Article Cite This: J. Org. Chem. 2019, 84, 973−982
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Manganese-Catalyzed Acceptorless Dehydrogenative Coupling of Alcohols With Sulfones: A Tool To Access Highly Substituted Vinyl Sulfones Satyadeep Waiba, Milan K. Barman, and Biplab Maji* Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India
J. Org. Chem. 2019.84:973-982. Downloaded from pubs.acs.org by KAROLINSKA INST on 01/18/19. For personal use only.
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ABSTRACT: The development of first-row-transition-metal catalysts that can match with the reactivities of the noble metals is considered to be challenging yet very much a desirable goal in homogeneous catalysis. It has become even more fascinating to develop processes where these metals show a unique reactivity and selectivity than their higher congeners. Herein, we report on the catalytic activity of a pincer complex of the abundant earth metal manganese for an unprecedented acceptorless dehydrogenative coupling of alkyl sulfones with alcohols. Thus, highly functionalized vinyl sulfones were obtained in moderate to good yields. Both benzylic and aliphatic alcohols could be utilized, and several functional groups including bromides and iodides are tolerated under the reaction conditions. The reaction is environmentally benign, producing dihydrogen and water as byproducts. Preliminary mechanistic experiments involving kinetic, deuterium-labeling, and NMR experiments were performed.
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INTRODUCTION Vinyl sulfones are versatile building blocks in organic synthesis.1 In medicinal chemistry,2 they act as inhibitors for many types of cysteine proteases,3 SrtA,4 and caspase-3.5 They also act as antitrypanosomal agents6 and neuroprotective agents toward Parkinson’s disease therapy.7 Recently, vinyl sulfones are also used as a fluorogenic probe for selective labeling of live cells.8 Given its importance, considerable amounts of efforts are devoted to their synthesis (Scheme 1A).2a,7,9 Classically, vinyl sulfones are synthesized via Knoevenagel condensation of aldehydes with sulfonylacetic acids followed by decarboxylation,9c Horner−Wadsworth− Emmons reactions of sulfonyl phosphonates and carbonyls,7 βelimination of halo- or selenosulfones,9d and oxidation of the corresponding sulfides9e and recently by cross-coupling of a sulfonyl source with an alkene or alkynes (Scheme 1A).9b However, most of these protocols suffer from the limited accessibility of starting materials, use of a stoichiometric amount of redox reagents, tedious procedures, multiple steps, harsh reaction conditions, and formation of copious byproducts. The homogeneous catalysis with 3d-transition metals as the alternative to the noble metals has captivated the synthetic chemists not only due to their earth’s abundance, low price, and less toxicity but also due to their potential novel reactivity and selectivity.10 In this context, the first-row-transition metals such as iron,11 cobalt,12 and nickel13 have achieved much © 2018 American Chemical Society
advancement in hydrogenation and dehydrogenation reactions. Manganese, the third most abundant transition metal in the earth’s crust, has recently emerged as a valuable noble metal replacer.14 Following the seminal work on manganesecatalyzed dehydrogenative imine synthesis by Milstein et al.,15 the Mn complexes have been utilized in various (de)hydrogenation and cascade reactions,16 and in some cases, they have even outperformed their higher congeners.17 In this regard, we have developed Mn-catalyzed direct olefination of methyl-substituted heteroarenes16i and αalkylations of ketones16j and nitriles16m using primary alcohols. However, despite such developments, reports exploring their potential unique catalytic activities for the development of novel transformations are limited.16g−i Continuing our recent focus on base-metal catalysis, we have envisioned that the transition-metal-catalyzed acceptorless dehydrogenative coupling ADC of alcohols with alkyl sulfone might serve as a versatile green tool for the synthesis of highly substituted vinyl sulfones (Scheme 1). The protocol will be highly sustainable as (a) alcohols are largely abundant from a variety of resources and are nontoxic alternative carbon resources.18 (b) The reaction will be highly environmentally benign as water and dihydrogen will be produced as the sole byproducts. (c) The route will versatile without the need for Received: November 15, 2018 Published: December 27, 2018 973
DOI: 10.1021/acs.joc.8b02911 J. Org. Chem. 2019, 84, 973−982
Article
The Journal of Organic Chemistry Table 1. Optimization of the Reaction Conditionsa
Scheme 1. (A) State-of-the-Art Syntheses of Vinyl Sulfones, (B) Noble-Metal-Catalyzed Coupling of Alcohols with Sulfones, (C) This Work
functional group manipulation. However, the successful reaction development should account for the acceptorless liberation of dihydrogen without the hydrogenation of the highly reactive Michael acceptors vinyl sulfones.1d,19 Another challenge will be the formation of byproducts via the elimination of sulfone. Herein, we report on a novel catalytic activity of a manganese(I)-pincer complex for the acceptorless dehydrogenative coupling of primary alcohols with alkyl sulfones (Scheme 1C). The catalyst operates under a low catalyst loading and tolerates several functional groups. While the reaction went smoothly with manganese, the cobalt and iron complexes stabilized by the same ligand backbone failed to deliver product under these conditions and previous homogeneous ruthenium20 and heteroeneous platinum21 catalyzed such reaction, producing stilbenes with the liberation of a stoichiometric amount of sulfonate as a byproduct. To the best of our knowledge, the transition-metal-catalyzed dehydrogenative coupling of alcohols with sulfones to form vinyl sulfones with the liberation of water and H2 is not reported thus far.
a
Reaction conditions: precatalyst (4 mol %), t-BuOK (20 mol %), 1a (0.15 mmol), 2a (0.1 mmol), t-AmOH (0.5 mL), 140 °C, 24 h under Ar. Isolated yields. bThe catalyst was generated in situ. cBenzaldehyde was detected as the major product. d>90% of benzyl alcohol was recovered; n.d. = not determined.
alkylation reaction,16m was found to be inactive (entry 3). The manganse(I) pincer complex Mn-3 was also found to be moderately active, and the product 3a was isolated in 59% yield (entry 4).2 To our delight, when the reaction was carried out with a triazole-based pincer catalyst Mn-4 bearing a methyl substituent at the para position,16a the yield of the product 3aa was significantly increased to 90% (entry 5). Gratifyingly, the use of the para phenyl-substituted manganese complex Mn516a delivered the desired product 3aa in 94% isolated yield (entry 1). With the catalyst Mn-5, the reaction condition was further optimized. The reaction was found to be highly sensitive toward the nature of the base used (entry 6). The change in the solvent to the nonpolar solvent toluene and the ethereal solvent 1,4-dioxane was also noticed to be less suitable (entry 7,
