Catalytic allylboron additions to aldimines are presented for which small amounts of Zn(OMe)₂ serve as the co-catalyst to accelerate allyl exchange and 1,3-borotropic shift processes. Low-yielding and moderately α- and diastereoselective reactions are thus turned into highly efficient γ-, diastereo-, and enantioselective transformations that exhibit considerable scope.

Multicomponent catalytic enantioselective transformations that entail the combination of butadiene or isoprene (common feedstock), an enoate (prepared in one step) and B₂(pin)₂ (commercially available) are presented. These processes constitute an uncommon instance of conjugate addition of an allyl moiety and afford the desired products in up to 83 % yield and 98:2 enantiomeric ratio. Based on DFT calculations stereochemical models and rationale for the observed profiles in selectivity are provided.

A catalytic method for the site- and enantioselective addition of commercially available di-B(pin)-methane to allylic phosphates is introduced (pin=pinacolato). Transformations may be facilitated by an NHC–Cu complex (NHC=N-heterocyclic carbene) and products obtained in 63–95 % yield, 88:12 to >98:2 S_N2′/S_N2 selectivity, and 85:15–99:1 enantiomeric ratio. The utility of the approach, entailing the involvement of different catalytic cross-coupling processes, is highlighted by its application to the formal synthesis of the cytotoxic natural product rhopaloic acid A.

A set of broadly applicable methods for efficient catalytic additions of easy-to-handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic α-ketoesters was developed. Accordingly, a large array of tertiary alcohols can be obtained in 60 to >98 % yield and up to 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of the small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh₃) results in much higher enantioselectivity. With α-ketoesters, on the other hand, not only does the opposite hold true, since Me substitution leads to substantially higher enantioselectivity, but the sense of the selectivity is reversed as well.

Catalytic allylboron additions to aldimines are presented for which small amounts of Zn(OMe)₂ serve as the co-catalyst to accelerate allyl exchange and 1,3-borotropic shift processes. Low-yielding and moderately α- and diastereoselective reactions are thus turned into highly efficient γ-, diastereo-, and enantioselective transformations that exhibit considerable scope.

Readily accessible and easy-to-handle Ru complexes capable of generating all-Z polynorbornene and polynorbornadiene by ring-opening metathesis polymerization (ROMP) with controllable selectivity, ranging from ≈50 to ≥95 % syndiotactic, are introduced. It is demonstrated that the rate of non-metathesis based polytopal isomerization and levels of syndiotacticity may be fine-tuned by the adjustment of monomer concentration and catalyst's steric and electronic characteristics.

A set of broadly applicable methods for efficient catalytic additions of easy-to-handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic α-ketoesters was developed. Accordingly, a large array of tertiary alcohols can be obtained in 60 to >98 % yield and up to 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of the small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh₃) results in much higher enantioselectivity. With α-ketoesters, on the other hand, not only does the opposite hold true, since Me substitution leads to substantially higher enantioselectivity, but the sense of the selectivity is reversed as well.

Multicomponent catalytic enantioselective transformations that entail the combination of butadiene or isoprene (common feedstock), an enoate (prepared in one step) and B₂(pin)₂ (commercially available) are presented. These processes constitute an uncommon instance of conjugate addition of an allyl moiety and afford the desired products in up to 83 % yield and 98:2 enantiomeric ratio. Based on DFT calculations stereochemical models and rationale for the observed profiles in selectivity are provided.

Readily accessible and easy-to-handle Ru complexes capable of generating all-Z polynorbornene and polynorbornadiene by ring-opening metathesis polymerization (ROMP) with controllable selectivity, ranging from ≈50 to ≥95 % syndiotactic, are introduced. It is demonstrated that the rate of non-metathesis based polytopal isomerization and levels of syndiotacticity may be fine-tuned by the adjustment of monomer concentration and catalyst's steric and electronic characteristics.

A catalytic method for the site- and enantioselective addition of commercially available di-B(pin)-methane to allylic phosphates is introduced (pin=pinacolato). Transformations may be facilitated by an NHC–Cu complex (NHC=N-heterocyclic carbene) and products obtained in 63–95 % yield, 88:12 to >98:2 S_N2′/S_N2 selectivity, and 85:15–99:1 enantiomeric ratio. The utility of the approach, entailing the involvement of different catalytic cross-coupling processes, is highlighted by its application to the formal synthesis of the cytotoxic natural product rhopaloic acid A.

Molybdenum-, tungsten-, and ruthenium-based complexes that control the stereochemical outcome of olefin metathesis reactions have been recently introduced. However, the complementary nature of these systems through their combined use in multistep complex molecule synthesis has not been illustrated. A concise diastereo- and enantioselective route that furnishes the anti-proliferative natural product neopeltolide is now disclosed. Catalytic transformations are employed to address every stereochemical issue. Among the featured processes are an enantioselective ring-opening/cross-metathesis promoted by a Mo monoaryloxide pyrrolide (MAP) complex and a macrocyclic ring-closing metathesis that affords a trisubstituted alkene and is catalyzed by a Mo bis(aryloxide) species. Furthermore, Z-selective cross-metathesis reactions, facilitated by Mo and Ru complexes, have been employed in the stereoselective synthesis of the acyclic dienyl moiety of the target molecule.

