一价铑卡宾介导的不对称硅氢及硼氢插入反应研究

本文主要由两部分内容组成：第一部分内容研究了一价铑与手性双烯配 体催化的烯基重氮酯与硅烷之间的不对称硅氢键插入反应；第二部分内容介 绍了一价铑与手性双烯配体催化的烷基重氮酯与胺硼烷络合物之间的不对 称硼氢键插入反应。 第一部分 Rh(I)卡宾对硅氢键的不对称插入研究 有机硅化学是有机合成中年轻且富有生命力的领域之一。有机硅化合物 广泛应用于合成化学、农业化学、材料科学等学科中。近年来，围绕碳硅键 的构建，已相继报道了很多新颖的合成策略。在本课题组利用一价铑/手性双 烯配体络合物与重氮化合物原位形成金属卡宾中间体，实现了对包括硅氢键 等多类 X-H 键的不对称插入反应的基础上，通过进一步拓展，实现了烯基重 氮化合物 α-位点对一系列硅烷化合物的不对称硅氢键插入反应，以极高立体 选择性和区域选择性得到一系列 α-芳乙烯基-α-硅基酯类化合物。通过动力 学实验验证了反应经历了协同历程，碳氢键的形成为决速步骤。产物经过简 单的转化可以方便地构建得到 1,4-二醇以及氨基酸酯类化合物。 第二部分 Rh(I)卡宾对硼氢键的不对称插入研究 有机硼化合物是有机合成中极为重要的合成砌块，广泛用于偶联，重排， 加成等反应中，受到化学家们的青睐。因此，高效构建碳硼键，尤其是合成 手性硼烷化合物是目前研究的热点之一。基于课题组一价铑/手性双烯配体 催化体系成功用于胺硼烷络合物对芳基重氮的插入反应，通过合理设计调控 催化剂的活性，实现了烷基重氮酯对胺硼烷络合物的不对称硼氢键插入反应， 以高收率、高对映选择性得到一系列具有 α-烷基-α-硼基酯类结构的化合物， 拓展了这类硼氢插入反应的底物应用范围。

This dissertation consists of two parts: In the first part, the asymmetric silicon hydrogen bond insertion reaction between alkenyldiazoesters and silanes catalyzed by rhodium(I) and chiral diene ligands was studied; In the second part, the Rh(I)/diene catalyzed asymmetric boron hydrogen bond insertion of alkyldiazoesters and amine-borane complexes was introduced. 1. Asymmetric insertion of Rh(I) carbene into Si-H bond The chemistry of silicone is one of the young and vibrant fields of organic synthesis. Organosilicons are widely used in synthetic chemistry, agricultural chemistry, materials science and other disciplines. In recent years, many asymmetric synthetic strategies have been reported successively for the construction of carbon-silicon bonds. Our group has been focusing on designing new ligands, which have been utilized successfully with rhodium(I) into asymmetric insertion reactions of various types of X-H bonds, including the insertion of aryldiazo compounds into silicon-hydrogen bonds. Through further investigation, we realized the asymmetric Si-H insertion of alkenyldiazoeasters’ α-site into silane compounds, thus a variety of α-arylvinyl-α-silyl ester compounds were obtained with extremely high stereoselectivity and regioselectivity. The kinetic experiments proved that the reaction went through a synergistic process, and the formation of carbon-hydrogen bonds was the ratedetermining step. The products can be easily converted to 1,4-diol and β-amino acid esters through simple transformation. 2. Asymmetric insertion of Rh (I) carbene into B-H bond Organoboron compounds are extremely important building blocks in organic synthesis, they are favored by chemists for their wide uses in coupling, rearrangement, addition and other reactions. Therefore, the efficient construction of carbon-boron bonds, especially the synthesis of chiral borane compounds, is one of the current research hotspots. Based on the successful utilization of the chiral rhodium(I)/diene catalytic system in our group for the insertion reaction of amine-borane complexes to aryldiazos, we further optimized the activity and selectivity of the catalysts, thus, the asymmetric B-H insertion between alkyldiazoesters and amine-boranes was realized, dlivering a series of compounds with α-alkyl-α-boronyl ester structures in high yields and high enantiopurities. This work expands the zoom of B-H insertions.

