Photoinduced Transition-Metal-Free Alkynylation of Alkyl Pinacol Boronates

Open AccessCCS ChemistryRESEARCH ARTICLE1 Jun 2021Photoinduced Transition-Metal-Free Alkynylation of Alkyl Pinacol Boronates Dunfa Shi, Chungu Xia and Chao Liu Shi State Key Laboratory for Oxo Synthesis Selective Oxidation, CAS Chemistry Northwestern Plant Resources, Suzhou Research Institute, Lanzhou Institute Chemical Physics, Chinese Academy Sciences, 730000 University Beijing 100049 Google Scholar More articles by this author , *Corresponding author: E-mail Address: [email protected] https://doi.org/10.31635/ccschem.020.202000371 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesTrack Citations ShareFacebookTwitterLinked InEmail An unprecedented visible-light-induced transition-metal-free alkynylation alkyl pinacol boronates has been demonstrated with alkynyl phenylsulfones as the reagents 4CzIPN organic photocatalyst. Common sodium methoxide (NaOMe) or hydroxide (NaOH) was used Lewis base generate photoactive tetra-coordinated boron species. Various functional groups were well tolerated. The selective monoalkynylation diboronates achieved keep one boryl group in product potential further transformations. Radical trapping experiments electron paramagnetic resonance (EPR) analysis confirmed generation radical intermediate. Download figure PowerPoint Introduction Organoboron compounds are valuable synthetic building blocks primarily because their highly transformable ability synthesis.1,2 In past decades, various organoboron have developed applied chemical synthesis. However, widely accessible compounds, (alkyl-Bpin) less explored C–C bond formation, although 1,2-boronate rearrangements (including Zweifel olefination3–5 Aggarwal coupling6–16) solved some problems. Arylboronates proven be great bond-forming coupling partners powerful versatile Suzuki–Miyaura couplings.17,18 alkylboronates generally recalcitrant substrates couplings only limited examples succeeded,19–26 polar C–B usually leads reluctant transmetallation. Recently, an effective strategy, activation alkylboron radicals reactions attracted increasing attention,27–36 it enlarge application alkylborons formation. Very recently, Renaud group37 a novel strategy situ transesterification from inactive alkyl-Bpin active alkyl-Bcat homolytic alkyl-Bpin. Catalytic under mild conditions attractive, method which anionic trifluoroborate salts dominant reagents.a Comparably, could readily available soluble most common solvents. Due preparation alkyl-Bpin, recent studies on alkyltrifluoroborates precursors those trifluoroborates. Therefore, using photocatalysis would appealing scarce demonstrated. 2016, Ley co-workers38–40 initiated photocatalytic (Csp3–Csp3 Csp3–Csp2) 4-Dimethylaminopyridine” proof (DMAP), 3-hydroxyl-quinuclidine, PPh3 base, specific benzylic ?-amino utilized (Scheme 1a). group41,42 successfully unactivated photoredox preformation ate complex phenyllithium (PhLi) reagent generated reacted olefins form Csp3–Csp3 bonds. Studer group43 also achieve protodeboronation PhLi at low-temperature solvent-switch operation make practical. Generally, alkoxide anions anion coordinate centers activate via formation trioxyl borate. If activated presence alkali metal photocatalysis, very practical Although triol boronate possibility,44 there no related reports date. Herein, we Csp3–Csp 1b). Scheme 1 | (a b) Photoinduced its alkynylation. LG = –SO2Ph. FG aryl amino groups. LG, leaving group; FG, group. Experimental Methods General procedure glovebox, flame-dried resealable reaction tube solvent flask (25 mL) equipped magnetic stirring bar charged (0.40 mmol), phenylsulfone 2 (0.60 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN; 6.4 mg, 0.008 NaOMe (54.0 1.0 mmol) NaOH (40.0 dioxane (8 mL). sealed Teflon screw cap taken out glovebox. stirred irradiation blue light-emitting diodes (LEDs; 3 W) fan room temperature 6 h. Upon completion, mixture quenched ammonium chloride (NH4Cl) solution extracted ethyl acetate. After removing vacuum, resulting residue purified flash column chromatography silica gel afford desired products. details characterization methods Supporting Information. Results Discussion Our focusing development new synthesis alkyl-Bpin.45–52 Considering challenge reactive