Asymmetric Formal [4 + 2] Annulation of o-Quinone Methides with β

Mar 13, 2018 - An asymmetric cascade reaction between β-keto acylpyrazoles and o-quinone methides in a formal [4 + 2] fashion to access potentially ...
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Cite This: J. Org. Chem. 2018, 83, 4221−4228

Asymmetric Formal [4 + 2] Annulation of o‑Quinone Methides with β‑Keto Acylpyrazoles: A General Approach to Optically Active trans3,4-Dihydrocoumarins Liying Cui, Dan Lv, Youming Wang, Zhijin Fan, Zhengming Li, and Zhenghong Zhou* Institute and State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, P. R. China S Supporting Information *

ABSTRACT: An asymmetric cascade reaction between βketo acylpyrazoles and o-quinone methides in a formal [4 + 2] fashion to access potentially pharmacological active trans-3,4dihydrocoumarins has been achieved efficiently by using a quinine-based chiral squaramide as the catalyst. The desired products were obtained in high yields with excellent diastereoand enantioselectivities (up to 96% yield, >19/1 dr and 96% ee) under mild reaction conditions.

hetero-Diels−Alder reaction between o-QMs and azlactones.6f Most recently, Deng developed a chiral amidine-catalyzed tandem Michael addition/lactonization of carboxylic acids and o-QMs that enables the asymmetric synthesis of cis-3,4dihydrocoumarins in excellent enantioselectivities.4e Since an aromatic phenoxide intermediate will be generated after the Michael addition of a nucleophile to o-QMs, we envisioned that the introduction of a good acylation unit in the Michael donor will facilitate the subsequent intermolecular lactonization to generate 3,4-dihydrocoumarins in a one-pot fashion. Such catalytic transformations will give new and general entries to 3,4-dihydrocoumarins. It is well documented that N-acyl azoles have a high degree of reactivity in nucleophilic reactions and have been considered to be mild acylating agents as alternatives to acyl halides and anhydrides.7 Therefore, β-keto acylpyrazoles are especially deserving to be noticed in the reaction with oQMs due to their unique characteristics: (i) The increased electron-withdrawing capability of the acyl pyrazole moiety will enhance activation of the substrate toward deprotonation of the methylene proton, and (ii) the facile nucleophilic cleavage of the C−N bond enables us to access to the desired lactonization product in a one-pot fashion under mild conditions. As a part of our ongoing research on the development of approaches to biorelevant heterocycles,8 we herein report the organocatalyzed [4 + 2] cyclization of β-keto acylpyrazoles and o-QMs, which provide new access to trans-3,4-dihydrocoumarins in high levels of diastereo- and enantioselectivity.

3,4-Dihydrocoumarins are found, as an important structural subunit, in many naturally occurring compounds.1 Biological studies reveal that 3,4-dihydrocoumarin derivatives show a wide range of biological activities, thus making them attractive candidates as lead compounds in drug discovery.2 Moreover, 3,4-dihydrocoumarins are also useful building blocks in the synthesis of some other important compounds.3 Given the significance of these compounds as important structural scaffolds in natural products and drug candidates, significant efforts have been devoted to the asymmetric synthesis of these fascinating molecules, and many methods have been reported in recent years.4 o-Quinone methides (o-QMs) are considerably more reactive than regular α,β-unsaturated ketones and esters since nucleophilic attack at the external carbon produces an aromatic phenol/phenoxide, and this aromatization process of the ring is highly thermodynamically favorable.5 Therefore, among these methods, the asymmetric formal [4 + 2] annulation between o-QMs and different two-carbon reaction partners represents a powerful approach for the facile construction of 3,4-dihydrocoumarins. 6 In 2008, Lectka reported a chiral ammonium fluoride promoted reaction of oQMs with silyl ketene acetals, affording the desired 3,4dihydrocoumarin products with ee values ranging from 72% to 90%.6a Later, NHC-catalyzed formal [4 + 2] cycloaddition of stabilized or in situ generated o-QM with other C2 reaction partners, such as ketenes,6b acrolein,6c and acyl imidazoles,6d were also realized with high levels of enantioselectivity. In addition, the synthesis of 3,4-dihydrocoumarin derivatives was also achieved by squaramide-catalyzed asymmetric addition of deconjugated butenolides4b or Meldrum’s acid6e to in situ generated o-QM as well as chiral Sc(III) complex catalyzed © 2018 American Chemical Society

Received: January 26, 2018 Published: March 13, 2018 4221

DOI: 10.1021/acs.joc.8b00234 J. Org. Chem. 2018, 83, 4221−4228

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The Journal of Organic Chemistry

Figure 1. Catalyst candidates.

product 3aa with comparable results as thiourea Ia (entries 2−4 vs entry 1). To further improve the enantioselectivity of this transformation, we then turn our attention to squaramide-based bidentate hydrogen bond donor catalysts. Generally, much better performances were observed for bifunctional squaramide catalysts IV−VIII bearing different chiral diamine backbone and N-substituent (entries 5−11). Eventually, we found the quinine-derived squaramide V to be optimal for this reaction. With this catalyst, 3,4-dihydrocoumarin 3aa was obtained as a single diastereomer in 92% yield with 94% ee (entry 7). For comparison, we attempted to synthesize other β-keto acyl compounds, such as 1-(1H-imidazol-1-yl)-3-phenylpropane1,3-dione and 1-phenyl-3-(1H-pyrrol-1-yl)propane-1,3-dione, and evaluate their reactivity in this transformation. Unfortunately, these two compounds are so reactive that only the dimerization product 3-benzoyl-4-hydroxy-6-phenyl-2H-pyran2-one could be isolated during their synthesis. Having identified squaramide V as the optimum catalyst for the reaction, other factors, such as solvent, catalyst loading, and reaction temperature, influencing the reaction were thoroughly investigated employing the reaction between 1-phenyl-3-(1Hpyrazol-1-yl)propane-1,3-dione (1a) and o-quinone methide (2a) as the model. The results are listed in Table 2. A careful examination of the solvents indicated that the asymmetric cascade Michael addition−lactonization could be carried out smoothly in several conventional solvents such as methylene chloride (94% ee), toluene (76% ee), ethyl acetate (88% ee), chloroform (87% ee), 1,2-dichloroethane (94% ee), ether (80% ee), acetonitrile (88% ee), and THF (88% ee) (entries 1−8). In terms of both yield and ee value, dichloromethane was the best choice for the reaction. Further investigation showed that there was almost negligible temperature effect when the reaction was carried out at 20 to −40 °C, giving the corresponding 3aa with ee value ranging from 91% to 95% (entries 1 and 9−11). A slightly improved enantioselectivity of 95% ee was observed by performing the reaction at 0 °C (entry 9). Adjusting the catalyst loading demonstrated no appreciable influence on the outcome of the

