3‑Pyridazinylnitrenes and 2‑Pyrimidinylnitrenes

Mild flash vacuum thermolysis of tetrazolo­[1,5-<i>b</i>]­pyridazines <b>8T</b> generates small amounts of 3-azidopyridazines <b>8A</b> (<b>8aA</b>, IR 2145, 2118 cm^–1; <b>8bA</b>, 2142 cm^–1). Photolysis of the tetrazoles/azides <b>8T/8A</b> in Ar matrix generates 3-pyridazinylnitrenes <b>9</b>, detected by ESR spectroscopy (<b>9a</b>: <i>D</i>/<i>hc</i> = 1.006; <i>E</i>/<i>hc</i> = 0.003 cm^–1). Cyanovinylcarbenes <b>11</b>, derived from 4-diazobut-2-enenitriles <b>10</b>, are also detected by ESR spectroscopy (<b>11a</b>: <i>D</i>/<i>hc</i> = 0.362; <i>E</i>/<i>hc</i> = 0.021 cm^–1). Carbenes <b>11</b> rearrange to cyanoallenes <b>12</b> and 3-cyanocyclopropenes <b>13</b>. Triazacycloheptatetraenes <b>20</b> were not observed in the photolyses of <b>8</b>. Photolysis of tetrazolo­[1,5-<i>a</i>]­pyrimidines/2-azidopyridmidines <b>18T/18A</b> in Ar matrices at 254 nm yields 2-pyrimidinylnitrenes <b>19</b>, observable by ESR, UV, and IR spectroscopy (<b>19a</b>: ESR: <i>D</i>/<i>hc</i> = 1.217; <i>E</i>/<i>hc</i> = 0.0052 cm^–1). Excellent agreement with the calculated IR spectrum identifies the 1,2,4-triazacyclohepta-1,2,4,6-tetraenes <b>20</b> (<b>20a</b>, 1969 cm^–1; <b>20b</b>, 1979 cm^–1). Compounds <b>20</b> undergo photochemical ring-opening to 1-isocyano-3-diazopropenes <b>23</b>. Further irradiation also causes Type II ring-opening of pyrimidinylnitrenes <b>19</b> to 2-(cyanimino)­vinylnitrenes <b>21</b> (<b>21a</b>: <i>D</i>/<i>hc</i> = 0.875; <i>E</i>/<i>hc</i> = 0.00 cm^–1), isomerization to cyaniminoketenimine <b>25</b> (2044 cm^–1), and cyclization to 1-cyanopyrazoles <b>22</b>. The reaction mechanisms are discussed and supported by DFT calculations on key intermediates and pathways. There is no evidence for the interconversion of 3-pyridazinylnitrenes <b>9</b> and 2-pyrimidinylnitrenes <b>19</b>

Readily Accessible and Easily Modifiable Ru-Based Catalysts for Efficient and <i>Z</i>‑Selective Ring-Opening Metathesis Polymerization and Ring-Opening/Cross-Metathesis

Rationally designed Ru-based catalysts for efficient <i>Z</i>-selective olefin metathesis are featured. The new complexes contain a dithiolate ligand and can be accessed in a single step from commercially available precursors in 68–82% yield. High efficiency and exceptional <i>Z</i> selectivity (93:7 to >98:2 <i>Z</i>:<i>E</i>) were achieved in ring-opening metathesis polymerization (ROMP) and ring-opening/cross-metathesis (ROCM) processes; the transformations typically proceed at 22 °C and are operationally simple to perform. Complete conversion was observed with catalyst loadings as low as 0.002 mol %, and turnover numbers of up to 43 000 were achieved without rigorous substrate purification or deoxygenation protocols. X-ray data and density functional theory computations provide support for key design features and shed light on mechanistic attributes

Reactivity and Selectivity Differences between Catecholate and Catecho­thiolate Ru Complexes. Implications Regarding Design of Stereoselective Olefin Metathesis Catalysts

The origins of the unexpected finding that Ru catecho­thiolate complexes, in contrast to cate­cholate derivatives, promote exceptional <i>Z</i>-selective olefin metathesis reactions are elucidated. We show that species containing a catecho­thiolate ligand, unlike cate­cholates, preserve their structural integrity under commonly used reaction conditions. DFT calculations indicate that, whereas alkene coordination is the stereo­chemistry-determining step with cate­cholate complexes, it is through the metalla­cyclo­butane formation that the identity of the major isomer is determined with catecho­thiolate systems. The present findings suggest that previous models for <i>Z</i> selectivity, largely based on steric differences, should be altered to incorporate electronic factors as well