[1] FRéMONT DP, MARION N, NOLAN SP. Carbenes: Synthesis, properties, and organometallic chemistry[J]. Coordination Chemistry Reviews, 2009, 253(7-8): 862-892.
[2] FISCHER D E O. Auf dem Weg zu Carben‐ und Carbin‐Komplexen Nobel‐Vortrag[J]. Angewandte Chemie, 1974, 86(16): 651-663.
[3] SCHROCK RR. Alkylidene complexes of niobium and tantalum[J]. Accounts of Chemical Research, 1979, 12(3): 98-104.
[4] DAVIES HM, HEDLEY SJ. Intermolecular reactions of electron-rich heterocycles with copper and rhodium carbenoids[J]. Chem Soc Rev, 2007, 36(7): 1109-1119.
[5] DAVIES HM, MANNING JR. Catalytic C-H functionalization by metal carbenoid and nitrenoid insertion[J]. Nature, 2008, 451(7177): 417-424.
[6] ZHOU JL, WANG LJ, XU H, et al. Highly Enantioselective Synthesis of Multifunctionalized Dihydrofurans by Copper-Catalyzed Asymmetric
[4 + 1] Cycloadditions of α-Benzylidene-β-ketoester with Diazo Compound[J]. ACS Catalysis, 2013, 3(4): 685-688.
[7] ALAMSETTI SK, SPANKA M, SCHNEIDER C. Synergistic Rhodium/Phosphoric Acid Catalysis for the Enantioselective Addition of Oxonium Ylides to ortho-Quinone Methides[J]. Angew Chem Int Ed Engl, 2016, 55(7): 2392-2396.
[8] HANSEN J, AUTSCHBACH J, DAVIES HM. Computational study on the selectivity of donor/acceptor-substituted rhodium carbenoids[J]. J Org Chem, 2009, 74(17): 6555-6563.
[9] YOSHINORI. YAMAMOTO NA. Selective reactions using allylic metals[J]. Chemical Reviews, 1993, 93(6): 2207-2293.
[10] TACKE F P, MüLLER B, THEIS B, et al. Sila-haloperidol, a silicon analogue of the dopamine (D2) receptor antagonist haloperidol: synthesis, pharmacological properties, and metabolic fate[J]. ChemMedChem, 2008, 3(1): 152-164.
[11] JOHANSSON L W, POPP F, TACKE R, et al. In vitro metabolism of haloperidol and sila-haloperidol: new metabolic pathways resulting from carbon/silicon exchange[J]. Drug Metabolism and Disposition, 2010, 38(1): 73-83.
[12] MOREIRA L, LIMA EJ. Bioisosterism: a useful strategy for molecular modification and drug design[J]. Current Medicinal Chemistry, 2005, 12(1): 23-49.
[13] ZHOU C, WANG X, QUAN XC, et al. Silicon-Containing Complex II Acaricides─Design, Synthesis, and Pharmacological Optimization[J]. Journal of Agricultural and Food Chemistry, 2022, 70(36): 11063-11074.
[14] WEI G, HUANG WM, WANG WJ, et al. Expanding the Chemical Space of Succinate Dehydrogenase Inhibitors via the Carbon-Silicon Switch Strategy[J]. Journal of Agricultural and Food Chemistry, 2021, 69(13): 3965-3971.
[15] BIKZHANOVA GA, TOULOKHNOVA IS, GATELY S, et al. Novel silicon-containing drugs derived from the indomethacin scaffold: Synthesis, characterization and evaluation of biological activity[J]. Silicon Chemistry, 2007, 3: 209-217.
[16] HENRY MJ. Mode of action of the fungicide flusilazole in ustilago maydis[J]. Pesticide Science, 1990, 28(1): 35-42.
[17] EFSA. Peer review of the pesticide risk assessment of the active substance silthiofam[J]. EFSA Journal, 2016, 14(8): e04574.
[18] HAGA TK. Synthesis and Chemistry of Agrochemicals IV[M]. IV. 1995, Washington, DC: American Chemical Society, 1995: 15-24.
[19] ZHOU C, CHENG JG, BEADLE R, et al. Design, synthesis and acaricidal activities of Cyflumetofen analogues based on carbon-silicon isosteric replacement[J]. Bioorganic & Medicinal Chemistry, 2020, 28(22): 115509-115519.