Initially, a model reaction of 1-phenyl-3-(1H-pyrazol-1yl)propane-1,3-dione (1a) with stable o-quinone methide (2a) was investigated under the catalysis of several of thiourea9 and squaramide-based10 chiral Brønsted bases (Figure 1). The results are summarized in Table 1. Table 1. Catalyst Screeninga

entry

catalyst

time (h)

yield (%)b

ee (%)c

1 2 3 4 5 6 7 8 9 10 11

Ia Ib II III IVa IVb V VI VIIa VIIb VIII

4 1 2 1 2 1 1 0.5 1 1 2

72 73 77 63 65 75 92 77 69 81 76

79 82 −79 −76 89 88 −94 −87 −88 −73 −86

All reactions were carried out with β-keto acylpyrazole 1a (0.10 mmol), o-quinone methide 2a (0.20 mmol), and catalyst (10 mol %) in dichloromethane (1 mL) at 20 °C. bIsolated yield. cDetermined by HPLC analysis with a chiral stationary phase. a

As we anticipated, the desired [2 + 4] annulation product 3aa could be obtained in 72% yield with >19/1 dr and 79% ee when thiourea Ia containing a (1R,2R)-1,2-diphenylethane-1,2diamine skeleton was employed (entry 1). Other thioureas, such as (1R,2R)-cyclohexane-1,2-diamine derived thiourea Ib and cinchona alkaloid-based thioureas II and III also proved to be efficient for this reaction, delivering the desired cyclization 4222

DOI: 10.1021/acs.joc.8b00234 J. Org. Chem. 2018, 83, 4221−4228

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The Journal of Organic Chemistry Table 2. Optimization of Reaction Conditionsa

Table 3. Substrate Scope of Squaramide V-Catalyzed [4 + 2] Annulation Reaction

entry

solvent

time (h)

yield (%)b

ee (%)c

entry

3 (Ar, R)

yield (%)b

ee (%)c

1 2 3 4 5 6 7 8 9d 10e 11f 12g 13h

CH2Cl2 toluene ethyl acetate chloroform 1,2-dichloroethane ether acetonitrile THF CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2

1 0.4 1 1 0.5 0.7 0.7 1.5 4 8 45 4 5

92 74 78 77 75 95 95 91 94 95 89 94 94

94 76 88 87 94 80 88 88 95 94 91 95 92

1 2 3 4 5 6 7 8 9 10 11 12 13 14d 15 16d 17e 18e 19e 20e

3aa (Ph, 4-MeOC6H4) 3ba (4-FC6H4, 4-MeOC6H4) 3ca (3-FC6H4, 4-MeOC6H4) 3da (2-FC6H4, 4-MeOC6H4) 3ea (4-ClC6H4, 4-MeOC6H4) 3fa (3-ClC6H4, 4-MeOC6H4) 3ga (4-BrC6H4, 4-MeOC6H4) 3ha (3-BrC6H4, 4-MeOC6H4) 3ia (4-MeC6H4, 4-MeOC6H4) 3ja (3-MeC6H4, 4-MeOC6H4) 3ka (2-MeC6H4, 4-MeOC6H4) 3la (2,4-Me2C6H3, 4-MeOC6H4) 3ma (3,5-Me2C6H3, 4-MeOC6H4) 3na (3-MeOC6H4, 4-MeOC6H4) 3oa (2-Naph, 4-MeOC6H4) 3pa (2-thienyl, 4-MeOC6H4) 3ab (Ph, (E)-PhCH = CH) 3ac (Ph, (E)-4-BrC6H4CH = CH) 3ad (Ph, (E)- 4-MeC6H4CH = CH) 3ae (Ph, (E)- 4-MeOC6H4CH = CH)

94 93 81 86 96 90 96 93 75 74 80 81 84 89 91 93 50 41 69 77

95 90 91 93 93 94 90 93 90 94 95 93 93 94 90 96 90 94 94 95

Unless otherwise specified, all reactions were carried out with β-keto acylpyrazole 1a (0.10 mmol), o-quinone methide 2a (0.20 mmol), and catalyst V (10 mol %) in solvent (1 mL) at 20 °C. bIsolated yield. c Determined by HPLC analysis with a chiral stationary phase. dThe reaction was performed at 0 °C. eThe reaction was carried out at −20 °C. fThe reaction was conducted at −40 °C. gThe reaction took place at 0 °C with a catalyst loading of 5 mol %. hThe reaction ran at 0 °C with a catalyst loading of 2.5 mol %. a

Unless otherwise specified, all reactions were carried out with β-keto acylpyrazole 1 (0.10 mmol), o-quinone methide 2 (0.20 mmol), and catalyst V (5 mol %) in dichloromethane (1 mL) at 0 °C for 4 h. b Isolated yield. cDetermined by HPLC analysis with a chiral stationary phase. dThe catalyst loading is 10 mol %. e1.3 equiv of o-quinone methide 2 was employed. a

reaction. The use of 5 mol % of catalyst V led to the formation of 3aa with an identical yield and ee value (entry 12). Further decreasing the catalyst loading to 2.5 mol % resulted in a slightly decreased ee value (enry 13). With the optimal reaction conditions in hand, we set out to explore the scope of this cascade Michael addition− lactonization process. The results are collected in Table 3. First, we submitted various β-keto acylpyrazoles to this reaction. It was found that a broad range of β-keto acylpyrazoles (1) could readily participate in this reaction. Generally, the reaction proceeded smoothly, and the desired annulation products 3 were obtained as single diastereomers in good yields with excellent enantioselectivities (90−96% ee) within 4 h. Both electron-withdrawing and electron-donating substituents on the phenyl group of 1 were readily tolerated regardless of the substitution pattern (entries 2−14). 2Naphthyl-substituted β-keto acylpyrazole 1o worked well to give the 3,4-dihydrocoumarin 3oa in 91% yield with >19/1 d.r. and 90% ee (entry 15). By replacing the phenyl group of the βketo acylpyrazole 1a with an electron-rich heteroaryl, the reaction also ran smoothly to afford the annulation product 3pa in good yield and excellent enantioselectivity in the presence of 10 mol % of catalyst V (entry 16). Unfortunately, aliphatic βketo acylpyrazole, such as 1-(1H-pyrazol-1-yl)butane-1,3-dione, was completely inactive under the optimal reaction conditions and failed to generate the corresponding cyclization product. We next studied the scope of this process in terms of the o-QM to this process. When (E)-2-styryl-substituted o-QM 2b was employed, the corresponding cyclization product 3ab was obtained with almost unaltered ee value albeit in a somewhat decreased yield (entry 17). The introduction of either electronwithdrawing or electron-donating substituent on the phenyl

ring of the styryl group demonstrated no obvious influence on the stereochemical outcome of the reaction. Again, in all cases studied, the reaction proceeded smoothly and was typically completed within 4 h to afford the corresponding annulation products 3ac−3ae as a single diastereomer in good yields with excellent enantioselectivities (entries 18−20, 94−95% ee). The relative and absolute configuration of the product 3ea is unequivocally established by X-ray analysis (see the Supporting Information), and the remaining configurations are assumed by analogy.11 The proposed catalytic cycle is depicted in Figure 2. The deprotonation of 1-phenyl-3-(1H-pyrazol-1-yl)propane-1,3dione (1a) forms a hydrogen-bond-paired enolate A, which nucleophilically attacks the o-QM (2a) with the restoration of aromaticity as the driving force to generate a phenoxide intermediate B. Subsequent lactonization furnishes the final [4 + 2] annulation product 3aa with the 7S,8R absolute configuration as the predominant enantiomer and accompanied by the release of the pyrazole moiety. The 3,4-dihydrocoumarin products obtained in these formal [4 + 2] annulations would find more application in organic synthesis. For example, under basic hydrolytic conditions, hydrolytic decarboxylation of 3,4-dihydrocoumarin 3aa took place smoothly to give an inseparable mixture of hydroxyl ketone 4 and the related lactol 4′ in good yield. Subsequent methylation of the phenolic hydroxyl group afforded chiral βdiaryl-substituted ketone 5, an important type of intermediates 4223

