs, 27 C, 24 h acid work-up P D / P = 1.6 C 5 11 D P D C 5 11 P C 5 11 D D not observed C C 5 11 D D C 5 11 methyl acrylate 1 mol% of Ir cat., 10 mol% of quinucidine 25 mol% of Bu 4 NP 4 2 C 3 CN, blue LEDs, 27 C, 24 h acid work-up C 5 D 11 C 5 11 C 5 11 D P D / P = 1.7 P D P not observed Irreversible C- abstraction prior to the turnover-limiting transition state Dual role of TBAP in both accelerating the C abstraction from alcohols and enhancing the rate of addition of the resulting radical to Michael acceptors Raffaele Wipf Group Page 18 of 26 12/29/2015

19 19 Cyclopropyl radical clock Et methyl acrylate 1 mol% of Ir cat., 10 mol% of quinucidine C 3 CN, blue LEDs, 27 C, 24 h acid work-up catalysis none with 25 mol% of Bu 4 NP 4 2 k rel 1 9 Et C abstraction from the alcohol to generate the radical is ratelimiting (rate constant for cyclopropyl rearrangement on similar sistems = to s 1 at 25 C). Ninefold rate enhancement was observed upon addition of 25 mol% TBAP TBAP facilitate C- abstraction from alcohol via hydrogen bond activation Raffaele Wipf Group Page 19 of 26 12/29/2015

20 Conclusion Selective -activation of alcohol C bonds in the presence of allylic, benzylic, -oxy, and -acyl C groups via a photoredox protocol. 20 Cooperation of three distinct catalysts: - an iridium-based photoredox catalyst - quiniclidine as AT catalyst - TBAP as hydrogen-bonding catalyst Demonstration of the role of TBAP in facilitating the highly selective a hydrogen atom abstraction from alcohols, on the basis of kinetic analyses, NMR structural data, and kinetic isotope effects Raffaele Wipf Group Page 20 of 26 12/29/2015

21 Department of Chemistry Acknowledgment 21 Raffaele Wipf Group Page 21 of 26 12/29/2015

22 Raffaele Wipf Group Page 22 of 26 12/29/2015

23 Raffaele Wipf Group Page 23 of 26 12/29/2015

24 Raffaele Wipf Group Page 24 of 26 12/29/2015

25 Raffaele Wipf Group Page 25 of 26 12/29/2015

26 Raffaele Wipf Group Page 26 of 26 12/29/2015