one-pot synthesis of 2-naphthols from nitrones and mbh...

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ORGANIC CHEMISTRYF R O N T I E R S

Volume 5 | Number 22 | 21 November 2018

ORGANIC CHEMISTRYFRONTIERS

RESEARCH ARTICLE

Cite this: Org. Chem. Front., 2018, 5,3210

Received 11th September 2018,Accepted 29th September 2018

DOI: 10.1039/c8qo00988k

rsc.li/frontiers-organic

One-pot synthesis of 2-naphthols from nitronesand MBH adducts via decarboxylative N–O bondcleavage†

Sang Hoon Han,a Ashok Kumar Pandey,a Heeyoung Lee,a Saegun Kim,a

Dahye Kang,b Young Hoon Jung,a Hyung Sik Kim,a Sungwoo Hong *c,b andIn Su Kim *a

The efficient synthesis of 2-naphthols is important for their further development as bioactive compounds

and chiral ligands as well as other synthetic purposes. Herein, we describe the unprecedented one-pot

synthesis of 2-naphthols through an acid-mediated decarboxylative N–O bond cleavage of bridged ben-

zoxazepine intermediates, which were in turn generated from aryl nitrones and Morita–Baylis–Hillman

(MBH) adducts under cationic rhodium(III) catalysis. A range of 2-naphthol derivatives including anthra-

cen-2-ol, phenanthren-2-ol, and 11H-benzo[b]fluoren-7-ol were formed with excellent site selectivities

and functional group compatibilities. To gain mechanistic insight into this process, a series of mechanistic

investigations and DFT calculations were also performed.

Introduction

Development of a convenient and efficient route for the syn-thesis of 2-naphthols is attractive from the perspectives ofboth organic and medicinal chemistry because of theirremarkable potential as versatile synthetic intermediates forthe preparation of bioactive natural products1 and chiralligands.2 Over the past few decades, a range of syntheticapproaches have been intensively investigated. Traditionalstrategies rely on intramolecular cyclization reactions, such aselectrophilic cyclization,3 oxidative cyclization,4 photo- orthermal-promoted cyclization,5 and intramolecular aldol orDieckmann condensation.6 Alternative methods comprise thetransition-metal-catalyzed hydroxylation of preactivated arylsurrogates, such as aryl halides, aryl silanes, and aryl boronicacids, with various hydroxyl sources including water.7

However, these methods suffer from inherent drawbacks

including multistep syntheses to produce the startingmaterials and harsh reaction conditions as well as the gene-ration of regioisomeric mixtures. Therefore, it remains crucialto develop more efficient methodologies for synthesizing2-naphthols from readily available substrates under mild reac-tion conditions. The N–O bond cleavage reactions have beenrecognized as a powerful strategy for the construction ofaminoalcohols or hydroxyl ketones.8 A variety of reductivesystems such as RANEY® nickel/H2,

8a,b TiCl4/AcOH/H2O,8c

SmI2/H2O,8d,e Mo(CO)6/H2O,

8f,g and Zn/AcOH8h,i have beenemployed. While the radical-mediated α-decarboxylative N–Obond cleavage reaction of alkyl hydroxamates has beenreported,9 the ionic α-decarboxylative N–O bond cleavageremains unexplored. Notably, the combination of theα-decarboxylative N–O bond cleavage and an aromatizationreaction may constitute a highly valuable strategy for the for-mation of various naphthol products, which are key intermedi-ates in the preparation of 1,1′-bi-2-naphthol (BINOL).2 Veryrecently, our group disclosed the unique reactivity of Morita–Baylis–Hillman (MBH) adducts in C–H functionalization reac-tions for the formation of 2-benzazepines10 from benzylaminesand bridged benzoxazepines11 from aryl nitrones. With recentprogress in Rh(III)-catalyzed C–H functionalization ofnitrones11,12 and a rational design based on anα-decarboxylative N–O bond cleavage followed by aromatiza-tion, we herein describe the one-pot synthesis of 2-naphtholsusing aryl nitrones and MBH adducts as the starting materials(Scheme 1). This protocol is in sharp contrast to the report ofLi et al. that describes the formation of 1-naphthols using aryl

†Electronic supplementary information (ESI) available: Experimental pro-cedures, characterization data, density functional theory (DFT) calculation data,X-ray crystallographic data of 3pa and 1H and 13C NMR spectra for all com-pounds. CCDC 1858383. For ESI and crystallographic data in CIF or other elec-tronic format see DOI: 10.1039/c8qo00988k

aSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.

E-mail: [email protected]; Fax: +82 31 292 8800; Tel: +82 31 290 7788bDepartment of Chemistry, Korea Advanced Institute of Science and Technology

(KAIST), Daejeon 34141, Republic of KoreacCenter for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science

(IBS), Daejeon 34141, Republic of Korea. E-mail: [email protected];

Fax: +82 42 350 2810; Tel: +82 42 350 2811

3210 | Org. Chem. Front., 2018, 5, 3210–3218 This journal is © the Partner Organisations 2018

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nitrones and cyclopropenones under Rh(III) catalysis.13

Notably, the formation of 1-naphthols was suggested bymigratory insertion of the Rh–C(sp2) bond into the iminemoiety to afford the Rh(III) aminoxide intermediate, whichmight further undergo elimination of tBuNO to provide1-naphthol.