DOI: 10.1021/acs.joc.8b00234 J. Org. Chem. 2018, 83, 4221−4228

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The Journal of Organic Chemistry

In conclusion, we have developed a highly efficient diastereoand enantioselective formal [4 + 2] annulation reaction for the synthesis of dihydrocoumarin derivatives via bifunctional Brønsted base catalysis. Under the catalysis of a chiral quinine-based squaramide, the cascade Michael addition/ lactonization of a wide range of β-keto acylpyrazoles and oQMs took place smoothly to deliver the desired dihydrocoumarins in high yields with excellent diastereo- and enantioselectivities. This platform facilitates rapid access to chiral trans3,4-disubstituted dihydrocoumarins.

■

Figure 2. Proposed catalytic circle.

EXPERIMENTAL SECTION

General Information. Materials were obtained from commercial suppliers and were used without further purification. NMR spectra were obtained with a 400 MHz spectrometer (1H 400 MHz, 13C 100.6 MHz) in CDCl3. The chemical shifts are reported as δ values (ppm) relative to tetramethylsilane. HRMS spectra were recorded with a QTOF mass spectrometer, equipped with an ESI source. Optical rotation values were measured with instruments operating at λ = 589 nm, corresponding to the sodium D line at 20 °C. Enantiomeric excesses were determined by HPLC analysis with a chiral stationary phase. General Procedure for the Chiral Squaramide Vb-Catalyzed Michael Addition Reactions. A mixture of β-keto acylpyrazoles 1 (0.10 mmol), o-quinone methides 2 (0.20 or 0.13 mmol), and squaramide catalyst V (3.2 mg, 0.005 mmol) in dichloromethane (1 mL) was stirred at 0 °C for 4 h. After the completion of the reaction, the reaction mixture was directly purified by column chromatography on silica gel (100−200 mesh, petroleum ether/ethyl acetate = 4/1) to afford the desired chiral trans-3,4-dihydrocoumarins 3. The title compounds were fully characterized by 1H, 13C NMR, HRMS, and specific rotation data. (7S,8S)-7-Benzoyl-8-(4-methoxyphenyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-6-one (3aa). White solid, mp 151−153 °C, 1 37.8 mg, 94% yield, [α]20 D 83.76 (c 0.83, CHCl3), >19/1 dr, 95% ee. H NMR (400 MHz, CDCl3): δ 7.89 (d, J = 7.6 Hz, 2 H), 7.59 (t, J = 7.2 Hz, 1 H), 7.47 (t, J = 7.6 Hz, 2 H), 7.10 (d, J = 8.8 Hz, 2 H), 7.10 (d, J = 8.8 Hz, 2 H), 6.84 (d, J = 8.8 Hz, 2 H), 6.69 (s, 1 H), 6.32 (s, 1 H), 5.95 (d, J = 1.2 Hz, 1 H), 5.94 (d, J = 1.2 Hz, 1 H), 4.88 (d, J = 7.2 Hz, 1 H), 4.62 (d, J = 6.8 Hz, 1 H), 3.76 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 193.5, 165.2, 159.1, 147.7, 145.4, 144.7, 135.4, 133.9, 131.3, 128.9, 128.8, 128.7, 116.3, 114.6, 107.5, 101.8, 98.9, 55.3, 55.1, 43.5.

for the synthesis of many pharmaceuticals and natural products. It is worth noting that this type of compound is generally obtained via transition-metal-catalyzed conjugate addition of organoboron reagents to enone.12 This newly developed process offered an alternative organocatalytic indirect approach to access these synthetic valuable compounds. Moreover, according to a literature procedure,13 the ketone/lactol mixture (4/4′) could be conveniently converted into 2,4-cis-chroman 6, a class of compounds that are found widely in bioactive natural products, without appreciable loss in optical purity via Lewis acid mediated silane reduction (Scheme 1). To overcome the inherent limitation in scope of using stabilized substrates, we have tried application of this reaction to o-quinone methide 2a generated in situ upon the treatment of the corresponding 2-sulfonylalkyl phenol 7 with aqueous sodium hydrocarbonate. Although the reaction ran smoothly to give the corresponding annulation product 3aa, in this case, an obvious decrease in both yield and enantioselectivity was observed.

