From Bifunctional to Trifunctional (tricomponent Nucleophile-transition Metal-lewis Acid) Catalysis: the Catalytic, Enantioselective α-fluorination of Acid Chlorides

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2011 Apr 26

PMID 21513338

Citations 11

Authors

Jeremy Erb

Daniel H Paull

Travis Dudding

Lee Belding

Thomas Lectka

Affiliations

Soon will be listed here.

Abstract

We report in full detail our studies on the catalytic, asymmetric α-fluorination of acid chlorides, a practical method that produces an array of α-fluorocarboxylic acid derivatives in which improved yield and virtually complete enantioselectivity are controlled through electrophilic fluorination of a ketene enolate intermediate. We discovered, for the first time, that a third catalyst, a Lewis acidic lithium salt, could be introduced into a dually activated system to amplify yields of aliphatic products, primarily through activation of the fluorinating agent. Through our mechanistic studies (based on kinetic data, isotopic labeling, spectroscopic measurements, and theoretical calculations) we were able to utilize our understanding of this "trifunctional" reaction to optimize the conditions and obtain new products in good yield and excellent enantioselectivity.

Citing Articles

Enantioselective α-heterofunctionalization reactions of catalytically generated C1-Lewis base enolates.

Piringer M, Stockhammer L, Vogl L, Weinzierl D, Zebrowski P, Waser M Tetrahedron Chem. 2024; 9:100063.

PMID: 38846753 PMC: 7616070. DOI: 10.1016/j.tchem.2024.100063.

Photochemical Wolff Rearrangement Initiated Generation and Subsequent α-Chlorination of C1 Ammonium Enolates.

Weinzierl D, Piringer M, Zebrowski P, Stockhammer L, Waser M Org Lett. 2023; 25(17):3126-3130.

PMID: 37098273 PMC: 10167681. DOI: 10.1021/acs.orglett.3c00986.

Enantioselective α-Chlorination Reactions of in Situ Generated C1 Ammonium Enolates under Base-Free Conditions.

Stockhammer L, Weinzierl D, Bogl T, Waser M Org Lett. 2021; 23(15):6143-6147.

PMID: 34319102 PMC: 8353620. DOI: 10.1021/acs.orglett.1c02256.

Traversing Steric Limitations by Cooperative Lewis Base/Palladium Catalysis: An Enantioselective Synthesis of α-Branched Esters Using 2-Substituted Allyl Electrophiles.

Schwarz K, Pearson C, Cintron-Rosado G, Liu P, Snaddon T Angew Chem Int Ed Engl. 2018; 57(26):7800-7803.

PMID: 29701289 PMC: 6038818. DOI: 10.1002/anie.201803277.

Ketones as directing groups in photocatalytic sp C-H fluorination.

Bume D, Pitts C, Ghorbani F, Harry S, Capilato J, Siegler M Chem Sci. 2017; 8(10):6918-6923.

PMID: 29147517 PMC: 5637129. DOI: 10.1039/c7sc02703f.

References

Blackmond D . Kinetic resolution using enantioimpure catalysts: mechanistic considerations of complex rate laws. J Am Chem Soc. 2001; 123(4):545-53. DOI: 10.1021/ja002562o. View

Ishimaru T, Shibata N, Horikawa T, Yasuda N, Nakamura S, Toru T . Cinchona alkaloid catalyzed enantioselective fluorination of allyl silanes, silyl enol ethers, and oxindoles. Angew Chem Int Ed Engl. 2008; 47(22):4157-61. DOI: 10.1002/anie.200800717. View

Taggi A, Hafez A, Wack H, Young B, Ferraris D, Lectka T . The development of the first catalyzed reaction of ketenes and imines: catalytic, asymmetric synthesis of beta-lactams. J Am Chem Soc. 2002; 124(23):6626-35. DOI: 10.1021/ja0258226. View

Hunt K, Grieco P . Oxabicyclo[3.2.1]octenes in organic synthesis--direct ring opening of oxabicyclo[3.2.1] systems employing silyl ketene acetals in concentrated solutions of lithium perchlorate-diethyl ether: application to the synthesis of the C(19)-C(27) fragment.... Org Lett. 2001; 3(3):481-4. DOI: 10.1021/ol0003836. View

