Enantioselective Oxidation of Alkenylbenzoates Catalyzed by Chiral Hypervalent Iodine(III) To Yield 4‐Hydroxyisochroman‐1‐ones

Abstract

In this study, the enantioselective oxylactonization of ortho‐alk‐1‐enylbenzoates with chiral hypervalent iodine(III) reagents yielded 3‐alkyl‐4‐hydroxyisochroman‐1‐ones with high enantiomeric purity (ca. 90 % ee). The enantioselective oxidation was also performed under catalytic conditions, in which a catalytic amount (10 mol‐%) of a chiral iodoarene was oxidized to the hypervalent iodine species in situ using a stoichiometric co‐oxidant, m‐chloroperbenzoic acid (mCPBA). The catalytic oxidation mediated by chiral hypervalent iodine(III) species yielded enantiocontrolled syn products, while the direct oxidation of the substrate with mCPBA occurred as background oxidation to give racemic anti products. Under optimized conditions, the catalytic oxylactonization led to high levels of enantioselectivity (ca. 90 % ee) and improved syn/anti selectivities (ca. 80 % syn). The product distribution indicated that the lactate side‐chain on the chiral iodoarene precatalyst plays an important role in enhancing both the enantioselectivity and the catalytic efficiency in the oxylactonization.

Enantioselective, Catalytic Fluorolactonization Reactions with a Nucleophilic Fluoride Source

“…6 We hypothesized that a hypervalent iodine catalysis of a nucleophilic fluorination pathway (“F − ”) could provide a complementary approach to regioisomeric fluorolactone products containing a C–F stereogenic center (Scheme 1, bottom), in a manner analogous to that observed in recently described enantioselective acetoxylactonization reactions. 7 Herein, we report the development of an enantioselective, catalytic fluorolactonization reaction for the preparation of 4-fluoroisochromanones in high enantio- and diastereoselectivity.…”

Iodoarene-Catalyzed Cyclizations of Unsaturated Amides

“…Recent examples include the catalytic enantioselective spirolactonization of phenols, 3 dioxygenation of styrenes, 4 and intramolecular C-H/C-H cross-coupling. 5 This ability to effect "metallike" synthetic transformations without the toxicity, supply or cost issues of transition metal salts is attractive.…”

“…There are few examples in the literature of iodoarene-catalyzed reactions involving alkenes. 4,13 One issue with these processes is the potential for undesired oxidation of the olefin in preference to the iodoarene especially as common oxidants for the conversion of iodoarenes into the active iodine(III) species include peracids. We began our investigation with N-allylbenzamide 1a and used reaction conditions similar to that used by us in previous reports, namely iodobenzene as the precatalyst with an oxidant, m-CPBA, an acid, TFA, and a solvent, acetonitrile, at room temperature (Table 1, entry 1).…”

Oxidative Heterocycle Formation Using Hypervalent Iodine(III) Reagents

“…In recent years, chiral hypervalent iodine(III) reagents have received immense attention and have been applied extensively in the stereoselective synthesis of heterocycles. In 2010, Fujita et al [53,54] documented an enantiodifferentiating endo-selective oxylactonization of ortho-alkenylbenzoates 55 by using a series of optically active lactate-derived iodine(III) reagents such as 57 (Scheme 14). This stereocontrolled transformation allowed efficient access to optically active 4-oxyisochromanones 56.…”