Scheme 1. Basic Hydrolytic Decarboxylation of 3aa and Subsequent Transformation

4224

DOI: 10.1021/acs.joc.8b00234 J. Org. Chem. 2018, 83, 4221−4228

Note

The Journal of Organic Chemistry HRMS (ESI) m/z calcd for C24H22NO6 [M + NH4]+: 420.1442, found 420.1435. HPLC analysis (Chiralpak OD-H column, Hexane:2propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 15.75 (major) and 63.24 min (minor). (7S,8S)-7-(4-Fluorobenzoyl)-8-(4-methoxyphenyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ba). White solid, mp 71−73 °C, 39.1 mg, 93% yield, [α]20 D 86.62 (c 1.30, CHCl3), >19/1 dr, 90% ee. 1H NMR (400 MHz, CDCl3): δ 7.91 (dd, J = 8.8, 5.2 Hz, 2 H), 7.13 (t, J = 8.8 Hz, 2 H), 7.09 (d, J = 8.8 Hz, 2 H), 6.83 (d, J = 8.8 Hz, 2 H), 6.68 (s, 1 H), 6.31 (s, 1 H), 5.95 (d, J = 1.2 Hz, 1 H), 5.94 (d, J = 1.2 Hz, 1 H), 4.83 (d, J = 7.6 Hz, 1 H), 4.62 (d, J = 7.6 Hz, 1 H), 3.76 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 191.9, 166.1 (d, J = 256.7 Hz), 165.10, 159.1, 147.7, 145.2, 144.8, 132.0, 131.5 (d, J = 9.7 Hz), 131.0, 128.9, 116.6, 116.0 (d, J = 22.1 Hz), 114.6, 107.5, 101.8, 98.9, 55.3, 54.8, 43.3. HRMS (ESI) m/z calcd for C24H21FNO6 [M + NH4]+: 438.1347, found 438.1344. HPLC analysis (Chiralpak OD-H column, Hexane:2-propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 13.93 (major) and 35.05 min (minor). (7S,8S)-7-(3-Fluorobenzoyl)-8-(4-methoxyphenyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ca). White solid, mp 159− 161 °C, 34.1 mg, 81% yield, [α]20 D 99.8 (c 1.00, CHCl3), >19/1 dr, 91% ee. 1H NMR (400 MHz, CDCl3): δ 7.66 (d, J = 8.0 Hz, 1 H), 7.54 (td, J = 9.2, 2.0 Hz, 1 H), 7.45 (dt, J = 8.0, 5.6 Hz, 1 H), 7.28 (dt, J = 8.0, 2.0 Hz, 1 H), 7.09 (d, J = 8.4 Hz, 2 H), 6.84 (d, J = 8.8 Hz, 2 H), 6.69 (s, 1 H), 6.30 (s, 1 H), 5.96 (d, J = 1.2 Hz, 1 H), 5.95 (d, J = 1.2 Hz, 1 H), 4.81 (d, J = 8.0 Hz, 1 H), 4.63 (d, J = 8.0 Hz, 1 H), 3.77 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 192.4, 165.0, 162.8 (d, J = 247.5 Hz), 159.2, 147.7, 145.3, 144.8, 137.7 (d, J = 6.4 Hz), 130.9, 130.6 (d, J = 7.6 Hz), 129.0, 124.4 (d, J = 3.0 Hz), 121.0 (d, J = 21.4 Hz), 116.6, 115.4 (d, J = 22.6 Hz), 114.7, 107.5, 101.8, 98.9, 55.3, 55.0, 43.3. HRMS (ESI) m/z calcd for C24H21FNO6 [M + NH4]+: 438.1347, found 438.1343. HPLC analysis (Chiralpak OD-H column, Hexane:2-propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 13.92 (major) and 63.39 min (minor). (7S,8S)-7-(2-Fluorobenzoyl)-8-(4-methoxyphenyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3da). White solid, mp 173− 175 °C, 36.2 mg, 86% yield, [α]20 D 71.6 (c 1.00, CHCl3), >19/1 dr, 93% ee. 1H NMR (400 MHz, CDCl3): δ 7.72 (dt, J = 7.6, 2.0 Hz, 1 H), 7.54−7.60 (m, 1 H), 7.21 (t, J = 7.6 Hz, 1 H), 7.17 (dd, J = 7.6, 4.4 Hz, 1 H), 7.10 (d, J = 8.4 Hz, 2 H), 6.83 (d, J = 8.4 Hz, 2 H), 6.71 (s, 1 H), 6.26 (s, 1 H), 5.94 (s, 2 H), 4.87 (d, J = 8.0 Hz, 1 H), 4.58 (dd, J = 7.2, 2.0 Hz, 1 H), 3.77 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 191.5 (d, J = 3.6 Hz), 165.2, 161.4 (d, J = 253.8 Hz), 159.0, 147.7, 145.7, 144.6, 135.7 (d, J = 9.4 Hz), 131.3 (d, J = 1.8 Hz), 130.8, 129.0, 125.0 (d, J = 3.2 Hz), 123.9 (d, J = 11.8 Hz), 116.7 (d, J = 23.8 Hz), 116.2, 114.5, 107.5, 101.8, 99.0, 59.4, 55.2, 43.1. HRMS (ESI) m/z calcd for C24H21FNO6 [M + NH4]+: 438.1347, found 438.1345. HPLC analysis (Chiralpak OD-H column, Hexane:2-propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 12.92 (major) and 23.88 min (minor). (7S,8S)-7-(4-Chlorobenzoyl)-8-(4-methoxyphenyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ea). White solid, mp 190− 192 °C, 41.9 mg, 96% yield, [α]20 D 55.67 (c 1.20, CHCl3), >19/1 dr, 93% ee. 1H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 8.4 Hz, 2 H), 7.43 (d, J = 8.4 Hz, 2 H), 7.08 (d, J = 8.8 Hz, 2 H), 6.83 (d, J = 8.4 Hz, 2 H), 6.77 (s, 1 H), 6.30 (s, 1 H), 5.95 (d, J = 1.2 Hz, 1 H), 5.94 (d, J = 1.2 Hz, 1 H), 4.81 (d, J = 8.0 Hz, 1 H), 4.61 (d, J = 7.6 Hz, 1 H), 3.76 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 192.4, 165.0, 159.2, 147.7, 145.2, 144.8, 140.5, 134.0, 130.9, 130.1, 129.2, 128.9, 116.6, 114.7, 107.5, 101.8, 98.9, 55.3, 54.8, 43.3. HRMS (ESI) m/z calcd for C24H21ClNO6 [M + NH4]+: 454.1052, found 454.1047. HPLC analysis (Chiralpak OD-H column, Hexane:2-propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 220 nm): Rt = 14.37 (major) and 25.72 min (minor). (7S,8S)-7-(3-Chlorobenzoyl)-8-(4-methoxyphenyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3fa). White solid, mp 65−67 °C, 39.3 mg, 90% yield, [α]20 D 165.28 (c 0.53, CHCl3), >19/1 dr, 94% ee. 1H NMR (400 MHz, CDCl3): δ 7.82 (s, 1 H), 7.74 (d, J = 7.6 Hz, 1 H), 7.54 (d, J = 7.6 Hz, 1 H), 7.39 (t, J = 8.0 Hz, 1 H), 7.09 (d, J = 8.4 Hz, 2 H), 6.84 (d, J = 8.4 Hz, 2 H), 6.67 (s, 1 H), 6.29 (s, 1 H),