[20] GRIBBLE JR, PIRNOT MT, BANDAR JS, et al. Asymmetric Copper Hydride-Catalyzed Markovnikov Hydrosilylation of Vinylarenes and Vinyl Heterocycles[J]. Journal of the American Chemical Society, 2017, 139(6): 2192-2195.
[21] WEN HA, WAN XL, HUANG Z. Asymmetric Synthesis of Silicon-Stereogenic Vinylhydrosilanes by Cobalt-Catalyzed Regio- and Enantioselective Alkyne Hydrosilylation with Dihydrosilanes[J]. Angewandte Chemie-International Edition, 2018, 57(21): 6319-6323.
[22] CHENG B, LIU WB, LU Z. Iron-Catalyzed Highly Enantioselective Hydrosilylation of Unactivated Terminal Alkenes[J]. Journal of the American Chemical Society, 2018, 140(15): 5014-5017.
[23] KITANOSONO T, ZHU L, LIU C, et al. An Insoluble Copper(II) Acetylacetonate–Chiral Bipyridine Complex that Catalyzes Asymmetric Silyl Conjugate Addition in Water[J]. Journal of the American Chemical Society, 2015, 137(49): 15422-15425.
[24] ZHANG YX, HANG J, GUO YY, et al. Access to Enantioenriched Organosilanes from Enals and β-Silyl Enones: Carbene Organocatalysis[J]. Angewandte Chemie International Edition, 2018, 57(17): 4594-4598.
[25] LANDAIS Y, PLANCHENAULT D. Asymmetric metal carbene insertion into the Si-H bond[J]. Tetrahedron Letters, 1994, 35(26): 4565-4568.
[26] RICHARD T.BUCK, MICHAEL P. DOYLE, MARTIN J. DRYSDALE, et al. Asymmetric rhodium carbenoid insertion into the Si-H bond[J]. Tetrahedron Letters, 1996, 37(42): 7631-7634.
[27] DAVIES ML, HANSE T, RUTBERG J, et al. Rhodium(II) (S)-N-(arylsulfonyl)prolinate catalyzed asymmetric insertions of vinyl- and phenylcarbenoids into the Si-H bond[J]. Tetrahedron Letters, 1997, 38(10): 1741-1744.
[28] KITAGAKI S, KINOSHITA M, MASAKOTAKEBA, et al. Enantioselective Si-H insertion of methyl phenyldiazoacetate catalyzed by dirhodium(II) carboxylates incorporating N-phthaloyl-(S)-amino acids as chiral bridging ligands[J]. Tetrahedron: Asymmetry, 2000, 11(19): 3855-3859.
[29] YASUTOMI Y, SUEMATSU H, KATSUKI T. Iridium(III)-Catalyzed Enantioselective Si−H Bond Insertion and Formation of an Enantioenriched Silicon Center[J]. Journal of the American Chemical Society, 2010, 132(13): 4510-4511.
[30] IGLESIAS MJ, NICASIO MC, CABALLERO A, et al. Silver-catalyzed silicon-hydrogen bond functionalization by carbene insertion[J]. Dalton Trans, 2013, 42(4): 1191-1195.
[31] KAN SB, LEWIS RD, CHEN K, et al. Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life[J]. Science, 2016, 354(6315): 1048-1051.
[32] NAKAGAWA Y, CHANTHAMATH S, FUJISAWA I, et al. Ru(ii)-Pheox-catalyzed Si-H insertion reaction: construction of enantioenriched carbon and silicon centers[J]. Chem Commun (Camb), 2017, 53(26): 3753-3756.
[33] WANG Y, CUI H, WEI ZW, et al. Engineering catalytic coordination space in a chemically stable Ir-porphyrin MOF with a confinement effect inverting conventional Si-H insertion chemoselectivity[J]. Chem Sci, 2017, 8(1): 775-780.
[34] LIU Z, LI Q, YANG Y, et al. Silver(i)-promoted insertion into X-H (X = Si, Sn, and Ge) bonds with N-nosylhydrazones[J]. Chem Commun (Camb), 2017, 53(16): 2503-2506.
[35] LIU Z, HUO J, FU T, et al. Palladium(0)-catalyzed C(sp(3))-Si bond formation via formal carbene insertion into a Si-H bond[J]. Chem Commun (Camb), 2018, 54(81): 11419-11422.
