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. 2024 Mar 13;146(10):6604-6617.
doi: 10.1021/jacs.3c12020. Epub 2024 Mar 3.

Cobalt-Catalyzed Enantioselective Hydroboration of α-Substituted Acrylates

Manoj D Patil  1 , Kiron Kumar Ghosh  1 , T V RajanBabu  1
Affiliations

Cobalt-Catalyzed Enantioselective Hydroboration of α-Substituted Acrylates

Manoj D Patil et al. J Am Chem Soc. .

Abstract

Even though metal-catalyzed enantioselective hydroborations of alkenes have attracted enormous attention, few preparatively useful reactions of α-alkyl acrylic acid derivatives are known, and most use rhodium catalysts. No examples of asymmetric hydroboration of the corresponding α-arylacrylic acid esters are known. In our continuing efforts to search for new applications of earth-abundant cobalt catalysts for broadly applicable organic transformations, we have identified 2-(2-diarylphosphinophenyl)oxazoline ligands and mild reaction conditions for efficient and highly regio- and enantioselective hydroboration of α-alkyl- and α-aryl- acrylates, giving β-borylated propionates. Since the C-B bonds in these compounds can be readily replaced by C-O, C-N, and C-C bonds, these intermediates could serve as valuable chiral synthons, some from feedstock carbon sources, for the synthesis of propionate-bearing motifs including polyketides and related molecules. Two-step syntheses of "Roche" ester from methyl methacrylate (79%; er 99:1), arguably the most widely used chiral fragment in polyketide synthesis, and tropic acid esters (∼80% yield; er ∼93:7), which are potential intermediates for several medicinally important classes of compounds, illustrate the power of the new methods. Mechanistic studies confirm the requirement of a cationic Co(I) species [(L)Co]+as the viable catalyst in these reactions and rule out the possibility of a [L]Co-H-initiated route, which has been well-established in related hydroborations of other classes of alkenes. A mechanism involving an oxidative migration of a boryl group to the β-carbon of an η4-coordinated acrylate-cobalt complex is proposed as a plausible route.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Examples of medicinally relevant molecules accessible from the hydroboration product 2 (Scheme 1). Highlights (red) show fragments from the starting acrylate.
Figure 2.
Figure 2.
Ligand control in regio- and enantioselective hydroboration of 1,3-dienes
Figure 3.
Figure 3.
Selected bis-phosphine ligands for enantioselective hydroboration of methyl methacrylate. For a more complete list, See SI p. S22.
Figure 4.
Figure 4.
Phosphino-oxazoline ligands for Co-catalyzed enantioselective hydroboration of methyl methacrylate (Scheme 2)
Figure 5.
Figure 5.
A. Solid-state structure of the best catalyst precursor (L9)CoBr2. The structure has been deposited at CCDC and has the following number: CCDC-2290864. See Supporting Information for the details of the synthesis of the ligand and the cobalt-complex. B. Solid-state structure of the K-trifluoroborate 2l derived from 2d (Figure 6) showing the absolute configuration (S) of the hydroboration product. Details of the structure has been deposited at CCDC and has the following number: CCDC-2294815.
Figure 6.
Figure 6.
Scope of acrylate esters as precursors in enantioselective hydroboration. For 2h and 2j 5 mol% LCoBr2 was used. a Boronate 2j was identified as the corresponding alcohol. See Supporting Information for details.
Figure 7.
Figure 7.
Scope of aryl substituents in enantioselective hydroboration of alkyl 2-arylacrylates
Figure 8.
Figure 8.
Proposed mechanisms for hydroboration of alkenes using a borohydride reagent (e.g., HBPin). Mechanism I. Metal hydride addition followed by σ-bond metathesis. Mechanism II. Alkene metal complex formation, oxidative migration (of BPin or H) followed by reductive elimination. Only oxidative migrations to C3 are shown.
Figure 9.
Figure 9.
Studies showing that LCo–H (L = dppe), isolated (Eq 6a, 6b) or in situ generated (Eq 7, 8), is not a viable catalyst for hydroboration of MMA. Under conditions where cationic Co(I) is generated (this work), there is 100% conversion to the hydroboration product (Eq 9).
Figure 10.
Figure 10.
Generation (Eq 11) and lack of reactivity (Eq 12 A) of a neutral Co(I) complex [(DPPF)Co(μ)-Br)]2 in hydroboration of acrylates. In the presence of ZnBr2 (generated from reduction of CoBr2 by Zn) the hydroboration proceeds as expected (Eq 12 B).
Figure 11.
Figure 11.
Mechanism of hydroboration of 1,3-dienes forming a 4,3-adduct (ref. 25b).
Scheme 1.
Scheme 1.
Co-Catalyzed Enantioselective Hydroboration of α-Substituted Acrylates (this work)
Scheme 2.
Scheme 2.
Enantioselective Hydroboration of MMA and a Synthesis of Roche Ester
Scheme 3.
Scheme 3.
Catalytic Enantioselective Approaches to β-Borylated t-Butyl 2-Methylpropionate
Scheme 4.
Scheme 4.
Catalytic Enantioselective versus Stoichiometric Methods for Synthesis of 2-Hydroxymethyl Esters
Scheme 5.
Scheme 5.
Asymmetric Catalytic Routes to Methyl Tropates via Enantioselective Hydroboration of α-Arylacrylates and a Comparison to the Current Best Method
Scheme 6.
Scheme 6.
Synthesis of (R)-Ibuprofen via Enantioselective Hydroboration
See this image and copyright information in PMC

