Enantiodifferentiating endo‐Selective Oxylactonization of ortho‐Alk‐1‐enylbenzoate with a Lactate‐Derived Aryl‐λ³‐Iodane

Abstract

Ongoing efforts have been dedicated to the development of reaction processes controlled by chiral hypervalent iodine reagents with high enantioselectivity. [1][2][3][4][5][6][7][8][9][10][11][12] The oxidation of sulfides into sulfoxides, [2] the a-oxygenation of ketones, [3,4] the dioxygenation of alkenes, [4,5,12] and the dearomatization of phenols [6-8, 9b] have been reported, and most of these reactions resulted in an encouraging level of enantioselectivity. Kita and co-workers reported dearomatizing spirolactonization of naphthols (78-86 % ee) using a spirocyclic iodine(III) reagent.[6] Ishihara and co-workers recently reported that higher enantioselectivities were obtained for the spirolactonization by using a chiral iodine compound derived from lactic acid. [8] Our studies with optically active hypervalent iodine compounds have been focused on mechanisms of the reaction concerned [11] as well as synthetic applications.[12] Asymmetric oxidation of 4-acyloxybut-1-ene into 3-acyloxytetrahydrofuran (up to 64 % ee) was achieved by using chiral hypervalent iodine(III) reagents, 1 and 2, which have a lactate moiety as a chiral source.[12] During the course of these studies for the asymmetric oxidative cyclization of alkenes, we found that oxidation of ortho-alk-1-enylbenzoate with the hypervalent iodine reagent regio-and diastereoselectively gave 3-alkyl-4-oxyisochroman-1-one in a practically useful degree of enantiomeric purity (90-98 % ee); the isochromanone framework is a biologically relevant building block of natural products. [13,14] Herein, we report the synthetic utility of such enantiodifferentiating endo-selective oxylactonizations.The series of optically active hypervalent iodine (III) reagents 1-6 employed in this report is shown in Scheme 1. On the basis of reagents 1 and 2 reported previously, [12] the structures of the iodine reagents were tuned for improved enantioselectivity. The X-ray crystallographic structures of 1-4 showed a typical T-shape orientation around the iodine center, where the two acetoxy ligands occupied apical positions (see the Supporting Information).2-Ethenylbenzoic acid (7 a) was subjected to the reaction conditions with the optically active hypervalent iodine(III) reagent. The reaction was carried out in the presence of paratoluenesulfonic acid (TsOH) to activate the iodine reagent, and the tosylate also worked as a nucleophile to give lactones 8 a and 9 a ( Table 1). The reaction proceeded regioselectively to give the d-lactone product 8 a as the major product. The reaction with 6 gave a higher ee value of 8 a with high regioselectitvity (Table 1, entry 5).It is remarkable that the oxylactonization proceeds with endo selectivity [15,16] in addition to the high enantioselectivity. For elucidation of the mechanism of the endo selectivity and its synthetic applications, we varied the nucleophile and the substrate in the oxylactonization. When boron trifluoride diethyl etherate was employed as an activator in the presence Scheme 1. Optically active hypervalent iodine(III) rea...

Conformationally-Flexible Chiral Hypervalent Organoiodine Catalysts for Enantioselective Oxidative Transformations

“…26 30 Fujita s group developed the highly enantio and endo selective oxylactonization of alkenylbenzoic acid derivatives with chiral monoester or diester derived iodosylarenes 24 or 25 in the presence of excess amounts of BF 3 ·Et 2 O and acetic acid (Scheme 8). 26 Interestingly, through ESI MS (electrospray ionization mass spectrometry) analysis of iodosylarene 25 they detected some molecular related ion signals that may be due to species having interactions between internal lactate side chain with iodine(III) moiety (Scheme 8).…”

“…Recently, Fujita s group applied their enantioselective oxylactonization method 26 to the asymmetric synthesis of 4 oxyisochroman 1 one polyketide metabolites. 27 They also succeeded in catalytic oxylactonization using chiral iodoarene 26 (10 mol %) in the presence of mCPBA (Scheme 9).…”

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.…”

Recent progress in the trifluoromethylation of alkenes with Togni's reagents

“…On the basis of experimental results and related precedent, the reaction mechanism proposed is as depicted in Scheme 12. The reactive intermediate A, arising from the reaction between Togni's reagent 1 and Cu(I), reacts with enamide to produce the iodo(III) cyclopropane B, 39,40 which is expected to be in equilibrium with the corresponding α-iodo(III) imine.…”