Broadly Applicable Ytterbium-Catalyzed Esterification, Hydrolysis, and

Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

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Broadly Applicable Ytterbium-Catalyzed Esterification, Hydrolysis, and Amidation of Imides Ceĺ ine Guissart, Andre Barros, Luis Rosa Barata, and Gwilherm Evano* Laboratoire de Chimie Organique, Service de Chimie et PhysicoChimie Organiques, Université libre de Bruxelles (ULB), Avenue F. D. Roosevelt 50, CP160/06, 1050 Brussels, Belgium

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ABSTRACT: An efficient, broadly applicable, operationally simple, and divergent process for the transformation of imides into a range of carboxylic acid derivatives under mild conditions is reported. By simply using catalytic amounts of ytterbium(III) triflate as a Lewis acid promoter in the presence of alcohols, water, amines, or N,O-dimethylhydroxylamine, a broad range of imides is smoothly and readily converted to the corresponding esters, carboxylic acids, amides, and Weinreb amides in good yields. This method notably enables an easy cleavage of oxazolidinone-based auxiliaries.

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high catalyst loadings or large amounts of the nucleophile− which is often used as the solvent−and lack generality. More recently, remarkably efficient nickel-catalyzed amidation and esterification of aliphatic Boc-protected amides were reported by the Garg group.17 The esterification of N-Boc amides was also shown to efficiently proceed under cobalt catalysis by the group of Gosmini later on,18 and earlier this year, the esterification of N-acyloxazolidinones was reported using nickel catalysis.19 Despite its apparent simplicity, the cleavage of imides can still be challenging, and a unified procedure for their divergent transformation to a range of carboxylic acid derivatives still needs to be developed. Bearing in mind all the limitations mentioned above and due to the problems we met during one of our research projects for the cleavage of oxazolidinonederived imides, we decided to try to develop a divergent, efficient, and broadly applicable process that would rely on the use of catalytic amounts of a Lewis acid and that would enable an easy conversion of imides to a variety of carboxylic acid derivatives. With this goal in mind, we first focused our attention on the esterification of imides starting from 1a and allyl alcohol 2a as model substrates. The efficiency of a catalytic amount of metal triflates to promote the esterification was therefore evaluated using acetonitrile as the solvent at 90 °C for 48 h; the selected results are shown in Figure 1. Among all catalysts evaluated, ytterbium(III) triflate was found to be the most efficient to promote the formation of ester 3a. Performing the reaction with 3.0 equiv of the starting alcohol instead of 1.5 brought further improvement as the esterification product 3a could be obtained in 93% yield. The solvent, temperature, and reaction time were also briefly studied, and our initial conditions based

mid all chiral auxiliaries, oxazolidinones are definitely among the most widely used in organic synthesis, with Evans’ diastereoselective alkylation and aldolization of chiral imides certainly being the most iconic examples.1 Achiral oxazolidinone-derived imides have also been shown to be ideal substrates in a broad range of catalytic enantioselective transformations, mostly due to their facile chelation with an important number of metals.2 Many other reactions also yield oxazolidinone-derived imides, with the most striking recent examples certainly being based on the chemistry of ynamides that offers excellent entries to a range of oxazolidinone-derived imides with a variety of substitution patterns and/or stereocenters.3 The success and attractiveness of all these transformations however rely on the cleavage of the oxazolidinone that is usually not required in the final products. Classical methods include the reduction of oxazolidinone-derived imides to the corresponding alcohols with boron or aluminum hydrides,4 their transformation to the corresponding esters by treatment with an alkoxide,5 carboxylic acids upon reaction with lithium hydroperoxide,6 or Weinreb amides upon treatment with AlMe3 and N,O-dimethylhydroxylamine.4a,7 While all these methods have clearly proven their efficiency over the years, they require rather harsh conditions and/or reagents that reduce their functional group tolerance, and they often lack efficiency and generality. In addition to these processes, and in an effort to overcome these limitations, procedures for the Lewis acid-promoted aminolysis of imides with primary amines using Cp2TiCl2 or Cp2ZrCl28 were reported and for their transformation to hydroxamic acids using Sm(OTf)3.9 The esterification of imides was in addition shown to be rather efficiently catalyzed by several Lewis acids including Ti(OR)4,10 [tBu2SnCl(OH)]2, MgBr2 or Sc(OTf)3,11 Sm(OTf)3,7,12 SmI2,13 and LaI3.14 Isolated examples were also reported with Yb(OTf)315 and Er(OTf)3.16 Despite the efficiency of these transformations, they still require either © XXXX American Chemical Society