Results and discussion

One-pot synthesis of 2-naphthol was initiated by examiningthe reaction of 1a with 2a using the Rh(III)-catalyzed C–Hfunctionalization followed by acid hydrolysis, as shown inTable 1. Treatment with aqueous 1 N HCl solution at 60 °Cprovided 2-naphthol (3aa) in 45% yield (Table 1, entry 2). Toour delight, a high yield (82%) of 3aa was observed at highertemperature (120 °C), as shown in entry 3. This process alsoproceeded with a lower loading of 1 N HCl solution to give3aa, albeit resulting in 60% yield (Table 1, entry 4). In

addition, this process was also compatible with aqueous 2 NHCl solution to afford 3aa in 81% yield (Table 1, entry 5).However, this reaction was found to be ineffective with organicacids such as AcOH and TFA (Table 1, entries 6 and 7).Notably, it was found that basic hydrolysis conditions(aqueous 1 N NaOH) also gave 3aa in 39% yield (Table 1,entry 8). These observations suggested that the decarboxyl-ation of the ester functionality on a bridged benzoxazepineintermediate under acidic or basic hydrolysis conditions mightinitiate the formation of 3aa. It should be mentioned that 3aacan be formed starting from MBH acetate 2b containing abulkier ester group (–CO2

tBu) and MBH carbonate 2c in com-parable yields (Table 1, entries 9 and 10). Moreover, thisprocess was successfully scaled up to 1.06 g of 1a to give 3aa in71% yield (Table 1, entry 11).

To evaluate the substrate scope and limitation of thisprocess, a range of aryl nitrones were employed under theoptimal reaction conditions (Table 2). Aryl nitrones 1b–1e fea-turing electron-rich groups and halogen atoms at the para-position were found to possess good reactivity, affording thedesired 2-naphthols 3ba–3ea in good to high yields. However,the coupling of 2a with aryl nitrones 1f and 1g bearing elec-tron-deficient groups (CO2Me and NO2), which can often beproblematic in the C–H activation step, resulted in the for-

Scheme 1 Formation of 2-naphthols using aryl nitrones and MBHadducts.

Table 1 Selected optimization of reaction conditionsa

Entry Substrate Reagent T (°C) Yieldb (%)

1 2a — 120 N.R.2 2a 1 N HCl (0.2 mL) 60 453 2a 1 N HCl (0.2 mL) 120 824 2a 1 N HCl (0.1 mL) 120 605 2a 2 N HCl (0.2 mL) 120 816 2a AcOH (0.2 mmol) 120 Trace7 2a TFA (0.2 mmol) 120 Trace8 2a 1 N NaOH (0.2 mL) 120 399 2b 1 N HCl (0.2 mL) 120 8210 2c 1 N HCl (0.2 mL) 120 7911c 2a 1 N HCl (6.0 mL) 120 71

a Reaction conditions: Condition A: 1a (0.2 mmol), 2a–2c (0.4 mmol),[RhCp*Cl2]2 (2.5 mol%), AgSbF6 (10 mol%), DCE (1 mL), O2 gas at60 °C for 7 h in pressure tubes. Condition B: Reagent (quantity noted)under air at the indicated temperature for 16 h in pressure tubes.b Isolated yield by flash column chromatography. cGram-scale experi-ment: 1a (1.06 g, 6 mmol) was used.

Table 2 Scope of aryl nitronesa

a Reaction conditions: (i) 1a–1v (0.2 mmol), 2a and 2d (0.4 mmol),[RhCp*Cl2]2 (2.5 mol%), AgSbF6 (10 mol%), DCE (1 mL) under O2 gasat 60 °C for 7 h in pressure tubes. (ii) 1 N HCl (0.2 mL), 120 °C, 16 hunder air. b Isolated yield by flash column chromatography.

Organic Chemistry Frontiers Research Article

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mation of the corresponding naphthols 3fa (59%) and 3ga(50%) in a slightly decreased reactivity.