5.95 (d, J = 1.2 Hz, 1 H), 5.94 (d, J = 1.2 Hz, 1 H), 4.82 (d, J = 8.4 Hz, 1 H), 4.63 (d, J = 8.4 Hz, 1 H), 3.76 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 192.5, 165.0, 159.1, 147.7, 145.2, 144.8, 137.2, 135.2, 133.8, 130.7, 130.1, 129.0, 128.7, 126.7, 116.6, 114.6, 107.5, 101.8, 98.9, 55.2, 54.8, 43.2. HRMS (ESI) m/z calcd for C24H21ClNO6 [M + NH4]+: 454.1052, found 454.1054. HPLC analysis (Chiralpak OD-H column, Hexane:2-propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 16.07 (major) and 97.83 min (minor). (7S,8S)-7-(4-Bromobenzoyl)-8-(4-methoxyphenyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ga). White solid, mp 188− 190 °C, 46.2 mg, 96% yield, [α]20 D 35.32 (c 0.47, CHCl3), >19/1 dr, 90% ee. 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.8 Hz, 2 H), 7.60 (d, J = 8.8 Hz, 2 H), 7.08 (d, J = 8.4 Hz, 2 H), 6.83 (d, J = 8.4 Hz, 2 H), 6.68 (s, 1 H), 6.30 (s, 1 H), 5.95 (d, J = 0.8 Hz, 1 H), 5.94 (d, J = 0.8 Hz, 1 H), 4.80 (d, J = 8.0 Hz, 1 H), 4.62 (d, J = 7.6 Hz, 1 H), 3.77 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 192.6, 165.0, 159.2, 147.7, 145.3, 144.8, 134.4, 132.2, 130.9, 130.1, 129.3, 128.9, 116.6, 114.67, 107.5, 101.8, 98.9, 55.3, 54.8, 43.3. HRMS (ESI) m/z calcd for C24H21BrNO6 [M + NH4]+: 498.0547, found 498.0545. HPLC analysis (Chiralpak IC column, Hexane:2-propanol = 75:25, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 29.11 (major) and 33.93 min (minor). (7S,8S)-7-(3-Bromobenzoyl)-8-(4-methoxyphenyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ha). White solid, mp 143− 145 °C, 44.8 mg, 93% yield, [α]20 D 74.25 (c 1.33, CHCl3), >19/1 dr, 93% ee. 1H NMR (400 MHz, CDCl3): δ 7.97 (s, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.69 (d, J = 8.0 Hz, 1 H), 7.33 (t, J = 8.0 Hz, 1 H), 7.09 (d, J = 8.8 Hz, 2 H), 6.84 (d, J = 8.8 Hz, 2 H), 6.68 (s, 1 H), 6.29 (s, 1 H), 5.95 (d, J = 1.2 Hz, 1 H), 5.94 (d, J = 1.2 Hz, 1 H), 4.80 (d, J = 8.0 Hz, 1 H), 4.63 (d, J = 8.0 Hz, 1 H), 3.77 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 192.4, 165.0, 159.2, 147.7, 145.3, 144.8, 137.4, 136.7, 131.6, 130.8, 130.4, 129.0, 127.1, 123.2, 116.6, 114.7, 107.5, 101.8, 98.9, 55.3, 54.8, 43.2. HRMS (ESI) m/z calcd for C24H21BrNO6 [M + NH4]+: 498.0547, found 498.0538. HPLC analysis (Chiralpak OD-H column, Hexane:2-propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 19.56 (major) and 135.20 min (minor). (7S,8S)-8-(4-Methoxyphenyl)-7-(4-methylbenzoyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ia). White solid, mp 167− 169 °C, 31.2 mg, 75% yield, [α]20 D 100.67 (c 0.30, CHCl3), >19/1 dr, 90% ee. 1H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.4 Hz, 2 H), 7.27 (d, J = 8.0 Hz, 2 H), 7.09 (d, J = 8.8 Hz, 2 H), 6.83 (d, J = 8.4 Hz, 2 H), 6.69 (s, 1 H), 6.32 (s, 1 H), 5.94 (d, J = 1.2 Hz, 1 H), 5.93 (d, J = 1.2 Hz, 1 H), 4.86 (d, J = 6.8 Hz, 1 H), 4.60 (d, J = 6.4 Hz, 1 H), 3.76 (s, 3 H), 2.41 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 193.0, 165.3, 159.1, 147.7, 145.4, 145.0, 144.7, 132.8, 131.5, 129.6, 128.9, 128.7, 116.3, 114.6, 107.6, 101.7, 99.0, 55.3, 55.1, 43.6, 21.7. HRMS (ESI) m/z calcd for C25H24NO6 [M + NH4]+: 434.1598, found 434.1593. HPLC analysis (Chiralpak OD-H column, Hexane:2propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 15.69 (major) and 25.41 min (minor). (7S,8S)-8-(4-Methoxyphenyl)-7-(3-methylbenzoyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ja). White solid, mp 122− 124 °C, 30.8 mg, 74% yield, [α]20 D 103.19 (c 1.13, CHCl3), >19/1 dr, 94% ee. 1H NMR (400 MHz, CDCl3): δ 7.69 (s, 1 H), 7.68 (d, J = 7.6 Hz, 1 H), 7.40 (d, J = 7.6 Hz, 1 H), 7.35 (t, J = 7.6 Hz, 1 H), 7.10 (d, J = 8.4 Hz, 2 H), 6.84 (d, J = 8.4 Hz, 2 H), 6.69 (s, 1 H), 6.31 (s, 1 H), 5.94 (s, 2 H), 4.87 (d, J = 6.8 Hz, 1 H), 4.61 (d, J = 6.4 Hz, 1 H), 3.76 (s, 3 H), 2.39 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 193.7, 165.3, 159.1, 147.7, 145.4, 144.7, 138.8, 135.4, 134.8, 131.3, 129.2, 128.8, 128.7, 125.9, 116.4, 114.6, 107.5, 101.8, 98.9, 55.2, 55.1, 43.5, 21.3. HRMS (ESI) m/z calcd for C25H24NO6 [M + NH4]+: 434.1598, found 434.1597. HPLC analysis (Chiralpak OD-H column, Hexane:2propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 15.53 (major) and 53.04 min (minor). (7S,8S)-8-(4-Methoxyphenyl)-7-(2-methylbenzoyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ka). White solid, mp 120− 122 °C, 33.3 mg, 80% yield, [α]20 D 99.0 (c 0.20, CHCl3), >19/1 dr, 95% ee. 1H NMR (400 MHz, CDCl3): δ 7.48 (d, J = 7.6 Hz, 1 H), 7.37 (dt, J = 7.6, 1.2 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 7.21 (d, J = 7.6 Hz, 1 H), 7.05 (d, J = 8.8 Hz, 2 H), 6.83 (d, J = 8.4 Hz, 2 H), 6.69 (s, 1 4225

