Cinchona Alkaloid Catalyzed Enantioselective [4 + 2] Annulation of

Apr 19, 2017 - First, the electrophilic addition of the chiral amine catalyst 4e to the ortho-substituted aryl 2,3-butadienoate 2a delivered two of th...
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Cinchona Alkaloid Catalyzed Enantioselective [4 + 2] Annulation of Allenic Esters and in Situ Generated ortho-Quinone Methides: Asymmetric Synthesis of Functionalized Chromans Yu-Hua Deng,†,‡,§ Wen-Dao Chu,§ Xiang-Zhi Zhang,§ Xu Yan,§ Ke-Yin Yu,§ Liang-Liang Yang,§ Hanmin Huang,†,‡ and Chun-An Fan*,§,∥ †

State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China ‡ University of Chinese Academy of Sciences, Beijing 100049, China § State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, 222 Tianshui Nanlu, Lanzhou 730000, China ∥ Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China S Supporting Information *

ABSTRACT: A novel enantioselective [4 + 2] annulation of the allenoates having a unique positive ortho-effect with in situ generated ortho-quinone methides has been developed under the catalysis of Cinchona alkaloid. This chiral amine-catalyzed reaction provides an alternative route to asymmetric catalytic construction of synthetically interesting, highly functionalized chiral chromans in good to excellent enantioselectivities (up to 97% ee).

C

with different two-carbon partners (Scheme 1) via organocatalysis (e.g., chiral ammonium fluoride,4 chiral NHC,5 chiral

hromans as one of the important heterocyclic units constitute the core of many bioactive natural products (Figure 1),1 for example guadial A,2a guajadials C−D,2b and

Scheme 1. Catalytic Enantioselective [4 + 2] Annulations of o-QMs To Construct the Chroman-Type Scaffold

Figure 1. Compounds with 2,4-substituted chroman unit.

heliannuol E.2c Numerous catalytic asymmetric methodologies using organocatalysts or transition-metal catalysts have been developed for the synthesis of this privileged structural motif.1 Despite many advances, the development of novel asymmetric catalytic methods to access the enantiomerically enriched chromans continues to be highly appealing in modern asymmetric synthesis. ortho-Quinone methides (o-QMs), which feature as powerful intermediates in synthetic organic chemistry, medicinal chemistry, and material chemistry, have been extensively used for the preparation of chromans through (formal) hetero-Diels− Alder and electrocyclization reactions.3 Stimulated by the rapid development of asymmetric catalysis, recently the construction of chiral chroman-type building blocks has been disclosed by using the catalytic enantioselective [4 + 2] annulation of o-QMs © 2017 American Chemical Society

phosphoric acid,6 chiral squaramide,7 chiral amine8) or metal catalysis (e.g., chiral scandium complex,9 chiral rhodium complex10). Among these pioneering works, it should be noted that the relevant methodologies were predominantly developed on the basis of asymmetric Brønsted acid catalysis.6,7 Therefore, it is of great significance to design an asymmetric Received: February 16, 2017 Published: April 19, 2017 5433

DOI: 10.1021/acs.joc.7b00370 J. Org. Chem. 2017, 82, 5433−5440

Note

The Journal of Organic Chemistry catalytic methodology of o-QMs using a different catalytic activation mode for the asymmetric synthesis of functionalized chiral chromans. Since Lu and co-workers first reported the phosphine catalyzed [3 + 2] cyclization of allenic esters with electrondeficient olefins in 1995,11 allenoates have been extensively employed as an attractive substrate class for Lewis base catalyzed reactions.12 In sharp contrast to the well-developed chiral phosphine catalysis of allenoates,13 the corresponding catalysis of chiral amine analogues is not well explored, and only a few examples have been reported.14,15 To our knowledge, however, the chiral amine-catalyzed [4 + 2]annulation of o-QMs with allenoates is yet to be reported (Scheme 1). In connection with our recent interest in developing asymmetric catalysis of quinone methides,16 we herein report our preliminary results on the unprecedented Cinchona alkaloid catalyzed enantioselective [4 + 2] annulation of allenic esters and in situ generated o-QMs.17 Initially, the asymmetric [4 + 2] annulation of allenoates and in situ generated o-QMs was evaluated by the screening of silicon protecting groups of o-QM precursors in the model reaction (Table 1). Compared with the phenol substrates (1a′ and 1a″) bearing triisopropylsilyl (TIPS) and tert-butyldiphenylsilyl (TBDPS) groups (entries 2 and 3), tert-butyldimethylsilyl (TBS)-protected o-QM precursor 1a (entry 1) gave the

desirable result (60% yield, 91% ee) in the presence of CsF as fluoride source and THF as solvent under the catalysis of Cinchona alkaloid-derived amine 4c. Notably, the related triethylsilyl (TES)-protected o-QM precursor was not accessible due to its chemical instability. After examining the influence of the efficiency of in situ generation of o-QMs (entries 1−3), the subsequent solvent screening revealed that THF was still the better choice for our model reaction (entries 1 and 4−9). Additionally, while using KF instead of CsF as the fluoride source (entry 10), this reaction proceeded very slowly (90 h, 47% yield) despite the high stereocontrol for 3aa (91% ee). To further improve the reaction outcome, several organocatalysts derived from Cinchona alkaloids (entries 11− 14) as well as some additives (entries 15−17) were examined. As compared with the case using Cinchona alkaloid-derived amine 4c bearing a 9-anthracenylmethyl ether moiety (entry 1), the catalyst 4a with a less bulky benzyl ether motif led to a decrease in yield and enantioselectivity (48% yield, 89% ee, entry 11). Notably, the catalyst 4b with the hydrogen bonding donor group gave an analogous decrease in enantiocontrol and reactivity (46% yield, 80% ee, entry 12), possibly showing a negative influence of phenolic hydroxy group in current nucleophilic catalysis. When the catalysts 4d and 4e with phenolic alkyl substituents (R1 = i-Pr, neopentyl) were employed in this model (entries 13 and 14), pleasingly the latter one having a steric neopentyl group gave the better result (62% yield, 93% ee) for desired product 3aa. Encouraged by these promising results, the effect of additives (e.g., Na2SO4, MgSO4, 4 Å molecular sieve) was further examined (entries 15−17), in which Na2SO4 gave the optimal result with a 67% yield and 93% ee under the catalysis of chiral amine 4e (entry 15). With the above optimized reaction conditions, the scope of allenoates as two-carbon partners was first examined. As shown in Table 2, a series of aryl 2,3-butadienoates with orthosubstituents on the benzene ring (e.g., OMe, OEt, Me, i-Pr, tBu, Br) were effective in the current reaction (entries 1 and 4−

Table 1. Survey of Catalytic Reaction Conditionsa

entry

R

cat.

solvent

t [h]

yield (%)b

ee (%)c

1 2 3 4 5 6 7 8 9 10d 11 12 13 14 15e 16f 17g

TBS TIPS TBDPS TBS TBS TBS TBS TBS TBS TBS TBS TBS TBS TBS TBS TBS TBS

4c 4c 4c 4c 4c 4c 4c 4c 4c 4c 4a 4b 4d 4e 4e 4e 4e

THF THF THF Et2O CH2Cl2 toluene CHCl3 CH3CN EtOAc THF THF THF THF THF THF THF THF

25 25 49 33 33 24 29 29 29 90 72 72 72 27 27 27 27

60 57 40 19 trace nr 13 38 trace 47 48 46 54 62 67 trace 40

91 88 92 91 ND ND 84 91 ND 91 89 80 92 93 93 ND 93

Table 2. Effect of Allenoates in [4 + 2] Annulationa

a Reaction conditions (unless otherwise noted): o-QM precursor 1a, 1a′, or 1a″ (0.15 mmol), allenoate 2a (0.10 mmol), CsF (0.14 mmol), catalyst 4 (0.01 mmol), additive (100 mg) (if applicable), and solvent (2.0 mL), 0 °C. bIsolated yield. cDetermined by HPLC analysis on a chiral stationary phase. dKF was used instead of CsF. eNa2SO4 (100 mg) as additive. f4 Å molecular sieve (100 mg) as additive. gMgSO4 (100 mg) as additive. ND = not determined.