Readily Accessible and Easily Modifiable Ru-Based Catalysts for Efficient and <i>Z</i>‑Selective Ring-Opening Metathesis Polymerization and Ring-Opening/Cross-Metathesis

Rationally designed Ru-based catalysts for efficient <i>Z</i>-selective olefin metathesis are featured. The new complexes contain a dithiolate ligand and can be accessed in a single step from commercially available precursors in 68–82% yield. High efficiency and exceptional <i>Z</i> selectivity (93:7 to >98:2 <i>Z</i>:<i>E</i>) were achieved in ring-opening metathesis polymerization (ROMP) and ring-opening/cross-metathesis (ROCM) processes; the transformations typically proceed at 22 °C and are operationally simple to perform. Complete conversion was observed with catalyst loadings as low as 0.002 mol %, and turnover numbers of up to 43 000 were achieved without rigorous substrate purification or deoxygenation protocols. X-ray data and density functional theory computations provide support for key design features and shed light on mechanistic attributes

The Influence of Anionic Ligands on Stereoisomerism of Ru Carbenes and Their Importance to Efficiency and Selectivity of Catalytic Olefin Metathesis Reactions

Investigations detailed herein provide insight regarding the mechanism of stereochemical inversion of stereogenic-at-Ru carbene complexes through a nonolefin metathesis-based polytopal rearrangement pathway. Computational analyses (DFT) reveal that there are two key factors that generate sufficient energy barriers that are responsible for the possibility of isolation and characterization of high-energy, but kinetically stable, intermediates: (1) donor–donor interactions that involve the anionic ligands and the strongly electron donating carbene groups and (2) dipolar effects arising from the syn relationship between the anionic groups (iodide and phenoxide). We demonstrate that a Brønsted acid lowers barriers to facilitate isomerization, and that the positive influence of a proton source is the result of its ability to diminish the repulsive electronic interactions originating from the anionic ligands. The implications of the present studies regarding a more sophisticated knowledge of the role of anionic units on the efficiency of Ru-catalyzed olefin metathesis reactions are discussed. The electronic basis for the increased facility with which allylic alcohols participate in olefin metathesis processes will be presented as well. Finally, we illustrate how a better understanding of the role of anionic ligands has served as the basis for successful design of Ru-based <i>Z</i>-selective catalysts for alkene metathesis

N‑Heterocyclic Carbene–Copper-Catalyzed Group‑, Site‑, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes

The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75–90% yield, 87:13 to >98:2 S_N2′/S_N2 (branched/linear) selectivity and 83:17–99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and <i>Z</i>-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC–Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate’s phosphate group to form the branched propargyl addition products as the dominant isomers via Cu­(III) π-allyl intermediate complexes

N‑Heterocyclic Carbene–Copper-Catalyzed Group‑, Site‑, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes

The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75–90% yield, 87:13 to >98:2 S_N2′/S_N2 (branched/linear) selectivity and 83:17–99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and <i>Z</i>-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC–Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate’s phosphate group to form the branched propargyl addition products as the dominant isomers via Cu­(III) π-allyl intermediate complexes

Enantioselective Synthesis of Trisubstituted Allenyl–B(pin) Compounds by Phosphine–Cu-Catalyzed 1,3-Enyne Hydroboration. Insights Regarding Stereochemical Integrity of Cu–Allenyl Intermediates

