Asymmetric Synthesis of 4,8-Dihydroxyisochroman-1-one Polyketide Metabolites Using Chiral Hypervalent Iodine(III)

Abstract

Stereoselective oxylactonization of ortho-alkenylbenzoate with chiral hypervalent iodine is applied to the asymmetric synthesis of 4-oxyisochroman-1-one polyketide metabolites including 4-hydroxymellein (1), a derivative of fusarentin 2, monocerin (3), and an epimer of monocerin epi-3.

Vicinal Difunctionalization of Alkenes with Iodine(III) Reagents and Catalysts

“…[36] The power of the present transformation was then again demonstrated within short syntheses of several polyketide metabolites. [40] For example, Fujita investigated the cyclization of the chiral homoallylic ether 81 (Scheme 13). In the presence of the achiral iodine reagent PhIA C H T U N G T R E N N U N G (OAc) 2 21, two diastereomers 82 and 83 are formed as equimolar mixtures, which indicates that the chiral center of the substrate does not exercise influence over the stereochemistry of the cyclization.…”

“…Under such conditions, dioxygenation reactions are capable of generating a series of interesting building blocks for various syntheses of biologically interesting molecules. [40] In the cases of 87 b,c, catalyst control was operating overcoming eventual stereochemical influences through the 1,3-diol groups of the products. [41] Efforts to generate efficient enantioselective catalyses employing the chiral aryl iodides are ongoing.…”

Conformationally-Flexible Chiral Hypervalent Organoiodine Catalysts for Enantioselective Oxidative Transformations

“…27 They also succeeded in catalytic oxylactonization using chiral iodoarene 26 (10 mol %) in the presence of mCPBA (Scheme 9). 27 The asymmetric oxidative double cyclization of various (E) 2 (4 hydroxybut 1 en 1 yl)benzoates gave the corresponding dihydrofuran fused isochromanones in moderate yields with good to high enantioselectivities.…”

Asymmetric Synthesis with Hypervalent Iodine Reagents

“…Further elaboration of this reaction principle using substrates such as 2-ethenylbenzoic acid 29 and methyl ortho-alkenylbenzoates provided enantiodifferentiating endo-selective oxylactonizations after oxidation with chiral iodine reagents 27 and 28 (Scheme 12) [51,52]. The protocol developed here was found quite useful in the synthesis of several polyketide metabolites [53,54]. In addition to the stoichiometric use of iodine(III) reagents, these oxylactonization reactions can also be performed using only a catalytic amount of chiral iodoarenes in presence of mCPBA as terminal oxidant [51].…”