entry

allenoate

product

t [h]

yield (%)b

ee (%)c

1 2 3 4 5 6 7 8 9 10 11

2a (R = o-C6H4OMe) 2b (R = m-C6H4OMe) 2c (R = p-C6H4OMe) 2d (R = o-C6H4OEt) 2e (R = o-C6H4Me) 2f (R = o-C6H4iPr) 2g (R = o-C6H4tBu) 2h (R = o-C6H4Br) 2i (R = C6H5) 2j (R = 2,6-C6H3(Me)2) 2k (R = C2H5)

3aa 3ab 3ac 3ad 3ae 3af 3ag 3ah 3ai 3aj 3ak

27 24 24 51 15 24 96 15 27 65 27

67 −d 36e 62 62 50 51 53 35e trace trace

93 92 93 92 92 88 93 95

a

Performed with 1a (0.15 mmol) and 2a−2k (0.10 mmol) in the presence of CsF (0.14 mmol), the catalyst 4e (0.01 mmol), and the additive Na2SO4 (100 mg) in THF (2.0 mL) at 0 °C. bIsolated yield. c Determined by HPLC analysis using a chiral stationary phase. dA mixture of products was obtained. eSome unidentified byproducts were isolated. 5434

DOI: 10.1021/acs.joc.7b00370 J. Org. Chem. 2017, 82, 5433−5440

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The Journal of Organic Chemistry

analysis.18 It should be noted that it is essential to use KF instead of CsF under standard conditions for our annulation using o-QM precursors 1b, 1g, and 1h, leading to the improved yields for the formation of 3ba, 3ga, and 3ha. Besides, to further explore the limitations of our [4 + 2] annulation, two additional examples using o-QM precursors 1k″ and 1l″ were designed (Scheme 2). Unexpectedly, it was

8), leading to the desired products 3aa and 3ad−3ah in moderate yields with high enantioselectivities. Notably, while using meta-methoxyphenyl, para-methoxyphenyl, or phenyl 2,3butadienoate (entries 2, 3 and 9) as substrate, the decreased reaction yield was observed, indicating that the importance of the presence of an ortho-substituent in aryl 2,3-butadienoates. However, the reaction employing 2,6-dimethylphenyl 2,3butadienoate with two ortho-groups on the benzene ring (entry 10) was very sluggish, probably due to its unfavorable steric hindrance. In addition, one example using alkyl 2,3butadienoate (entry 11) was also investigated, but only trace products were observed. Next, we also explored the scope of in situ generated o-QMs in our asymmetric catalytic [4 + 2] annulation reaction. As tabulated in Table 3, a series of o-QM precursors with sterically

Scheme 2. Asymmetric Catalytic [4 + 2] Annulation with Chemically Stable o-QMs

Table 3. Generality of Asymmetric Catalytic [4 + 2] Annulationa,b,c

found that 1k″ and 1l″ as o-QM precursors were highly unstable during our efforts to their preparation. In order to expand the synthetic utilities of o-QMs in the asymmetric synthesis of functionalized chromans, we individually prepared two corresponding o-QMs 1k and 1l, which readily reacted with the allenoate 2a under the catalysis of 4e to give 3ka and 3la in moderate yields and good ee’s. Considering the potential of this methodology in the construction of chromans with diverse substitutions, two selective transformations of the above product 3la were preliminarily pursued. As shown in Scheme 3, 3la could Scheme 3. Selective Reduction Transformation

a Performed with 1a−1j (0.15 mmol) and 2a (0.10 mmol) in the presence of CsF (0.14 mmol), the catalyst 4e (0.01 mmol), and the additive Na2SO4 (100 mg) in THF (2.0 mL) at 0 °C. bThe yields refer to the isolated products, and the ee values were determined by HPLC analysis using a chiral stationary phase. cThe absolute configuration of 3ea (30% probability ellipsoids) was established by X-ray crystallographic analysis, and accordingly the reaction enantioselectivity in other cases was assigned by analogy. dKF (0.14 mmol) was used instead of CsF.

undergo the selective hydrogenation reduction by using different palladium catalysts, in which the treatment of 3lc with Pd/C and Pd(OH)2/C afforded the monohydrogenated product 5 (90% yield, 89% ee) and the fully hydrogenated product 6 (9:1 dr, 85% yield, 84% ee), respectively. To rationalize our chiral amine-catalyzed asymmetric [4 + 2] annulation reaction, a possible catalytic cycle was proposed in Scheme 4. First, the electrophilic addition of the chiral amine catalyst 4e to the ortho-substituted aryl 2,3-butadienoate 2a delivered two of the resonance stabilized zwitterionic intermediates, I-A and I-B. Due to the steric effect of the αposition in I-B, the resonance species I-A bearing a less sterically hindered γ-nucleophilic site could be predominantly involved in the subsequent reaction with the transient o-QMs, which were formed in situ from a desilylation/elimination cascade of silylated phenol 1. To avoid unfavorable steric interactions between the aryl substituent of o-QMs and the quinidine backbone of the catalyst 4e, the zwitterionic homoenolate might preferentially attack the Re face of o-QMs during the [4 + 2] annulation in II. Finally, the elimination of

and electronically different R1 and R2 substituents at the rings A and B (1a−1j) were subjected to the chiral-amine catalyzed annulation conditions, and the corresponding chroman-type products 3aa−3ja could be obtained in moderate yields with good enantiomeric excesses (up to 97% ee) in most cases. Compared with the examples using the substrates bearing the electron-withdrawing groups (1d, 1e, and 1j), generally the oQM precursors with the electron-donating groups R1 and R2 at the rings A and B gave higher yields (3ba, 3ca, and 3ga−3ia), partially due to the positive electron-donating effect in diarylmethyl chlorides for in situ formation of o-QMs through elimination of tert-butyldimethylsilyl chloride. The R absolute configuration and (E)-olefinic stereochemistry in the product 3ea were determined unambiguously by X-ray crystallographic 5435

DOI: 10.1021/acs.joc.7b00370 J. Org. Chem. 2017, 82, 5433−5440

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The Journal of Organic Chemistry

