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Prof. Marder: Zinc-Catalyzed Borylation of Primary, Secondary and Tertiary Alkyl Halides
Professor Todd Marder's group at Julius Maximilian University of Würzburg works on organometallic chemistry, homogeneous catalysis, luminescence, nonlinear optics, liquid crystals, crystal engineering, and small molecule triggers of stem cell differentiation. TCI is pleased to introduce their recent study on Zinc-Catalyzed Borylation of Primary, Secondary and Tertiary Alkyl Halides:
(We thank Prof. Marder and Dr. Bose for writing the abstract; for full article, please refer to the link below)
More information about “Dioxaborolane” reagents, e. g. Bis[(pinacolato)boryl]methane, can be found by searching “dioxaborolane” on our website
Alkyl Boronates from Alkyl Halides Research Article
Zinc-Catalyzed Borylation of Primary, Secondary and Tertiary Alkyl Halides with Alkoxy Diboron Reagents at Room Temperature
Angew. Chem. Int. Ed. 2014, 53, 1799-1803 and Angew. Chem. 2014, 126, 1829-1834.
Introduction:
Organoboronates are important in medicinal chemistry[1] and they are often used as synthetic intermediates for transition-metal catalyzed cross-coupling, conjugate addition and many other reactions.[2] Herein, a simple zinc-catalyzed route to primary, secondary and some tertiary alkylboronates using the diboron(4) reagents B2pin2 or B2neop2 (pin = pinacolato; neop = neopentaneglycolato) is reported. This follows the first report of any metal catalyzed borylation of alkyl halides, which used a copper catalyst,[3a] and our report of the Cu-catalyzed borylation of aryl halides.[3b]
Alkylboronates can be prepared easily by stirring an alkyl halide with a catalyst comprising ZnCl2 and the readily available N-heterocyclic carbene (NHC) ligand IMes (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene), in the presence of a commercially available diboron(4) reagent and an appropriate base (either KOtBu or KOMe) in MTBE (MeOtBu) as the solvent at room temperature.
Scope:
1- Borylation of primary alkyl halides:
Primary alkyl halides having different functional groups such as ether, ketal, ester, cyano and alcohol groups were converted to the corresponding alkylboronates in good yields, in the presence of a Zn-catalyst at room temperature (Scheme 1).
2- Borylation of secondary alkyl halides:
As illustrated in Scheme 2, unactivated secondary alkyl halides can be smoothly borylated to provide the desired alkylboronates in excellent yields.
3- Borylation of tertiary alkyl halides:
In addition to primary and secondary alkyl electrophiles, ZnCl2/IMescan also catalyzed the borylation of some tertiary alkyl halides. Thus, reactions of 1-bromo and 1,3-dibromoadamantane gave the corresponding mono- and bis- boronates in moderate to good yields (Scheme 3).
Conclusion:
A new catalyst system, incorporating the inexpensive, earth-abundant and extremely low toxicity metal zinc, in the presence of a readily accessible NHC ligand is capable of borylating primary, secondary and even some tertiary alkyl iodides and bromides under mild conditions (room temperature). A related ZnBr2-NHC catalyst system also borylates aryl halides[4a] and, most recently, we have shown that ZnCl2, in the presence of 4,4’-di-tBu-bipyridine as ligand, borylates both aryl C-X bonds and the C-H bonds adjacent to them.[4b]
References:
- 1)a) M. A. Beenen, C. An, J. A. Ellman, J. Am. Chem. Soc. 2008, 130, 6910-6911; b) L. J. Milo, J. H. Lai, Jr., W. Wu, Y. Liu, H. Maw, Y. Li, Z. Jin, Y. Shu, S. E. Poplawski, Y. Wu, D. G. Sanford, J. L. Sudmeier, W. W. Bachovchin, J. Med. Chem. 2011, 54, 4365-4377; c) H. Einsele, Rec. Results Cancer Res. 2010, 184, 173-187; d) M. Ilies, L. Di Costanzo, D. P. Dowling, K. J. Thorn, D. W. Christianson, J. Med. Chem. 2011, 54, 5432-5443; e) N. Suzuki, T. Suzuki, Y. Ota, T. Nakano, M. Kurihara, H. Okuda, T. Yamori, H. Tsumoto, H. Nakagawa, N. Miyata, J. Med. Chem. 2009, 52, 2909-2922.
- 2)R. Jana, T. P. Pathak, M. S. Sigman, Chem. Rev. 2011, 111, 1417-1492; b) Boronic Acids: Preparation and Applications in Organic Synthesis, Medicine and Materials (Ed.: D. G. Hall), 2nd ed., Wiley-VCH, Weinheim, 2011.
- 3) a) C.-T. Yang, Z.-Q. Zhang, H. Tajuddin, C.-C. Wu, J. Liang, J.-H. Liu, Y. Fu, M. Czyzewska, P. G. Steel, T. B. Marder, L. Liu, Angew. Chem. 2012, 124, 543-547; Angew. Chem. Int. Ed. 2012, 51, 528-532; b) C. Kleeberg, L. Dang, Z. Lin, T. B. Marder, Angew. Chem. 2009, 121, 5454-5458; Angew. Chem. Int. Ed. 2009, 48, 5350-5354.
- 4) a) S. K. Bose, T. B. Marder, Org. Lett. 2014, 16, 4562-4565; b) S. K. Bose, A. Bießenberger, A. Eichhorn, P. G. Steel, Z. Lin, T. B. Marder, Angew. Chem. 2015, 127, ASAP. DOI: 10.1002/ange.201505603; Angew. Chem. Int. Ed. 2015, 54, ASAP. DOI: 10.1002/anie.201505603.