[36] WANG EH, PING YJ, LI ZR, et al. Iron Porphyrin Catalyzed Insertion Reaction of N-Tosylhydrazone-Derived Carbenes into X-H (X = Si, Sn, Ge) Bonds[J]. Org Lett, 2018, 20(15): 4641-4644.
[37] SHEFFIELD W, ABSHIRE A, DARKO A. Effect of Tethered, Axial Thioether Coordination on Rhodium(II)-Catalyzed Silyl-Hydrogen Insertion[J]. European Journal of Organic Chemistry, 2019, 2019(37): 6347-6351.
[38] HUANG MY, YANG JM, ZHAO YT, et al. Rhodium-Catalyzed Si–H Bond Insertion Reactions Using Functionalized Alkynes as Carbene Precursors[J]. ACS Catalysis, 2019, 9(6): 5353-5357.
[39] JAGANNATHAN J R, FETTINGER J C, SHAW J T, et al. Enantioselective Si-H Insertion Reactions of Diarylcarbenes for the Synthesis of Silicon-Stereogenic Silanes[J]. J Am Chem Soc, 2020, 142(27): 11674-11679.
[40] YANG LL, EVANS D, XU B, et al. Enantioselective Diarylcarbene Insertion into Si-H Bonds Induced by Electronic Properties of the Carbenes[J]. J Am Chem Soc, 2020, 142(28): 12394-12399.
[41] YANG LL, OUYANG J, ZOU HN, et al. Enantioselective Insertion of Alkynyl Carbenes into Si-H Bonds: An Efficient Access to Chiral Propargylsilanes and Allenylsilanes[J]. J Am Chem Soc, 2021, 143(17): 6401-6406.
[42] YANG LL, CAO J, ZHAO TY, et al. Chiral Dirhodium Tetraphosphate-Catalyzed Enantioselective Si-H Bond Insertion of alpha-Aryldiazoacetates[J]. J Org Chem, 2021, 86(14): 9692-9698.
[43] LIU B, XU MH. Rhodium(I)-Catalyzed Enantioselective C(sp3)—H Functionalization via Carbene-Induced Asymmetric Intermolecular C—H Insertion[J]. Chinese Journal of Chemistry, 2021, 39(7): 1911-1915.
[44] ZHU DX, XIA H, LIU JG, et al. Regiospecific and Enantioselective Arylvinylcarbene Insertion of a C-H Bond of Aniline Derivatives Enabled by a Rh(I)-Diene Catalyst[J]. J Am Chem Soc, 2021, 143(6): 2608-2619.
[45] ZHU D X, LIU J G, XU M H. Stereodivergent Synthesis of Enantioenriched 2,3-Disubstituted Dihydrobenzofurans via a One-Pot C-H Functionalization/Oxa-Michael Addition Cascade[J]. J Am Chem Soc, 2021, 143(23): 8583-8589.
[46] SUN YT, RAO XF, XU WC, XU MH. Rhodium(I)-catalyzed C–S bond formation via enantioselective carbenoid S–H insertion: catalytic asymmetric synthesis of α-thioesters[J]. Organic Chemistry Frontiers, 2022, 9(13): 3467-3472.
[47] WANG TY, CHEN XX, ZHU DX, et al. Rhodium(I) Carbene-Promoted Enantioselective C-H Functionalization of Simple Unprotected Indoles, Pyrroles and Heteroanalogues: New Mechanistic Insights[J]. Angew Chem Int Ed Engl, 2022, 61(34): e202207008.
[48] CHEN D, ZHU DX, XU MH. Rhodium(I)-Catalyzed Highly Enantioselective Insertion of Carbenoid into Si–H: Efficient Access to Functional Chiral Silanes[J]. Journal of the American Chemical Society, 2016, 138(5): 1498–1501.
[49] JAGANNATHAN JR, FETTINGER JC, SHAW JT, et al. Enantioselective Si–H Insertion Reactions of Diarylcarbenes for the Synthesis of Silicon-Stereogenic Silanes[J]. Journal of the American Chemical Society, 2020, 142(27): 11674-11679.
