Direct and Asymmetric Aldol Reactions of N‐Azidoacetyl‐1, 3‐thiazolidine‐2‐thione Catalyzed by Chiral Nickel(II) Complexes. A New Approach to the Synthesis of β‐Hydroxy‐α‐Amino Acids. Issue 38 (26th May 2022)

• Record Type: Journal Article
• Authors: Teloxa, Saul F.; Mellado‐Hidalgo, Miguel; Kennington, Stuart C. D.; Romea, Pedro; Urpí, Fèlix; Aullón, Gabriel; Font‐Bardia, Mercè
• Is Part Of: Chemistry. Volume 28:Issue 38(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-26
• Subjects: asymmetric synthesis -- aldol reaction -- catalysis -- nickel(II) complexes -- peptides; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202200671
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A direct and asymmetric triisopropylsilyltrifluoromethanesulfonate (TIPSOTf) mediated aldol reaction of N ‐azidoacetyl‐1, 3‐thiazolidine‐2‐thione with aromatic aldehydes catalyzed by a chiral nickel(II)‐Tol‐BINAP complex has been developed (BINAP=2, 2'‐bis(diphenylphosphino)‐1, 1'‐binaphthyl). The catalytic protocol gives the corresponding anti α‐azido‐β‐silyloxy adducts with outstanding stereocontrol and in high yields. Theoretical calculations account for the stereochemical outcome of the reaction and lay the foundations for a mechanistic model. In turn, the easy removal of the thiazolidinethione yields a wide array of enantiomerically pure derivatives in a straightforward and efficient manner. Such a noteworthy character of the heterocyclic scaffold together with the appropriate manipulation of the azido group open a new route to the synthesis of di‐ and tripeptide blocks containing a β‐aryl‐β‐hydroxy‐α‐amino acid. Abstract : Enantiomerically pure anti N ‐β‐aryl‐β‐silyloxy‐α‐azidoacetyl thioimides are efficiently prepared through a direct aldol reaction from N ‐azidoacetyl‐1, 3‐thiazolidine‐2‐thione and a wide array of aromatic aldehydes catalyzed by 2–6 mol% [Tol‐BINAP]Ni(II) complexes. The straightforward removal of the heterocyclic scaffold facilitates their conversion into a variety of chiral intermediates. Indeed, treatment of the resultant thioimides with α‐amino ester hydrochlorides gives access to the corresponding dipeptides as well as the appropriate manipulation of the azido group yields peptidic fragments of kasumigamide and atrutamycin.