DOI: 10.1021/acs.joc.8b00234 J. Org. Chem. 2018, 83, 4221−4228

Note

The Journal of Organic Chemistry

(d, J = 8.8 Hz, 2 H), 6.83 (d, J = 8.8 Hz, 2 H), 6.67 (s, 1 H), 6.35 (s, 1 H), 5.95 (d, J = 1.2 Hz, 1 H), 5.94 (d, J = 1.2 Hz, 1 H), 4.68 (d, J = 7.6 Hz, 1 H), 4.66 (d, J = 7.6 Hz, 1 H), 3.76 (s, 3 H), 2.35 (s, 6 H). 13C NMR (100.6 MHz, CDCl3): δ 185.5, 164.8, 159.1, 147.6, 145.3, 144.7, 142.5, 135.5, 133.5, 131.0, 128.9, 128.5, 116.5, 114.6, 107.6, 101.8, 98.9, 56.4, 55.2, 43.6. HRMS (ESI) m/z calcd for C22H20NO6S [M + NH4]+: 426.1006, found 426.1006. HPLC analysis (Chiralpak AD-H column, Hexane:2-propanol = 75:25, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 27.20 (minor) and 46.83 min (major). (7S,8R)-7-Benzoyl-8-((E)-styryl)-7,8-dihydro-6H-[1,3]dioxolo[4,5g]chromen-6-one (3ab). White solid, mp 173−175 °C, 19.9 mg, 50% 1 yield, [α]20 D 44.18 (c 0.67, CHCl3), >19/1 dr, 90% ee. H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 7.6 Hz, 2 H), 7.62 (t, J = 7.6 Hz, 1 H), 7.50 (t, J = 7.6 Hz, 2 H), 7.23−7.32 (m, 5 H), 6.68 (s, 1 H), 6.61 (s, 1 H), 6.49 (d, J = 16.0 Hz, 1 H), 6.12 (dd, J = 15.6, 7.6 Hz, 1 H), 5.98 (d, J = 1.2 Hz, 1 H), 5.97 (d, J = 1.2 Hz, 1 H), 4.75 (d, J = 6.0 Hz, 1 H), 4.23 (t, J = 7.2 Hz, 1 H). 13C NMR (100.6 MHz, CDCl3): δ 193.2, 165.1, 147.9, 145.3, 144.8, 135.9, 135.3, 134.0, 133.9, 129.0, 128.7, 128.6, 128.2, 126.6, 126.5, 114.8, 107.1, 101.8, 99.2, 53.4, 42.3. HRMS (ESI) m/z calcd for C25H22NO5 [M + NH4]+: 416.1492, found 416.1486. HPLC analysis (Chiralpak IC column, Hexane:2-propanol = 75:25, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 25.34 (major) and 31.68 min (minor). (7S,8R)-7-Benzoyl-8-((E)-4-bromostyryl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ac). White solid, mp 164−166 °C, 1 19.6 mg, 41% yield, [α]20 D 45.11 (c 0.47, CHCl3), >19/1 dr, 94% ee. H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 7.6 Hz, 2 H), 7.62 (t, J = 7.6 Hz, 1 H), 7.50 (t, J = 7.6 Hz, 2 H), 7.41 (d, J = 8.8 Hz, 2 H), 7.17 (d, J = 8.4 Hz, 2 H), 6.68 (s, 1 H), 6.58 (s, 1 H), 6.40 (d, J = 15.6 Hz, 1 H), 6.11 (dd, J = 15.6, 7.6 Hz, 1 H), 5.99 (d, J = 1.2 Hz, 1 H), 5.97 (d, J = 1.2 Hz, 1 H), 4.73 (d, J = 6.0 Hz, 1 H), 4.21 (t, J = 6.8 Hz, 1 H). 13C NMR (100.6 MHz, CDCl3): δ 193.1, 165.0, 147.9, 145.3, 144.8, 135.2, 134.7, 134.1, 132.8, 131.7, 129.0, 128.7, 128.0, 127.4, 122.0, 114.4, 107.1, 101.9, 99.3, 53.2, 42.2. HRMS (ESI) m/z calcd for C25H21BrNO5 [M + NH4]+: 494.0598, found 494.0589. HPLC analysis (Chiralpak IC-H column, Hexane:2-propanol = 75:25, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 30.34 (major) and 34.78 min (minor). (7S,8R)-7-Benzoyl-8-((E)-4-methylstyryl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ad). White solid, mp 176−178 °C, 1 28.5 mg, 69% yield, [α]20 D 87.53 (c 0.93, CHCl3), >19/1 dr, 94% ee. H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 7.2 Hz, 2 H), 7.62 (t, J = 7.2 Hz, 1 H), 7.49 (t, J = 7.2 Hz, 2 H), 7.20 (d, J = 8.0 Hz, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 6.68 (s, 1 H), 6.60 (s, 1 H), 6.45 (d, J = 15.6 Hz, 1 H), 6.06 (dd, J = 15.6, 7.6 Hz, 1 H), 5.98 (d, J = 1.2 Hz, 1 H), 5.96 (d, J = 1.2 Hz, 1 H), 4.74 (d, J = 6.4 Hz, 1 H), 4.21 (t, J = 6.8 Hz, 1 H), 2.32 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 193.3, 165.2, 147.8, 145.2, 144.7, 138.1, 135.2, 134.0, 133.8, 133.0, 129.3, 128.9, 128.7, 126.4, 125.5, 114.9, 107.1, 101.8, 99.2, 53.4, 42.3, 21.2. HRMS (ESI) m/z calcd for C26H24NO5 [M + NH4]+: 430.1649, found 430.1652. HPLC analysis (Chiralpak IC-H column, Hexane:2-propanol = 75:25, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 25.61 (major) and 31.20 min (minor). (7S,8R)-7-Benzoyl-8-((E)-4-methoxystyryl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ae). White solid, mp 130−132 °C, 1 33.0 mg, 77% yield, [α]20 D 72.91 (c 1.10, CHCl3), >19/1 dr, 95% ee. H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 7.2 Hz, 2 H), 7.61 (t, J = 7.2 Hz, 1 H), 7.49 (t, J = 7.6 Hz, 2 H), 7.24 (d, J = 8.0 Hz, 2 H), 6.82 (d, J = 8.8 Hz, 2 H), 6.68 (s, 1 H), 6.60 (s, 1 H), 6.42 (d, J = 15.6 Hz, 1 H), 5.98 (d, J = 1.2 Hz, 1 H), 5.97 (dd, J = 15.6, 7.6 Hz, 1 H), 5.96 (d, J = 1.2 Hz, 1 H), 4.73 (d, J = 6.4 Hz, 1 H), 4.19 (t, J = 6.8 Hz, 1 H), 3.79 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 193.4, 165.2, 159.6, 147.8, 145.2, 144.7, 135.3, 134.0, 133.3, 129.0, 128.7, 128.6, 127.7, 124.3, 115.0, 114.0, 107.2, 101.8, 99.2, 55.3, 53.5, 42.4. HRMS (ESI) m/z calcd for C26H24NO6 [M + NH4]+: 446.1598, found 446.1601. HPLC analysis (Chiralpak IC-H column, Hexane:2-propanol = 75:25, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 46.00 (major) and 50.49 min (minor). Hydrolytic Decarboxylation of Compound 3aa and the Subsequent Transformation. To a solution of 3aa (242 mg, 0.6