Catalytic enantio­selective boron–hydride additions to 1,3-enynes, which afford allenyl–B­(pin) (pin = pinacolato) products, are disclosed. Transformations are promoted by a readily accessible bis-phosphine–Cu complex and involve commercially available HB­(pin). The method is applicable to aryl- and alkyl-substituted 1,3-enynes. Trisubstituted allenyl–B­(pin) products were generated in 52–80% yield and, in most cases, in >98:2 allenyl:propargyl and 92:8–99:1 enantiomeric ratio. Utility is highlighted through a highly diastereo­selective addition to an aldehyde, and a stereospecific catalytic cross-coupling process that delivers an enantiomerically enriched allene with three carbon-based substituents. The following key mechanistic attributes are elucidated: (1) Spectroscopic and computational investigations indicate that low enantio­selectivity can arise from loss of kinetic stereo­selectivity, which, as suggested by experimental evidence, may occur by formation of a propargylic anion generated by heterolytic Cu–C cleavage. This is particularly a problem when trapping of the Cu–allenyl intermediate is slow, namely, when an electron deficient 1,3-enyne or a less reactive boron–hydride reagent (e.g., HB­(dan) (dan = naphthalene-1,8-diaminato)) is used or under non-optimal conditions (e.g., lower boron–hydride concentration causing slower trapping). (2) With enynes that contain a sterically demanding <i>o</i>-aryl substituent considerable amounts of the propargyl–B­(pin) isomer may be generated (25–96%) because a less sterically demanding transition state for Cu/B exchange becomes favorable. (3) The phosphine ligand can promote isomerization of the enantiomerically enriched allenyl–B­(pin) product; accordingly, lower ligand loading might at times be optimal. (4) Catalytic cross-coupling with an enantiomerically enriched allenyl–B­(pin) compound might proceed with high stereospecificity (e.g., phosphine–Pd-catalyzed cross-coupling) or lead to considerable racemization (e.g., phosphine–Cu-catalyzed allylic substitution)

Pentacoordinate Ruthenium(II) Catecholthiolate and Mercaptophenolate Catalysts for Olefin Metathesis: Anionic Ligand Exchange and Ease of Initiation

The investigations disclosed offer insight regarding several key features of Ru-based catecholthiolate olefin metathesis catalysts. Factors influencing the facility with which the two anionic ligands undergo exchange and those that affect the rates of catalyst release are elucidated by examination of more than a dozen new complexes. These studies shed light on how different chelating groups can influence Ru–S bond strength and, as a result, the facility of catecholthiolate rotation. The trans influence series ether < ester ≈ iodide < amine ≈ thioether ≈ olefin < isonitrile ≈ phosphite has been established through X-ray structural analysis and shown to correlate well with the barrier for catecholthiolate rotation (trans effect) determined by variable-temperature NMR experiments and computational studies (DFT). It is found that, apart from electronic factors, chelate geometry has a more notable effect on the rate of catalyst release (five- vs six-membered chelate ring and mono- vs bidentate ligand). Polytopal processes involving pentacoordinate Ru­(II) carbene complexes are shown to be distinct from previously reported fluxional events that involve tetracoordinate species and which are capable of causing diminished polymer syndiotacticity. Ru mercaptophenolate complexes have been synthesized and isolated as a single diastereomer (O–C trans to the NHC). This latter set of species promotes representative olefin metathesis reactions readily and gives <i>Z</i> selectivity levels that are higher than those when the corresponding catecholate systems are used, but less so in comparison to catecholthiolate complexes. A rationale for variations in stereoselectivity is presented

Regarding a Persisting Puzzle in Olefin Metathesis with Ru Complexes: Why are Transformations of Alkenes with a Small Substituent <i>Z</i>‑Selective?

An enduring question in olefin metathesis is that reactions carried out with widely accessible Ru dichloro complexes, which typically favor <i>E</i> alkenes, generate <i>Z</i> isomers preferentially when substrates bearing a smaller substituent are used; <i>Z</i> enol ethers, alkenyl sulfides, 1,3-enynes, alkenyl halides, or alkenyl cyanides can be prepared reliably with reasonable efficiency and selectivity. Transformations thus proceed via the more hindered <i>syn</i>-substituted metallacyclobutanes, which is mystifying because catalyst features implemented in the more recently developed and broadly applicable <i>Z</i>-selective catalysts are absent in the Ru dichloro systems. Herein, we describe experimental and computational investigations that offer a plausible rationale for these puzzling selectivity trends. The following will be demonstrated. (1) Kinetic <i>Z</i> selectivity depends on the relative barrier for olefin association/dissociation versus metallacyclobutane formation/cleavage. There can be appreciable stereochemical control when metallacyclobutane formation/breakage is turnover-limiting. (2) Stereoelectronicnot purely stericeffects are central: achieving the p-orbital overlap needed for alkene formation while minimizing steric repulsion between the incipient olefin substituent and a catalyst’s anionic ligand during the cycloreversion step is crucial. We show that similar stereoelectronic factors are probably operative in the more recently introduced <i>Z</i>-selective (and enantioselective) olefin metathesis transformations promoted by stereogenic-at-Ru complexes containing a bidentate aryloxide ligand