Molybdenum-, tungsten-, and ruthenium-based complexes that control the stereochemical outcome of olefin metathesis reactions have been recently introduced. However, the complementary nature of these systems through their combined use in multistep complex molecule synthesis has not been illustrated. A concise diastereo- and enantioselective route that furnishes the anti-proliferative natural product neopeltolide is now disclosed. Catalytic transformations are employed to address every stereochemical issue. Among the featured processes are an enantioselective ring-opening/cross-metathesis promoted by a Mo monoaryloxide pyrrolide (MAP) complex and a macrocyclic ring-closing metathesis that affords a trisubstituted alkene and is catalyzed by a Mo bis(aryloxide) species. Furthermore, Z-selective cross-metathesis reactions, facilitated by Mo and Ru complexes, have been employed in the stereoselective synthesis of the acyclic dienyl moiety of the target molecule.

A broadly applicable Ru-catalyzed protocol for Z-selective ring-opening/cross-metathesis (ROCM) is disclosed. In addition to reactions relating to terminal alkenes of different sizes, the first examples of Z-selective ROCM processes involving heteroaryl olefins, 1,3-dienes, and O- and S-substituted alkenes as well as allylic and homoallylic alcohols are reported. Z-Selective transformations with an α-substituted allylic alcohol are shown to afford congested Z alkenes with high diastereoselectivity. Transformations are performed in the presence of 2.0–5.0 mol % of a recently disclosed Ru-based dithiolate complex that can be easily prepared in a single step from commercially available starting materials. Typically, transformations proceed at ambient temperature and are complete within eight hours; products are obtained in up to 97 % yield, >98:2 Z/E, and >98:2 diastereomeric ratio. The present investigations reveal a mechanistically significant attribute of the Ru-based dithiolates that arises from electrostatic interactions with anionic S-based ligands.

The first examples of Lewis base catalyzed enantioselective boryl conjugate additions (BCAs) that generate products containing boron-substituted quaternary carbon stereogenic centers are disclosed. Reactions are performed in the presence of 1.0–5.0 mol % of a readily accessible chiral accessible N-heterocyclic carbene (NHC) and commercially available bis(pinacolato)diboron; cyclic or linear α,β-unsaturated ketones can be used and rigorous exclusion of air or moisture is not necessary. The desired products are obtained in 63–95 % yield and 91:9 to >99:1 enantiomeric ratio (e.r.). The special utility of the NHC-catalyzed approach is demonstrated in the context of an enantioselective synthesis of natural product antifungal (−)-crassinervic acid.

A broadly applicable Ru-catalyzed protocol for Z-selective ring-opening/cross-metathesis (ROCM) is disclosed. In addition to reactions relating to terminal alkenes of different sizes, the first examples of Z-selective ROCM processes involving heteroaryl olefins, 1,3-dienes, and O- and S-substituted alkenes as well as allylic and homoallylic alcohols are reported. Z-Selective transformations with an α-substituted allylic alcohol are shown to afford congested Z alkenes with high diastereoselectivity. Transformations are performed in the presence of 2.0–5.0 mol % of a recently disclosed Ru-based dithiolate complex that can be easily prepared in a single step from commercially available starting materials. Typically, transformations proceed at ambient temperature and are complete within eight hours; products are obtained in up to 97 % yield, >98:2 Z/E, and >98:2 diastereomeric ratio. The present investigations reveal a mechanistically significant attribute of the Ru-based dithiolates that arises from electrostatic interactions with anionic S-based ligands.

The availability of enantiomerically enriched carbonyl-containing compounds is essential to the synthesis of biologically active molecules. Since catalytic enantioselective conjugate addition (ECA) reactions directly generate the latter valuable class of molecules, the design and development of such protocols represents a compelling objective in modern chemistry. Herein, we disclose the first solution to the problem of ECA of alkenyl groups to acyclic trisubstituted enones, an advance achieved by adopting an easily modifiable and fully catalytic approach. The requisite alkenylaluminum reagents are synthesized with exceptional site- and/or stereoselectivity by a Ni-catalyzed hydroalumination process, and the necessary enones are prepared through a site- and stereoselective zirconocene-catalyzed carboalumination/acylation reaction. The all-catalytic procedure is complete within four hours, furnishing the desired products in up to 77 % overall yield and 99:1 enantiomeric ratio.

