Silacyclopentadienes constitute a class of promising organicmaterials for optoelectronic applications, such as organic light-emitting diodes(OLEDs). For rapid screening of optimal properties, the developmentof efficient and divergent synthetic methodologies for silacyclopentadienederivatives is required. Herein, a versatile synthetic method for2-substituted 1-silaindenes is communicated. Ruthenium-catalyzed trans-selective hydrosilylation of alkynesusing dimethyl(2-vinylphenyl)silane, which is readily prepared from 2-bromostyrene,gives branch-type adducts exclusively. Following ring-closing metathesis(RCM) using Grubbs II catalyst provides a wide varietyof 2-substituted 1-silaindenes.
As shown in , the carboamination reactions are effective for transformations involving derivatives of several different amino acids including phenylalanine (1a), valine (1b), serine (1c), and alanine (1d-e). The reactions are tolerant of functionalized aryl groups on N-1 (e.g., p-chlorophenyl and p-cyanophenyl) and several different protecting groups on N-4 (e.g., benzyl, allyl, and p-methoxyphenyl). Electron-rich, -neutral, and -poor aryl bromides can be employed as coupling partners, although use of β-bromostyrene provided low yields (ca. 25%) of the desired allylpiperazine derivative. In most cases the cyclizations afforded cis-2,6-disubstituted piperazines with >20:1 dr, although cyclizations of 1c proceed with slightly lower (14:1) diastereoselectivity.,
As shown in , our approach to the construction of 2,6-disubstituted piperazines employs a key Pd-catalyzed carboamination reaction,, which generates the heterocyclic ring and forms two bonds simultaneously. Retrosynthetic analysis of the carboamination substrates (1) suggested these compounds could be prepared in a straightforward and modular fashion from simple precursors: amino acids (readily available in enantiopure form), allylic amines, and aryl halides. In addition to the synthetic utility of this strategy, the key cyclization reaction is a fundamentally interesting and challenging transformation. The generation of six-membered rings through Pd-catalyzed carboamination or carboetherification reactions between heteroatom-tethered alkenes and aryl/alkenyl halides has not been previously described, nor has the construction of heterocyclic rings bearing more than one nitrogen atom been achieved using this method. Thus, this transformation represents a significant advance in Pd-catalyzed alkene carboamination methodology.
In conclusion, we have developed a new, stereoselective, asymmetric synthesis of N-aryl-2,6-disubstituted piperazines. This strategy allows the modular construction of a number of derivatives containing different substituents at C2, C6, N1, and N4 from simple starting materials. The key cyclizations are the first examples of 6-membered ring formation in Pd-catalyzed carboamination reactions between alkene-tethered amines and aryl halides. Further studies on the scope, stereochemical outcome, and applications of these transformations are currently underway.