with a sodium lamp, and concentrations (c) were reported in g × (100 mL)−1. The chiral HPLC analyses were recorded on an HPLC machine equipped with a 1525 binary HPLC pump and a 2998 photodiode array detector and measured at the indicated wavelength (210−280 nm) using the indicated chiral column (Ø = 0.46 cm, length = 25.0 cm). ortho-Quinone methides and its precursors 1a−1j,19a 1k″,19a 1l″,19a 1k,19b and 1l19b were prepared according to the reported literature procedures. The allenic esters 2a−2k were prepared according to the reported literature procedures.20 The catalyst 4e was prepared according to the reported literature procedure.21 (1S,2R,4S,5R)-2-((S)-(Anthracen-9-ylmethoxy)(6-(neopentyloxy)quinolin-4-yl)methyl)-5-vinylquinuclidine (4e). Flash column chromatographic eluent (flushed by 10% Et3N/petroleum ether in advance): DCM/MeOH = 20:1 (v/v), light yellow gum, 0.45 g, 0.8 1 mmol, 38% yield, [α]22 D +170 (c 0.1, CHCl3). H NMR (400 MHz, CDCl3) δ = 8.84 (s, 1H), 8.49 (s, 1H), 8.20−8.00 (m, 5H), 7.69 (br, 1H), 7.55−7.32 (m, 5H), 7.02 (br, 1H), 5.80−5.30 (m, 4H), 5.08− 4.50 (m, 2H), 3.70−2.60 (m, 7H), 2.20−2.00 (m, 1H), 1.98−1.32 (m, 4H), 1.20−0.80 (m, 10H) ppm. 13C NMR (150 MHz, CDCl3) δ = 157.6, 147.3, 145.4, 144.5, 140.3, 131.5, 131.3, 130.9, 128.8, 128.4, 128.0, 127.9, 126.0, 124.8, 124.3, 122.1, 118.5, 113.8, 101.4, 78.2, 78.1, 77.9, 62.9, 60.4, 50.0, 49.2, 39.6, 31.8, 27.9, 26.6, 21.9 ppm. IR: υ̅ = 3345, 3056, 2953, 2869, 2370, 1620, 1589, 1508, 1455, 1240, 1224, 1071, 1018, 864, 734, 641 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C39H43N2O2: 571.3319; found 571.3327. General Procedure for Asymmetric Formal [4 + 2] Cycloaddition of o-QM Precursors. To a 10 mL Schlenk tube were added a fluoride source (0.14 mmol) and Na2SO4 (100 mg). The solids were flame-dried under high vacuum and allowed to cool to ambient temperature under argon atmosphere. To the solids were added a magnetic stirrer and catalyst 4e (0.01 mmol). Then the solution of allenic esters 2 (0.1 mmol) in THF (1 mL) was added. The resulting slurry was vigorously stirred at 0 °C under an argon atmosphere, and then the solution of o-QMs precursors 1 (0.15 mmol) in THF (1 mL) was added. The resulting mixture was stirred vigorously at the same temperature for the indicated time. The mixture was filtered through a short pad of silica gel, and the filtrate was evaporated. The resulting residue was purified by flash column chromatography on silica gel eluting with petroleum ether/ethyl acetate, giving the cycloaddition products 3. The racemic samples 3 used for the chiral HPLC analysis were prepared by employing a 1:1 mol mixture of Cinchona alkaloid-derived amine 4c and its pseudo-enantiomer-derived one as the catalyst. All products were identified by NMR spectroscopy, and the enantiomeric excesses were determined by HPLC analysis on chiral stationary phase. 2-Methoxyphenyl (R,E)-2-(4-Phenylchroman-2-ylidene)acetate (3aa). Following the above General Procedure, the reaction gave the product 3aa (27 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 40:1 (v/v), colorless oil, 24.9 mg, 0.067 mmol, 1 67% yield, 93% ee, [α]20 D −110 (c 0.2, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.32−7.22 (m, 4H), 7.19−7.12 (m, 3H), 7.08 (d, J = 8.1 Hz, 1H), 7.03−6.97 (m, 2H), 6.95−6.90 (m, 3H), 5.89 (s, 1H), 4.17 (t, J = 6.6 Hz, 1H), 3.76 (s, 3H), 3.71 (dd, J = 7.6, 15.8 Hz, 1H), 3.58 (dd, J = 4.9, 16.0 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.8, 165.5, 151.4, 141.3, 139.7, 128.7, 128.6, 128.5, 127.9, 127.0, 126.59, 126.57, 123.3, 123.1, 120.7, 116.6, 112.4, 97.5, 55.9, 39.0, 30.8 ppm. IR: υ̅ = 3366, 2960, 2922, 2372, 1726, 1647, 1605, 1457, 1376, 1260, 1096, 1023, 799, 744 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C24H20O4Na 395.1254; found 395.1259. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98/2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 16.1 min, t (minor) = 14.0 min). 4-Methoxyphenyl (R,E)-2-(4-Phenylchroman-2-ylidene)acetate (3ac). Following the above General Procedure, the reaction gave the product 3ac (24 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 40:1 (v/v), colorless oil, 13.4 mg, 0.036 mmol, 1 36% yield, 92% ee, [α]20 D −120 (c 0.2, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.32−7.20 (m, 4H), 7.15−7.10 (m, 2H), 7.09−7.03 (m,

Scheme 4. Proposed Reaction Mechanism

the chiral tertiary amine catalyst in zwitterionic species III produced the chroman-type products 3 with the regeneration of the catalyst 4e, wherein the E configuration of products might be attributable to the electrostatic repulsion between the ester enolate moiety and the oxygen lone pair of the hydrobenzopyran ring. In summary, we have developed a novel enantioselective [4 + 2] annulation of allenoates with in situ generated o-QMs under the catalysis of chiral tertiary amine derived from Cinchona alkaloid. A series of synthetically interesting, highly functionalized chiral chromans were achieved with good to excellent enantioselectivities. Importantly, a unique positive orthosubstituent effect in aryl 2,3-butadienoates was revealed unprecedentedly in the allenoate-based synthetic transformations, constituting the main driving force of the reactivity and selectivity observed in the present [4 + 2] annulation. Besides, this fluoride-mediated one-pot protocol for in situ formation of o-QMs provides the feasibility using the chemically unstable oQMs that could not be exploited usually as isolable species. This methodology not only offers an alternative approach to the catalytic asymmetric construction of functionalized chiral chromans but also enriches the chemistry of ortho-quinone methides in asymmetric catalysis.

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EXPERIMENTAL SECTION

General Methods. Unless otherwise noted, all moisture or oxygen-sensitive reactions were carried out under an argon atmosphere in oven or heat-dried flasks. The solvents used were purified by distillation over the drying agents indicated and were transferred under argon: THF (Na), CH2Cl2 (CaH2), toluene (Na), Et2O (Na). All other commercial reagents were used as received without further purification unless otherwise stated. All reactions were monitored by thin-layer chromatography (TLC) on silica gel F254 plates using UV light as the visualizing agent and a solution of ammonium molybdate tetrahydrate (50 g/L) in EtOH followed by heating as developing agents. The products were purified by flash column chromatography on silica gel (200−300 meshes). 1H and 13C NMR spectra were recorded in CDCl3 solution at 400 or 600 MHz. Chemical shifts were denoted in ppm (δ) and calibrated by using residual undeuterated solvent (CDCl3 (7.27 ppm) or tetramethylsilane (0.00 ppm)) as the internal reference for 1H NMR and the deuterated solvent (CDCl3 (77.00 ppm) or tetramethylsilane (0.00 ppm)) as the internal standard for 13C NMR. Multiplicities were indicated as follows: s (singlet), d (doublet), t (triplet), m (multiplet), q (quartet), br (broad), and dd (double doublet). High-resolution mass spectral analysis (HRMS) data were obtained using an Orbitrap instrument equipped with an ESI source. The IR spectra were recorded by means of an ATR technique. Optical rotations were measured using a 0.1 mL cell with a 1 cm path length on an Autopol IV automatic polarimeter 5436

