Chiral Hypervalent Organoiodine-Catalyzed Enantioselective Oxidative Spirolactonization of Naphthol Derivatives

Abstract

Highly enantioselective oxidative dearomatization of 2-naphthol derivatives was achieved for the first time by using conformationally flexible organoiodine catalysts derived from 2-aminoalcohol as a chiral source. Moreover, with the use of these catalysts, excellent enantioselectivities were also achieved for 1-naphthol derivatives, which had previously been obtained with only lower enantioselectivities. Furthermore, the product obtained from the present reaction could be transformed to a highly functionalized spirolactone in high yield and with excellent stereoselectivity.

Synthesis of [7]Helicene Enantiomers and Exploratory Study of Their Conversion into Helically Chiral Iodoarenes and Iodanes

“…We decided to redirect our efforts towards one of the iodane-mediated benchmark reactions that would only require catalytic amountsofour helicenes, that is, the dearomative spirolactonization of naphthols. [87][88][89][90][91][92] The propanoic acid-tethered 1-naphthol 20 was treated with 15 mol %o f( M)-17 a as precatalysti nt he presence of m-CPBA as terminal oxidant in CH 2 Cl 2 at 20 8C. The expected spirolactone 21 was thus obtained in 32 %y ield, but with an egligible enantiocontrol ( Table 2, entry 1).…”

“…At this stage, the total lack of enantiocontrol led us to contemplatef urther elaboration of our bis-iodinated helicenes by installing additional motifs in order to extent the helical scaffold. We thus opted for chiral lactate/lactamide units,w hich have amply demonstratedt heir high efficiency in spirolactonization reactions [87][88][89][90] and can be mounted onto our bisphenol 13 (see the Supporting Information for detailso nt he synthesis of these lactate/lactamided erivatives).W ei ndeed saw an et improvement when the reactionw as runu sing the bis-methyl lactate (M)-17 c,a st he spirolactone 21 was isolated in 55 % yield with 14 % ee (entry 3). Of particular note is that the precatalyst( M)-17 c was entirely recovered afterwards (2.0 mg), which is indicative of its clean conversioni nto an iodanyl species during the catalytic process, and hence of its stability and resistance toward overoxygenation.…”

“…Inverting the helicity of the pre-catalyst by using (P)-17 c only and slightly impacted the enantiomeric excess, which was down to 8% (entry 4). Since lactamide derivatives were reportedt ob es ystematically far superiort ot heir simple ester counterparts in similar catalytic processes, [87][88][89][90] we were eager to test pre-catalysts (M)-and (P)-17 d.S ince the (M)-helix of the bis-lactate 17 c appeared to be as lightly better asymmetry inductor,t he mesitylamide (M)-17 d was the first to be used, but disappointingly,n oe nantiocontrol was observed (entry 5). Surprisingly,i ti si ts diastereomer (P)-17 d that pleasingly gave us the best result with the formation of 21 in 58 %y ield with 52 % ee (entry 6).…”

Recent Application of Chiral Aryliodine Based on the 2-Iodo­resorcinol Core in Asymmetric Catalysis

“…In 2017, the Ishihara group found that the first generation precatalyst is insufficient for the oxidation of 2-naphthols, which are less reactive than 1-naphthols with respect to reactivity and enantioselectivity. 17 In order to overcome these limitations, the chiral aryliodine 8a, derived from 2amino alcohol instead of lactate, was utilized as a chiral source (Scheme 6), and the desired cyclohexadienone spirolactones 15 were obtained with excellent yields and enantioselectivities (up to 99% yield, 99% ee).…”

Enantioselective Iodine(I/III) Catalysis in Organic Synthesis

“…Recent results from the same group provided a useful methodology for the spirolactonization of 2‐naphthol derivatives 23 in excellent yields and enantioselectivities. In both cases, the chiral resorcinol‐derived iodine catalyst 12a makes use of the 2‐amino alcohol concept instead of the common lactate‐based scaffold (Scheme ) ,…”