Total synthesis of (12R)- and (12S)-12-hydroxymonocerins: stereoselective oxylactonization using a chiral hypervalent iodine(iii) species

Abstract

The first total syntheses of (12R)-and (12S)-12-hydroxymonocerins are described. The oxolane-fused isochroman-1-one framework is stereoselectively constructed via a double oxy-cyclization using a lactatebased chiral hypervalent iodine reagent. A catalytic variant of the double oxy-cyclization is also demonstrated using a chiral iodoarene as the precatalyst and m-CPBA as the co-oxidant.

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

“…[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. For example, Fujita and co-workers described catalytic conditions for the cyclization of a substrate related to 79 (Scheme 12) using mCPBA as terminal oxidant.…”

“…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…”

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].…”

Hypervalent Iodine‐Catalyzed Oxidative Functionalizations Including Stereoselective Reactions

“…In addition, it was also demonstrated that intramolecular hydrogen‐bonding interactions and additional achiral alcohols play crucial roles in the selectivity. Fujita and co‐workers have achieved hypervalent iodine‐catalyzed enantioselective oxylactonization with up to 91 % enantiomeric excess by using a similar type of chiral lactate‐based iodine(III) catalysts 84b–d. Very recently, Kita and co‐workers85 introduced chiral ortho ‐functionalized spirobiindanes 188 as precatalyst and spirolactonizations were achieved with up 92 % enantiomeric excess.…”