A Catalytic Intermolecular Formal Ene Reaction between Ketone-Derived Silyl Enol Ethers and Alkynes.

A catalytic formal ene reaction between ketone-derived silyl enol ethers and terminal alkynes is described. This transformation is uniquely capable of bimolecular assembly of 2-siloxy-1,4-dienes and can be used to access ß,γ-unsaturated ketones containing quaternary carbons in the α-position.

Oxyboration with and without a Catalyst: Borylated Isoxazoles via B-O σ-Bond Addition.

Herein we report an oxyboration reaction with activated substrates that employs B-O σ bond additions to C-C π bonds to form borylated isoxazoles, which are potential building blocks for drug discovery. Although this reaction can be effectively catalyzed by gold, it is the first example of uncatalyzed oxyboration of C-C π bonds by B-O σ bonds--and only the second example that is catalyzed. This oxyboration reaction is tolerant of groups incompatible with alternative lithiation/borylation and palladium-catalyzed C-H activation/borylation technologies for the synthesis of borylated isoxazoles.

NMR spectroscopy studies of electronic effects and equilibrium in the organogold-to-boron transmetalation reaction and studies towards its application to the alkoxyboration addition of boron-oxygen σ bonds to alkynes.

Electronic effects in the transmetalation of an aryl group from gold to boron were investigated by NMR spectroscopy. The transmetalation reaction is more facile for increasingly electrophilic boron reagents and is in equilibrium under certain conditions. Observed tetracoordinate boronate compounds suggest a two-step, associative transmetalation reaction mechanism in which the organogold complex first delivers a nucleophilic phenyl group to the empty p orbital of boron. For certain substrates, this tetracoordinate intermediate decomposes to the tricordinate, final transmetallation product, and in others this tricordinate species remains in equilibrium with a tetracoordinate anionic boron compound. Experimental and theoretical investigations into the extension of this transmetalation reaction from a mechanistic step in our previously reported intramolecular gold-catalyzed addition of boron-oxygen σ bonds across alkynes to an intermolecular variant are discussed.2014 Elsevier Ltd. All rights reserved.

Alkoxyboration: ring-closing addition of B-O σ bonds across alkynes.

For nearly 70 years, the addition of boron-X σ bonds to carbon-carbon multiple bonds has been employed in the preparation of organoboron reagents. However, the significantly higher strength of boron-oxygen bonds has thus far precluded their activation for addition, preventing a direct route to access a potentially valuable class of oxygen-containing organoboron reagents for divergent synthesis. We herein report the realization of an alkoxyboration reaction, the addition of boron-oxygen σ bonds to alkynes. Functionalized O-heterocyclic boronic acid derivatives are produced using this transformation, which is mild and exhibits broad functional group compatibility. Our results demonstrate activation of this boron-O σ bond using a gold catalysis strategy that is fundamentally different from that used previously for other boron addition reactions.

Mechanistic Studies of Azaphilic versus Carbophilic Activation by Gold(I) in the Gold/Palladium Dual-Catalyzed Rearrangement of Alkenyl Vinyl Aziridines.

A vinyl aziridine activation strategy cocatalyzed by palladium(0) and a gold(I) Lewis acid has been developed. This rearrangement installs a C-C and a C-N bond in one synthetic step to form pyrrolizidine and indolizidine products. Two proposed mechanistic roles for the gold cocatalyst were considered: (1) carbophilic gold catalysis or (2) azaphilic gold catalysis. Mechanistic studies support an azaphilic Lewis acid activation of the aziridine over a carbophilic Lewis acid activation of the alkene.

Organogold reactivity with palladium, nickel, and rhodium: transmetalation, cross-coupling, and dual catalysis.

Using two transition metals to simultaneously catalyze a reaction can offer distinct opportunities for reactivity and selectivity when compared to using single-metal catalyst systems. Creating dual transition metal catalytic systems is complicated, however, by challenges in predicting compatible reactivities and designing turnover pathways for both metals. In this Account, we describe our development of dual-metal catalysis reactions involving gold and a second transition metal. The unique rearrangement intermediates accessible through gold-only catalysis, which exploits the soft Lewis acidity of Au(I), make gold an attractive partner for dual-metal catalysis reactions. Because of the complexity of achieving simultaneous turnover of two catalysts and predicting compatibilities, our approach has been to first gain a fundamental understanding of the reactivity of the two metals with each other, both in stoichiometric and monocatalyzed reactions. To this end, we have investigated the combined reactivity of organogold compounds with palladium, nickel, and rhodium. We narrate the intricacies of turning over two catalysts simultaneously and thereby illuminate the valuable role of fundamental studies in identifying the optimal conditions to promote desirable two-metal reactivity and compatibility. Transmetalation, redox reactivity, and new mechanisms for dual-metal catalytic turnover were probed from this standpoint. We have applied the knowledge gained through these studies to the development of reactions that are dual-catalyzed by gold and palladium, as well as nickel- and rhodium-catalyzed reactions of organogold compounds. More broadly, these new reactions expand the reactivity available to catalytic organogold intermediates via trapping and functionalization reactions with other transition metals. Our investigations reveal strategies useful for designing dual-metal reactions with gold. First, the versatility of gold as a transmetalation partner suggests that many potential methods may exist to intercept catalytic organogold intermediates with a second transition metal. Second, ligands on both metals should be selected carefully in order to prevent catalyst deactivation. Finally, reactions must be designed such that any oxidative steps involving the second metal outcompete undesired reactions with redox-active organogold compounds. We believe that the application of these principles will allow for the design of a diverse set of dual-catalyzed functionalizations befitting the wide variety of gold-catalyzed transformations already established.

Solid-state NMR spectroscopy of Pb-rich apatite.

Pb-containing hydroxylapatite phases synthesized under aqueous conditions were investigated by X-ray diffraction and solid-state nuclear magnetic resonance (NMR) techniques to determine the Pb, Ca distribution. 31P and 1H magic-angle spinning (MAS) NMR results indicate slight shifts of the isotropic chemical shift with increased Ca content and complex lineshapes at compositions with near equal amounts of Ca and Pb. 31P{207Pb} and 1H{207Pb} rotational-echo double resonance (REDOR) results for intermediate compositions show that resolved spectral features cannot be assigned simply in terms of local Ca, Pb configurations or coexisting phases. 207Pb MAS NMR spectra are easily obtained for these materials and contain well-resolved resonances for crystallographically unique A1 and A2 Pb sites. Splitting of the A1 and A2 207Pb resonances for pure hydroxyl-pyromorphite (Pb10(PO4)6(OH)2) compared to natural pyromorphite (Pb5(PO4)3Cl) suggests symmetry reduced from hexagonal. We find that 207Pb{1H} CP/MAS NMR is impractical in Pb-rich hydroxylapatites due to fast 207Pb relaxation.