DOI: 10.1021/acs.joc.7b00370 J. Org. Chem. 2017, 82, 5433−5440

Note

The Journal of Organic Chemistry 1H), 7.03−6.90 (m, 4H), 6.88−6.80 (m, 2H), 5.80 (s, 1H), 4.17 (t, J = 6.4 Hz, 1H), 3.78 (s, 3H), 3.73 (dd, J = 7.6, 15.8 Hz, 1H), 3.56 (dd, J = 5.2, 15.8 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.7, 166.3, 157.0, 151.4, 144.2, 141.2, 128.74, 128.68, 128.5, 127.9, 127.1, 126.5, 123.3, 122.5, 116.6, 114.3, 97.7, 55.6, 39.0, 30.8 ppm. IR: υ̅ = 3446, 2962, 2837, 1758, 1710, 1635, 1504, 1365, 1248, 1191, 1103, 997, 834, 762 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C24H20O4 395.1254; found 395.1247. The ee value was determined by the chiral HPLC analysis (IB-3, n-hexane/2-propanol = 98:2, v = 1.0 mL/min−1, λ = 256.0 nm, t (major) = 15.5 min, t (minor) = 14.5 min). 2-Ethoxyphenyl (R,E)-2-(4-Phenylchroman-2-ylidene)acetate (3ad). Following the above General Procedure, the reaction gave the product 3ad (51 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 40:1 (v/v), light yellow oil, 23.9 mg, 0.062 mmol, 1 62% yield, 93% ee, [α]20 D −115 (c 0.2, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.35−7.21 (m, 4H), 7.16−7.12 (m, 3H), 7.10−7.06 (m, 1H), 7.03−6.97 (m, 2H), 6.95−6.88 (m, 3H), 5.89 (s, 1H), 4.17 (t, J = 6.4 Hz, 1H), 4.03−3.94 (m, 2H), 3.72 (dd, J = 7.6, 15.8 Hz, 1H), 3.56 (dd, J = 5.2, 15.8 Hz, 1H), 1.27 (t, J = 7.1 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.5, 165.4, 151.3, 150.7, 141.3, 140.1, 128.7, 128.6, 128.5, 127.9, 127.0, 126.5, 126.4, 123.2, 123.0, 120.6, 116.6, 113.7, 97.5, 64.4, 39.0, 30.8, 14.7 ppm. IR: υ̅ = 3373, 2958, 2923, 2367, 1726, 1649, 1605, 1457, 1377, 1260, 1155, 1097, 1039, 796, 744 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C25H22O4Na 409.1410; found 409.1422. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98:2, v = 1.0 mL/min−1, λ = 256.0 nm, t (major) = 14.2 min, t (minor) = 11.8 min). o-Tolyl (R,E)-2-(4-Phenylchroman-2-ylidene)acetate (3ae). Following the above General Procedure, the reaction gave the product 3ae (15 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 40:1 (v/v), colorless oil, 22.1 mg, 0.062 mmol, 62% yield, 1 92% ee, [α]20 D −110 (c 0.1, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.31−7.22 (m, 4H), 7.20−7.16 (m, 2H), 7.15−7.07 (m, 4H), 7.04− 6.99 (m, 1H), 6.99−6.94 (m, 2H), 5.86 (s, 1H), 4.19 (t, J = 6.1 Hz, 1H), 3.80 (dd, J = 7.2, 15.6 Hz, 1H), 3.49 (dd, J = 5.2, 15.6 Hz, 1H), 2.07 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.7, 165.6, 151.4, 149.3, 141.3, 130.9, 130.4, 128.8, 128.6, 128.5, 127.8, 127.0, 126.7, 126.4, 125.7, 123.3, 122.1, 116.6, 97.7, 39.0, 30.8, 16.1 ppm; IR: υ̅ = 3365, 2958, 2923, 2373, 1722, 1649, 1605, 1458, 1382, 1261, 1098, 1027, 795 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C24H20O3Na 379.1305; found 379.1313. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98:2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 9.7 min, t (minor) = 9.1 min). 2-Isopropylphenyl (R,E)-2-(4-Phenylchroman-2-ylidene)acetate (3af). Following the above General Procedure, the reaction gave the product 3af (24 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 50:1 (v/v), colorless oil, 19.2 mg, 0.05 mmol, 1 50% yield, 92% ee, [α]21 D −100 (c 0.1, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.41−7.20 (m, 5H), 7.20−7.10 (m, 5H), 7.05−6.92 (m, 3H), 5.87 (s, 1H), 4.20 (t, J = 6.0 Hz, 1H), 3.83 (dd, J = 7.0, 15.6 Hz, 1H), 3.55−3.44 (m, 1H), 2.97−2.88 (m, 1H), 1.15 (d, J = 6.8 Hz, 3H), 1.12 (d, J = 6.8 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.7, 166.0, 151.4, 148.0, 141.2, 140.4, 128.9, 128.62, 128.56, 127.8, 127.0, 126.5, 126.40, 126.36, 126.0, 123.3, 122.5, 116.6, 97.8, 39.0, 30.8, 27.4, 22.9 ppm. IR: υ̅ = 3342, 2959, 2922, 2368, 1722, 1649, 1605, 1457, 1261, 1100, 1026, 794, 749 cm−1. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C26H24O3Na 407.1618; found 407.1628. The ee value was determined by the chiral HPLC analysis (IC-3, n-hexane/2propanol = 99/1, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 9.3 min, t (minor) = 11.4 min). 2-(tert-Butyl)phenyl (R,E)-2-(4-phenylchroman-2-ylidene)acetate (3ag). Following the above General Procedure, the reaction gave the product 3ag (96 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 50:1 (v/v), colorless oil, 20.4 mg, 0.051 mmol, 1 51% yield, 88% ee, [α]20 D −75 (c 0.2, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.38−7.33 (m, 1H), 7.30−7.17 (m, 6H), 7.16−7.05 (m, 3H), 7.04−6.92 (m, 3H), 5.88 (s, 1H), 4.20 (t, J = 6.0 Hz, 1H), 3.89 (dd, J = 6.8, 15.6 Hz, 1H), 3.49−3.42 (m, 1H), 1.27 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.9, 166.0, 151.3, 149.0, 141.24,

141.16, 128.9, 128.60, 128.57, 127.7, 127.02, 127.01, 126.6, 126.4, 125.4, 124.2, 123.4, 116.6, 98.2, 38.9, 34.4, 30.7, 30.1 ppm. IR: υ̅ = 3371, 2923, 2372, 1723, 1649, 1605, 1458, 1366, 1260, 1100, 1027, 793, 753 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C27H26O3Na 421.1774; found 421.1781. The ee value was determined by the chiral HPLC analysis (IC-3, n-hexane/2-propanol = 99:1, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 9.6 min, t (minor) = 12.6 min). 2-Bromophenyl (R,E)-2-(4-Phenylchroman-2-ylidene)acetate (3ah). Following the above General Procedure, the reaction gave the product 3ah (15 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 40:1 (v/v), colorless oil, 22.3 mg, 0.053 mmol, 1 53% yield, 93% ee, [α]21 D −70 (c 0.1, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.57 (d, J = 7.6 Hz, 1H), 7.40−7.20 (m, 5H), 7.20−7.05 (m, 5H), 7.05−6.90 (m, 2H), 5.89 (s, 1H), 4.20 (t, J = 5.6 Hz, 1H), 3.77 (dd, J = 7.2, 15.8 Hz, 1H), 3.52 (dd, J = 5.2, 15.8 Hz, 1H) ppm. 13 C NMR (100 MHz, CDCl3) δ = 169.6, 165.0, 151.3, 148.3, 141.1, 133.2, 128.8, 128.7, 128.6, 128.3, 127.8, 127.1, 127.0, 126.4, 124.0, 123.4, 116.6, 97.2, 38.9, 30.9 ppm. IR: υ̅ = 3371, 2957, 2923, 2372, 1654, 1599, 1459, 1383, 1261, 1211, 1095, 1045, 794, 746 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C23H18BrO3 421.0434; found 421.0446. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 99:1, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 14.9 min, t (minor) = 14.0 min). Phenyl (R,E)-2-(4-Phenylchroman-2-ylidene)acetate (3ai). Following the above General Procedure, the reaction gave the product 3ai (27 h, flash column chromatographic eluent: petroleum ether/ ethyl acetate = 40:1 (v/v), light brown oil, 12.0 mg, 0.035 mmol, 35% 1 yield, 95% ee, [α]20 D −100 (c 0.1, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.40−7.24 (m, 6H), 7.24−7.18 (m, 1H), 7.18−7.12 (m, 2H), 7.12−6.98 (m, 4H), 6.97−6.90 (m, 1H), 5.83 (s, 1H), 4.18 (t, J = 6.4 Hz, 1H), 3.72 (dd, J = 7.2, 16.0 Hz, 1H), 3.57 (dd, J = 7.2, 16.0 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 169.0, 166.0, 151.3, 150.7, 141.2, 129.2, 128.8, 128.7, 128.5, 127.9, 127.1, 126.5, 125.5, 123.4, 121.8, 116.6, 97.6, 39.0, 30.9 ppm; IR: υ̅ = 3420, 2962, 1763, 1720, 1640, 1484, 1364, 1213, 1099, 803 cm−1. HRMS (ESI-TOF) m/ z: [M + Na]+ calcd for C23H18O3Na 365.1148; found 365.1144. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2propanol = 98:2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 9.9 min, t (minor) = 9.2 min). 2-Methoxyphenyl (R,E)-2-(4-(2-Methoxyphenyl)chroman-2ylidene)acetate (3ba). Following the above General Procedure, the reaction gave the product 3ba (7 d, flash column chromatographic eluent: petroleum ether/ethyl acetate = 20:1 (v/v), colorless oil, 30.1 1 mg, 0.075 mmol, 75% yield, 95% ee, [α]21 D −40 (c 0.1, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.28−7.20 (m, 2H), 7.19−7.13 (m, 1H), 7.07 (d, J = 8.0 Hz, 1H), 7.01−6.95 (m, 2H), 6.94−6.87 (m, 4H), 6.86−6.80 (m, 2H), 5.85 (s, 1H), 4.60 (t, J = 6.4 Hz, 1H), 3.83− 3.74 (m, 1H), 3.80 (s 3H), 3.75 (s 3H), 3.43 (dd, J = 5.4, 15.6 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 169.5, 165.4, 157.1, 151.8, 151.4, 139.9, 129.5, 128.6, 128.5, 128.2, 128.1, 126.5, 126.4, 123.24, 123.17, 120.7, 120.6, 116.4, 112.5, 110.6, 97.3, 55.9, 55.4, 32.7, 29.4 ppm. IR: υ̅ = 3343, 2958, 2923, 1722, 1649, 1600, 1459, 1382, 1260, 1097, 1026, 800, 745 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C25H22O5Na 425.1359; found 425.1368. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98:2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 12.8 min, t (minor) = 15.2 min). 2-Methoxyphenyl (R,E)-2-(4-(3-Methoxyphenyl)chroman-2ylidene)acetate (3ca). Following the above General Procedure, the reaction gave the product 3ca (48 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 20:1 (v/v), colorless oil, 26.1 1 mg, 0.065 mmol, 65% yield, 91% ee, [α]20 D −100 (c 0.1, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.27−7.14 (m, 3H), 7.08−7.05 (m, 1H), 7.03−6.90 (m, 5H), 6.80−6.68 (m, 3H), 5.89 (s, 1H), 4.14 (t, J = 6.0 Hz, 1H), 3.78−3.69 (m, 1H), 3.76 (s 3H), 3.74 (s 3H), 3.56 (dd, J = 5.2, 15.8 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.7, 165.5, 159.8, 151.4, 151.3, 142.9, 139.8, 129.6, 128.7, 128.5, 126.5, 126.4, 123.3, 123.1, 120.7, 120.3, 116.6, 113.6, 112.5, 112.4, 97.5, 55.8, 55.1, 39.0, 30.6 ppm. IR: υ̅ = 3343, 2959, 2922, 2372, 1722, 1649, 5437

