AsymmetricCounteranion-DirectedCatalysis
M1 Yuki Hirao

Contents
1. Introduction
・ACDC
・BINOL-derived chiral catalyst

2. Applications
・Mukaiyama aldol reaction
・Diels-Alder reaction

2

Contents
1. Introduction
・ACDC
・BINOL-derived chiral catalyst

2. Applications
・Mukaiyama aldol reaction
・Diels-Alder reaction3

Benjamin List

https://www.kofo.mpg.de/en/research/homogeneous-catalysis-4What is ACDC?
ACDC : Asymmetric Counteranion-Directed Catalysis
Asymmetric counteranion-directed catalysis refers to theinduction of enantioselectivity in a reaction proceeding
through a cationic intermediate by means of ion pairingwith a chiral, enantiomerically pure anion provided by thecatalyst.

Phase-Transfer Catalysis

ACDC

P=product
S=substrate
X=anion5

M. Mahlau, B. List, Angew. Chem. Int. Ed. 2013, 52, 518.

Example of ACDC

S.Mayer, B. List, Angew. Chem. Int. Ed. 2006, 45, 4193.

G. L. Hamilton, E. J. Kang, M. Mba, F. D. Toste, Science. 2007, 317, 496.
6

Silylium Lewis Acid Catalysis

7

“Silylium” ACDC

P=product
Nu=nucleophile
E=electrophile

DOI: 10.1002/anie.201900932

8

Contents
1. Introduction・ACDC
・BINOL-derived chiral catalyst

2. Applications
・Mukaiyama aldol reaction
・Diels-Alder reaction

9BINOL-Derived Chiral Catalyst
first report of BINOL-derived phosphoric acidT. Akiyama, J. Itoh, K. Yokota, K, Fuchibe, Angew. Chem. Int. Ed. 2004, 43, 1566.

10

D. Uraguchi, M, Terada, J. Am. Chem. Soc. 2004, 126, 5356.

BINOL-Derived Chiral Catalyst

11

Imidodiphosphorimidate (IDPi)

reactivity
selectivity

Imidodiphosphorimidate (IDPi)
DOI: 10.1002/anie.201900932

12

IDPi Catalyst

13

Applications

14

Contents
1. Introduction
・ACDC
・BINOL-derived chiral catalyst

2. Applications
・Mukaiyama aldol reaction
・Diels-Alder reaction15

Mukaiyama Aldol Reaction

16

Single Aldolization

M. B. Boxer, H. Yamamoto, J. Am. Chem, Soc. 2006, 128, 48.
L. Schreyer, P. S. J. Kaib, V. N. Wakchaure, C. Obradors, R. Properzi, S. Lee, B. List, Science. 2018, 362, 216.

17

Previously Reported Catalyst

P. Garcia, F. Lay, P. Garcia, C. Rabalakos, B. List, Angew. Chem. Int. Ed. 2009, 48, 4363.

18

Previously Reported Catalyst○ aromatic aldehyde○ catalyst loading△ ketene silyl acetal× aliphatic aldehyde

19

P. Garcia, F. Lay, P. Garcia, C. Rabalakos, B. List, Angew. Chem. Int. Ed. 2009, 48, 4363.

Catalyst Optimization (Aromatic Aldehyde)

・meta and para-substituted phenylgroup(R1) of the IDPi revealed aprofound enhancement ofenantioselectivity.

20

L. Schreyer, P. S. J. Kaib, V. N. Wakchaure, C. Obradors, R. Properzi, S. Lee, B. List, Science. 2018, 362, 216.

Catalyst Optimization (Aliphatic Aldehyde)

L. Schreyer, P. S. J. Kaib, V. N. Wakchaure, C. Obradors, R. Properzi, S. Lee, B. List, Science. 2018, 362, 216.

21

Substrate Scope

Reactions were performed with 0.5 mmol of aldehydes. *Using IDPi 4c. †Using IDPi 4d and 1.4 equivalents of enolsilane 2b. ‡Using IDPi 4d and1.2 equivalents of enolsilane 2b.§Using IDPi 4e. ||Reactions were performed in CHCl3/n-hexane (5:4) at −78℃ using IDPi 4e.

