Radical boron migration of allylboronic esters
A photocatalyzed 1,3-boron shift of allylboronic esters is reported. The boron atom migration through the allylic carbon skeleton proceeds via consecutive 1,2-boron migrations and Smiles-type rearrangement to furnish a variety of terminally functionalized alkyl boronates. Several types of migrating variations of heteronuclei radicals and dearomatization processes are also tolerated, allowing for further elaboration of highly functionalized boron-containing frameworks.
Introduction<!>Results and discussion
<p>Rearrangements have been fascinating topics to organic chemists due to their innate charm and versatile use in skeleton reconstruction. 1,2 The classic ionic-type named reactions, such as Pinacol, Favorskii, Beckmann, Claisen and Smiles rearrangements, involve the re-organization of certain carbon skeletons. [3][4][5][6] In contrast, the examples for heteroatom shis are relatively rare. For example, the Brook rearrangement 7,8 and Doyle-Kirmse reactions [9][10][11][12] involve silyl and thiol group migrations. A series of 1,2-boryl migrations of a-boryl expoxides and carboxylic acids have been reported by Yudin and coworkers. 13,14 Besides the ionic type functional group migrations (FGM), the rearrangements that involve free radicals have demonstrated versatile reactivities towards remote FGM for the construction of more complex molecular frameworks. [15][16][17][18][19] Recent progress on aryl, cyano, alkynyl, and carbonyl group migration protocols have been well-documented for the construction of new C-C bonds via radical pathways. 1,20-32 Boron shi chemistry, which represents tremendous importance for the broad utility of boronic acids and esters, has attracted much attention of organic chemists. The rst example of radical type boron shi was reported by Batey and Smil. 33 In 2019, Aggarwal described a radical 1,2-boron shi of diboronates under photocatalysis to access 1,2-difunctionalized boronates (Fig. 1A). 34 Studer and co-workers applied the boron migration protocol to 1,3-difunctionalized triuoromethylated alkynyl boronates (Fig. 1B). 35 In contrast, the analogous 1,3-shi process has encountered inevitable difficulties because of the disfavored four-membered cyclic transition state and no example of gboron migration has been reported. [36][37][38][39][40][41][42] Theoretical studies on such 1,3-boron migrating processes have been concluded to be thermodynamically infavorable and experimentally inaccessible. 43 We envisioned that through consecutive boron migration on the carbon skeleton, the boronic ester moiety could switch to the remote end of the allylic backbones for the formation of more stable radical intermediates. Herein, we described a radical 1,3-boron migration process merging double 1,2-boron shis of allylboronates and Smiles-type rearrangement of arylsulfonyl radicals to generate aryl g-boronates (Fig. 1C). Moreover, this boron migration protocol could be further extended to other heteronuclei radicals and the formation of dearomatized frameworks.</p><!><p>Our investigations began with the model reaction of sodium arylsulfonate 1a and allylboronic ester 2a. The desired 1,3- Cite this: Chem. Sci., 2022, 13, 1946   All publication charges for this article have been paid for by the Royal Society of Chemistry boron migration product 3a could be obtained in 95% yield under blue LED irradiation for 12 h with 10-phenylphenothiazine (PTH) as the photocatalyst and acetic acid as the additive in CHCl 3 (entry 1). For other photocatalysts such as Ir(ppy) 3 and 4CzIPN, lower yields were noted (20-35%, entries 2 and 3). Replacing the PTH photocatalyst with Acr + ClO 4</p><p>À led to a slightly lower yield. (entry 4). The reaction could not occur in DMF or MeOH (entry 5 and 6). In the absence of acetic acid, the reaction yield was reduced signicantly (entry 7). Control experiments indicated that light and the photocatalyst are necessary for this boron shi strategy (entries 8 and 9, see the ESI †) (Table 1).</p><p>With the optimized reaction conditions in hand, we explored the generality of the protocol with various sodium arylsulfonates and allylboronic esters (Fig. 2). Arylsulfonates bearing either electron-withdrawing or electron-donating groups delivered the desired 1,3-boron shi products in moderate to good yields (3b-3l, 25-87%). The ortho-uorinated arylsulfonate provided the product 3h in 80% yield, while the migration of para-and meta-uorinated substrates was less efficient (30% for 3e and 27% for 3j). Multiple uorine or chlorine substituted arylsulfonates could be tolerated (3k and 3l). Heteroarene 3m was compatible with the reaction conditions, and the low yield was due to the electronic effect of thiophene. Allylboronates with various substitutions were also investigated. For example, substrates bearing the cyclohexyl group gave the boronation product with a lower efficiency (3n, 38%). The arylboronate 3o with unsymmetrical alkyl substituents was afforded in 44% yield (R 1 ¼ Me, R 2 ¼ n-Hex). Furthermore, this boron shi was proven successful with stabilized benzyl radical precursors (R 1 ¼ Ar, R 2 ¼ H). Aryl substituted allylboronates have been subjected to the standard conditions and diarylpropylboronic products were readily accessed. The a-phenyl-substituted allylboronic esters containing phenyl, para-methyl and para-uorine phenyl and naphthyl could deliver the corresponding products (3p-3s). The low yields of 3e, 3n and 3q were due to the loss in the purication process.