DOI: 10.1021/acs.joc.7b00370 J. Org. Chem. 2017, 82, 5433−5440

Note

The Journal of Organic Chemistry 1605, 1458, 1378, 1260, 1097, 1024, 791, 750 cm−1. HRMS (ESITOF) m/z: [M + Na]+ calcd for C25H22O5Na 425.1359; found 425.1369. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98:2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 31.5 min, t (minor) = 21.8 min). 2-Methoxyphenyl (R,E)-2-(4-(3-(Trifluoromethyl)phenyl)chroman-2-ylidene)acetate (3da). Following the above General Procedure, the reaction gave the product 3da (24 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 40:1 (v/v), white gum, 22.0 mg, 0.050 mmol, 50% yield, 90% ee, [α]21 D −100 (c 0.1, CHCl3)). 1H NMR (400 MHz, CDCl3) δ = 7.54−7.50 (m, 1H),7.45− 7.40 (m, 2H), 7.36−7.28 (m, 2H), 7.20−7.15 (m, 1H), 7.10 (dd, J = 0.9, 8.2 Hz, 1H), 7.05−6.98 (m, 2H), 6.96−6.89 (m, 3H), 5.92 (s, 1H), 4.27−4.22 (m, 1H), 3.77−3.69 (m, 1H), 3.76 (s, 3H), 3.65−3.58 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 167.9, 165.5, 151.4, 142.4, 139.7, 131.4, 131.1 (q, 2JC−F = 32.1 Hz, 1C), 129.2, 128.9, 128.5, 126.7, 125.6, 124.7 (q, 3JC−F = 3.8 Hz, 1C), 124.1 (q, 3JC−F = 3.8 Hz, 1C), 124.0 (q, 1JC−F = 270.8 Hz, 1C), 123.5, 123.1, 120.7, 116.9, 112.4, 97.9, 55.8, 38.9, 30.6 ppm. IR: υ̅ = 3373, 2957, 2921, 726, 1651, 1603, 1459, 1376, 1260, 1099, 1026, 801, 752 cm−1. HRMS (ESITOF) m/z: [M + Na]+ calcd for C25H19F3O4Na 463.1128; found 463.1139. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98:2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 19.6 min, t (minor) = 15.1 min). 2-Methoxyphenyl (R,E)-2-(4-(4-Chlorophenyl)chroman-2ylidene)acetate (3ea). Following the above General Procedure, the reaction gave the product 3ea (30 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 40:1 (v/v), white solid, mp 186−189 °C, 20.3 mg, 0.050 mmol, 50% yield, 92% ee, [α]21 D −160 (c 0.1, CHCl3)). 1H NMR (400 MHz, CDCl3) δ = 7.30−7.23 (m, 3H), 7.20−7.14 (m, 1H), 7.10−7.05 (m, 3H), 7.05−6.99 (m, 2H), 6.97− 6.90 (m, 3H), 5.89 (s, 1H), 4.17 (t, J = 6.0 Hz, 1H), 3.85−3.72 (m, 1H), 3.77 (s, 3H), 3.52−3.43 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.1, 165.4, 151.4, 139.9, 139.7, 132.8, 129.3, 128.79, 128.78, 128.67, 126.6, 125.9, 123.4, 123.1, 120.7, 116.8, 112.4, 97.9, 55.9, 38.5, 30.6 ppm. IR: υ̅ = 3372, 2957, 2922, 2374, 1721, 1654, 1606, 1590, 1460, 1381, 1260, 1098, 1025, 795, 746 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C24H20ClO4 407.1045; found 407.1055. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98:2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 20.0 min, t (minor) = 17.4 min). 2-Methoxyphenyl (R,E)-2-(4-(Naphthalen-1-yl)chroman-2ylidene)acetate (3fa). Following the above General Procedure, the reaction gave the product 3fa (48 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 50:1 (v/v), white gum, 29.6 1 mg, 0.070 mmol, 70% yield, 93% ee, [α]20 D +10 (c 0.2, CHCl3)). H NMR (400 MHz, CDCl3) δ = 8.08−8.02 (m, 1H), 7.90−7.85 (m, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.51−7.44 (m, 2H), 7.36 (t, J = 7.9 Hz, 1H), 7.27 (t, J = 7.2 Hz, 1H), 7.16−7.02 (m, 3H), 6.95 (t, J = 7.2 Hz, 1H), 6.87−6.81 (m, 4H), 5.89 (s, 1H), 4.98 (t, J = 6.4 Hz, 1H), 3.87 (dd, J = 7.7, 15.7 Hz, 1H), 3.72 (dd, J = 5.3, 15.7 Hz, 1H), 3.60 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.7, 165.2, 151.7, 151.3, 139.7, 136.8, 134.0, 131.4, 129.0, 128.7, 128.5, 127.8, 126.6, 126.45, 126.44, 125.6, 125.5, 123.4, 123.1, 123.0, 120.6, 116.6, 112.3, 97.7, 55.7, 35.0, 30.2 ppm. IR: υ̅ 3376, 2957, 2921, 2853, 2369, 1725, 1654, 1606, 1499, 1378, 1259, 1098, 1025, 798, 751 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C28H22O4Na 445.1410; found 445.1419. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98:2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 44.6 min, t (minor) = 33.2 min). 2-Methoxyphenyl (R,E)-2-(8-Methoxy-4-phenylchroman-2ylidene)acetate (3ga). Following the above General Procedure, the reaction gave the product 3ga (6 d, flash column chromatographic eluent: petroleum ether/ethyl acetate = 20:1 (v/v), colorless oil, 28.1 1 mg, 0.070 mmol, 70% yield, 97% ee, [α]20 D −120 (c 0.1, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.32−7.22 (m, 3H), 7.18−7.12 (m, 3H), 7.02−6.85 (m, 5H), 6.55 (d, J = 7.6 Hz, 1H), 6.00 (s, 1H), 4.18 (t, J = 6.4 Hz, 1H), 3.93 (s, 3H), 3.80−3.73 (m, 1H), 3.75 (s, 3H), 3.52 (dd, J = 5.2, 15.6 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.3, 165.5, 151.4, 147.9, 141.3, 140.8, 139.9, 128.6, 127.9, 127.6,

