Letter pubs.acs.org/OrgLett
Reversal of Enantioselectivity Approach to BINOLs via Single and Dual 2‑Naphthol Activation Modes Hun Young Kim,† Shinobu Takizawa,*,‡ Hiroaki Sasai,‡ and Kyungsoo Oh*,† †
Center for Metareceptome Research, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak, Seoul 06974, Republic of Korea ‡ The Institute of Scientific and Industrial Research (ISIR), Osaka University, Mihogaoka, Ibaraki-shi, Osaka 567-0047, Japan S Supporting Information *
ABSTRACT: A mechanism-driven enantiodivergent approach to chiral 1,1′-bi-2naphthols via catalytic asymmetric oxidative coupling of 2-naphthol derivatives is described for the first time. By utilizing 2-naphthol derivatives with low oxidation potential, the substrates were activated by either chiral mononuclear or dinuclear vanadium(V) catalyst to promote distinctively different asymmetric reaction pathways: single versus dual substrate activation mechanisms.
Scheme 1. BINOLs from Different 2-Naphthol Activation Modes
1,1′-Bi-2-naphthols (BINOLs) are one of the most privileged molecular entities in material, organic, and physical chemistry.1 The unique biaryl structural feature of BINOLs has laid the theoretical foundation for the axial chirality phenomena where the barrier to axial C−C bond rotation can be measured to provide a half-life of axial chirality.2 Such distinctive stereochemical properties of BINOLs have been instrumental for the birth of catalytic asymmetric synthesis in modern chemistry and, most recently, for the development of chiral materials with precise molecular recognition properties.3 Among numerous synthetic methods to chiral BINOLs, the enantioselective oxidative couplings of 2-naphthol derivatives have been the focus of intense investigation due to the use of a mild oxidant such as molecular oxygen.4 Representatively, the Cu-catalyzed enantioselective oxidative couplings specifically work well for 2naphthol derivatives with an electron-withdrawing group at the C-3 position such as ester,5 whereas the Fe- and V-catalyzed enantioselective 2-naphthol couplings do not require such coordinating sites (Scheme 1A).6 While these different metal catalyst types provide the substrate-specific orthogonal methods, the preparation of respective enantiomeric products requires the use of both enantiomeric catalysts. Mechanistically, the transition-metal-catalyzed naphthol couplings are complex in nature due to the involvement of free-radical or metal-bound radical species.7 However, there are widely accepted mechanistic pathways that support the formation of a complex between the chiral dinuclear metal catalysts and two molecules of naphthol within a tight chiral environment.8 In contrast, the formation of chiral mononuclear catalysts can be postulated where only one molecule of naphthol is coordinated to the catalyst center for the oxidative coupling reaction (Scheme 1B). If the current mechanistic interpretation for the enantioselective naphthol coupling stands, the reactivities and the selectivities of mononuclear and dinuclear metal catalysts are expected to be quite different. How to utilize such mechanistic difference in the synthesis of © 2017 American Chemical Society
BINOLs has not been exploited. Herein, we reveal the mechanism-driven enantiodivergent approach to BINOLs via strikingly different reaction mechanisms of 2-naphthol couplings based on single and dual 2-naphthol activation using the respective mononuclear and dinuclear metal catalysts. To investigate the stereochemical outcomes of intramolecular-manner and intermolecular couplings of 2-naphthols, we utilized the chiral vanadium(V) complexes with distinctive mononuclear and dinuclear structures.9 In addition, the oxidative coupling reaction was sped up by using the 2naphthol derivatives with lower oxidation potentials than 2naphthol itself, namely 4-substituted 2-naphthol derivatives.10 A chiral dinuclear vanadium catalyst (Ra,S,S)-3a was first explored Received: June 8, 2017 Published: July 11, 2017 3867
DOI: 10.1021/acs.orglett.7b01734 Org. Lett. 2017, 19, 3867−3870
Letter
Organic Letters