H), 6.30 (s, 1 H), 5.96 (d, J = 1.2 Hz, 1 H), 5.95 (d, J = 1.2 Hz, 1 H), 4.69 (d, J = 7.6 Hz, 1 H), 4.56 (d, J = 7.6 Hz, 1 H), 3.77 (s, 3 H), 2.17 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 197.2, 165.5, 159.1, 147.7, 145.6, 144.7, 138.9, 136.5, 132.0, 131.9, 130.8, 129.0, 127.9, 125.7, 116.6, 114.6, 107.4, 101.8, 99.0, 58.1, 55.3, 43.4, 20.3. HRMS (ESI) m/ z calcd for C25H24NO6 [M + NH4]+: 434.1598, found 434.1599. HPLC analysis (Chiralpak OD-H column, Hexane:2-propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 11.47 (major) and 48.96 min (minor). (7S,8S)-8-(4-Methoxyphenyl)-7-(2,4-dimethylbenzoyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-6-one (3la). White solid, mp 64−66 °C, 34.9 mg, 81% yield, [α]20 D 64.0 (c 0.40, CHCl3), >19/1 dr, 93% ee. 1H NMR (400 MHz, CDCl3): δ 7.44 (d, J = 8.0 Hz, 1 H), 7.06 (d, J = 7.6 Hz, 1 H), 7.05 (d, J = 8.4 Hz, 2 H), 7.02 (s, 1 H), 6.83 (d, J = 8.8 Hz, 2 H), 6.69 (s, 1 H), 6.30 (s, 1 H), 5.95 (s, 2 H), 4.70 (d, J = 7.2 Hz, 1 H), 4.55 (d, J = 7.2 Hz, 1 H), 3.77 (s, 3 H), 2.34 (s, 3 H), 2.17 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 196.5, 165.6, 159.1, 147.7, 145.6, 144.6, 142.7, 139.4, 133.5, 132.9, 131.0, 128.9, 128.5, 126.4, 116.6, 114.5, 107.4, 101.7, 99.0, 57.8, 55.3, 43.5, 21.4, 20.6. HRMS (ESI) m/z calcd for C26H26NO6 [M + NH4]+: 448.1755, found 448.1750. HPLC analysis (Chiralpak OD-H column, Hexane:2propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 9.97 (major) and 14.77 min (minor). (7S,8S)-8-(4-Methoxyphenyl)-7-(3,5-dimethylbenzoyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-6-one (3ma). White solid, mp 154−156 °C, 36.2 mg, 84% yield, [α]20 D 93.0 (c 1.20, CHCl3), >19/1 dr, 93% ee. 1H NMR (400 MHz, CDCl3): δ 7.48 (s, 1 H), 7.22 (s, 1 H), 7.10 (d, J = 8.8 Hz, 2 H), 6.84 (d, J = 8.8 Hz, 2 H), 6.69 (s, 1 H), 6.31 (s, 1 H), 5.94 (s, 2 H), 4.86 (d, J = 7.2 Hz, 1 H), 4.61 (d, J = 6.8 Hz, 1 H), 3.77 (s, 3 H), 2.35 (s, 6 H). 13C NMR (100.6 MHz, CDCl3): δ 193.8, 165.4, 159.1, 147.6, 145.4, 144.6, 138.6 135.7, 135.4, 131.4, 128.8, 126.5, 116.4, 114.6, 107.6, 101.7, 99.0, 55.3, 55.0, 43.5, 21.2. HRMS (ESI) m/z calcd for C26H26NO6 [M + NH4]+: 448.1755, found 448.1751. HPLC analysis (Chiralpak IC column, Hexane:2propanol = 75:25, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 30.45 (minor) and 41.54 min (major). (7S,8S)-7-(3-Methoxybenzoyl)-8-(4-methoxyphenyl)-7,8-dihydro6H-[1,3]dioxolo[4,5-g]chromen-6-one (3na). White solid, mp 52−54 °C, 37.2 mg, 86% yield, [α]20 D 141.0 (c 0.53, CHCl3), >19/1 dr, 94% ee. 1H NMR (400 MHz, CDCl3): δ 7.47 (d, J = 7.6 Hz, 1 H), 7.38 (d, J = 2.0 Hz, 1 H), 7.37 (t, J = 8.0 Hz, 1 H), 7.13 (dd, J = 8.0, 2.0 Hz, 1 H), 7.10 (d, J = 8.4 Hz, 2 H), 6.84 (d, J = 8.4 Hz, 2 H), 6.69 (s, 1 H), 6.32 (s, 1 H), 5.94 (d, J = 1.2 Hz, 1 H), 5.93 (d, J = 1.2 Hz, 1 H), 4.86 (d, J = 7.2 Hz, 1 H), 4.61 (d, J = 6.8 Hz, 1 H), 3.81 (s, 3 H), 3.76 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 193.4, 165.2, 160.0, 159.1, 147.7, 145.4, 144.7, 136.6, 131.3, 129.8, 128.8, 121.2, 120.6, 116.3, 114.6, 112.7, 107.5, 101.8, 98.9, 55.4, 55.2 (2 C), 43.6. HRMS (ESI) m/z calcd for C25H24NO7 [M + NH4]+: 450.1547, found 450.1547. HPLC analysis (Chiralpak IC-H column, Hexane:2-propanol = 75:25, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 57.21 (minor) and 61.75 min (major). (7S,8S)-7-(2-Naphthoyl)-8-(4-methoxyphenyl)-7,8-dihydro-6H[1,3]dioxolo[4,5-g]chromen-6-one (3oa). White solid, mp 89−91 °C, 1 41.2 mg, 91% yield, [α]20 D 30.15 (c 1.30, CHCl3), >19/1 dr, 90% ee. H NMR (400 MHz, CDCl3): δ 8.43 (s, 1 H), 7.86−7.96 (m, 4 H), 7.63 (t, J = 7.2 Hz, 1 H), 7.57 (t, J = 7.2 Hz, 1 H), 7.14 (d, J = 8.8 Hz, 2 H), 6.84 (d, J = 8.8 Hz, 2 H), 6.72 (s, 1 H), 6.32 (s, 1 H), 5.95 (s, 2 H), 5.05 (d, J = 7.2 Hz, 1 H), 4.69 (d, J = 7.2 Hz, 1 H), 3.75 (s, 3 H). 13C NMR (100.6 MHz, CDCl3): δ 193.4, 165.3, 159.1, 147.7, 145.4, 144.7, 135.8, 132.8, 132.4, 131.3, 130.9, 129.8, 129.1, 128.9, 127.8, 127.1, 123.9, 116.5, 114.7, 107.6, 101.8, 99.0, 55.2, 55.1, 43.7. HRMS (ESI) m/z calcd for C28H24NO6 [M + NH4]+: 470.1598, found 470.1595. HPLC analysis (Chiralpak OD-H column, Hexane:2-propanol = 70:30, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 14.75 (major) and 27.74 min (minor). (7S,8S)-8-(4-Methoxyphenyl)-7-(thiophene-2-carbonyl)-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromen-6-one (3pa). White solid, mp 140−142 °C, 38.0 mg, 93% yield, [α]20 D 124.8 (c 1.00, CHCl3), >19/1 dr, 96% ee. 1H NMR (400 MHz, CDCl3): δ 7.78 (dd, J = 4.0, 0.8 Hz, 1 H), 7.68 (dd, J = 4.8, 0.8 Hz, 1 H), 7.13 (dd, J = 4.8, 4.0 Hz, 1 H), 7.10 4226

DOI: 10.1021/acs.joc.8b00234 J. Org. Chem. 2018, 83, 4221−4228

Note

The Journal of Organic Chemistry

146.6, 141.6, 141.1, 136.7, 129.3, 128.5, 128.0, 126.0, 117.7, 114.0, 108.3, 100.8, 98.5, 78.2, 55.2, 42.7, 40.8. HPLC analysis (Chiralpak ICH column, Hexane:2-propanol = 90:10, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 5.27 (minor) and 6.24 min (major).

