C₃‐Symmetric Trisimidazoline‐Catalyzed Enantioselective Bromolactonization of Internal Alkenoic Acids

Abstract

A method for conducting enantioselective bromolactonization reactions of trisubstituted alkenoic acids, using the C(3)-symmetric trisimidazoline 1 and 1,3-dibromo-5,5-dimethyl hydantoin as a bromine source, has been developed. The process generates chiral δ-lactones that contain a quaternary carbon. The results of studies probing geometrically different olefins show that (Z)-olefins rather than (E)-olefins are favorable substrates for the process. The method is not only applicable to acyclic olefin reactants but can also be employed to transform cyclic trisubstituted olefins into chiral spirocyclic lactones. Finally, the synthetic utility of the newly developed process is demonstrated by its application to a concise synthesis of tanikolide, an antifungal marine natural product.

Enantioselective Bromolactonization of Trisubstituted Olefinic Acids Catalyzed by Chiral Pyridyl Phosphoramides

“…However, the halolactonization process conducted using trisubstituted olefinic acids remains underdeveloped despite its ability to produce various types of lactones containing two contiguous stereocenters with tetrasubstituted carbons. The sole example of a highly enantioselective halolactonization reaction was reported by Fujioka and co‐workers, in which the 6‐ exo cyclization was performed using chiral trisimidazoline catalysts [Scheme , reaction (1)] . In contrast, a general method for the 5‐ exo ‐ and 6‐ endo cyclization of trisubstituted olefins through a highly enantioselective bromolactonization reaction has not been developed yet, although a few examples of 5‐ exo cyclization with moderate stereoselectivity were reported [Scheme , reactions (2) and (3)] .…”

“…The sole example of ah ighly enantioselective halolactonization reactionwas reported by Fujioka and co-workers, in which the 6-exo cyclization was performed using chiral trisimidazoline catalysts[ Scheme 1, reaction (1)]. [12,13] In contrast, ag eneral method for the 5-exo-a nd 6-endo cyclization of trisubstituted olefins through ah ighly enantioselective bromolactonization reactionh as not been developed yet,a lthough af ew exampleso f5 -exo cyclization with moderate stereoselectivity werer eported [Scheme1,r eactions (2) and (3)]. [14] In this study,e nantioselective bromolactonizationr eactions with two distinct modes of cyclization enabled by using pyridylp hosphoramidea sasingle catalysta re described.From the resultso fo ur previouss tudy on pyridinium phosphoramide,w epredicted that Brønsted acid catalystsc ould be utilizedf or the enantioselective bromolactonization of olefinic acids.…”

Catalytic, Asymmetric Halofunctionalization of Alkenes—A Critical Perspective

“…The C 3 -symmetric trisimidazoline 25 catalyzes the bromolactonization of 1,1-disubstituted, [37] trisubstituted, and tetrasubstituted [38] olefins in the presence of 1,3-dibromo-5,5dimethylhydantoin (DBDMH; Scheme 16). All of the examples are 5-aryl-substituted hexenoic acids (R 1 ) but both aromatic and aliphatic substituents can be incorporated at the terminus (R 2 /R 3 ).…”

Katalytische asymmetrische Halogenfunktionalisierung von Alkenen – eine kritische Betrachtung

“…In dem von Denmark verwendeten System wird (S)-17 zusammen mit dem Cokatalysator Triphenylphosphinsulfid eingesetzt (Schema 9), und das Substratspektrum ist auf 5-Aryl-4-pentenole beschränkt. [30] Alkohole mit Z-konfigurierten Doppelbindungen ergeben fast ausschließlich das Produkt der exo-Cyclisierung mit guter bis hoher Enantioselektivität, dagegen liefern Alkohole mit E-konfigurierten Das C 3 -symmetrische Trisimidazolin 25 katalysiert die Bromlactonisierung von 1,1-disubstituierten, [37] trisubstituierten und tetrasubstituierten [38] Alkenen in Gegenwart von 1,3-Dibrom-5,5-dimethylhydantoin (DBDMH; Schema 16…”