Tropanes as Scaffolds for Phosphorus–Olefin Ligands and Their Application in Asymmetric Catalysis

Abstract

Tropane‐derived phosphorus–olefin hybrid ligands bearing various combinations of P‐units (chiral BINOL‐derived units/achiral PPh2‐units) with a tropene skeleton (chiral/achiral) have been synthesized and used in Cu‐catalysed conjugate 1,4‐additions of diethylzinc to cyclic enones and in Rh‐catalysed 1,4‐additions of phenylboronic acid (Hayashi–Miyaura reaction) with cyclic and acyclic enones. Whereas in Cu‐catalysed reactions only moderate yields and ee values (up to 49 % ee) were obtained, up to 97 % ee was observed in the Hayashi–Miyaura reaction with various substrates. The most promising results in both reactions were achieved with ligands 11 and 15, which contain a chiral alkene/achiral P‐unit or an achiral alkene/chiral P moiety, respectively, and where the metal is complexed on the exo side of the tropene skeleton. In contrast, ligands with an endo coordination mode showed only low (13) or no activity (12) in all of the 1,4‐additions. NMR and ESI‐MS experiments revealed the presence of two cationic [RhI(15)2]+ species in solution.

Total Synthesis of (±)‐Scopolamine: Challenges of the Tropane Ring

“…[26][27][28] The N-methyl group in 4 could alternatively be introduced by dealkoxycarbonylation with TMSI followed by reductive methylation. [29] Due to the moderate yields encountered for dealkoxycarbonylation of 7, the use of potentially hazardous diazo compounds 9 and the expensive catalyst [Rh 2 (OOct) 4 ], an alternative pathway was investigated. Another attractive method for the construction of the tropinone skeleton was realized by Robinson in 1917 (later optimized by Schöpf ) who used an ingenious three component one-pot reaction between succinaldehyde, methylamine hydrochloride and acetonedicarboxylic acid.…”

Pyrroles as Dienes in (4+3) Cycloadditions

“…Cycloadduct 41 thus obtained is reduc-tively debrominated to afford desired 8-azabicyclo[3.2.1]octenone 42, a valuable meso intermediate for the synthesis of tropinoids and other natural products. 35,36,39,[43][44][45][46][47][48][49][50] Starting from meso 42, Mann and de Almeida Barbosa reported a synthetic route to (±)-scopoline (Scheme 10). 39 The Noyori group converted 42 into (-)-hyoscyamine in 3-4 steps.…”

Synthesis, Structure, and Reactivity of Binaphthyl Supported Dihydro[1,6]diazecines

“…Monoolefine and diolefine ligands are often key players in homogeneous catalysis and have found various applications in asymmetric transformations [1,2]. The preferred structures are either rigid, based on bicyclic diene skeletons [3,4,5], semi-rigid, consisting of a mono-ene as part of a cycle which is linked to P [6,7] or S [8,9] functionalities as second coordination site, or flexible with the olefin part being a freely rotating pending side arm attached at a chiral back bone [10,11,12,13,14,15,16,17,18,19,20]. Some examples showing structural diversity are depicted in Figure 1.…”