Richard R. Schrock

Recent Advances in High Oxidation State Mo and W Imido Alkylidene Chemistry

In 1956 Eleuterio invoked what is now known as an olefin metathesis reaction in order to explain how certain heterogeneous Mo catalysts could produce polyethylene from propylene; he proposed that propylene was converted into 2-butene and ethylene and that ethylene was then selectively polymerized.i An intense interest in the catalytic olefin metathesis reaction developed in the 1970s as a consequence of the ability to synthesize various polymers from cyclic olefins using tungsten, molybdenum, and rhenium catalysts (prepared using a variety of recipes) and as people became aware of potential applications of olefin metathesis in organic chemistry. The accepted mechanism of the olefin metathesis reaction, the basic version of which is shown in equation 1, was proposed in 1971 by Herrison and Chauvin (equation 2),ii but no 2RCH=CHR′⇄RCH=CHR+R′CH=CHR′.(cis and trans equilibrated also) (1) (2) M=CHR complexes were known at that time that would react with olefins catalytically in a metathesis-like fashion. Therefore a search began for M=C complexes that would carry out the metathesis reaction rapidly and catalytically, could be isolated and studied, could be varied in great detail, and could tolerate various functional groups of interest in catalytic organic transformations.

Catalytic Z-selective olefin cross-metathesis for natural product synthesis

Alkenes are found in many biologically active molecules, and there are a large number of chemical transformations in which alkenes act as the reactants or products (or both) of the reaction. Many alkenes exist as either the E or the higher-energy Z stereoisomer. Catalytic procedures for the stereoselective formation of alkenes are valuable, yet methods enabling the synthesis of 1,2-disubstituted Z alkenes are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and of allylic amides, used until now only in E-selective processes. The corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. These transformations, promoted by catalysts that contain the highly abundant and inexpensive metal molybdenum, are amenable to gram-scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. The utility of this method is demonstrated by its use in syntheses of an anti-oxidant plasmalogen phospholipid, found in electrically active tissues and implicated in Alzheimer’s disease, and the potent immunostimulant KRN7000.

Highly efficient molybdenum-based catalysts for enantioselective alkene metathesis

Discovery of efficient catalysts is one of the most compelling objectives of modern chemistry. Chiral catalysts are in particularly high demand, as they facilitate synthesis of enantiomerically enriched small molecules that are critical to developments in medicine, biology and materials science. Especially noteworthy are catalysts that promote—with otherwise inaccessible efficiency and selectivity levels—reactions demonstrated to be of great utility in chemical synthesis. Here we report a class of chiral catalysts that initiate alkene metathesis with very high efficiency and enantioselectivity. Such attributes arise from structural fluxionality of the chiral catalysts and the central role that enhanced electronic factors have in the catalytic cycle. The new catalysts have a stereogenic metal centre and carry only monodentate ligands; the molybdenum-based complexes are prepared stereoselectively by a ligand exchange process involving an enantiomerically pure aryloxide, a class of ligands scarcely used in enantioselective catalysis. We demonstrate the application of the new catalysts in an enantioselective synthesis of the Aspidosperma alkaloid, quebrachamine, through an alkene metathesis reaction that cannot be promoted by any of the previously reported chiral catalysts.

Catalytic Asymmetric Olefin Metathesis

This paper provides a survey of the first examples of efficient catalytic enantioselective olefin metathesis reactions. Mo-catalyzed asymmetric ring-closing (ARCM) and ring-opening (AROM) reactions allow access to myriad optically enriched compounds that are otherwise difficult to access.

Olefin metathesis by molybdenum imido alkylidene catalysts

Abstract A “well-defined” alkylidene complex of the type Mo(CHCMe2Ph)(N-2,6-i-Pr2C6H3)[OCMe(CF3)2]2 has proven to be a useful initiator in catalytic olefin metathesis reactions of interest to organic chemists. A variety of related molybdenum imido alkylidene complexes can be prepared readily from a common precursor. This article is a summary of what is known about the details of the steps in a metathesis reaction catalyzed by complexes of the type Mo(CHR′)(NAr)(OR)2, and how the activity and stability of complexes of this type change upon altering each of the ligands in the pseudo-tetrahedral species. Some recent asymmetric ring-closing metathesis reactions are also discussed briefly.