Received: June 18, 2018

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DOI: 10.1021/acs.orglett.8b01896 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

irradiation, and the catalyst loading reduced to 2 mol %, although with less efficiency. Electron-rich as well as electron poor aromatic-derived imides could be transformed into esters 3m−3t without any noticeable influence of the electronic properties of the starting material. Importantly, various functional groups were found to be compatible with the reactions conditions since an alkene (3e, 3i−l), an amine (3o), a nitro (3q), a methyl ester (3r),20 a nitrile (3s), or an allyl ether (3t) were well-tolerated. Furthermore, the transformation could be successfully applied to obtain the more complex cholic acid-derived ester 3u and to the esterification of an oxazolidinone-derived cycloadduct to yield 3v. After examining the reactivity of different imides, we next briefly evaluated the influence of the starting alcohol (Scheme 1). All primary alcohols performed well under the reaction conditions to give esters 3a, 3w−y in high yields, and a secondary alcohol could be used for the preparation of 3z but with reduced efficiency. Tertiary alcohols were found to be incompatible with the reaction conditions. Finally, we could demonstrate that this esterification can be extended to other imides. Indeed, pyrrolidinone and chiral oxazolidinonesderived imides 1b−d were shown to be excellent substrates, affording the corresponding ester 3b in good yields, provided that the reaction was performed at a higher temperature and/ or with a prolonged reaction time with sterically hindered substrates. Interestingly, chiral oxazolidinones could be efficiently recovered. With the success met for the esterification of imides, we next focused on their hydrolysis. A brief optimization (not shown) revealed that it was best performed in a 4/1 mixture of acetonitrile and water using the same amount of Yb(OTf)3, providing the corresponding acids 4 in good to excellent yields (Scheme 2). As in the previous case, aliphatic and aromatic imides were smoothly converted into acids 4a−4i, and an allyl group is still tolerated as demonstrated by the 88% yield

Figure 1. Optimization of the esterification of imides.

on the use of acetonitrile at 90 °C for 48 h gave the best results. Having these optimized conditions in hand, we then studied the scope and limitations of this esterification by first evaluating the reactivity of a series of imides possessing various substitution patterns with ethanol or dodecanol (Scheme 1). The reaction was found to perform well with a Scheme 1. Ytterbium-Catalyzed Esterification of Imides

Scheme 2. Ytterbium-Catalyzed Hydrolysis of Imides

wide range of imides providing the corresponding esters 3b−v in good to excellent yields. Vinylic (including acrylic, crotonic, senecioic, and methacrylic derivatives) and aliphatic imides were efficiently converted to the corresponding esters 3b−l provided that the temperature was raised to 110 °C when the steric hindrance was more important (3g and 3h). In the last case, the reaction time can be shortened to 1 h with microwave B

DOI: 10.1021/acs.orglett.8b01896 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters

imides could however not be cleanly converted to the corresponding amides due to competing Michael addition. We then moved to the study of the amidation with secondary amines and found that only cyclic secondary amines were valid partners. We therefore studied the scope and limitations of the process with pyrrolidine 5b, and, as evidenced by the results displayed in Scheme 4, the same

obtained for 4j. As for the esterification, 4k and 4l were obtained in excellent yields and pyrrolidinone- and chiral oxazolidinone-derived imides 1b−1e could be readily hydrolyzed using these simple reaction conditions that compare well with the use of lithium hydroperoxide typically used for such hydrolyses. We next evaluated the use of amines as nucleophiles. Using n-butylamine 5a revealed that the corresponding primary amides could be obtained under the exact same conditions as the ones reported for the esterification. They were therefore applied to a range of imides to yield the corresponding primary amides 6a−r in good yields (Scheme 3). Despite a lower yield