obtained in 51% yield with 90% ee (entry 6). While we further attempted to improve the catalyst turnover number by employing TMSCl,6d the result was not satisfactory (entry 7). Other chiral dinuclear vanadium(V) catalysts were also examined; however, the reactivity as well as enantioselectivity could not be improved further with the 0.1 mol % catalyst loading (entries 8 and 9). Next, we examined the chiral mononuclear vanadium(V) catalysts to investigate the effect of the single 2-naphthol activation mode for the formation of chiral BINOL 2a. The use of mononuclear vanadium(V) catalyst 3d in different chlorinated solvents provided an excellent reactivity, and provided the (R)-BINOL 2a as a major enantiomer (entries 10−12).12 The choice of solvent turned out to be CCl4, where the (R)-BINOL 2a was obtained in 58% yield with 87% ee at −20 °C (entries 13−15). To improve the reaction conversion and rate, we increased the amount of the catalyst 3d loading to 10 mol % (entry 16). The relationship of catalyst structure with reactivity and enantioselectivity was further examined with various mononuclear vanadium(V) catalysts, and the phenanthrene-derived mononuclear vanadium(V) catalyst 3h was identified as the optimal catalyst (entries 17−20). The solubility issue of the vanadium(V) catalyst 3h at −10 °C prompted the evaluation of the reaction temperature, while the amount of the catalyst loading was reduced to 5 mol % (entries 21 and 22). Thus, the optimized single 2-naphthol activation conditions provided the (R)-BINOL 2a in 91% yield with 87% ee using 5 mol % mononuclear vanadium(V) catalyst 3h at ambient temperature (entry 22). Our control experiments also confirmed the reversal of enantioselectivity of BINOL products by the two distinctive catalyst modes (entry 23) and the necessity of molecular oxygen for the catalyst turnover number (entry 24).13 The scope and limitation of the reversal of enantioselectivity approach in the oxidative coupling of 2-naphthols was next explored under the optimized conditions (Scheme 2). The enantioselective BINOL synthesis using the chiral dinuclear vanadium catalyst (Ra,S,S)-3a was applied to 4-alkyl-2-naphthol derivatives to give the corresponding (S)-BINOLs 2a−d with excellent yields and selectivities. The employment of 7methoxy-4-pentyl-2-naphthol, an electron-rich arene, provided a chiral (S)-BINOL 2e with the same level of enantioselectivity of 90%. In contrast, an electron-deficient 6-chloro-4-pentyl-2naphthol required a higher catalyst loading of 1 mol % of (Ra,S,S)-3a, providing (S)-BINOL 2f in 71% yield with 88% ee. While the use of 2-naphthol with an alkyl halide substituent led to the formation of (S)-BINOL 2g in 85% yield with 90% ee, the 2-naphthol with an ester moiety gave (S)-BINOL 2h in 85% ee. The aryl-substituted 2-naphthols were better suited with 1 mol % of catalyst (Ra,S,S)-3a loading, where (S)BINOLs 2i−k were obtained in 71−86% yields with 93−96% ee’s. The effect of a substituent at 3-position was also investigated, and (S)-BINOLs 2l,m were obtained in 71−85% ee. The enantioselective BINOL synthesis using chiral mononuclear vanadium(V) catalyst was also scrutinized using 5 mol % of 3h. While the observed enantioselectivities were slightly lower than those of dinuclear vanadium(V) catalyst, the general trend of reactivity as well as selectivity of the mononuclear vanadium(V) catalyst mirrored the cases of the dinuclear vanadium(V) catalysts. Thus, the 4-alkyl-substituted-2-naphthols provided (R)-BINOLs 2a−g, the products with opposite absolute configuration to the products from the dinuclear
as a catalyst that prompted the catalytic asymmetric oxidative coupling of 4-pentyl-2-napthol 1a at ambient temperature (Table 1). Upon employing only 5 mol % of (Ra,S,S)-3a in the Table 1. Optimization of Asymmetric Aerobic Oxidative Couplings of 4-Pentyl-2-naphthol 1aa
entry
cat (mol %)
solvent
T (°C)
eeb (%)
yieldc (%)
d
3a (5) 3a (1) 3a (0.5) 3a (0.2) 3a (0.1) 3a (0.01) 3a (0.01) 3b (0.1) 3c (0.1) 3d (3) 3d (3) 3d (3) 3d (3) 3d (3) 3d (3) 3d (10) 3e (10) 3f (10) 3g (10) 3h (10) 3h (10) 3d (5) 3i (10) 3a (0.1)
CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CHCl3 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CH2Cl2
23 23 23 23 23 23 23 23 23 23 23 23 0 −10 −20 −10 −10 −10 −10 −10 23 23 −10 23
93 93 92 93 93 90 90 72 51 46 52 72 80 85 86 85 45 82 60 85 87 87 30 93
(S)-2a, 91 (S)-2a, 90 (S)-2a, 91 (S)-2a, 90 (S)-2a, 87 (S)-2a, 51 (S)-2a, 38 (S)-2a, 65 (S)-2a, 50 (R)-2a, 91 (R)-2a, 98 (R)-2a, 98 (R)-2a, 72 (R)-2a, 61 (R)-2a, 58 (R)-2a, 78 (R)-2a, 61 (R)-2a, 60 (R)-2a, 45 (R)-2a, 73 (R)-2a, 93 (R)-2a, 91 (S)-2a, 42 (R)-2a,
