Preparation of Macrocyclic

The first examples of catalyst-controlled stereoselective macrocyclic ring-closing metathesis reactions that generate Z-enoates as well as (E,Z)- or (Z,E)-dienoates are disclosed. Reactions promoted by 3.0–10 mol % of a Mo-based monoaryloxide pyrrolide complex proceed to completion within 2–6 h at room temperature. The desired macrocycles are formed in 79:21 to >98:2 Z/E selectivity; stereoisomerically pure products can be obtained in 43–75% yield after chromatography. Utility is demonstrated by application to a concise formal synthesis of the natural product (+)-aspicilin.United States. National Institutes of Health (GM-59426

Toward a simulation approach for alkene ring-closing metathesis : scope and limitations of a model for RCM

A published model for revealing solvent effects on the ring-closing metathesis (RCM) reaction of di-Et diallylmalonate 7 has been evaluated over a wider range of conditions, to assess its suitability for new applications. Unfortunately, the model is too flexible and the published rate consts. do not agree with exptl. studies in the literature. However, by fixing the values of important rate consts. and restricting the concn. ranges studied, useful conclusions can be drawn about the relative rates of RCM of different substrates, precatalyst concn. can be simulated accurately and the effect of precatalyst loading can be anticipated. Progress has also been made toward applying the model to precatalyst evaluation, but further modifications to the model are necessary to achieve much broader aims

The influence of structure on reactivity in alkene metathesis

Abstract Alkene metathesis has grown from a niche technique to a common component of the synthetic organic chemistry toolbox, driven in part by the development of more active catalyst systems, or those optimized for particular purposes. While the range of synthetic chemistry achieved has been exciting, the effects of structure on reactivity have not always been particularly clear, and rarely quantified. Understanding these relationships is important when designing new catalysts, reactions, and syntheses. Here, we examine what is known about the effect of structure on reactivity from two perspectives: the catalyst, and the substrate. The initiation of the precatalyst determines the rate at which active catalyst enters the catalytic cycle; the rate and selectivity of the alkene metathesis reaction is dependent on how the substrate and active catalyst interact. The tools deployed in modern studies of mechanism and structure/activity relationships in alkene metathesis are discussed

Mechanistically designed dual-site catalysts for the alternating ROMP of norbornene and cyclooctene

A chelating P,O ligand, designed according to recently worked-out mechanistic concepts, converts an unselective first-generation ruthenium carbene complex into a chemoselective ROMP catalyst that assembles an alternating copolymer from a mixture of norbornene and cyclooctene

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>

Asymmetric Induction and Enantiodivergence in Catalytic Radical C–H Amination via Enantiodifferentiative H-Atom Abstraction and Stereoretentive Radical Substitution

Control of enantioselectivity remains a major challenge in radical chemistry. The emergence of metalloradical catalysis (MRC) offers a conceptually new strategy for addressing this and other outstanding issues. Through the employment of D2-symmetric chiral amidoporphyrins as the supporting ligands, Co(II)-based MRC has enabled the development of new catalytic systems for asymmetric radical transformations with a unique profile of reactivity and selectivity. With the support of new-generation HuPhyrin chiral ligands whose cavity environment can be fine-tuned, the Co-centered d-radicals enable to address challenging issues that require exquisite control of fundamental radical processes. As showcased with asymmetric 1,5-C–H amination of sulfamoyl azides, the enantiocontrol of which has proven difficult, the judicious use of HuPhyrin ligand by tuning the bridge length and other remote nonchiral elements allows for controlling both the degree and sense of asymmetric induction in a systematic manner. This effort leads to successful development of new Co(II)-based catalytic systems that are highly effective for enantiodivergent radical 1,5-C–H amination, producing both enantiomers of the strained five-membered cyclic sulfamides with excellent enantioselectivities. Detailed deuterium-labeling studies, together with DFT computation, have revealed an unprecedented mode of asymmetric induction that consists of enantiodifferentiative H-atom abstraction and stereoretentive radical substitution