127.0, 126.5, 123.1, 122.9, 120.7, 120.4, 112.5, 111.1, 98.1, 56.2, 55.9, 39.1, 30.7 ppm. IR: υ̅ 3346, 2959, 2923, 2375, 1723, 1649, 1589, 1460, 1378, 1261, 1154, 1098, 1043, 797, 743 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C25H22O5Na 425.1359; found 425.1369. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2propanol = 98/2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 29.2 min, t (minor) = 27.4 min). 2-Methoxyphenyl (R,E)-2-(6-Methoxy-4-phenylchroman-2ylidene)acetate (3ha). Following the above General Procedure, the reaction gave the product 3ha (6 d, flash column chromatographic eluent: petroleum ether/ethyl acetate = 20:1 (v/v), light yellow oil, 32.5 mg, 0.081 mmol, 81% yield, 96% ee, [α]21 D −90 (c 0.1, CHCl3)). 1 H NMR (400 MHz, CDCl3) δ = 7.32−7.22 (m, 3H), 7.19−7.12 (m, 3H), 7.05−6.98 (m, 2H), 6.97−6.88 (m, 2H), 6.82−6.78 (m, 1H), 6.48−6.43 (m, 1H), 5.84 (s, 1H), 4.13 (t, J = 6.0 Hz, 1H), 3.76 (s, 3H), 3.73−3.62 (m, 1H), 3.70 (s, 3H), 3.55 (dd, J = 4.7, 16.0 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 169.2, 165.6, 155.4, 151.4, 145.5, 141.1, 139.8, 128.7, 127.9, 127.5, 127.1, 126.5, 123.2, 120.7, 117.3, 113.8, 113.7, 112.4, 96.8, 55.9, 55.6, 39.3, 30.9 ppm. IR: υ̅ = 3371, 2923, 2854, 2369, 1723, 1647, 1604, 1459, 1378, 1261, 1098, 1039, 796, 744 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C25H22O5Na 425.1359; found 425.1366. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98:2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 25.1 min, t (minor) = 21.2 min). 2-Methoxyphenyl (R,E)-2-(6-Methyl-4-phenylchroman-2ylidene)acetate (3ia). Following the above General Procedure, the reaction gave the product 3ia (24 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 40:1 (v/v), light brown oil, 25.8 mg, 0.067 mmol, 67% yield, 96% ee, [α]20 D −90 (c 0.1, CHCl3)). 1 H NMR (400 MHz, CDCl3) δ = 7.32−7.27 (m, 2H), 7.26−7.22 (m, 1H), 7.18−7.12 (m, 3H), 7.07−6.89 (m, 5H), 6.73 (s, 1H), 5.85 (s, 1H), 4.12 (t, J = 6.0 Hz, 1H), 3.78−3.68 (m, 1H), 3.75 (s, 3H), 3.52 (dd, J = 4.8, 16.0 Hz, 1H), 2.23 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 169.0, 165.5, 151.4, 149.3, 141.5, 139.8, 132.8, 129.0, 128.6, 127.9, 126.9, 126.5, 126.2, 123.1, 120.7, 116.3, 112.4, 97.1, 55.9, 39.0, 31.0, 20.7 ppm. IR: υ̅ = 3374, 2923, 2374, 1600, 1460, 1383, 1260, 1098, 1026, 796, 746 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C25H22O4Na 409.1410; found 409.1420. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98/2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 15.0 min, t (minor) = 13.2 min). 2-Methoxyphenyl (R,E)-2-(4,6-Diphenylchroman-2-ylidene)acetate (3ja). Following the above General Procedure, the reaction gave the product 3ja (60 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 40:1 (v/v), white gum, 13.6 mg, 0.030 1 mmol, 30% yield, 87% ee, [α]21 D −30 (c 0.1, CHCl3)). H NMR (400 MHz, CDCl3) δ = 7.50−7.43 (m, 3H), 7.40−7.34 (m, 2H), 7.32−7.28 (m, 3H), 7.26−7.23 (m, 1H), 7.20−7.13 (m, 5H), 7.04−7.00 (m, 1H), 6.98−6.90 (m, 2H), 5.91 (s, 1H), 4.24 (t, J = 6.0 Hz, 1H), 3.80−3.72 (m, 1H), 3.77 (s, 3H), 3.58 (dd, J = 4.2, 15.6 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.6, 165.4, 151.4, 151.0, 141.2, 140.3, 139.8, 136.5, 128.7, 127.9, 127.4, 127.2, 127.12, 127.09, 126.84, 126.77, 126.6, 123.1, 120.7, 117.0, 112.4, 97.7, 55.9, 39.2, 30.9 ppm. IR: υ̅ = 3345, 2923, 2857, 2367, 1721, 1649, 1606, 1459, 1379, 1260, 1100, 1028, 795, 745, 699 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C30H24O4Na 471.1567; found 471.1577. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 98/2, v = 1.0 mL·min−1, λ = 256.0 nm, t (major) = 29.8 min, t (minor) = 24.1 min). General Procedure for Asymmetric Formal [4 + 2] Cycloaddition of o-QMs 1k and 1l. Under an argon atmosphere, the allenic ester 2a (19.0 mg, 0.10 mmol) and the catalyst 4e (5.7 mg, 0.01 mmol) were added to the solution of o-QM 1k or 1l (0.15 mmol) in dry THF (2 mL) at 0 °C, and the mixture was stirred for 72 h. The solution was concentrated under reduced pressure, and the crude product was purified by flash column chromatography on silica gel to afford the cycloaddition product 3ka or 3la. 2-Methoxyphenyl (R,E)-2-(4-(4-Methoxyphenyl)-6,7-methylenedioxychroman-2-ylidene)acetate (3ka). Following the above General 5438

DOI: 10.1021/acs.joc.7b00370 J. Org. Chem. 2017, 82, 5433−5440

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The Journal of Organic Chemistry Procedure, the reaction gave the product 3ka (72 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 10:1 (v/v), colorless oil, 30.5 mg, 0.068 mmol, 68% yield, 97% ee, [α]19 D −90 (c 0.2, CHCl3)). 1H NMR (400 MHz, CDCl3) δ = 7.25 (s, 1H), 7.18− 7.13 (m, 1H), 7.08−6.98 (m, 3H), 6.95−6.88 (m, 2H), 6.83 (d, J = 8.8 Hz, 2H), 6.60 (s, 1H), 6.36 (s, 1H), 5.91 (s, 2H), 5.83 (s, 1H), 4.00 (t, J = 6.4 Hz, 1H), 3.78 (s, 3H), 3.76 (s, 3H), 3.63 (dd, J = 7.6, 15.6 Hz, 1H), 3.49 (dd, J = 5.2, 16.0 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 169.0, 165.5, 158.5, 151.4, 147.2, 145.7, 143.4, 139.7, 133.4, 128.8, 126.5, 123.1, 120.7, 119.0, 114.0, 112.4, 107.6, 101.3, 98.6, 97.0, 55.8, 55.2, 38.1, 31.1 ppm. IR: υ̅ = 3345, 2922, 2375, 1722, 1648, 1460, 1381, 1259, 1098, 1035, 799, 745 cm−1. HRMS (ESITOF) m/z: [M + Na]+ calcd for C26H22O7Na 469.1258; found 469.1269. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 80/20, v = 1.0 mL·min−1, λ = 245.2 nm, t (major) = 12.0 min, t (minor) = 10.5 min). 2-Methoxyphenyl (R,E)-2-(4-(E)-Styryl-6,7-methylenedioxychroman-2-ylidene)acetate (3la). Following the above General Procedure, the reaction gave the product 3la (72 h, flash column chromatographic eluent: petroleum ether/ethyl acetate = 15:1 to 10:1 (v/v), colorless oil, 30.1 mg, 0.068 mmol, 68% yield, 87% ee, [α]20 D −80 (c 0.2, CHCl3)). 1H NMR (400 MHz, CDCl3) δ = 7.36−7.27 (m, 4H), 7.24−7.16 (m, 2H), 7.08−7.04 (m, 1H), 6.98−6.91 (m, 2H), 6.64 (s, 1H), 6.59 (s, 1H), 6.41 (d, J = 15.6 Hz, 1H), 6.14 (dd, J = 7.2, 16.0 Hz, 1H), 5.94 (s, 2H), 5.88 (s, 1H), 3.79 (s, 3H), 3.62 (q, J = 6.4 Hz, 1H), 3.51 (dd, J = 7.1, 15.6 Hz, 1H), 3.39 (dd, J = 5.2, 15.6 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.8, 165.7, 151.4, 147.3, 145.5, 143.4, 139.8, 136.7, 132.1, 129.6, 128.5, 127.6, 126.6, 126.4, 123.2, 120.7, 117.7, 112.4, 107.2, 101.4, 98.8, 97.2, 55.9, 36.7, 29.2 ppm. IR: υ̅ = 3342, 2957, 2922, 2372, 1721, 1648, 1598, 1479, 1439, 1259, 1148, 1100, 1033, 850, 794, 745 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C27H22O6Na 465.1309; found 465.1321. The ee value was determined by the chiral HPLC analysis (IA-3, nhexane/2-propanol = 80/20, v = 1.0 mL·min−1, λ = 245.2 nm, t (major) = 11.0 min, t (minor) = 12.3 min). Selective Reduction Transformation of 3la to the Chroman 5. To a solution of 3la (0.10 mmol, 44.2 mg, 87% ee) in THF/ CH3OH (1:1 v/v, 2 mL) was added Pd/C (5%, 13.3 mg, 30% w/w). Then the flask was purged with H2 three times, and the reaction mixture was stirred at 15 °C under a H2 atmosphere for 9 h. Following evaporation of solvent, the purification of the residue by flash column chromatography on silica gel provided the product 5. 2-Methoxyphenyl (R,E)-2-(4-(2-Phenylethyl)-6,7-methylenedioxychroman-2-ylidene)acetate (5). Flash column chromatographic eluent: petroleum ether/ethyl acetate = 15:1 (v/v), light brown oil, 1 40.0 mg, 0.090 mmol, 90% yield, 89% ee, [α]21 D −10 (c 0.1, CHCl3). H NMR (400 MHz, CDCl3) δ = 7.25−7.18 (m, 2H), 7.18−7.08 (m, 4H), 7.03−6.99 (m, 1H), 6.92−6.85 (m, 2H), 6.48 (d, J = 3.6 Hz, 2H), 5.85 (s, 2H), 5.83 (s, 1H), 4.06−3.96 (m, 1H), 3.71 (s, 3H), 2.72−2.50 (m, 4H), 1.82−1.66 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ = 169.2, 165.8, 151.4, 146.9, 145.2, 143.1, 141.5, 139.7, 128.4, 126.6, 125.9, 123.2, 120.7, 119.8, 112.3, 107.1, 101.3, 98.8, 97.4, 55.8, 36.2, 33.0, 32.7, 27.7 ppm. IR: υ̅ = 3372, 2958, 2923, 2856, 2373, 1722, 1649, 1604, 1460, 1380, 1261, 1147, 1097, 1033, 798, 744 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C27H24O6Na 467.1466; found 467.1477. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2-propanol = 80/20, v = 1.0 mL·min−1, λ = 245.2 nm, t (major) = 9.9 min, t (minor) = 14.2 min). Selective Reduction Transformation of 3la to the Chroman 6. To a solution of 3la (0.10 mmol, 44.2 mg, 87% ee) in THF/ CH3OH (1:1 v/v, 2 mL) was added Pd(OH)2/C (20%, 22.1 mg, 50% w/w). Then the flask was purged with H2 three times, and the reaction mixture was stirred at 15 °C under a H2 atmosphere for 9 h. Following evaporation of solvent, the purification of the residue by flash column chromatography on silica gel provided the product 6. 2-Methoxyphenyl (2S,4S)-2-(4-(2-Phenylethyl)-6,7-methylenedioxychroman-2-yl)acetate (6). Flash column chromatographic eluent: petroleum ether/ethyl acetate = 15:1 (v/v), light brown oil, 37.9 mg, 0.085 mmol, 85% yield, 9:1 dr, 84% ee, [α]20 D +30 (c 0.1, CHCl3). 1H NMR (400 MHz, CDCl3) δ = 7.24−7.18 (m, 2H), 7.16−