Scheme 4. Ytterbium-Catalyzed Amidation of Imides with Pyrrolidine

Scheme 3. Ytterbium-Catalyzed Amidation of Imides with nButylamine

features as the ones observed for the preparation of primary amides apply for this transformation in terms of scope, influence of the electronic properties of the starting imides, and functional group tolerance. To further study this amidation, we then briefly investigated the influence of the nature of the amine (Scheme 5). Primary amines led to the corresponding amides 6ai−an in good to excellent yields, and even the less nucleophilic aniline could be used provided that the reaction temperature was raised to 110 °C, providing 6am in 73% yield. Interestingly, when using ethanolamine, the reaction was found to be totally chemoin the presence of an electron-donating group for 6g and 6h, the reaction performs well in most cases, even in the presence of bulkier substituents (6d and 6e). In the last case, the reaction time can be shortened to 1 h by using microwave irradiation and the catalyst loading reduced to 2 mol %, with reduced efficiency however in the last case. In addition to the features observed for the esterification, TBS and PMB protected alcohols are stable under the reaction conditions as proven by the high yields obtained for 6n and 6p. Remarkably, an ester was found to be untouched (6l),20 and pyrrolidinone- or chiral oxazolidinones-derived imides are also suitable partners for the reaction as imides 1b−1e were readily converted to the corresponding primary amide 6a. Conjugated

Scheme 5. Ytterbium-Catalyzed Amidation of Imides with Various Amines

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DOI: 10.1021/acs.orglett.8b01896 Org. Lett. XXXX, XXX, XXX−XXX

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Lewis acid smoothly promotes the cleavage of a wide range of imides into the corresponding esters, carboxylic acids, amides, and Weinreb amides. Compared to previously reported procedures, our process is certainly one of the broadest and relies on user-friendly and mild reactions conditions which should facilitate the post-transformation of oxazolidinonederived imides, versatile intermediates in chemical synthesis.

selective as amide 6an was formed exclusively. Other cyclic amines such as morpholine can also be used as shown by the amidation of 1a to 6ao. To further demonstrate the potential of our transformation, we then applied our conditions to the amidation of Evans’ diastereoselective alkylation and aldolization products 1f and 1g. As evidenced by the results presented in Scheme 6, imide

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Scheme 6. Application of the Ytterbium-Catalyzed Amidation of Imides to Evans’ Alkylation and Aldolization Products

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b01896.

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1f was smoothly converted into the corresponding primary amide 6ap with an excellent yield, and the amidation of 1g also proceeded smoothly. Importantly, the reactions proceeded with complete retention of the stereochemical information.21 In a final effort to further highlight the synthetic potential of this ytterbium-catalyzed cleavage of imides, we next envisioned its extension to the preparation of Weinreb amides, a transformation that is typically performed with N,O-dimethylhydroxylamine hydrochloride and trimethylaluminum. For the sake of practicality, we decided to directly use commercially available N,O-dimethylhydroxylamine hydrochloride instead of the corresponding volatile free base that would then be generated in situ with additional diisopropylethylamine. Under these conditions, various imides could be readily and successfully converted to the corresponding Weinreb amides as shown by the results presented in Scheme 7. It is important

Experimental procedures, characterization, and copies of NMR spectra (PDF) Primary NMR data files (ZIP)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Gwilherm Evano: 0000-0002-2939-4766 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Our work was supported by the Université libre de Bruxelles (ULB) and the FNRS (CDR J.0058.17 Keteniminium). REFERENCES

