Iridium‐Catalyzed Reductive Strecker Reaction for Late‐Stage Amide and Lactam Cyanation

Abstract

A new iridium-catalyzed reductive Strecker reaction for the direct and efficient formation of α-amino nitrile products from a broad range of (hetero)aromatic and aliphatic tertiary amides, and N-alkyl lactams is reported. The protocol exploits the mild and highly chemoselective reduction of the amide and lactam functionalities using IrCl(CO)[P(C H ) ] (Vaska's complex) in the presence of tetramethyldisiloxane, as a reductant, to directly generate hemiaminal species able to undergo substitution by cyanide upon treatment with TMSCN (TMS=trimethylsilyl). The protocol is simple to perform, broad in scope, efficient (up to 99 % yield), and has been successfully applied to the late-stage functionalization of amide- and lactam-containing drugs, and naturally occurring alkaloids, as well as for the selective cyanation of the carbonyl carbon atom linked to the N atom of proline residues within di- and tripeptides.

A Celebration of Science amidst Nature: The 54th Bürgenstock Conference

“…Thetopic of his lecture was the catalytic approaches for simplifying complex molecule synthesis.H is research focuses on catalytic stereoselective synthesis,a nd on the investigation of new methodologies,which are able to simplify the synthesis of structurally complex frameworks,n atural products and molecules of biological importance.Main contributions of his research linked to new, highly enantioselective methods development, total synthesis of complex natural products,n ew cooperative catalyst designs,a nd new cascade reactions.D uring his presentation he showed his results on the (total/retro) synthesis of manzamine A, [25] (AE)-epi-epiquinamide, [26] (AE)-vincadifformine, [27] (À)-himalensine A, [28] late-stage functionalization of amides and lactams. [29] He also presented examples of BIMPcatalyzed reactions (BIMP/ bifunctional iminophosphoranetype catalysts), such as nitro-Mannich reactions ( Figure 5), [30] and sulfa-Michael addition reactions. [31] On Tu esday evening,wewere entertained by aBossa nova concert performed by four excellent instrumentalists:P ierre Gillet (7 string guitar), BenoîtM inon (7 string guitar), Thibault Dille (accordion) and Marcos Della Rocha (percussions).…”

Ein Fest der Wissenschaft inmitten der Natur: Die 54. Bürgenstock‐Konferenz

“…Während seiner Präsentation zeigte er seine Ergebnisse zur Total/Retro-Synthese von Manzamin A, [25] (AE)-Epi-Epichinamid, [26] (AE)-Vincadifformin, [27] (À)-Himalensin A [28] sowie die Spätfunktionalisierung von Amiden und Lactamen. [29] Er präsentierte auch Beispiele fürB IMP-katalysierte Reaktionen ("BIMP" steht fürb ifunktionelle Iminophosphoran-Katalysatoren), wie Nitro-Mannich-Reaktionen (Abbildung 5) [30] und Sulfa-Michael-Additionsreaktionen. [31] Am Dienstagabend wurden wir von einem Bossa-Nova-Konzert mit vier hervorragenden Instrumentalisten unterhalten:P ierre Gillet (7-Saiter), BenoîtM inon (7-Saiter), Thibault Dille (Akkordeon) und Marcos Della Rocha (Percussions).…”

Direct Transformations of Amides: Tactics and Recent Progress

“…按照这一机理, 叔酰胺需要含 α-H. 然而, 我们 课题组的结果表明不含 α-H 的叔酰胺同样可进行催化 还原官能化(图式 10d) [49] . 这随后得到 Dixon 小组 [50] 的 证实. 值得一提的是, Dixon 的方法…”