7.09 (m, 4H), 7.01−6.97 (m, 1H), 6.92−6.85 (m, 2H), 6.62 (s, 1H), 6.31 (s, 1H), 5.78 (dd, J = 1.2, 4.8 Hz, 2H), 4.44−4.36 (m, 1H), 3.75 (s, 3H), 3.00 (dd, J = 6.7, 15.3 Hz, 1H), 2.95−2.86 (m, 1H), 2.82 (dd, J = 6.7, 15.3 Hz, 1H), 2.71−2.61 (m, 1H), 2.58−2.47 (m, 1H), 2.33− 2.25 (m, 1H), 2.19−2.09 (m, 1H), 1.76−1.65 (m, 1H), 1.62−1.51 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.7, 151.0, 149.6, 146.2, 142.0, 141.9, 139.6, 128.45, 128.35, 128.2, 127.0, 125.9, 122.8, 120.8, 117.4, 112.4, 106.0, 100.8, 98.7, 72.5, 55.9, 40.7, 37.1, 33.9, 33.8, 32.3 ppm. IR: υ̅ = 3375, 2954, 2923, 2858, 2371, 1759, 1604, 1460, 1383, 1261, 1117, 1037, 936, 858, 745 cm−1. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C27H26O6Na 469.1622; found 469.1635. The ee value was determined by the chiral HPLC analysis (IA-3, n-hexane/2propanol = 80/20, v = 1.0 mL·min−1, λ = 245.2 nm, t (major) = 9.8 min, t (minor) = 9.1 min).

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b00370. Copies of 1H and 13C NMR and HPLC spectra for all new compounds (PDF) X-ray crystallographic data for 3ea (CIF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Chun-An Fan: 0000-0003-4837-3394 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful for financial support from the National Natural Science Foundation of China (21572083, 21322201, 21290180), the Fundamental Research Funds for the Central Universities (lzujbky-2015-48, lzujbky-2016-ct02, lzujbky-2016ct07), the Program for Changjiang Scholars and Innovative Research Team in University (IRT_15R28), the 111 Project of the Ministry of Education of the People’s Republic of China (111-2-17), and the Chang Jiang Scholars Program (C.-A.F.).

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REFERENCES

(1) (a) Chemistry of Heterocyclic Compounds: Chromans and Tocopherols, Vol. 36; Ellis, G. P.; Lockhart, I. M.), Eds.; WileyInterscience: New York, 1981. (b) Shen, H. C. Tetrahedron 2009, 65, 3931 and references therein. (2) (a) Shao, M.; Wang, Y.; Jian, Y.-Q.; Huang, X.-J.; Zhang, D.-M.; Tang, Q.-F.; Jiang, R.-W.; Sun, X.-G.; Lv, Z.-P.; Zhang, X.-Q.; Ye, W.C. Org. Lett. 2012, 14, 5262. (b) Gao, Y.; Li, G.-T.; Li, Y.; Hai, P.; Wang, F.; Liu, J.-K. Nat. Prod. Bioprospect. 2013, 3, 14. (c) Macías, F. A.; Varela, R. M.; Torres, A.; Molinillo, J. M. G. Tetrahedron Lett. 1999, 40, 4725. (3) For selected reviews on the chemistry of o-QMs in the past 5 years, see: (a) Willis, N. J.; Bray, C. D. Chem. - Eur. J. 2012, 18, 9160. (b) Bai, W.-J.; David, J. G.; Feng, Z.-G.; Weaver, M. G.; Wu, K.-L.; Pettus, T. R. R. Acc. Chem. Res. 2014, 47, 3655. (c) Singh, M. S.; Nagaraju, A.; Anand, N.; Chowdhury, S. RSC Adv. 2014, 4, 55924. (d) Caruana, L.; Fochi, M.; Bernardi, L. Molecules 2015, 20, 11733. (e) Wang, Z.; Sun, J. Synthesis 2015, 47, 3629. (f) Jaworski, A. A.; Scheidt, K. A. J. Org. Chem. 2016, 81, 10145. (4) For one example catalyzed by chiral ammonium fluoride, see: Alden-Danforth, E.; Scerba, M. T.; Lectka, T. Org. Lett. 2008, 10, 4951. (5) For selected examples catalyzed by chiral NHCs, see: (a) Lv, H.; You, L.; Ye, S. Adv. Synth. Catal. 2009, 351, 2822. (b) Lee, A.; Scheidt, K. A. Chem. Commun. 2015, 51, 3407. (c) Wang, Y.; Pan, J.; Dong, J.; 5439

