Synthesis and Application of Easily Recyclable Thiomorpholines for Use in Sulfur Ylide Mediated Asymmetric Epoxidation of Aldehydes

Abstract

Chiral nonracemic thiomorpholines have been synthesized in four to six steps from limonene or achiral alkenes using alpha-methylbenzylamine to control absolute stereochemistry. These aminosulfides have been used to generate sulfur ylides, which have been applied in the asymmetric epoxidation of aldehydes as easily recoverable catalysts. Excellent yields (up to 98 %), enantioselectivities (up to 97:3 e.r.), and diastereoselectivities (>or=98:2 trans/cis) were achieved in these epoxidations and the sulfides were easily recovered in high yield (up to 97 %) by simple acid/base extraction.

Diastereoselective and Enantioselective Formal [4+1] Ylide Annulation Leading to Optically Active Isoxazoline N‐Oxides

“…[2] At the same time, asymmetric processes (including direct sulfide catalyzed asymmetric reactions and indirect sulfide catalyzed asymmetric reactions) which involved sulfur ylides for the cascade reactions is another research topic of importance [3,4,2d] . To the best of our knowledge, whether the direct sulfide‐catalyzed asymmetric reactions or indirect sulfide‐catalyzed asymmetric reactions, the asymmetric [2+1] annulations, such as aldehyde epoxidations [3a–g,4a−g] and aldimine aziridinations, [3i–j] have been well established. However, only a few types of indirect sulfide‐catalyzed asymmetric [4+1] annulations to construct five‐membered cyclic compounds have been successfully developed in the past years [2d–f,4i−p] .…”

“…As shown in Scheme 2, the asymmetric [4+1] ylide annulations of the α‐benzoyl sulfonium salts 1 and α‐bromonitroalkene 2 a proceeded to afford isoxazoline N ‐oxide 3 aa at room temperature under the same conditions. The chiral sulfonium salt 1 a ‐ 1 which include Br − has appeared to be an efficient intermediate for asymmetric cyclization reactions to construct three‐membered cyclic compounds, [4a–h] but the asymmetric [4+1] ylide annulation of α‐bromonitroalkene 2 a with 1 a ‐ 1 became complicated and low yield was isolated. Other chiral sulfonium salts, such as 1 a ‐ 2 , 1 a ‐ 3 , were also explored and only moderate yields were obtained due to their low solubility in organic solvents.…”

Organokatalytische asymmetrische Epoxidierungen – Reaktionen, Mechanismen und Anwendungen

“…Es wurde festgestellt, dass der Katalysator 130 am besten mit Benzyliodid als Reagens wirkt und zu mittleren Ausbeuten, hoher Diastereoselektivität und geringer Enantioselektivität führt. [111] In allen Fällen waren jedoch lange Reaktionszeiten (7-14 d) erforderlich. [ Neben den von Campher abgeleiteten und C 2 -symmetrischen Sulfidkatalysatoren wurden mehrere andere Zusätze entwickelt.…”

“…[ [108] Der Aufbau von 128 a wurde mit der Entwicklung des Katalysators 131 verbessert (Schema 41). [ [111] In allen Fällen waren jedoch lange Reaktionszeiten (7-14 d) erforderlich. Es wurde demonstriert, dass das Sulfid 133 bei Benzaldehyd katalytisch wirkt, wodurch das trans-Diphenylepoxid in hoher Ausbeute und mit guter Diastereo-und Enantioselektivität gebildet wird.…”

Synthesis of 6- and 7-Membered N-Heterocycles Using α-Phenylvinylsulfonium Salts

“…We have observed similar effects in thiomorpholines previously. 18 To demonstrate synthetic utility, N-Ts morpholine cis-15a was deprotected using a sodium/naphthalene reduction and isolated as the hydrochloride salt 17 in excellent yield as a single diastereoisomer (Scheme 4). The S N Ar deprotection of N-Ns morpholine cis-15i with 2-mercaptoethanol and DBU 19 was also achieved, leading to the HCl salt 17 in excellent yield.…”