Pd-H/Lewis base cooperative catalysis confers asymmetric allylic alkylation of esters atom-economy and stereodivergence
Abstract
The construction of Csp3-Csp3 with high stereoselectivity, even in a stereodivergent way, has been a long-standing theme in organic synthesis. As an atom- and step-economic transformation, transition metal hydride-mediated allylic alkylation of enolizable carbonyl compounds with readily available allenes, alkynes or 1,3-dienes as the unconventional allylating reagents has recently emerged as a promising protocol for the stereoselective construction of Csp3-Csp3 bonds with high efficiency. Due to their less enolizability and weak nucleophilicity, simple esters remain challenging substrates for these coupling reactions. On the other hand, the strategy of metal/organo combined catalysis has recently emerged as one of the wide-ranging disciplines and powerful tools in asymmetric synthesis. Considering the recent achievements of chiral Lewis base catalysis in catalytic asymmetric α-functionalization of esters through a “rebound” mechanism, the cooperative combination of chiral Lewis bases and metal hydride catalysis may offer great opportunities to the aforementioned chemistry. Recently, the groups of Snaddon and Zi have made remarkable progresses in this area through palladium and chiral Lewis base cooperative catalysis.
Keywords
The construction of Csp3-Csp3 with high stereoselectivity, even in a stereodivergent way, has been a long-standing theme in organic synthesis. As an atom- and step-economic transformation, transition metal hydride-mediated allylic alkylation of enolizable carbonyl compounds with readily available allenes, alkynes or 1,3-dienes as the unconventional allylating reagents has recently emerged as a promising protocol for the stereoselective construction of Csp3-Csp3 bonds with high efficiency[1-3]. Due to their less enolizability and weak nucleophilicity, simple esters remain challenging substrates for these coupling reactions. Additionally, the strategy of metal/organo combined catalysis has recently emerged as one of the wide-ranging disciplines and powerful tools in asymmetric synthesis[4-7]. Considering the recent achievements of chiral Lewis base catalysis in catalytic asymmetric α-functionalization of esters through a “rebound” mechanism[8-13], the cooperative combination of chiral Lewis bases and metal hydride catalysis may offer great opportunities to the aforementioned chemistry. Recently, the groups of Snaddon and Zi have made remarkable progress in this area through palladium and chiral Lewis base cooperative catalysis[14-16].
In 2022, Snaddon described an enantioselective α-alkylation of esters 1 with oxyallenes 2 enabled by Pd/chiral isothiourea cooperative catalysis[14] [Scheme 1]. In this procedure, the isothiourea catalyst is believed to first react with the pentafluorophenyl (Pfp) ester 2 to liberate PfpO- anion and generate an acylammonium ion (Int-1), which is intercepted by the Pd catalyst to afford the C1-ammonium enolate
Scheme 1. Pd/Lewis base cooperative catalysis for direct alkylation of acyclic esters with alkoxyallenes.
Simultaneously, Zi, Tang and co-workers independently developed a stereodivergent coupling of alkoxylallenes 2 with pentafluorophenyl esters 1 through the combined catalysis of a chiral Lewis base and a chiral palladium catalyst[15] [Scheme 2]. Through the combination of (S)-L1-Pd and (S)-LB-1, anti-4 could be obtained with up to > 99% ee and > 20:1 dr. Instead, (R)-L2-Pd and (S)-LB-1 together rendered the reaction highly
Scheme 2. Stereodivergent coupling of alkoxylallenes with pentafluorophenyl esters employing Pd/ chiral Lewis base cooperative catalysis.
Very recently, Zi group contributed another stereodivergent protocol by describing the diastereodivergent alkylation of 1,3-dienes 5 with pentafluorophenyl esters employing Pd/chiral Lewis base cooperative catalysis, providing structurally important 6 in high yields with excellent selectivities[16] [Scheme 3]. The absolute and relative stereochemistry of the product could be selected via a judicious choice of palladium and isothiourea combinations. Under the optimized conditions, a variety of 1,3-dienes with an aryl or heteroaryl substituent, as well as a broad scope of pentafluorophenyl acetates 1, were successfully tolerated in this transformation. As a synthetic utility of this protocol, the coupling products were converted through the transformation of the pentafluorophenyl group to alcohols, esters, and amides with two adjacent chiral centers with high levels of diastereo- and enantio- selectivity. Moreover, based on the current protocol, a concise synthesis of the analgesic tapentadol 9 could be realized with an overall yield of 47% in eight steps.
Scheme 3. Stereodivergent alkylation of esters with 1,3-dienes enabled by Pd/isothiourea cooperative catalysis.