[50] DOYLE MP. Chiral catalysts for enantioselective carbenoid cyclopropanation reactions[J]. Recueil Des Travaux Chimiques Des Pays-Bas et de la Belgique, 1991, 110(7-8): 305-316.
[51] LANDAIS Y, PARRA-RAPADO L, PLANCHENAULT D. Mechanism of metal-carbenoid insertion into the SiH bond[J]. Tetrahedron Letters, 1996, 38(2): 229-232.
[52] DIAZ DB, YUDIN AK. The versatility of boron in biological target engagement[J]. Nature Chemistry, 2017, 9: 731–742.
[53] BAKER SJ, TOMSHO JW, BENKOVIC SJ. Boron-containing inhibitors of synthetases[J]. Chemical Society Reviews, 2011, 40(8): 4279-4285.
[54] BAKER SJ, DING CZ, AKAMA T, et al. Therapeutic potential of boron-containing compounds[J]. Future Medicinal Chemistry, 2009, 1(7): 1275-1288.
[55] GROZIAK MP. Boron Therapeutics on the Horizon[J]. American Journal of Therapeutics, 2001, 8(5): 321–328.
[56] BROWN HC. From little acorns to tall oaks: from boranes through organoboranes[J]. Science, 1980, 210(4469): 485-492.
[57] XU L, WANG GH, et al. Recent advances in catalytic C−H borylation reactions[J]. Tetrahedron Letters, 2017, 73(51): 7123-7157.
[58] WANG GH, XU L, LI PF. Double N,B-Type Bidentate Boryl Ligands Enabling a Highly Active Iridium Catalyst for C–H Borylation[J]. Journal of the American Chemical Society, 2015, 137(25): 8058–8061.
[59] IBRAHEEM AI, JONATHAN HB, TODD BM, et al. C−H Activation for the Construction of C−B Bonds[J]. Chemical Reviews, 2010, 110(2): 890–931.
[60] ISHIYAMA T, MURATA M, MIYAURA N. Palladium(0)-Catalyzed Cross-Coupling Reaction of Alkoxydiboron with Haloarenes: A Direct Procedure for Arylboronic Esters[J]. The Journal of Organic Chemistry, 1995, 60(23): 7508–7510.
[61] BURGESS K, OHLMEYER MJ. Transition-metal promoted hydroborations of alkenes, emerging methodology for organic transformations[J]. Chemical Reviews, 1991, 91(6): 1179–1191.
[62] ZHAO Q, DEWHURST RD, BRAUNSCHWEIG H, et al. A New Perspective on Borane Chemistry: The Nucleophilicity of the B-H Bonding Pair Electrons[J]. Angew Chem Int Ed Engl, 2019, 58(11): 3268-3278.
[63] LI X, CURRAN DP. Insertion of reactive rhodium carbenes into boron-hydrogen bonds of stable N-heterocyclic carbene boranes[J]. J Am Chem Soc, 2013, 135(32): 12076-12081.
[64] CHENG QQ, ZHU SF, ZHANG YZ, et al. Copper-catalyzed B-H bond insertion reaction: a highly efficient and enantioselective C-B bond-forming reaction with amine-borane and phosphine-borane adducts[J]. J Am Chem Soc, 2013, 135(38): 14094-14097.
[65] CHENG QQ, XU H, ZHU SF, et al. Enantioselective Copper-Catalyzed B—H Bond Insertion Reaction of α-Diazoketones[J]. Acta Chimica Sinica, 2015, 73(4)
[66] ALLEN TH, CURRAN DP. Relative Reactivity of Stable Ligated Boranes and a Borohydride Salt in Rhodium(II)-Catalyzed Boron-Hydrogen Insertion Reactions[J]. J Org Chem, 2016, 81(5): 2094-2098.
[67] ALLEN TH, KAWAMOTO T, GARDNER S, et al. N-Heterocyclic Carbene Boryl Iodides Catalyze Insertion Reactions of N-Heterocyclic Carbene Boranes and Diazoesters[J]. Org Lett, 2017, 19(13): 3680-3683.
[68] YANG JM, LI ZQ, LI ML, et al. Catalytic B-H Bond Insertion Reactions Using Alkynes as Carbene Precursors[J]. J Am Chem Soc, 2017, 139(10): 3784-3789.