reactions, attempted important formations functionalized alkynes, continuous efforts community, including 1,2-metalate rearrangements,53–64 halides, salts, carboxylic acids, aliphatic alcohols, alkanes,65–73 so forth. It that necessary carbon photocatalysis. before investigating optimal alkynlation our testing interaction several bases 11B NMR tetrahydrofuran (THF)-d8 (Figure 1). Cyclohexyl (Cy-Bpin) 1j (33.9 ppm NMR, Figure 1, spectrum 1) model 5 min analysis. caesium fluoride (CsF), tert-butoxide (NaOtBu), DMAP (2.5 equiv) showed obvious signals species spectra 2–4). When peak 7.9 observed assigned alkylborate coordination 1j.74,75 Moreover, equiv resulted partial 5). Along amount NaOMe, signal decreased increased 5–8). 2.5 used, nearly single 8). These phenomena suggested excess full center. between Cy-Bpin d8-THF temperature. Before studying photoinduced reduction measured together known photocatalytic-active cyclohexyl trifluoroborates, boronate, phenyl borate reference same standard (Figures 2a–2d). As result, CyBF3K is 1.61 V versus Ag/AgCl THF. value Akita’s Aggarwal’s 1.12 1.03 V, respectively. 1.33 Ag/AgCl, smaller than CyBF3K. This result high possibility NaOMe. (a–d) Reduction potentials different According initial hypothesis, photocatalyst W LED base. addition/elimination strategy.76 We first 2a test following understanding above effect (Table Obviously, THF, afforded 3aj 80% yield after h entry detection significant THF made isolation troublesome.77 Switching avoided problem without decrease efficiency 2). Using 91% determined condition 3). shown not fully convert borate; low obtained 4), demonstrating importance coordination. efficient short time, yields (entries 6). Bases such DMAP, PPh3, isonicotinonitrile transformation,38–40 solvents dimethylformamide (DMF), dimethyl sulfoxide (DMSO), methanol (MeOH), (see Section Information). Lowering loading 1.3 incomplete consumption starting boronates, corresponding products relatively Control detected when performed absence dark entries 7 Table Reaction Parameters Alkyl-Bpin Entry Base(equivalent) (%)a 1. (2.0), instead 80 2. (2.0) 3. (2.5) 91 ( 88)b, 84b,c, 71b,d 4. (1.0) 16 5. CsF 11 6. NaOtBu 14 7. n.d. 8. Abbreviations: n.d., detected; rt, temperature; GC, gas chromatography. aDetermined GC naphthalene internal standard. bYield based isolated product. c (1.3 equiv). d (1.0 With hand, investigated substrate scope First, primary evaluated. 2, kinds installed good 3aa, ab, 3ac). Halo substituents, Br Cl, tolerated give moderate 3ad 3ae). Different groups, ester 3af), ether 3ag), acetal 3ah), compatible transformation. addition, indole derivative target alkyne 3ai). Subsequently, secondary screened Both acyclic cyclic excellent 3aj– 3ar). Boc-protected piperidinyl suitable 3ak). tolerance thioether exhibited advantage large-scale (5.0 carried condition; 0.57 g (62%) remaining CyBpin 1j). To demonstrate utility natural derivatives protocol. cholesterol provided 3as. Carbohydrates fragments retained transformation derived glucose galactose gave 3at 3au. Estrone efficiently 3av yield, ketone functionality. Substrate condition: (0.4 (0.6 (0.008 (8.0 mL), supplied LEDs (3 W), Yields a0.016 mmol used. b0.2 scale. c5.0 d.r., diastereomeric ratio; Next, sulfone evaluated partner Aromatic alkynes bearing electron-donating substituents behaved, para-, ortho-, meta-substituted phenyls all 3bj, 3cj, 3dj, 3ej). aromatic halogen C–Cl C–Br 3fj 3gj), allowed functionalizations alkynes. Heteroaryl worked 3hj 3ij). noteworthy sulfones transformation, 3jj 3kj). sulfones. conditions: a0.024 came tertiary trace Meanwhile, clear evidence decomposed NaOMe.78 presumed bulky prevented center Bpin. aspect, size oxyl-base then chosen might suffer poor solubility dioxane, Bpin beneficial chemoselectivity toward delight, simply switching conditions, ran smoothly both sluggish period min, while compensated extending 9 importantly, found did destroy during long observation addressed case nonreactivity sulfone. left enough time these modifications, series alkynylated 4). piperonyl 3ba), C–F 3bb), C–CF3 3bc), C–OMe 3bd, 3be, 3bf), 4 Substrates aTHF solvent. 