mmol) in tetrahydrofuran (6 mL) was added a solution of sodium hydroxide (64 mg, 1.6 mmol) in water (6 mL), and the resulting mixture was stirred at 60 °C for 1 h. After cooling to room temperature, the reaction mixture was extracted with ethyl acetate (3 × 10 mL). The combined organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (100−200 mesh, PE/EtOAc = 5/1) to afford 176.2 mg of the desired mixture of hydroxy ketone 4 and lactol 4′ as a colorless oil in 78% yield (4/4′ = 1.25:1, 4′ dr = 8:1). 1 H NMR (CDCl3): For lactol 4′ (major): δ 7.69 (dd,, J = 8.0, 1.2 Hz, 2 H), 7.41 (t, J = 7.2 Hz, 2 H), 7.36 (t, J = 7.6 Hz, 1H), 7.16 (d, J = 8.4 Hz, 2 H), 6.85 (d, J = 8.4 Hz, 2 H), 6.53 (s, 1 H), 6.26 (d, J = 0.8 Hz, 1 H), 5.87 (d, J = 1.2 Hz, 1 H), 5.84 (d, J = 1.2 Hz, 1 H), 4.33 (dd, J = 12.8, 5.6 Hz), 3.80 (s, 3 H), 3.08 (d, J = 2.4 Hz, 1 H), 2.42 (dd, J = 13.6, 5.6 Hz, 1 H), 2.03 (dt, J = 13.2, 2.4 Hz, 1 H). For lactol 4′ (minor, incomplete data): δ 7.08 (d, J = 8.6 Hz, 2 H), 6.88 (d, J = 8.4 Hz, 2 H), 6.60 (s, 1 H), 6.18 (d, J = 0.4 Hz, 1H), 4.31 (dd, J = 7.2, 6.4 Hz, 1 H), 3.80 (s, 3 H), 3.27 (s, 1 H), 2.63 (dd, J = 13.6, 6.0 Hz, 1 H), 2.45 (dd, J = 13.6, 9.6 Hz, 1 H). For hydroxy ketone 4: 1H NMR (CDCl3): δ 8.01 (dd, J = 8.4, 1.2 Hz, 2 H), 7.59 (t, J = 7.6 Hz, 1 H), 7.47 (t, J = 8.0 Hz, 2 H), 7.25 (d, J = 8.6 Hz, 2 H), 6.87 (d, J = 8.6 Hz, 2 H), 7.35 (s, 1 H), 6.49 (s, 1 H); 6.41 (s, 1 H), 5.79 (d, J = 1.2 Hz, 1 H), 5.78 (d, J = 1.2 Hz, 1 H), 4.95 (dd, J = 10.4, 3.6 Hz, 1 H), 3.87 (dd, J = 18.0, 10.4 Hz, 1 H), 3.79 (s, 3 H), 3.71 (dd, J = 18.0, 3.2 Hz, 1 H). Combined 13C NMR (CDCl3): δ 200.5, 158.4, 158.1, 148.1, 147.0, 146.7, 146.3, 144.0, 141.9 (2 C), 136.3, 135.8 (2 C), 133.8, 129.7, 128.7 (2 C), 128.5, 128.4, 128.3, 125.2, 124.0, 117.8, 114.0, 108.1, 107.4, 100.9 (2 C), 100.2, 98.9, 97.5, 55.3 (2 C), 45.0, 43.3, 38.4, 36.5. To a solution of a ketone (4)/lactol (4′) mixture (86.6 mg, 0.23 mmol) in acetone (2 mL) was added potassium carbonate (191 mg, 1.38 mmol) and methyl iodide (229 mg, 1.61 mmol). After stirring at room temperature for 48 h, the resulting mixutre was diluted with water (10 mL) and extracted with ethyl acetate (3 × 5 mL). The combined organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (100−200 mesh, petroleum ether/ethyl acetate = 15/1) to afford the desired methylation product 5. (S)-3-(6-Methoxybenzo[d][1,3]dioxol-5-yl)-3-(4-methoxyphenyl)1-phenylpropan-1-one (5). Colorless oil, 58.4 mg, 65% yield, [α]20 D −16.44 (c 1.67, CHCl3), 91% ee. 1H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 7.2 Hz, 2 H), 7.55 (t, J = 7.2 Hz, 1 H), 7.44 (t, J = 7.6 Hz, 2 H), 7.19 (d, J = 8.4 Hz, 2 H), 6.81 (d, J = 8.4 Hz, 2 H), 6.61 (s, 1 H), 6.50 (s, 1 H), 5.86 (d, J = 1.2 Hz, 1 H), 5.85 (d, J = 1.2 Hz, 1 H), 5.06 (t, J = 7.2 Hz, 1 H), 3.76 (s, 3 H), 3.71 (s, 3 H), 3.65 (dd, J = 16.8, 8.0 Hz, 1 H), 3.59 (dd, J = 16.8, 7.2 Hz, 1 H). HRMS (ESI) m/z calcd for C24H22NaO5 [M + Na]+: 413.1359, found 413.1362. 13C NMR (100.6 MHz, CDCl3): δ 198.4, 157.8, 151.7, 146.2, 141.0, 137.0, 135.7, 132.9, 128.8, 128.5, 128.1, 125.4, 113.7, 107.9, 101.0, 95.0, 56.5, 55.1, 44.0, 38.6. HPLC analysis (Chiralpak AD-H column, Hexane:2-propanol = 75:25, flow rate = 1.0 mL/min, wavelength = 254 nm): Rt = 13.42 (major) and 15.26 min (minor). To a solution of a ketone (4)/lactol (4′) mixture (86.6 mg, 0.23 mmol) in CH2Cl2 (2 mL) were added successively triethylsilane (401 mg, 3.5 mmol) and BF3·Et2O (131 mg, 0.92 mmol) at −78 °C. The resulting mixture was stirred at the same temperature for 1.5 h and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (100−200 mesh, petroleum ether/ethyl acetate = 12/1) to give the corresponding cis-chromane 6. (6R,8S)-8-(4-methoxyphenyl)-6-phenyl-7,8-dihydro-6H-[1,3]dioxolo[4,5-g]chromene (6). Colorless oil, 56.4 mg, 68% yield, [α]20 D 15.93 (c 0.97, CHCl3), >19/1 dr, 91% ee. 1H NMR (400 MHz, CDCl3): δ 7.48 (d, J = 7.2 Hz, 2 H), 7.40 (t, J = 7.2 Hz, 2 H), 7.32 (t, J = 7.2 Hz, 1 H), 7.14 (d, J = 8.4 Hz, 2 H), 6.87 (d, J = 8.4 Hz, 2 H), 6.50 (s, 1 H), 6.24 (s, 1 H), 5.86 (d, J = 1.2 Hz, 1 H), 5.84 (d, J = 1.2 Hz, 1 H), 5.13 (dd, J = 10.8, 1.2 Hz, 1 H), 4.22 (dd, J = 12.0, 5.6 Hz, 1 H), 3.81 (s, 3 H), 2.37 (ddd, J = 13.6, 6.0, 1.2 Hz, 1 H), 2.19 (dt, J = 12.0, 1.2 Hz, 1 H). 13C NMR (100.6 MHz, CDCl3): δ 158.4, 150.2,

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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.8b00234. CIF file for compound 3ea (CIF) X-ray structure data of compound 3ea, copies of NMR and HRMS spectra, and HPLC analysis (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Zhijin Fan: 0000-0001-5565-0949 Zhenghong Zhou: 0000-0001-7753-4236 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful to the Key Laboratory of Elemento-Organic Chemistry and Collaborative Innovation Center of Chemical Science and Engineering for generous financial support for our programs.

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REFERENCES

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