Enantioselective Addition of Pyrazoles to Dienes**

Abstract

We report the first enantioselective addition of pyrazoles to 1,3-dienes. Secondary and tertiary allylic pyrazoles can be generated with excellent regioselectivity. Mechanistic studies support a pathway distinct from previous hydroaminations: a Pd(0)-catalyzed ligand-toligand hydrogen transfer (LLHT). This hydroamination tolerates a range of functional groups and provides a breakthrough in hydrofunctionalization of dienes.

Transition-Metal-Free Regioselective Intermolecular Hydroamination of Conjugated 1,3-Dienes with Heterocyclic Amines

“…Feedstock dienes, such as myrcene and isoprene, surprisingly provided 1,4-hydroaminated products 3l – m (53–62%) with high regioselectivities. It is noteworthy to mention that the selectivity (1,4-hydroamination) we observed for the feedstock dienes ( 1l and 1m ) is different from the selectivity that Chen and Dong reported (1,2-hydroamination). Similar 1,4-hydroamination was witnessed when 4-bromo-3,5-dimethylpyrazole was used as an aminating agent with isoprene ( 3n , 60%).…”

“…To date, there have been only a few reports on the regioselective hydroamination of pyrazoles with dienes (Scheme a). All of the pioneering reports by Breit, Chen, and Dong are based on transition-metal catalysis, where they have utilized pyrazoles (and other N -heterocycles) with allenes and dienes to achieve enantioselective hydroaminated products. Therefore, the design of a transition-metal free protocol to apply these nitrogen heterocycles for a regioselective transformation is in high demand.…”

Palladium-Catalyzed Asymmetric Sequential Hydroamination of 1,3-Enynes: Enantioselective Syntheses of Chiral Imidazolidinones

“…The process also meets the requirements of green chemistry and sustainable development . Over the past decades, transition-metal-catalyzed hydroamination of unsaturated hydrocarbons, such as alkenes, allenes, 1,3-dienes, alkynes, and enynes, has been a valuable strategy to access various functionalized alkylamines and allylamines via the formation of a C–N bond. This approach has been applied to the synthesis of numerous pharmaceuticals and natural products …”

Cobalt-Catalyzed Z to E Geometrical Isomerization of 1,3-Dienes

“…However, these protocols are generally minimally stereoselective to furnish a mixture of E / Z isomers. The configuration of double bonds has dramatic influence on the physical and biological properties, as well as chemical reactivities . Transition-metal-catalyzed cross-coupling of stereochemically functionalized alkenes affords an efficient approach to access 1,3-dienes with high stereoselectivity .…”