(1) (a) Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem. Soc. 1981, 103, 2127. (b) Evans, D. A. Aldrichimica Acta 1982, 15, 23. (2) For examples, see: (a) Evans, D. A.; Miller, S. J.; Leckta, T.; von Matt, P. J. Am. Chem. Soc. 1999, 121, 7559. (b) Evans, D. A.; Johnson, D. S. Org. Lett. 1999, 1, 595. (c) Evans, D. A.; Willis, M. C.; Johnston, J. N. Org. Lett. 1999, 1, 865. (3) For representative examples, see: (a) Mulder, J. A.; Hsung, R. P.; Frederick, M. O.; Tracey, M. R.; Zificsak, C. A. Org. Lett. 2002, 4, 1383. (b) Minko, Y.; Pasco, M.; Lercher, L.; Botoshansky, M.; Marek, I. Nature 2012, 490, 522. (c) Dos Santos, M.; Davies, P. W. Chem. Commun. 2014, 50, 6001. (d) Peng, B.; Huang, X.; Xie, L.-G.; Maulide, N. Angew. Chem., Int. Ed. 2014, 53, 8718. (4) For representative examples, see: (a) Evans, D. A.; Bender, S. L. Tetrahedron Lett. 1986, 27, 799. (b) Evans, D. A.; Sjogren, E. B.; Bartroli, J.; Dow, R. L. Tetrahedron Lett. 1986, 27, 4957. (c) Prashad, M.; Har, D.; Kim, H.-Y.; Repic, O. Tetrahedron Lett. 1998, 39, 7067. (d) Prashad, M.; Shieh, W.-Ch; Liu, Y. Tetrahedron 2016, 72, 17. (5) For representative examples, see: (a) Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc. 1982, 104, 1737. (b) Evans, D. A.; Morrissey, M. M.; Dorow, R. L. J. Am. Chem. Soc. 1985, 107, 4346. (6) (a) Evans, D. A.; Britton, T. C.; Ellman, J. A. Tetrahedron Lett. 1987, 28, 6141. Lithium hydroxide can also be used, although with reduced efficiency. For representative examples, see: (b) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. J. Am. Chem. Soc. 1986, 108, 6395. (c) Woiwode, T. F.; Wandless, T. J. J. Org. Chem. 1999, 64, 7670. (7) For representative examples, see: Lee, E.; Jeong, E. J.; Kang, E. J.; Sung, L. T.; Hong, S. K. J. Am. Chem. Soc. 2001, 123, 10131. (8) Yokomatsu, Y.; Arakawa, A.; Shibuya, S. J. Org. Chem. 1994, 59, 3506. (9) Sibi, M. P.; Hasegawa, H.; Ghorpade, S. R. Org. Lett. 2002, 4, 3343.

Scheme 7. Ytterbium-Catalyzed Amidation of Imides to Weinreb Amides

to note that the reaction could easily be performed on a 5 g scale, with the Weinreb amide 8a then being obtained in 85% yield, which further demonstrates the robustness and practicality of our process.21 In conclusion, we have developed a divergent, efficient, and broadly applicable system for the cleavage of imides with various nucleophiles. The use of ytterbium(III) triflate as a D

DOI: 10.1021/acs.orglett.8b01896 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters (10) (a) Evans, D. A.; Ellman, J. A.; Dorow, R. L. Tetrahedron Lett. 1987, 28, 1123. (b) Gothelf, K. V.; Hazell, R. G.; Jørgensen, K. A. J. Org. Chem. 1996, 61, 346. (11) Orita, A.; Nagano, Y.; Hirano, J.; Otera, J. Synlett 2001, 2001, 0637. (12) Evans, D. A.; Coleman, P. J.; Carlos Dias, L. Angew. Chem., Int. Ed. Engl. 1997, 36, 2738. (13) Magnier-Bouvier, C.; Reboule, I.; Gil, R.; Collin, J. Synlett 2008, 2008, 1211. (14) Fukuzawa, S.; Hongo, Y. Tetrahedron Lett. 1998, 39, 3521. (15) Ivashkin, P.; Couve-Bonnaire, S.; Jubault, P.; Pannecoucke, X. Org. Lett. 2012, 14, 5130. (16) Zhang, W.; Tan, D.; Lee, R.; Tong, G.; Chen, W.; Qi, B.; Huang, K.-W.; Tan, C.-H.; Jiang, Z. Angew. Chem., Int. Ed. 2012, 51, 10069. (17) (a) Dander, J. E.; Baker, E. L.; Garg, N. K. Chem. Sci. 2017, 8, 6433. (b) Hie, L.; Baker, E. L.; Anthony, S. M.; Desrosiers, J.-N.; Senanayake, C.; Garg, N. K. Angew. Chem., Int. Ed. 2016, 55, 15129. (18) Bourne-Branchu, Y.; Gosmini, C.; Danoun, G. Chem. - Eur. J. 2017, 23, 10043. (19) Huang, P.-Q.; Geng, H. Green Chem. 2018, 20, 593. (20) The chemoselectivity can be attributed to the chelation of the imide to the catalyst: under our standard conditions, a methyl ester (methyl p-toluate) was found to be unreactive. (21) Attempts at esterification and Weinreb amide formation from 1f and 1g were less successful due to steric hindrance and competing opening of the oxazolidinone, respectively.

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DOI: 10.1021/acs.orglett.8b01896 Org. Lett. XXXX, XXX, XXX−XXX