This transformation was found to be also compatible withmeta-substituted aryl nitrones 1h–1l. It should be noted thata complete regioselectivity at the less hindered C–H bond wasobserved in all cases. In addition, ortho-substituted arylnitrones 1m–1o were smoothly coupled with 2a to generatethe corresponding products 3ma–3oa in high yields.Moreover, di- and tri-substituted aryl nitrones 1p and 1q werealso proven to be good substrates for this transformation.The structure of the synthesized 2-naphthols was confirmedby X-ray crystallographic analysis of compound 3pa (see theESI† for details). Notably, π-extended 2-naphthol derivatives,such as anthracen-2-ol (3ra), phenanthren-2-ol (3sa), and11H-benzo[b]fluoren-7-ol (3ta), were also formed under theestablished reaction conditions. It is noteworthy that anthra-cen-2-ol (3ra) and phenanthren-2-ol (3sa) have been used ascore units for the generation of photophysical probes andpolymer compositions.14 To our delight, heterocycle-contain-ing nitrones 1u and 1v were also converted into the corres-ponding benzo[b]thiophen-5-ol (3ua) and 3-methyl-3H-benzo[e]indol-7-ol (3va) in 57% and 43% yields, respectively.15

Finally, α-substituted MBH adduct 2d was coupled with 1a togive 3-methyl-2-naphthol (3ad) in 11% yield, presumably dueto the increased steric effect of the tri-substituted alkeneintermediate for intramolecular exo-type [3 + 2] cycloadditionreaction.

To highlight the synthetic utility of 2-naphthols, the Lewisacid-mediated dimerization16 of 3aa and 3na was first per-formed, and BINOL derivatives 4aa and 4na were smoothlyformed in 80% and 76% yields, respectively (Scheme 2,eqn (1)). In addition, naphthophenazine 5sa was also formedin 70% yield via the IBX-mediated oxidative diketoneformation of 3sa followed by an annulation reaction witho-phenylenediamine (Scheme 2, eqn (2)).

To obtain mechanistic insight, a series of control experi-ments were performed (Scheme 3). First, α-hydroxy-γ-aminoester 6a, derived from the reductive N–O bond cleavage ofbridged benzoxazepine intermediate 6d,11 was subjected toeither aqueous 1 N HCl or 1 N NaOH solutions, and no for-mation of 3aa was observed (Scheme 3, eqn (1)). This result

indicates that the formation of 6a under acidic or basic hydro-lysis conditions might be completely excluded in the reactionpathway. Subsequently, the synthesized carboxylic acid 6b wasreadily converted into 3aa in 78% yield under identical reac-tion conditions, suggesting that 3aa might be generated fromintermediate 6b via an ionic decarboxylation process(Scheme 3, eqn (2)). This result can be further supported by noformation of 3aa from primary alcohol 6c (Scheme 3, eqn (3)).In addition, treatment of 6d with 1 N DCl/D2O resulted in aremarkable H/D exchange (85% D incorporation) at the C1-position of deuterio-3aa, indicating that a keto–enol tautomeri-zation step might be involved in the reaction pathway(Scheme 3, eqn (4)).

Scheme 2 Synthetic transformations.

Scheme 3 Mechanistic investigations.

Fig. 1 Free energy profile for the formation of 2-naphthol.

Research Article Organic Chemistry Frontiers


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To better understand the reaction mechanism, we carriedout quantum chemical calculations based on density func-tional theory (DFT) depicted in Fig. 1. Our calculations indi-cate that the bond length of the C–CO2

− bond in Int1 iselongated by the protonation of a nitrogen atom and deproto-nation of a carboxylic acid group (Fig. 1a), triggering N–Obond cleavage to release CO2 and produce Int2. The energybarrier traversing the transition state Int1-TS via concerted de-carboxylation and N–O bond cleavage is only 9.6 kcal mol−1,indicating that Int2 can be readily formed under the reactionconditions (Fig. 1b).

On the basis of these preliminary mechanistic investi-gations, a plausible reaction pathway is outlined, as shown inScheme 4. Initially, a cationic Rh(III) catalyst coordinates with1a to form rhodacyclic I via the C–H bond activation. Then,MBH adduct 2a is reacted with species I to obtain intermediateII, which undergoes β-O-elimination to deliver allylated inter-mediate III. Finally, an intramolecular exo-type [3 + 2] cyclo-addition reaction of III furnished bridged benzoxazepine inter-mediate 6d. Next, acid hydrolysis of bridged benzoxazepine 6dprovides carboxylic acid intermediate IV, which undergoes anacid-mediated α-decarboxylative N–O bond cleavage to affordβ-aminoketone intermediate V with expulsion of CO2. Then,aromatization of enol intermediate VI, formed through theketo–enol tautomerization, takes place to furnish the desired2-naphthol (3aa).

Conclusions

In conclusion, we described the one-pot synthesis of2-naphthols through the acid-mediated decarboxylative N–Obond cleavage of bridged benzoxazepines, which were gener-ated from aryl nitrones and Morita–Baylis–Hillman (MBH)adducts under cationic rhodium(III) catalysis. This transform-ation was applied to a wide range of substrates, and typicallyproceeded with excellent levels of site selectivity as well ashigh functional group tolerance. The formed 2-naphtholderivatives were readily converted into valuable organic mole-cules such as 1,1′-bi-2-naphthols and naphthophenazines.Mechanistic studies supported the hypothesis that bridgedbenzoxazepines containing a carboxylic acid moiety areinitially formed as crucial intermediates by acid hydrolysis,and then decarboxylative N–O bond cleavage followed by aro-matization takes place to provide 2-naphthols.