In summary, the groups of Snaddon and Zi have established several impressive protocols describing highly stereoselective α-alkylation of esters employing simple allenes and dienes via palladium hydride/chiral Lewis base catalysis. These are the few examples that successfully combine the chemistry of metal hydride-mediated asymmetric allylations and chiral Lewis base catalysis, allowing for the access of structurally diverse products with high efficiency and excellent stereocontrol. It is anticipated that the concept of metal/Lewis base cooperative catalysis will inspire more exciting discoveries in the future.
DECLARATIONS
Authors’ contributionsWrote the draft manuscript: Sayed M
Revised and rewrote some parts of the manuscript: Han Z, Gong L
Availability of data and materialsNot applicable.
Financial support and sponsorshipNot applicable.
Conflicts of interestAll authors declared that there is no conflict of interest.
Ethical approval and consent to participateNot applicable.
Consent for publicationNot applicable.
Copyright© The Author(s) 2023.
REFERENCES
1. Kadota I, Shibuya A, Gyoung YS, Yamamoto Y. Palladium/acetic acid catalyzed allylation of some pronucleophiles with simple alkynes. J Am Chem Soc 1998;120:10262-3.
2. Koschker P, Breit B. Branching out: rhodium-catalyzed allylation with alkynes and allenes. Acc Chem Res 2016;49:1524-36.
3. Li G, Huo X, Jiang X, Zhang W. Asymmetric synthesis of allylic compounds via hydrofunctionalisation and difunctionalisation of dienes, allenes, and alkynes. Chem Soc Rev 2020;49:2060-118.
4. Chen DF, Gong LZ. Organo/transition-metal combined catalysis rejuvenates both in asymmetric synthesis. J Am Chem Soc 2022;144:2415-37.
5. Chen DF, Han ZY, Zhou XL, Gong LZ. Asymmetric organocatalysis combined with metal catalysis: concept, proof of concept, and beyond. Acc Chem Res 2014;47:2365-77.
6. Shao Z, Zhang H. Combining transition metal catalysis and organocatalysis: a broad new concept for catalysis. Chem Soc Rev 2009;38:2745-55.
7. Nielsen CD, Linfoot JD, Williams AF, Spivey AC. Recent progress in asymmetric synergistic catalysis - the judicious combination of selected chiral aminocatalysts with achiral metal catalysts. Org Biomol Chem 2022;20:2764-78.
8. Schwarz KJ, Amos JL, Klein JC, Do DT, Snaddon TN. Uniting C1-ammonium enolates and transition metal electrophiles via cooperative catalysis: the direct asymmetric α-allylation of aryl acetic acid esters. J Am Chem Soc 2016;138:5214-7.
9. Schwarz KJ, Yang C, Fyfe JWB, Snaddon TN. Enantioselective α-benzylation of acyclic esters using π-extended electrophiles. Angew Chem Int Ed Engl 2018;57:12102-5.
10. Song J, Zhang ZJ, Chen SS, Fan T, Gong LZ. Lewis base/copper cooperatively catalyzed asymmetric α-amination of esters with diaziridinone. J Am Chem Soc 2018;140:3177-80.
11. Pearson CM, Fyfe JWB, Snaddon TN. A Regio- and stereodivergent synthesis of homoallylic amines by a one-pot cooperative-catalysis-based allylic alkylation/hofmann rearrangement strategy. Angew Chem Int Ed Engl 2019;58:10521-7.
12. Hutchings-Goetz LS, Yang C, Fyfe JWB, Snaddon TN. Enantioselective syntheses of strychnos and chelidonium alkaloids through regio- and stereocontrolled cooperative catalysis. Angew Chem Int Ed Engl 2020;59:17556-64.
13. Zhao F, Shu C, Young CM, Carpenter-Warren C, Slawin AMZ, Smith AD. Enantioselective synthesis of α-aryl-β2 -amino-esters by cooperative isothiourea and brønsted acid catalysis. Angew Chem Int Ed Engl 2021;60:11892-900.
14. Lin HC, Knox GJ, Pearson CM, Yang C, Carta V, Snaddon TN. A Pd-H/isothiourea cooperative catalysis approach to anti-aldol motifs: enantioselective α-alkylation of esters with oxyallenes. Angew Chem Int Ed Engl 2022;61:e202201753.
15. Zhu M, Wang P, Zhang Q, Tang W, Zi W. Diastereodivergent aldol-type coupling of alkoxyallenes with pentafluorophenyl esters enabled by synergistic palladium/chiral Lewis base catalysis. Angew Chem Int Ed Engl 2022;61:e202207621.
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How to Cite
Sayed, M.; Han, Z. Y.; Gong, L. Z. Pd-H/Lewis base cooperative catalysis confers asymmetric allylic alkylation of esters atom-economy and stereodivergence. Chem. Synth. 2023, 3, 20. http://dx.doi.org/10.20517/cs.2023.05
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