DOI: 10.1021/acs.joc.7b00370 J. Org. Chem. 2017, 82, 5433−5440

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The Journal of Organic Chemistry Yu, C.; Li, T.; Wang, X.-S.; Shen, S.; Yao, C. J. Org. Chem. 2017, 82, 1790. (6) For recent selected examples catalyzed by chiral phosphoric acids, see: (a) Hsiao, C.-C.; Liao, H.-H.; Rueping, M. Angew. Chem., Int. Ed. 2014, 53, 13258. (b) El-Sepelgy, O.; Haseloff, S.; Alamsetti, S. K.; Schneider, C. Angew. Chem., Int. Ed. 2014, 53, 7923. (c) Saha, S.; Schneider, C. Org. Lett. 2015, 17, 648. (d) Saha, S.; Schneider, C. Chem. - Eur. J. 2015, 21, 2348. (e) Zhao, J.-J.; Sun, S.-B.; He, S.-H.; Wu, Q.; Shi, F. Angew. Chem., Int. Ed. 2015, 54, 5460. (f) Hsiao, C.-C.; Raja, S.; Liao, H.-H.; Atodiresei, I.; Rueping, M. Angew. Chem., Int. Ed. 2015, 54, 5762. (g) Zhao, J.-J.; Zhang, Y.-C.; Xu, M.-M.; Tang, M.; Shi, F. J. Org. Chem. 2015, 80, 10016. (h) Wu, Q.; Zhao, J.; Sun, S.; Tu, M.; Shi, F. Huaxue Xuebao 2016, 74, 576. (i) Yu, X.-Y.; Chen, J.-R.; Wei, Q.; Cheng, H.-G.; Liu, Z.-C.; Xiao, W.-J. Chem. - Eur. J. 2016, 22, 6774. (j) Zhang, Y.-C.; Zhu, Q.-N.; Yang, X.; Zhou, L.-J.; Shi, F. J. Org. Chem. 2016, 81, 1681. (k) Tang, M.; Zhao, J.-J.; Wu, Q.; Tu, M.-S.; Shi, F. Synthesis 2017, 49, 2035. (7) For selected examples catalyzed by chiral squaramides, see: (a) Caruana, L.; Mondatori, M.; Corti, V.; Morales, S.; Mazzanti, A.; Fochi, M.; Bernardi, L. Chem. - Eur. J. 2015, 21, 6037. (b) Wu, B.; Gao, X.; Yan, Z.; Huang, W.-X.; Zhou, Y.-G. Tetrahedron Lett. 2015, 56, 4334. (c) Adili, A.; Tao, Z.-L.; Chen, D.-F.; Han, Z.-Y. Org. Biomol. Chem. 2015, 13, 2247. (d) Wu, B.; Gao, X.; Yan, Z.; Chen, M.-W.; Zhou, Y.-G. Org. Lett. 2015, 17, 6134. (8) For two examples catalyzed by chiral amines, see: (a) Zhou, D.; Mao, K.; Zhang, J.; Yan, B.; Wang, W.; Xie, H. Tetrahedron Lett. 2016, 57, 5649. (b) Zhu, Y.; Zhang, W.-Z.; Zhang, L.; Luo, S. Chem. - Eur. J. 2017, 23, 1253. (9) For one example catalyzed by chiral scandium complex, see: Hu, H.; Liu, Y.; Guo, J.; Lin, L.; Xu, Y.; Liu, X.; Feng, X. Chem. Commun. 2015, 51, 3835. (10) For one example catalyzed by chiral rhodium complex, see: Alamsetti, S. K.; Spanka, M.; Schneider, C. Angew. Chem., Int. Ed. 2016, 55, 2392. (11) Zhang, C.; Lu, X. J. Org. Chem. 1995, 60, 2906. (12) For selected reviews on Lewis base catalyzed reactions of allenic esters, see: (a) Cowen, B. J.; Miller, S. J. Chem. Soc. Rev. 2009, 38, 3102. (b) López, F.; Mascareñas, J. L. Chem. - Eur. J. 2011, 17, 418. (c) Yu, S.; Ma, S. Angew. Chem., Int. Ed. 2012, 51, 3074. (d) Pei, C.-K.; Shi, M. Chem. - Eur. J. 2012, 18, 6712. (e) Wang, Z.; Xu, X.; Kwon, O. Chem. Soc. Rev. 2014, 43, 2927. (13) For recent selected reviews on chiral phosphine-catalyzed reaction of allenic esters, see: (a) Marinetti, A.; Voituriez, A. Synlett 2010, 2010, 174. (b) Zhao, Q.-Y.; Lian, Z.; Wei, Y.; Shi, M. Chem. Commun. 2012, 48, 1724. (c) Xu, L.-W. ChemCatChem 2013, 5, 2775. (d) Wei, Y.; Shi, M. Chem. - Asian J. 2014, 9, 2720. (e) Fu, W.; Tang, W. ACS Catal. 2016, 6, 4814. (f) Wang, T.; Han, X.; Zhong, F.; Yao, W.; Lu, Y. Acc. Chem. Res. 2016, 49, 1369. (g) Yang, L.; Ma, J. Huaxue Xuebao 2016, 74, 130. (14) For selected examples on the chiral amine-catalyzed asymmetric [2 + 2] cyclization of allenoates: (a) Denis, J.-B.; Masson, G.; Retailleau, P.; Zhu, J. Angew. Chem., Int. Ed. 2011, 50, 5356. (g) Zhao, Q.-Y.; Huang, L.; Wei, Y.; Shi, M. Adv. Synth. Catal. 2012, 354, 1926. (h) Takizawa, S.; Arteaga, F. A.; Yoshida, Y.; Suzuki, M.; Sasai, H. Org. Lett. 2013, 15, 4142. (15) For selected examples on the chiral amine-catalyzed asymmetric [4 + 2] cyclization of allenoates in past 5 years, see: (a) Pei, C.-K.; Jiang, Y.; Wei, Y.; Shi, M. Angew. Chem., Int. Ed. 2012, 51, 11328. (b) Pei, C.-K.; Jiang, Y.; Shi, M. Org. Biomol. Chem. 2012, 10, 4355. (c) Wang, F.; Luo, C.; Shen, Y.-Y.; Wang, Z.-D.; Li, X.; Cheng, J.-P. Org. Lett. 2015, 17, 338. (d) Zhang, S.; Luo, Y.-C.; Hu, X.-Q.; Wang, Z.-Y.; Liang, Y.-M.; Xu, P.-F. J. Org. Chem. 2015, 80, 7288. (e) Ashtekar, K. D.; Ding, X.; Toma, E.; Sheng, W.; Gholami, H.; Rahn, C.; Reed, P.; Borhan, B. Org. Lett. 2016, 18, 3976. (f) Kasten, K.; Cordes, D. B.; Slawin, A. M. Z.; Smith, A. D. Eur. J. Org. Chem. 2016, 2016, 3619. (g) Ni, C.; Tong, X. J. Am. Chem. Soc. 2016, 138, 7872 and references therein. (16) (a) Chu, W.-D.; Zhang, L.-F.; Bao, X.; Zhao, X.-H.; Zeng, C.; Du, J.-Y.; Zhang, G.-B.; Wang, F.-X.; Ma, X.-Y.; Fan, C.-A. Angew.

Chem., Int. Ed. 2013, 52, 9229. (b) Deng, Y.-H.; Zhang, X.-Z.; Yu, K.Y.; Yan, X.; Du, J.-Y.; Huang, H.; Fan, C.-A. Chem. Commun. 2016, 52, 4183. (c) Zhang, X.-Z.; Du, J.-Y.; Deng, Y.-H.; Chu, W.-D.; Yan, X.; Yu, K.-Y.; Fan, C.-A. J. Org. Chem. 2016, 81, 2598. (d) Zhang, X.-Z.; Deng, Y.-H.; Yan, X.; Yu, K.-Y.; Wang, F.-X.; Ma, X.-Y.; Fan, C.-A. J. Org. Chem. 2016, 81, 5655. (17) During the preparation of this manuscript, a competitive report involving Cinchona alkaloid catalyzed enantioselective [4 + 2] annulation of allenic esters and in situ generated o-QMs has been presented recently: Chen, P.; Wang, K.; Guo, W.; Liu, X.; Liu, Y.; Li, C. Angew. Chem., Int. Ed. 2017, 56, 3689. (18) CCDC 1407842 (3ea) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam. ac.uk/data_request/cif. (19) (a) Mattson, A. E.; Scheidt, K. A. J. Am. Chem. Soc. 2007, 129, 4508. (b) Jurd, L. Tetrahedron 1977, 33, 163. (20) (a) Clavier, H.; Jeune, K. L.; de Riggi, I.; Tenaglia, A.; Buono, G. Org. Lett. 2011, 13, 308. (b) Cowen, B. J.; Saunders, L. B.; Miller, S. J. J. Am. Chem. Soc. 2009, 131, 6105. (c) Himbert, G.; Fink, D.; Diehl, K.; Rademacher, P.; Bittner, A. J. Chem. Ber. 1989, 122, 1161. (d) Himbert, G.; Fink, D.; Diehl, K. Chem. Ber. 1988, 121, 431. (e) Zhu, X.-F.; Schaffner, A.-P.; Li, R. C.; Kwon, O. Org. Lett. 2005, 7, 2977. (21) (a) Liu, Y.; Sun, B.; Wang, B.; Wakem, M.; Deng, L. J. Am. Chem. Soc. 2009, 131, 418. (b) Berkessel, A.; Guixà, M.; Schmidt, F.; Neudörfl, J. M.; Lex, J. Chem. - Eur. J. 2007, 13, 4483.

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DOI: 10.1021/acs.joc.7b00370 J. Org. Chem. 2017, 82, 5433−5440