ExperimentalGeneral procedure and characterization data for the formationof 3aa–3ad

To an oven-dried sealed tube charged with N-tert-butyl-1-phe-nylmethanimine oxide (1a) (35.4 mg, 0.2 mmol, 100 mol%),[RhCp*Cl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%), AgSbF6 (6.9 mg,0.02 mmol, 10 mol%), DCE (1 mL) and methyl 2-(acetoxy-methyl)acrylate (2a) (63.2 mg, 0.4 mmol, 200 mol%) wereadded under air at room temperature. The reaction mixturewas degassed with O2 gas, and the resulting mixture wasallowed to stir at 60 °C for 7 h. The reaction mixture wascooled to room temperature, and aqueous 1 N HCl solution(0.2 mL) was added to the reaction mixture. The resultingmixture was stirred at 120 °C for 16 h and neutralized withaqueous 1 N NaOH. The aqueous layer was extracted withCH2Cl2 (10 mL) and the organic layer was washed with H2Oand brine, dried over MgSO4 and concentrated in vacuo. Theresidue was purified by flash column chromatography(n-hexanes/EtOAc = 8 : 1) to afford 23.6 mg of 3aa in 82% yield.

Naphthalen-2-ol (3aa)

18.7 mg (82%); light brown solid; mp = 113.5–114.5 °C;1H NMR (400 MHz, CDCl3) δ 7.79–7.75 (m, 2H), 7.68 (d, J =8.4 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 7.15(d, J = 2.0 Hz, 1H), 7.11 (dd, J = 8.8, 2.8 Hz, 1H), 5.21 (s, 1H);13C NMR (100 MHz, CDCl3) δ 153.3, 134.5, 129.8, 128.9, 127.7,126.5, 126.3, 123.6, 117.7, 109.4; IR (KBr) ν 3489, 3374, 3347,2924, 2853, 1628, 1465, 1213, 846, 745 cm−1; HRMS (quadru-pole, EI) calcd for C10H8O [M]+ 144.0575, found 144.0576.

7-Methylnaphthalen-2-ol (3ba)

25.0 mg (79%); light brown solid; mp = 113.3–114.5 °C; 1HNMR (400 MHz, CDCl3) δ 7.71–7.66 (m, 2H), 7.45 (s, 1H), 7.17(dd, J = 8.4, 2.0 Hz, 1H), 7.06 (d, J = 2.4 Hz, 1H), 7.03 (dd, J =8.8, 2.4 Hz, 1H), 5.12 (s, 1H), 2.49 (s, 3H); 13C NMR (100 MHz,CDCl3) δ 153.4, 136.2, 134.8, 129.5, 127.5, 127.1, 125.9, 125.4,

Scheme 4 Proposed reaction mechanism.



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116.7, 108.9, 21.7; IR (KBr) ν 3276, 3046, 2921, 2852, 1636,1510, 1430, 1212, 957, 829, 782 cm−1; HRMS (quadrupole, EI)calcd for C11H10O [M]+ 158.0732, found 158.0732.

7-Fluoronaphthalen-2-ol (3ca)

22.0 mg (68%); light brown solid; mp = 94.2–95.6 °C; 1H NMR(400 MHz, CDCl3) δ 7.75–7.71 (m, 2H), 7.28 (dd, J = 10.0,2.4 Hz, 1H), 7.12–7.04 (m, 3H), 5.32 (br s, 1H); 13C NMR(100 MHz, CDCl3) δ 161.3 (d, JC–F = 244.2 Hz), 154.2, 135.6(d, JC–F = 9.9 Hz), 130.1 (d, JC–F = 9.4 Hz), 129.8, 125.9,116.9 (d, JC–F = 2.5 Hz), 113.8 (d, JC–F = 25.4 Hz), 109.5 (d,JC–F = 21.0 Hz), 109.0 (d, JC–F = 5.3 Hz); IR (KBr) ν 3368,3050, 2922, 2854, 1638, 1515, 1361, 1201, 831 cm−1; HRMS(quadrupole, EI) calcd for C10H7FO [M]+ 162.0481, found162.0483.

7-Chloronaphthalen-2-ol (3da)

26.1 mg (73%); light brown solid; mp = 115.4–118.1 °C; 1HNMR (400 MHz, CDCl3) δ 7.73–7.65 (m, 3H), 7.26 (dd, J = 8.8,2.0 Hz, 1H), 7.10–7.05 (m, 2H), 5.04 (s, 1H); 13C NMR(100 MHz, CDCl3) δ 154.2, 135.3, 132.4, 129.8, 129.3, 127.1,125.0, 124.5, 117.9, 108.7; IR (KBr) ν 3485, 3071, 2921, 2852,1915, 1707, 1625, 1505, 1433, 1349, 1189, 1074, 884, 835,746 cm−1; HRMS (quadrupole, EI) calcd for C10H7ClO [M]+

178.0185, found 178.0182.