[69] KAN SB, HUANG X, GUMULYA Y, et al. Genetically programmed chiral organoborane synthesis[J]. Nature, 2017, 552(7683): 132-136.
[70] PANG Y, HE Q, LI ZQ, et al. Rhodium-Catalyzed B-H Bond Insertion Reactions of Unstabilized Diazo Compounds Generated in Situ from Tosylhydrazones[J]. J Am Chem Soc, 2018, 140(34): 10663-10668.
[71] BROOK AG. Molecular rearrangements of organosilicon compounds[J]. Accounts of Chemical Research, 1974, 7(3): 77–84.
[72] YE JH, QUACH L, PAULISCH T, et al. Visible-Light-Induced, Metal-Free Carbene Insertion into B-H Bonds between Acylsilanes and Pinacolborane[J]. J Am Chem Soc, 2019, 141(41): 16227-16231.
[73] LI J, HE H, HUANG M, et al. Iridium-Catalyzed B-H Bond Insertion Reactions Using Sulfoxonium Ylides as Carbene Precursors toward alpha-Boryl Carbonyls[J]. Org Lett, 2019, 21(22): 9005-9008.
[74] HUANG X, GARCIA-BORRAS M, MIAO K, et al. A Biocatalytic Platform for Synthesis of Chiral alpha-Trifluoromethylated Organoborons[J]. ACS Cent Sci, 2019, 5(2): 270-276.
[75] CHEN K, HUANG X, ZHANG SQ, et al. Engineered Cytochrome c-Catalyzed Lactone-Carbene B-H Insertion[J]. Synlett, 2019, 30(4): 378-382.
[76] ZHANG SS, XIE H, SHUB, et al. Iridium-catalyzed B-H insertion of sulfoxonium ylides and borane adducts: a versatile platform to alpha-boryl carbonyls[J]. Chem Commun (Camb), 2020, 56(3): 423-426.
[77] DRIKERMANN D, MOSSEL RS, AL-JAMMAL WK, et al. Synthesis of Allylboranes via Cu(I)-Catalyzed B-H Insertion of Vinyldiazoacetates into Phosphine-Borane Adducts[J]. Org Lett, 2020, 22(3): 1091-1095.
[78] OTOG N, CHANTHAMATH S, FUJISAWA I, et al. Catalytic Asymmetric Carbene Insertion Reactions into B−H Bonds Using a Ru(II)‐Pheox Complex[J]. European Journal of Organic Chemistry, 2021, 2021(10): 1564-1567.
[79] ANKUDINOV NM, CHUSOV DA, NELYUBINA YV, et al. Synthesis of Rhodium Complexes with Chiral Diene Ligands via Diastereoselective Coordination and Their Application in the Asymmetric Insertion of Diazo Compounds into E-H Bonds[J]. Angew Chem Int Ed Engl, 2021, 60(34): 18712-18720.
[80] ZHAO YT, SU YX, LI XY, et al. Dirhodium-Catalyzed Enantioselective B-H Bond Insertion of gem-Diaryl Carbenes: Efficient Access to gem-Diarylmethine Boranes[J]. Angew Chem Int Ed Engl, 2021, 60(45): 24214-24219.
[81] WENG CY, ZHU GY, ZHU BH, et al. A copper-catalyzed B–H bond insertion reaction of azide–ynamide with borane adducts via α-imino copper carbenes[J]. Organic Chemistry Frontiers, 2022, 9(10): 2773-2778.
[82] HUANG MY, ZHAO YT, ZHANG CD, et al. Highly Regio-, Stereo-, and Enantioselective Copper-Catalyzed B-H Bond Insertion of alpha-Silylcarbenes: Efficient Access to Chiral Allylic gem-Silylboranes[J]. Angew Chem Int Ed Engl, 2022, 61(26): e202203343.
[83] ZHANG G, ZHANG Z, HOU M, et al. Construction of boron-stereogenic compounds via enantioselective Cu-catalyzed desymmetric B-H bond insertion reaction[J]. Nat Commun, 2022, 13(1): 2624.
[84] CHEN D, ZHANG X, QI WY, et al. Rhodium(I)-catalyzed asymmetric carbene insertion into B-H bonds: highly enantioselective access to functionalized organoboranes[J]. J Am Chem Soc, 2015, 137(16): 5268-5271.