Radical-Induced 1,2-Boron Shift, Enabling 1,3-Difunctionalization of Allylboronic Esters

Radical 1,3-difunctionalizations of alkenes represent a significant challenge in organic synthesis. In this issue of Chem, Studer and co-workers report the radical 1,3-difunctionalization of allylboronic esters with concomitant 1,2-boron shift. Radical 1,3-difunctionalizations of alkenes represent a significant challenge in organic synthesis. In this issue of Chem, Studer and co-workers report the radical 1,3-difunctionalization of allylboronic esters with concomitant 1,2-boron shift. The radical 1,2-difunctionalization of alkenes has attracted great attention;1Chatgilialoglu C. Studer A. Encyclopedia of Radicals in Chemistry, Biology and Materials. John Wiley & Sons Ltd, 2012Crossref Google Scholar however, radical-induced 1,2-boron shifts are rare. In 1999, Batey and Smil first reported that alkyl radicals can induce 1,2-boron migration.2Batey R.A. Smil D.V. The first boron-tethered radical cyclizations and intramolecular homolytic substitutions at boron.Angew. Chem. Int. Ed. Engl. 1999; 38: 1798-1800Crossref PubMed Scopus (39) Google Scholar Very recently, the Aggarwal group demonstrated a radical 1,2-boron migration under thermodynamic control, undergoing the 1,2-boron shift to form thermodynamically stable secondary radicals from the primary β-boryl radicals.3Kaiser D. Noble A. Fasano V. Aggarwal V.K. 1,2-Boron shifts of β-boryl radicals generated from bis-boronic esters using photoredox catalysis.J. Am. Chem. Soc. 2019; 141: 14104-14109Crossref PubMed Scopus (20) Google Scholar Similarly, the development of a radical 1,3-difunctionalizion reaction of alkenes represents a significant challenge. Allylboronic esters are widely used as nucleophiles along with the loss of the highly valuable boron moiety.4Kennedy J.W.J. Hall D.G. Recent advances in the activation of boron and silicon reagents for stereocontrolled allylation reactions.Angew. Chem. Int. Ed. Engl. 2003; 42: 4732-4739Crossref PubMed Scopus (253) Google Scholar, 5Denmark S.E. Hall D.G. Lachance H. Organic reactions, allylboration of carbonyl compounds, 73. Wiley, 2012Google Scholar, 6Yus M. González-Gómez J.C. Foubelo F. Diastereoselective allylation of carbonyl compounds and imines: application to the synthesis of natural products.Chem. Rev. 2013; 113: 5595-5698Crossref PubMed Scopus (346) Google Scholar, 7Denmark S.E. Fu J. Catalytic enantioselective addition of allylic organometallic reagents to aldehydes and ketones.Chem. Rev. 2003; 103: 2763-2794Crossref PubMed Scopus (1024) Google Scholar Therefore, if the 1,3-difunctionalization reaction of allylboronic esters could be achieved and the boron moiety retained, it would not only enrich the boron chemistry in general but also enable preparation of valuable boron-containing compounds. As just reported in this issue of Chem,8Jana K. Bhunia A. Studer A. Radical 1,3-difunctionalization of allylboronic esters with concomitant 1,2-boron shift.Chem. 2020; 6: 512-522Google Scholar the Studer group has developed a radical 1,3-trifluoromethylation/alkynylation (azidylation or alkylation) of allylboronic esters with concomitant 1,2-boron migration (Figure 1). The authors first tested the radical 1,3-trifluoromethylation/alkynylation of allylboronic esters with alkynyl triflones as difunctional reagents and AIBN (α,α’-azobisisobutyronitrile) as an initiator. A plausible mechanism would involve (1) generation of a perfluoroalkyl radical in situ by alkynyl triflones and initiator AIBN; (2) attack of the double bond of the allylboronic ester by the perfluoroalkyl radical, generating alkyl radical A; (3) a radical-induced 1,2-boron migration dominated by thermodynamic effects, affording more stabilized rearranged alkyl radical B; (4) trapping of the rearranged radical B by an acetylenic triflone to give 1,2,3-trifunctionalized alkane products and trifluoromethylsulfonyl radical. One notable feature of this 1,3-trifluoromethylation/alkynylation reaction is that it exhibits good to excellent stereoselectivity. For example, the oxidation product 1 with complete stereospecificity and excellent diastereoselectivity (dr > 20:1) was obtained by using the enantioenriched allylboronic ester. The authors also confirmed that the resulting product could be converted to valuable substituted 2,3-dihydrofuran derivatives. This concept can also be applied to 1,3-trifluoromethylation/azidation reaction with trifluoromethanesulfonyl azide as a CF3-radical precursor and alkyl radical trapping reagent, affording the desired 1,2,3-trifunctionalized product 2 in 70% isolated yield under the standard conditions. In addition, the authors further investigated the photoredox-catalyzed 1,3-trifluoromethylation/alkylation of allylboronic esters with the Langlois reagent (CF3SO2Na) as the CF3-radical source and Michael acceptors as radical trapping reagents, which could deliver the 1-CF3-2-boron-3-alkyl product 3 in moderate yield. Finally, when using C4F9I as a radical precursor and trapping reagent, the allylation products were obtained and the boron moiety was not retained, possibly because of the fast elimination of syn-IBpin. In summary, Studer and co-workers have developed a radical 1,3-trifluoromethylation/alkynylation (azidylation or alkylation) of allylboronic esters with concomitant 1,2-boron shift, which affords synthetically valuable 1,2,3-trisubstituted alkane products with the trifluoromethyl group at position 1, boron moiety at position 2, and the alkynyl (azidyl or alkyl) at the 3 position. This method shows good to excellent stereoselectivity. Another key aspect is the simultaneous introduction of three very important functional groups in one molecule: the pharmaceutically relevant trifluoromethyl moiety and a borate as well as an alkynyl group which both can be utilized for further functionalizations. Q.S. acknowledges financial support from the National Natural Science Foundation of China ( 21772046 and 21931013 ). Radical 1,3-Difunctionalization of Allylboronic Esters with Concomitant 1,2-Boron ShiftJana et al.ChemJanuary 16, 2020In BriefBoronic esters currently used in transition-metal-catalyzed C-C couplings and in ionic allylation reactions are shown to engage in radical 1,3-difunctionalizations, where the synthetically valuable boron moiety remains in the product. This reactivity is documented for the preparation of 1,2,3-trisubstituted alkanes starting with allylboronic esters. Alkynyl triflones are used as bifunctional radical reagents in these cascades, and the pharmacologically important trifluoromethyl moiety gets installed along with an alkynyl substituent. The latter is important for for azide-alkyne click chemistry. Full-Text PDF Open Archive