7-Bromonaphthalen-2-ol (3ea)

33.9 mg (76%); light brown solid; mp = 130.4–133.8 °C; 1HNMR (400 MHz, CDCl3) δ 7.82 (d, J = 1.6 Hz, 1H), 7.70 (d, J =8.8 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.26 (dd, J = 8.4, 1.6 Hz,1H), 7.10 (dd, J = 8.8, 2.4 Hz, 1H), 7.04 (d, J = 2.4 Hz, 1H), 5.30(br s, 1H); 13C NMR (100 MHz, CDCl3) δ 154.1, 135.7, 129.8,129.3, 128.3, 127.3, 126.9, 120.7, 118.1, 108.7; IR (KBr) ν 3478,3070, 2923, 2855, 1904, 1625, 1432, 1197, 839, 737 cm−1;HRMS (quadrupole, EI) calcd for C10H7BrO [M]+ 221.9680,found 221.9678.

Methyl 7-hydroxy-2-naphthoate (3fa)

23.9 mg (59%); light brown solid; mp = 146.1–148.2 °C; 1HNMR (400 MHz, CDCl3) δ 8.45 (s, 1H), 7.90 (dd, J = 8.8, 1.2 Hz,1H), 7.81–7.77 (m, 2H), 7.27 (d, J = 2.4 Hz, 1H), 7.22 (dd, J =8.8, 2.4 Hz, 1H), 5.49 (s, 1H), 3.98 (s, 3H); 13C NMR (100 MHz,CDCl3) δ 167.5, 154.1, 133.7, 130.9, 129.6, 129.4, 128.0, 127.9,123.0, 120.2, 110.7, 52.2; IR (KBr) ν 3390, 3035, 2952, 2923,2852, 1717, 1693, 1605, 1435, 1251, 1206, 843 cm−1; HRMS(quadrupole, EI) calcd for C12H10O3 [M]+ 202.0630, found202.0629.

7-Nitronaphthalen-2-ol (3ga)

18.9 mg (50%); light yellow solid; mp = 151.1–155.0 °C; 1HNMR (400 MHz, CD3OD) δ 8.60 (d, J = 2.0 Hz, 1H), 7.98 (dd, J =8.8, 2.4 Hz, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.86 (d, J = 8.8 Hz,1H), 7.30 (dd, J = 7.6, 2.4 Hz, 1H), 7.27 (d, J = 2.4 Hz, 1H); 13CNMR (100 MHz, CD3OD) δ 158.4, 147.3, 135.2, 132.0, 130.6,130.4, 123.5, 123.3, 116.9, 111.6; IR (KBr) ν 3404, 3093, 2923,2853, 1914, 1710, 1608, 1529, 1339, 1207, 837, 734 cm−1;

HRMS (quadrupole, EI) calcd for C10H7NO3 [M]+ 189.0426,found 189.0425.

6-Methylnaphthalen-2-ol (3ha)

20.9 mg (66%); white solid; mp = 124.1–126.2 °C; 1H NMR(400 MHz, CDCl3) δ 7.66 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.4 Hz,1H), 7.54 (s, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.10 (s, 1H), 7.06 (d,J = 8.8 Hz, 1H), 5.02 (s, 1H), 2.47 (s, 3H); 13C NMR (100 MHz,CDCl3) δ 152.6, 133.0, 132.6, 129.2, 129.1, 128.8, 126.7, 126.1,117.6, 109.3, 21.4; IR (KBr) ν 3494, 3366, 3044, 2921, 2853,1912, 1604, 1509, 1342, 1174, 863 cm−1; HRMS (quadrupole,EI) calcd for C11H10O [M]+ 158.0732, found 158.0729.

6-Phenylnaphthalen-2-ol (3ia)

29.5 mg (67%); white solid; mp = 178.4–179.2 °C; 1H NMR(400 MHz, CDCl3) δ 7.97 (s, 1H), 7.81 (d, J = 8.8 Hz, 1H), 7.75(d, J = 8.8 Hz, 1H), 7.72–7.69 (m, 3H), 7.49–7.46 (m, 2H), 7.36(d, J = 7.6 Hz, 1H), 7.18 (d, J = 2.4 Hz, 1H), 7.13 (dd, J = 8.8,2.4 Hz, 1H), 5.19 (s, 1H); 13C NMR (100 MHz, CDCl3)δ 153.5, 141.1, 136.4, 133.7, 130.1, 129.1, 128.8, 127.2, 127.1,126.8, 126.2, 125.7, 118.2, 109.3; IR (KBr) ν 3363, 3056, 2923,2853, 1737, 1598, 1276, 1197, 1062, 754, 697 cm−1; HRMS(quadrupole, EI) calcd for C16H12O [M]+ 220.0888, found220.0885.

