Base-Free Cross-Couplings of Aryl Diazonium Salts in Methanol: Pd -Alkoxy as Reactivity-Controlling Intermediate.

Pd-catalyzed cross-coupling reactions of aryl diazonium salts are generally assumed to proceed via cationic Pd intermediates which in turn would be highly reactive in the subsequent transmetalation step. Contrary to this belief, we herein report our observation and rationalization of opposing reactivities of ArN in Suzuki (=effective) and Stille (=ineffective) cross-couplings in MeOH. Our systematic experimental and computational studies on the roles of transmetalating agent, solvent, base and the likely involvement of in situ formed diazoether derivatives challenge the currently accepted mechanism.

Divergent Reactivity of Stannane and Silane in the Trifluoromethylation of Pd : Cyclic Transition State versus Difluorocarbene Release.

The transmetalation is a key elementary step in cross-coupling reactions. Yet, the precise nature of its mechanism and transition state geometry are frequently elusive. This report discloses our study of the transmetalation of [Pd ]-F complexes with the silane- and stannane-based trifluoromethylation agents, R SiCF and R SnCF .

Computation and Experiment: A Powerful Combination to Understand and Predict Reactivities.

Computational chemistry has become an established tool for the study of the origins of chemical phenomena and examination of molecular properties. Because of major advances in theory, hardware and software, calculations of molecular processes can nowadays be done with reasonable accuracy on a time-scale that is competitive or even faster than experiments. This overview will highlight broad applications of computational chemistry in the study of organic and organometallic reactivities, including catalytic (NHC-, Cu-, Pd-, Ni-catalyzed) and noncatalytic examples of relevance to organic synthesis.

Pentafluorosulfanyl-containing flufenamic acid analogs: Syntheses, properties and biological activities.

Pentafluorosulfanyl-containing analogs of flufenamic acid have been synthesized in high yields. Computationally, pKa, LogP and LogD values have been determined. Initial bioactivity studies reveal effects as ion channel modulators and inhibitory activities on aldo-keto reductase 1C3 (AKR1C3) as well as COX-1 and COX-2.

Strain-accelerated formation of chiral, optically active buta-1,3-dienes.

The formal [2+2] cycloaddition-retroelectrocyclization (CA-RE) reactions between tetracyanoethylene (TCNE) and strained, electron-rich dibenzo-fused cyclooctynes were studied. The effect of ring strain on the reaction kinetics was quantified, revealing that the rates of cycloaddition using strained, cyclic alkynes are up to 5500 times greater at 298 K than those of reactions using unstrained alkynes. Cyclobutene reaction intermediates, as well as buta-1,3-diene products, were isolated and their structures were studied crystallographically.

Combining experimental and computational studies to understand and predict reactivities of relevance to homogeneous catalysis.

This article showcases three major uses of computational chemistry in reactivity studies: the application after, in combination with, and before experiment. Following a brief introduction of suitable computational tools, challenges and opportunities in the implementation of computational chemistry in reactivity studies are discussed, exemplified with selected case studies from our and other laboratories.

Trifluoromethylation of ketones and aldehydes with Bu₃SnCF₃.

The (trifluoromethyl)stannane reagent, Bu3SnCF3, was found to react under CsF activation with ketones and aldehydes to the corresponding trifluoromethylated stannane ether intermediates at room temperature in high yield. Only a mildly acidic extraction (aqueous NH4Cl) is required to release the corresponding trifluoromethyl alcohol products. The protocol is compatible with acid-sensitive functional groups.

Tandem nucleophilic addition/oxy-2-azonia-Cope rearrangement for the formation of homoallylic amides and lactams: total synthesis and structural verification of motuporamine G.

In the presence of a Lewis acid, β,γ-unsaturated ketones and oximes or imines undergo nucleophilic addition to produce zwitterion intermediates, and subsequent oxy-2-azonia-Cope rearrangements give homoallylic amides. In the case of 2-vinylcycloalkanones, the process results in ring enlargement, providing a novel route to 9- to 16-membered lactams. The preparative significance of this protocol was evidenced by a short synthesis of macrocyclic alkaloid motuporamine G.