22

L. Schreyer, P. S. J. Kaib, V. N. Wakchaure, C. Obradors, R. Properzi, S. Lee, B. List, Science. 2018, 362, 216.

Catalyst and Silyl GroupL. Schreyer, P. S. J. Kaib, V. N. Wakchaure, C. Obradors, R. Properzi, S. Lee, B. List, Science. 2018, 362, 216.

23

Proposed Catalytic Cycle

L. Schreyer, P. S. J. Kaib, V. N. Wakchaure, C. Obradors, R. Properzi, S. Lee, B. List, Science. 2018, 362, 216.

24

Enantioselectivity
IDPi

p

IDPi

IDPi
product

L. D. Amico, F. Zanardi, Angew. Chem. Int. Ed. 2019, 58, 3264
L. Schreyer, P. S. J. Kaib, V. N. Wakchaure, C. Obradors, R. Properzi, S. Lee, B. List, Science. 2018, 362, 216.

25

Single Reaction

DOI: 10.1002/anie.201900932

26

Mukaiyama Aldol Reaction

L. D. Amico, F. Zanardi, Angew. Chem. Int. Ed. 2019, 58, 3264.

27

Contents
1. Introduction
・ACDC
・BINOL-derived chiral catalyst

2. Applications
・Mukaiyama aldol reaction
・Diels-Alder reaction28Diels-Alder Reaction (ACDC)

T. Gatzenmeier, M. Gemmeren, Y. Xie, D. Höfler, M. Leutzsch, B. List, Science, 2016, 351, 949.
T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

29

Initial Try

cat 3DSI
cat 1

BALT
cat 2

cat 4

cat 5IDPi
cat 6

T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

cat 7

30

Reaction Development

31

T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

Substrate Scopewith catalyst 4a; bwith catalyst 4b;cwith catalyst 4c; dwith catalyst 4d (3 mol %).

aT. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

32

Substrate Scopeawith catalyst 4a; bwith catalyst 4b;cwith catalyst 4c; dwith catalyst 4d (3 mol%).

T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

33

Catalyst Recycling

T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

34

Scale-up Experiments

T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

35

Proposed Catalytic Cycle

T. Gatzenmeier, M. Gemmeren, Y. Xie, D. Höfler, M. Leutzsch, B. List, Science. 2016, 351, 949.
T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

36

Computational Studies

catalyst activation

T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

37

Most Favorable Transition StateNOFSPT. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

38

Interaction with the Chiral Ion Pair

T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

39

Summary
・ Asymmetric Counteranion-Directed Catalysis(ACDC) concept is well developed.

・BINOL-derived new IDPi catalyst promotes
various kinds of reactions.
➢ extremely low catalyst loading→high turnover, hydrolytically stable➢ highly selective catalysis→highly confined enantiopure catalysis
40Appendix

Synthesis of Catalysts

T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

42

Mechanistic Study (MAR)43

P. Garcia, F. Lay, P. Garcia, C. Rabalakos, B. List, Angew. Chem. Int. Ed. 2009, 48, 4363.

Scaled-up Aldol Reaction

44

L. Schreyer, P. S. J. Kaib, V. N. Wakchaure, C. Obradors, R. Properzi, S. Lee, B. List, Science. 2018, 362, 216.

Graphical Method of Buréssingle IDPi molecule is responsible for the activationof aldehyde

45

L. Schreyer, P. S. J. Kaib, V. N. Wakchaure, C. Obradors, R. Properzi, S. Lee, B. List, Science. 2018, 362, 216.

Self Repair Cycle

46

Computational Studies

catalyst activation

T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671.

47pKa of Catalyst

48

H. Y. Bae, D. Höfler, P. S. J. Kaib, P. Kasaplar, C. K. De, A. Döhring, S. Lee, K. Kaupmees, I. Leito, B. List, Nat. Chem. 2018, 10, 888

Electrophilic Reactivities of Michael Acceptors

49

D. S. Allgauer, H. Jangra, H. Asahara, Z. Li, Q. Chen, H. Zipse, A. R. Ofial, H. Mayr, J. Am. Chem. Soc. 2017, 139, 13318.

Catalyst Methylation

T. Gatzenmeier, M. Turberg, D. Yepes, Y. Xie, F. Neese, G. Bistoni, B. List, J. Am. Chem. Soc. 2018, 140, 12671

50