6-Chloronaphthalen-2-ol (3ja)

22.1 mg (62%); white solid; mp = 115.5–116.4 °C; 1H NMR(400 MHz, CDCl3) δ 7.74 (s, 1H), 7.66 (d, J = 9.2 Hz, 1H), 7.60(d, J = 8.8 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.13 (s, 2H), 5.14(br s, 1H); 13C NMR (100 MHz, CDCl3) δ 153.5, 132.8, 129.4,129.1, 129.0, 127.8, 127.3, 126.4, 118.8, 109.5; IR (KBr) ν 3386,3058, 2934, 2853, 1901, 1631, 1597, 1505, 1201, 915, 799 cm−1;HRMS (quadrupole, EI) calcd for C10H7ClO [M]+ 178.0185,found 178.0183.

6-Bromonaphthalen-2-ol (3ka)

27.2 mg (61%); light brown solid; mp = 123.8–126.0 °C; 1HNMR (400 MHz, CDCl3) δ 7.91 (s, 1H), 7.65 (d, J = 8.8 Hz, 1H),7.54 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.12 (s, 2H),5.10 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 153.6, 133.0, 129.9,129.8, 129.7, 128.9, 128.0, 118.7, 117.1, 109.5; IR (KBr) ν 3403,3061, 2923, 2853, 1901, 1626, 1588, 1265, 1200, 906, 799 cm−1;HRMS (quadrupole, EI) calcd for C10H7BrO [M]+ 221.9680,found 221.9680.

6-(Trifluoromethyl)naphthalen-2-ol (3la)

17.0 mg (40%); light brown solid; mp = 88.6–90.3 °C; 1H NMR(400 MHz, CDCl3) δ 8.06 (s, 1H), 7.83 (d, J = 9.2 Hz, 1H), 7.76(d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.19 (s, 2H), 5.34 (s,1H); 13C NMR (100 MHz, CDCl3) δ 155.1, 136.0, 130.8, 127.5,127.2, 125.6 (q, JC–F = 32.0 Hz), 125.5 (q, JC–F = 4.5 Hz), 124.5(q, JC–F = 270.0 Hz), 122.1 (q, JC–F = 3.0 Hz), 119.1, 109.5; IR(KBr) ν 3387, 3067, 2923, 1914, 1634, 1489, 1317, 12 502, 1118,921 cm−1; HRMS (quadrupole, EI) calcd for C11H7F3O [M]+

212.0449, found 212.0449.



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5-Methoxynaphthalen-2-ol (3ma)

28.2 mg (81%); sticky dark brown solid; 1H NMR (400 MHz,CDCl3) δ 8.17 (d, J = 8.8 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H),7.26–7.24 (m, 1H), 7.10 (d, J = 2.4 Hz, 1H), 7.06 (dd, J = 8.8,2.4 Hz, 1H), 6.67 (d, J = 7.6 Hz, 1H), 5.08 (s, 1H), 3.98 (s, 3H);13C NMR (100 MHz, CDCl3) δ 155.6, 153.9, 135.9, 126.8, 124.2,120.8, 118.8, 116.6, 109.3, 101.8, 55.4; IR (KBr) ν 3346, 3056,2923, 2851, 1913, 1628, 1580, 1383, 1214, 1101, 947, 780 cm−1;HRMS (quadrupole, EI) calcd for C11H10O2 [M]+ 174.0681,found 174.0682.

5-Chloronaphthalen-2-ol (3na)

29.3 mg (82%); light brown solid; mp = 95.4–97.1 °C; 1H NMR(400 MHz, CDCl3) δ 8.18 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.0 Hz,1H), 7.41 (dd, J = 7.6, 1.2 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.20(dd, J = 9.2, 2.4 Hz, 1H), 7.16 (d, J = 2.8 Hz, 1H), 5.36 (br s, 1H);13C NMR (100 MHz, CDCl3) δ 153.9, 135.8, 131.9, 126.6, 126.5,126.2, 125.6, 123.9, 118.7, 109.8; IR (KBr) ν 3288, 3061, 2923,2852, 1919, 1625, 1567, 1508, 1382, 1230, 970, 776 cm−1;HRMS (quadrupole, EI) calcd for C10H7ClO [M]+ 178.0185,found 178.0185.

5-(Trifluoromethyl)naphthalen-2-ol (3oa)

29.7 mg (70%); light brown solid; mp = 89.1–89.4 °C; 1H NMR(400 MHz, CDCl3) δ 8.11 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 8.0 Hz,1H), 7.71 (d, J = 6.8 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.26–7.24(m, 2H), 5.35 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 153.7,135.4, 131.1, 126.3 (q, JC–F = 2.3 Hz), 126.1 (q, JC–F = 29.8 Hz),124.9, 124.7 (q, JC–F = 251.8 Hz), 124.2, 122.4 (q, JC–F = 5.8 Hz),119.3, 110.4; IR (KBr) ν 3347, 2925, 2854, 1894, 1629, 1520,1317, 1199, 1106, 978, 788 cm−1; HRMS (quadrupole, EI) calcdfor C11H7F3O [M]+ 212.0449, found 212.0451.