Catalytic Reduction of Dinitrogen to Ammonia by Molybdenum: Theory versus Experiment

Molybdenum complexes that contain the triamidoamine ligand [(RNCH(2)CH(2))(3)N](3-) (R = 3,5-(2,4,6-iPr(3)C(6)H(2))(2)C(6)H(3)) catalyze the reduction of dinitrogen to ammonia at 22 degrees C and 1 atm with protons from 2,6-dimethylpyridinium and electrons from decamethylchromocene. Several theoretical studies have been published that bear on the proposed intermediates in the catalytic dinitrogen reduction reaction and their reaction characteristics, including DFT calculations on [(HIPTNCH(2)CH(2))(3)N]Mo species (HIPT =hexaisopropylterphenyl = 3,5-(2,4,6-iPr(3)C(6)H(2))(2)C(6)H(3)), which contain the actual triamidoamine ligand that is present in catalytic intermediates. Recent theoretical findings are compared with experimental findings for each proposed step in the catalytic reaction.

Synthesis of macrocyclic natural products by catalyst-controlled stereoselective ring-closing metathesis

Many natural products contain a C = C double bond through which various other derivatives can be prepared; the stereochemical identity of the alkene can be critical to the biological activities of such molecules. Catalytic ring-closing metathesis (RCM) is a widely used method for the synthesis of large unsaturated rings; however, cyclizations often proceed without control of alkene stereochemistry. This shortcoming is particularly costly when the cyclization reaction is performed after a long sequence of other chemical transformations. Here we outline a reliable, practical and general approach for the efficient and highly stereoselective synthesis of macrocyclic alkenes by catalytic RCM; transformations deliver up to 97% of the Z isomer owing to control induced by a tungsten-based alkylidene. Utility is demonstrated through the stereoselective preparation of epothilone C (refs 3–5) and nakadomarin A (ref. 6), the previously reported syntheses of which have been marred by late-stage, non-selective RCM. The tungsten alkylidene can be manipulated in air, delivering the products in useful yields with high stereoselectivity. As a result of efficient RCM and re-incorporation of side products into the catalytic cycle with minimal alkene isomerization, desired cyclizations proceed in preference to alternative pathways, even under relatively high substrate concentration.

Highly Z- and Enantioselective Ring-Opening/Cross-Metathesis Reactions Catalyzed by Stereogenic-at-Mo Adamantylimido Complexes

The first highly Z- and enantioselective class of ring-opening/cross-metathesis reactions is presented. Transformations are promoted in the presence of <2 mol % of chiral stereogenic-at-Mo monoaryloxide complexes bearing an adamantylimido ligand that are prepared and used in situ. Reactions involve meso oxabicyclic substrates and afford the desired pyrans in 50-85% yield and up to >98:<2 enantiomer ratio. Importantly, the desired chiral pyrans thus obtained bear a Z olefin either exclusively (>98:<2 Z/E) or predominantly (>or=87:13 Z/E).

Saturation of Cubic Optical Nonlinearity in Long-Chain Polyene Oligomers

The scaling of the cubic nonlinearity γ with chain length in polyenic molecules has received considerable theoretical attention. Earlier experimental investigations have been restricted to oligomers with fewer than 20 double bonds because of problems associated with the synthesis and solubility of conjugated molecules. These synthetic difficulties have been overcome in the present study by the use of modern living polymerization techniques. Solution measurements of γ as a function of chain length in long-chain (up to 240 double bonds) model polyene oligomers are reported. A saturation of the increase of γ with chain length is observed, and the onset of this saturation occurs for chain lengths considerably longer than predicted from theory.

Conjugation length dependence of Raman scattering in a series of linear polyenes: Implications for polyacetylene

We have measured the solid state Raman scattering spectra of a homologous series of linear polyenes, with the number of alternated double bonds varying from 3 to 12. While we find a linear dependence of the Raman shifts of resonantly coupled modes with inverse conjugation length, we have also followed the suggestion of previous work in examining the inverse square product of the several Raman frequencies as a function of the logarithm of the measured energy gap of the molecule. This provides a linear relationship, as found for trans‐polyacetylene, a result which is qualitatively consistent with the amplitude mode model of Horovitz and co‐workers. We also find, consistent with previous work on polyacetylene, a monotonic decrease in the ratios of oscillator strengths of the two strongest bands with conjugation length, as recently predicted by a series of molecular dynamics calculations. Suggested interpretations of a number of qualitative observations, including splitting of modes for shorter conjugation le...