</p><p>Photoredox-catalyzed and electrochemical dearomatization processes involving radicals have been explored with proven utility. [44][45][46][47][48][49][50] During the investigation of this 5-exo-trig cyclization process, we also observed the 6-exo-trig cyclization dearomatizated products in the reaction mixture. [51][52][53] As valuable pharmacophores, cyclic sulfones have been widely applied in medicinal chemistry and organic photoconducting materials due to their unique electronic and optical properties. [54][55][56] With a slight variation of the reaction conditions (eosin Y and DMF), the dearomatized product 4 could be readily afforded via 1,2boron shi and radical addition. As shown in Fig. 3, tetrohydrothiochromene sulfone 4a was achieved in 82% yield with excellent diastereoselectivity (>20 : 1, the absolute conguration was conrmed by XRD analysis). Similarly, electronwithdrawing group substituted 4b-4e were obtained in 47-86% yields. In the cases of 4d and 4e, small amounts of the protonated by-products were observed. Interestingly, 3-uoro and 3,4-diuoro substituted arylsulfonate substrates generated single dearomatized regioisomers in good yields (4f and 4g), which was governed by the regio-and chemoselective  In darkness 0</p><p>a Reaction conditions: la (0.3 mmol), 2a (02 mmol), 10phenylphenothiazine (PTH, 8 mol%), HOAc (4.0 equiv.), CHCI 3 (2 mL), Ar, irradiation with 60 W blue LEDs at r.t. for 12 h. b Crude yields were determined by 19 F NMR using 1,4-diuorobenzene as the internal standard. c The isolated yields were determined from the corresponding oxidized product.</p><p>nature of the cyclization step. Notably, dearomatized products 4h and 4i were furnished along the corresponding aromatized cyclic sulfones. Replacing the photocatalyst with Ru(bpy) 3 Cl 2 , the aromatic by-products were signicantly suppressed (De/Ar ¼ 10 : 1 for 4i and >20 : 1 for 4h). Next, different allylboronic esters were explored with sodium arylsulfonate 1a under this protocol (4j-4n). Substrates bearing veand sixmembered rings also afforded the corresponding products 4j and 4k in moderate yields (41-47%). The 2,2-diethyl and 2,2dipropyl alkenyl boronic esters delivered the dearomatized products 4l and 4m in 59% and 38% yields, respectively. The allylboronate derived from geranyl chloride gave 4n in 27% yield as a single diastereoisomer (d.r. > 19 : 1).</p><p>In order to better understand the reaction pathway, we have added a catalytic amount of thiophenol to quench the tertiary Cradical generated by 1,2-boron migration of the allylboronates (Fig. 4). A diverse set of aromatic substrates, regardless of their electronic properties were found to be compatible to produce the corresponding 1,2-difunctionalized products (5a-5e). Allylboronate containing a quaternary carbon center provided the corresponding product 5f with a diastereomeric ratio of 2.3 : 1. The heteroaryl sulfones bearing pyridine (5g) and oxazole (5h) could be tolerated. The alkyl sulfonates (5i and 5j) were also furnished in good yields. Moreover, other heteroatom radical precursors could be tolerated to construct C-P, C-Si and C-S bonds. For example, phosphate and diphenylmethylsilane delivered b-boronate products 5k and 5l in 60% and 82% yields, respectively. The mercaptan derivative afforded the thiolated boronate 5m in 35% yield in the mixture with the unshied product 5m 0 .</p><p>Based on the above results, a plausible mechanism was proposed (Fig. 5). First, the photocatalysts were activated to their excited state by blue light and they underwent single electron transfer (SET) with arylsulfonate to produce sulfone radical int I. The conjugate addition of int I to allylboronate 2 produced the secondary carbon radical int II and 1,2-boron shi generated the tertiary carbon radical int III. At this point, the radical int III could undergo different pathways depending on the conditions. Under condition A, 5-exo-trig cyclization followed by Smiles-type rearrangement afforded int IV which degraded to release SO 2 and the second 1,2-boron shi provided the b-carbon radical int V. Next, the hydrogen atom transfer (HAT) process occurred between radical int V and CHCl 3 to deliver the 1,3-boron shi products 3 and cCCl 3 (see deuteration experiments in the ESI † for details). Finally, the trichloromethyl radical underwent SET with PCc-to close the photoredox catalysis cycle. However under condition B, the tertiary radical int III could undergo 6-exo-trig cyclization to deliver the dearomatized product 4. Under condition C, the radical int III underwent HAT with thiophenol to form the 1,2-difunctionalized product 5.</p>