The availability of enantiomerically enriched carbonyl-containing compounds is essential to the synthesis of biologically active molecules. Since catalytic enantioselective conjugate addition (ECA) reactions directly generate the latter valuable class of molecules, the design and development of such protocols represents a compelling objective in modern chemistry. Herein, we disclose the first solution to the problem of ECA of alkenyl groups to acyclic trisubstituted enones, an advance achieved by adopting an easily modifiable and fully catalytic approach. The requisite alkenylaluminum reagents are synthesized with exceptional site- and/or stereoselectivity by a Ni-catalyzed hydroalumination process, and the necessary enones are prepared through a site- and stereoselective zirconocene-catalyzed carboalumination/acylation reaction. The all-catalytic procedure is complete within four hours, furnishing the desired products in up to 77 % overall yield and 99:1 enantiomeric ratio.

The first examples of Lewis base catalyzed enantioselective boryl conjugate additions (BCAs) that generate products containing boron-substituted quaternary carbon stereogenic centers are disclosed. Reactions are performed in the presence of 1.0–5.0 mol % of a readily accessible chiral accessible N-heterocyclic carbene (NHC) and commercially available bis(pinacolato)diboron; cyclic or linear α,β-unsaturated ketones can be used and rigorous exclusion of air or moisture is not necessary. The desired products are obtained in 63–95 % yield and 91:9 to >99:1 enantiomeric ratio (e.r.). The special utility of the NHC-catalyzed approach is demonstrated in the context of an enantioselective synthesis of natural product antifungal (−)-crassinervic acid.

The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2–7.5 mol % of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73 % Z) epilachnene (15-membered ring: 91 % Z), ambrettolide (17-membered ring: 91 % Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97 % Z), and nakadomarin A (15-membered ring: up to 97 % Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule.

An exceptionally site- and E-selective catalytic method for preparation of Si-containing alkenes through protosilylation of terminal alkynes is presented. Furthermore, the vinylsilanes obtained are used as substrates to generate vicinal or geminal borosilanes by another catalytic process; such products are derived from enantioselective protoborations of the Si-substituted alkenes. All transformations are catalyzed by N-heterocyclic carbene (NHC) copper complexes. Specifically, a commercially available imidazolinium salt, cheap CuCl (1.0 mol %) and Me₂PhSi–B(pin), readily and inexpensively prepared in one vessel, are used to convert terminal alkynes to (E)-β-vinylsilanes efficiently (79–98 % yield) and in >98 % E and >98 % β-selectivity. Vinylsilanes are converted to borosilanes with 5.0 mol % of a chiral NHC–Cu complex in 33–94 % yield and up to 98.5:1.5 enantiomeric ratio (e.r.). Alkyl-substituted substrates afford vicinal borosilanes exclusively; aryl- and heteroaryl-substituted alkenes deliver the geminal isomers preferentially. Different classes of chiral NHCs give rise to high enantioselectivities in the two sets of transformations: C₁-symmetric monodentate Cu complexes are most suitable for reactions of alkyl-containing vinylsilanes and bidentate sulfonate-bridged variants furnish the highest e.r. for substrates with an aryl substituent. Working models that account for the observed trends in selectivity are provided. Utility is demonstrated through application towards a formal enantioselective total synthesis of naturally occurring antibacterial agent bruguierol A.

Chiral olefin metathesis catalysts enable chemists to access enantiomerically enriched small molecules with high efficiency; synthesis schemes involving such complexes can be substantially more concise than those that would involve enantiomerically pure substrates and achiral Mo alkylidenes or Ru-based carbenes. The scope of research towards design and development of chiral catalysts is not limited to discovery of complexes that are merely the chiral versions of the related achiral variants. A chiral olefin metathesis catalyst, in addition to furnishing products of high enantiomeric purity, can offer levels of efficiency, product selectivity and/or olefin stereoselectivity that are unavailable through the achiral variants. Such positive attributes of chiral catalysts (whether utilized in racemic or enantiomerically enriched form) should be considered as general, applicable to other classes of transformations.

Chirale Olefinmetathesekatalysatoren bieten einen Weg für die hoch effiziente Synthese enantiomerenangereicherter Moleküle. Synthesen unter Beteiligung derartiger Komplexe können deutlich kürzer und praktischer sein als entsprechende Umsetzungen von enantiomerenreinen Substraten in Gegenwart von achiralen Molybdänalkylidenen oder Rutheniumcarbenen. Damit geht die Forschung auf dem Gebiet der chiralen Katalysatoren über die Entwicklung chiraler Varianten achiraler Verbindungen hinaus, denn ein chiraler Olefinmetathesekatalysator kann nicht nur Zugang zu Produkten hoher Enantiomerenreinheit bieten, sondern darüber hinaus auch Syntheseeffizienzen, Produktselektivitäten und/oder E/Z-Stereoselektivitäten bieten, die mit den achiralen Varianten nicht erreichbar sind. Dieses positive Attribut chiraler Katalysatoren (ob nun in racemischer oder enantiomerenangereichter Form eingesetzt) sollte allgemeingültig sein, d. h. auf andere Formen der chemischen Umwandlung übertragen werden können.