5-Fluoro-7-methoxynaphthalen-2-ol (3pa)

32.7 mg (85%); dark brown solid; mp = 100.6–103.2 °C; 1HNMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.8 Hz, 1H), 7.04 (s, 1H),6.97 (d, J = 9.2 Hz, 1H), 6.76 (s, 1H), 6.69 (d, J = 12.0 Hz, 1H),5.39 (br s, 1H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3)δ 159.5 (d, JC–F = 250.0 Hz), 158.3 (d, JC–F = 12.4 Hz), 154.8,136.8 (d, JC–F = 6.4 Hz), 122.7 (d, JC–F = 4.5 Hz), 115.4, 114.7 (d,JC–F = 17.1 Hz), 108.6 (d, JC–F = 3.3 Hz), 100.7 (d, JC–F = 3.4 Hz),100.5 (d, JC–F = 22.7 Hz), 55.5; IR (KBr) ν 3390, 2937, 2830,1628, 1463, 1391, 1242, 1098, 996, 788 cm−1; HRMS (quadru-pole, EI) calcd for C11H9FO2 [M]+ 192.0587, found 192.0584.

5,6,7-Trimethoxynaphthalen-2-ol (3qa)

36.0 mg (77%); sticky brown solid; 1H NMR (400 MHz, CDCl3)δ 7.93 (d, J = 9.2 Hz, 1H), 7.02 (s, 1H), 6.97 (d, J = 9.2 Hz, 1H),6.75 (s, 1H), 5.86 (br s, 1H), 4.04 (s, 3H), 3.94 (s, 3H), 3.92 (s,3H); 13C NMR (100 MHz, CDCl3) δ 153.8, 153.5, 148.0, 138.8,132.2, 123.6, 119.2, 115.2, 108.7, 101.1, 61.4, 61.2, 55.7; IR(KBr) ν 3390, 2937, 2830, 1628, 1463, 1391, 1242, 1098, 996,788 cm−1; HRMS (quadrupole, EI) calcd for C13H14O4 [M]+

234.0892, found 234.0896.

Anthracen-2-ol (3ra)

25.2 mg (65%); dark brown solid; mp = 213.4–216.2 °C; 1HNMR (400 MHz, CD3OD) δ 8.30 (s, 1H), 8.15 (s, 1H), 7.92–7.87(m, 3H), 7.39–7.31 (m, 2H), 7.20 (s, 1H), 7.12 (d, J = 9.2 Hz,1H); 13C NMR (100 MHz, CD3OD) δ 155.9, 134.6, 133.6, 131.4,130.9, 129.3, 129.2, 128.5, 127.1, 126.3, 125.0, 124.2, 121.1,107.8; IR (KBr) ν 3531, 3365, 3044, 2924, 1740, 1633, 1457,1169, 886, 741 cm−1; HRMS (quadrupole, EI) calcd forC14H10O [M]+ 194.0732, found 194.0730.

Phenanthren-2-ol (3sa)

27.2 mg (70%); dark brown solid; mp = 163.4–166.2 °C; 1HNMR (400 MHz, CDCl3) δ 8.57 (d, J = 8.4 Hz, 2H), 7.86 (d, J =8.0 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.65–7.59 (m, 2H), 7.54 (t,J = 7.6 Hz, 1H), 7.24–7.20 (m, 2H), 5.12 (s, 1H); 13C NMR(100 MHz, CDCl3) δ 154.1, 133.5, 131.0, 130.4, 128.6, 127.7,126.7, 126.0, 125.6, 124.7, 124.6, 122.0, 116.6, 111.8; IR (KBr)ν 3362, 3057, 2922, 2855, 1619, 1462, 1314, 1171, 810,742 cm−1; HRMS (quadrupole, EI) calcd for C14H10O [M]+

194.0732, found 194.0734.

11H-Benzo[b]fluoren-7-ol (3ta)

14.9 mg (32%); light brown solid; mp = 237.2–242.8 °C; 1HNMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 7.91 (d, J = 7.6 Hz, 1H),7.88 (s, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 7.6 Hz, 1H),7.41 (t, J = 7.2 Hz, 1H), 7.35 (t, J = 7.2 Hz, 1H), 7.26–7.24(m, 1H), 7.08 (dd, J = 8.8, 2.4 Hz, 1H), 4.84 (s, 1H), 4.05(s, 2H); 13C NMR (100 MHz, CDCl3) δ 153.0, 144.0, 141.2,141.1, 139.0, 134.1, 129.6, 128.6, 127.5, 126.9, 125.2,123.3, 120.6, 117.1, 116.3, 109.8, 36.2; IR (KBr) ν 3649, 3413,3324, 2922, 2853, 1615, 1463, 1266, 955, 727 cm−1; HRMS(quadrupole, EI) calcd for C17H12O [M]+ 232.0888, found232.0892.