Sasamoto N, Dubs C, Hamashima Y, Sodeoka M . Pd(II)-catalyzed asymmetric addition of malonates to dihydroisoquinolines. J Am Chem Soc. 2006; 128(43):14010-1. DOI: 10.1021/ja065646r. View

Zhu C, Shen X, Nelson S . Cinchona alkaloid-lewis acid catalyst systems for enantioselective ketene-aldehyde cycloadditions. J Am Chem Soc. 2004; 126(17):5352-3. DOI: 10.1021/ja0492900. View

Paull D, Weatherwax A, Lectka T . Catalytic, asymmetric reactions of ketenes and ketene enolates. Tetrahedron. 2011; 65(34):3771-6803. PMC: 3074489. DOI: 10.1016/j.tet.2009.05.079. View

Franzen J, Marigo M, Fielenbach D, Wabnitz T, Kjaersgaard A, Anker Jorgensen K . A general organocatalyst for direct alpha-functionalization of aldehydes: stereoselective C-C, C-N, C-F, C-Br, and C-S bond-forming reactions. Scope and mechanistic insights. J Am Chem Soc. 2005; 127(51):18296-304. DOI: 10.1021/ja056120u. View

Li X, Peng F, Li X, Wu W, Sun Z, Li Y . Enantioselective and regioselective organocatalytic conjugate addition of malonates to nitroenynes. Chem Asian J. 2010; 6(1):220-5. DOI: 10.1002/asia.201000561. View

10.

Hamashima Y, Yagi K, Takano H, Tamas L, Sodeoka M . An efficient enantioselective fluorination of various beta-ketoesters catalyzed by chiral palladium complexes. J Am Chem Soc. 2002; 124(49):14530-1. DOI: 10.1021/ja028464f. View

11.

Thomas C . Fluorinated natural products with clinical significance. Curr Top Med Chem. 2006; 6(14):1529-43. DOI: 10.2174/156802606777951109. View

12.

Mueller J, Sigman M . Mechanistic investigations of the palladium-catalyzed aerobic oxidative kinetic resolution of secondary alcohols using (-)-sparteine. J Am Chem Soc. 2003; 125(23):7005-13. DOI: 10.1021/ja034262n. View

13.

Dubs C, Hamashima Y, Sasamoto N, Seidel T, Suzuki S, Hashizume D . Mechanistic studies on the catalytic asymmetric Mannich-type reaction with dihydroisoquinolines and development of oxidative Mannich-type reactions starting from tetrahydroisoquinolines. J Org Chem. 2008; 73(15):5859-71. DOI: 10.1021/jo800800y. View

14.

Buono F, Blackmond D . Kinetic evidence for a tetrameric transition state in the asymmetric autocatalytic alkylation of pyrimidyl aldehydes. J Am Chem Soc. 2004; 125(30):8978-9. DOI: 10.1021/ja034705n. View

15.

Xu X, Wang K, Nelson S . Catalytic asymmetric [4 + 2] cycloadditions of ketenes and N-thioacyl imines: alternatives for direct mannich reactions of enolizable imines. J Am Chem Soc. 2007; 129(38):11690-1. DOI: 10.1021/ja074845n. View

16.

Poe S, Kobaslija M, McQuade D . Microcapsule enabled multicatalyst system. J Am Chem Soc. 2006; 128(49):15586-7. DOI: 10.1021/ja066476l. View

17.

Beeson T, MacMillan D . Enantioselective organocatalytic alpha-fluorination of aldehydes. J Am Chem Soc. 2005; 127(24):8826-8. DOI: 10.1021/ja051805f. View

18.

Nielsen L, Stevenson C, Blackmond D, Jacobsen E . Mechanistic investigation leads to a synthetic improvement in the hydrolytic kinetic resolution of terminal epoxides. J Am Chem Soc. 2004; 126(5):1360-2. DOI: 10.1021/ja038590z. View

19.

Brunet V, OHagan D . Catalytic asymmetric fluorination comes of age. Angew Chem Int Ed Engl. 2007; 47(7):1179-82. DOI: 10.1002/anie.200704700. View

20.

Parsons A, Smith A, Neel A, Johnson J . Dynamic kinetic asymmetric synthesis of substituted pyrrolidines from racemic cyclopropanes and aldimines: reaction development and mechanistic insights. J Am Chem Soc. 2010; 132(28):9688-92. DOI: 10.1021/ja1032277. View