1,2-diboronates subjected process position 3ca, 3cb, 3cc, 3cd, 3cf). Aggarwal’s42 previous report proceed 1,2-boron shift functionalization more steric- hindered position, suggesting likely occurred Interestingly, 1,5-diboronate, monodeborylative 3ce) even 2a. products, di-alkynylation observed. Some unknown byproducts must mixture. show transformations group, 3cf perform oxidation H2O2/NaOH homopropargyl alcohol 3cf-a yield. amination 1-amino-1,4-diazabicyclo[2.2.2]octane-1,4-diium iodide (H2N-DABCO) recently group45,79; amine 3cf-b synthesized diborylation olefins, protocol possibilities difunctionalization olefins. Selected diboronates. (0.3 (0.016 (0.9 (6.0 LEDs, a3cf-a prepared 3cf. bReaction 3cf-a: (0.2 3M (2 30% H2O2 30 min. cReaction 3cf-b: (0.15 H2N-DABCO KOtBu (0.36 °C, h, trifluoroacetic anhydride (TFAA) confirm reaction, experiment conducted models 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) 6a). completely inhibited, Cy-TEMPO 47% Furthermore, conducted. 5,5-dimethyl-1-pyrroline N-oxide (DMPO) added 2e, EPR (g 2.0066, AN 14.13 G, AH 21.30 linewidth 0.8) Two light on–off 6b). every 10 off, on. allowing (the time). increase condition. results exclude chain reaction. luminescence quenching (alkyl-Bpin + NaOMe) excited 4CzIPN* acetylene sulfone, quench Based experiments, plausible mechanism proposed 6c. Initially, 1-I. single-electron transfer (SET) 1-I 1-II catalyst radical. Then, addition triple intermediate 2-I. elimination sulfonyl recovered final SET regenerated ground state close catalytic cycle. (a–c) Mechanistic mechanism. Conclusion Widely Alkynyl reagents. irradiation. radical, subsequently proposed. Footnote See refs. 27–31, references therein. Information available. Conflict Interest There conflict interest report. Funding Financial support work National Natural Science Foundation China (nos. 21673261 91745110), Jiangsu Province BK20190002 BK20181194), Youth Innovation Promotion Association (no. 2018458), Program Frontier Sciences QYZDJ-SSW-SLH051). Acknowledgments authors thank Professor Xinquan Hu helpful revision manuscript. References Hall D. G.Boronic Acids: Preparation Applications Organic Synthesis, Medicine Materials,2nd ed.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2011; Vols. Dhillon R. S.Hydroboration Synthesis; Springer: 2007. Armstrong J.; Niwetmarin W.; V. K.Synthesis Functionalized Alkenes Coupling.Org. Lett.2017, 19, 2762–2765. Garcia-Ruiz C.; Myers E. L.; K.Stereodivergent Olefination Enantioenriched Boronic Esters.Angew. Chem. Int. Ed.2017, 56, 786–790. K.50 Years Olefination: A Coupling.Synthesis2017, 49, 3323–3336. Bonet A.; Odachowski M.; Leonori D.; Essafi S.; K.Enantiospecific sp2–sp3 Coupling Secondary Tertiary Esters.Nat. Chem.2014, 6, 584–589. Llaveria K.Stereospecific Esters N-Heteroaromatic Compounds.J. Am. Soc.2015, 137, 10958–10961. Conti-Ramsden P.; Harvey J. N.; K.Development Enantiospecific Soc.2016, 138, 9521–9532. 9. Aichhorn Bigler R.; ortho-Substituted Benzylic 1,2-Metalate Rearrangement/1,3-Borotropic Shift Sequence.J. Soc.2017, 139, 9519–9522. 10. Ganesh V.; K.Alkynyl Moiety Triggering 1,2-Metallate Shifts: p-Arylacetylenes.Angew. 9752–9756. 11. Wang Y. H.; Noble Sandford Trifluoromethyl-Radical-Induced Three-Component Furans.Angew. 1810–1814. 12. Wilson C. ortho- para-Phenols 16318–16322. 13. K.ortho-Directing Chromium Arene Complexes Efficient Mediators C(sp2)–C(sp3) Cross-Coupling Reactions.Angew. Ed.2018, 57, 1082–1086. 14. K.Chiral Aniline Stereospecific C(sp3)–C(sp2) Aryl Hydrazines.Org. Lett.2018, 20, 6144–6147. 15. Silvi Schrof Alkylation Furan Indole.Chem. Eur. J.2018, 24, 4279–4282. 16. Rubial B.; Collins B. S. 1,1-Diarylalkanes Rearrangement/Anti-SN 2? Elimination/Rearomatizing Allylic Sequence.Angew. Ed.2019, 58, 1366–1370. 17. Rygus P. G.; Crudden M.Enantiospecific Iterative Cross-Couplings.J. 18124–18137. 18. Miyaura Suzuki A.Palladium-Catalyzed Reactions Compounds.Chem. Rev.1995, 95, 2457–2483. 19. Bergmann A. Oldham You Brown M. K.Copper-Catalyzed Aryl-, Primary Alkyl-, Alkylboranes Bromides.Chem. Commun.2018, 54, 5381–5384. 20. Chen Cao Yin X.; Liao Y.; Jiang Ye J.Modular 1,1,2-Triarylethanes Enantioselective Arylboration Sequence.ACS Catal.2017, 7, 2425–2429. 21. Ziebenhaus Ghozati K.; Unsworth Nambo Voth Hutchinson Laberge Maekawa Imao D.Iterative Protecting Group-Free Leading Chiral Multiply Arylated Structures.Nat. Commun.2016, 11065. 22. Blaisdell T. Morken P.Hydroxyl