References

    1. Rentsch A; Landsberg D; Brodmann T; Bulow L; Girbig AK; Kalesse M Synthesis and pharmacology of proteasome inhibitors. Angew. Chem. Int. Ed 2013, 52, 5450–5488. - PubMed
    2. Smoum R; Rubinstein A; Dembitsky VM; Srebnik M Boron containing compounds as protease inhibitors. Chem. Rev 2012, 112, 4156–4220. - PubMed
    3. Touchet S; Carreaux F; Carboni B; Bouillon A; Boucher JL Aminoboronic acids and esters: From synthetic challenges to the discovery of unique classes of enzyme inhibitors. Chem. Soc. Rev 2011, 40, 3895–3914. - PubMed
    4. Dembitsky VM; Al Quntar AA; Srebnik M Natural and synthetic small boron-containing molecules as potential inhibitors of bacterial and fungal quorum sensing. Chem. Rev 2011, 111, 209–237. - PubMed
    1. Mellerup SK; Wang SN Boron-based stimuli responsive materials. Chem. Soc. Rev 2019, 48, 3537–3549. - PubMed
    2. Inglis SR; Strieker M; Rydzik AM; Dessen A; Schofield CJ A boronic-acid-based probe for fluorescence polarization assays with penicillin binding proteins and b-lactamases. J. Anal. Biochem 2012, 420, 41–47. - PubMed
    3. Jin S; Zhu CY; Cheng YF; Li MY; Wang BH Synthesis and carbohydrate binding studies of fluorescent α-amidoboronic acids and the corresponding bisboronic acids. Bioorg. Med. Chem. Lett 2010, 18, 1449–1455. - PMC - PubMed
    1. Hall DG Ed.; Boronic Acids. Wiley-VCH: Weinheim, 2011.
    1. Xu NX; Liang H; Morken JP Copper-catalyzed stereospecific transformations of alkylboronic esters. J. Am. Chem. Soc 2022, 144, 11546–11552. - PMC - PubMed
    2. Liu X; Zhu Q; Chen D; Wang L; Jin L; Liu C Aminoazanium of DABCO: An amination reagent for alkyl and aryl pinacol boronates. Angew. Chem. Int. Ed 2020, 59, 2745–2749. - PubMed
    3. Namirembe S; Morken JP Reactions of organoboron compounds enabled by catalyst-promoted metalate shifts. Chem. Soc. Rev 2019, 48, 3464–3474. - PMC - PubMed
    4. Sandford C; Aggarwal VK Stereospecific functionalizations and transformations of secondary and tertiary boronic esters. Chem. Commun 2017, 53, 5481–5494. - PubMed
    5. Mlynarski SN; Karns AS; Morken JP Direct stereospecific amination of alkyl and aryl pinacol boronates. J. Am. Chem. Soc 2012, 134, 16449–16451. - PMC - PubMed
    6. Scott HK; Aggarwal VK Highly enantioselective synthesis of tertiary boronic esters and their stereospecific conversion to other functional groups and quaternary stereocentres. Chem. Eur. J 2011, 17, 13124–13132. - PubMed
    7. Matteson DS; Kim GY Asymmetric alkyldifluoroboranes and their use in secondary amine synthesis. Org. Lett 2002, 4, 2153–2155. - PubMed
    8. Matteson DS Functional group compatibilities in boronic ester chemistry. J. Organomet. Chem 1999, 581, 51–65.

    1. For other recent reviews, see:

    2. Hu J; Ferger M; Shi Z; Marder TB Recent advances in asymmetric borylation by transition metal catalysis. Chem. Soc. Rev 2021, 50, 13129–13188. - PubMed
    3. Obligacion JV; Chirik PJ Earth-abundant transition metal catalysts for alkene hydrosilylation and hydroboration. Nature Rev. Chem 2018, 2, 15–34. - PMC - PubMed
    4. Burgess K; Ohlmeyer MJ Transition-metal promoted hydroborations of alkenes, emerging methodology for organic transformations. Chem. Rev 1991, 91, 1179–1191.

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