Benzo[b]thiophen-5-ol (3ua)

17.1 mg (57%); white solid; mp = 102.3–104.7 °C; 1H NMR(400 MHz, CDCl3) δ 7.71 (d, J = 8.8 Hz, 1H), 7.44 (d, J = 5.6 Hz,1H), 7.24 (d, J = 2.4 Hz, 1H), 7.20 (d, J = 5.6 Hz, 1H), 6.92 (dd,J = 8.8, 2.4 Hz, 1H), 5.09 (s, 1H); 13C NMR (100 MHz, CDCl3)δ 153.0, 140.8, 132.3, 127.8, 123.3, 123.2, 114.3, 108.5; IR (KBr)ν 3300, 2923, 2853, 1600, 1427, 1269, 1149, 946, 690 cm−1;HRMS (quadrupole, EI) calcd for C8H6OS [M]+ 150.0139, found150.0142.

3-Methyl-3H-benzo[e]indol-7-ol (3va)

17.0 mg (43%); dark brown solid; mp = 147.4–148.8 °C; 1HNMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.8 Hz, 1H), 7.46 (s, 2H),7.25 (d, J = 2.8 Hz, 1H), 7.15 (dd, J = 8.8, 2.4 Hz, 1H), 7.10 (d,J = 3.2 Hz, 1H), 6.93 (d, J = 2.8 Hz, 1H), 4.98 (br s, 1H), 3.88 (s,3H); 13C NMR (100 MHz, CDCl3) δ 151.4, 132.1, 130.0, 126.8,124.5, 123.5, 123.3, 121.1, 116.5, 111.7, 111.1, 99.6, 33.1; IR(KBr) ν 3243, 3058, 2927, 2854, 1715, 1624, 1536, 1387, 1226,1162, 947, 731 cm−1; HRMS (quadrupole, EI) calcd forC13H11NO [M]+ 197.0841, found 197.0839.



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3-Methylnaphthalen-2-ol (3ad)

3.5 mg (11%); light brown solid; mp = 148.8–151.7 °C; 1H NMR(400 MHz, CDCl3) δ 7.69 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.4 Hz,1H), 7.59 (s, 1H), 7.38–7.34 (m, 1H), 7.31–7.27 (m, 1H), 7.09 (s,1H), 5.01 (br s, 1H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3)δ 152.7, 133.4, 129.3, 129.2, 127.0, 126.3, 125.8, 125.5, 123.5,109.0, 16.4; IR (KBr) ν 3531, 3356, 3054, 2923, 2853, 1706,1629, 1516, 1395, 1245, 1095, 867, 747 cm−1; HRMS (orbitrap,ESI) calcd for C11H11O [M + H]+ 159.0810, found 159.0807.

Experimental procedure and characterization data for theformation of 4aa and 4na

To an oven-dried sealed tube charged with 2-naphthol (3aa)(43.3 mg, 0.3 mmol, 100 mol%) and anhydrous FeCl3(73.0 mg, 0.45 mmol, 150 mol%) was added H2O (1 mL) underair at room temperature. The reaction mixture was refluxed for3 h, and cooled to room temperature. The reaction mixturewas extracted with EtOAc (10 mL) and the organic layer waswashed with H2O and brine, dried over MgSO4 and concen-trated in vacuo. The residue was purified by flash columnchromatography (n-hexanes/EtOAc = 4 : 1) to afford 34.4 mg of4aa in 80% yield.

[1,1′-Binaphthalene]-2,2′-diol (4aa)

34.4 mg (80%); light brown solid; mp = 212.1–215.2 °C; 1HNMR (500 MHz, CDCl3) δ 7.97 (d, J = 9.0 Hz, 2H), 7.89 (d, J =8.0 Hz, 2H), 7.39–7.36 (m, 4H), 7.32–7.29 (m, 2H), 7.15 (d, J =8.0 Hz, 2H), 5.09 (s, 2H); 13C NMR (125 MHz, CDCl3) δ 152.7,133.4, 131.4, 129.4, 128.4, 127.4, 124.2, 124.0, 117.7, 110.8;IR (KBr) ν 3485, 3404, 3053, 2924, 2855, 1714, 1617, 1594,1378, 1213, 1142, 822, 749 cm−1; HRMS (quadrupole, EI) calcdfor C20H14O2 [M]+ 286.0994, found 286.0993.

5,5′-Dichloro-[1,1′-binaphthalene]-2,2′-diol (4na)

40.5 mg (76%); light brown solid; mp = 85.8–87.1 °C; 1H NMR(400 MHz, CDCl3) δ 8.45 (dd, J = 9.2, 0.8 Hz, 2H), 7.48–7.45 (m,4H), 7.20 (dd, J = 8.4, 7.2 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 5.11(s, 2H); 13C NMR (100 MHz, CDCl3) δ 153.3, 134.7, 132.6,128.2, 127.6, 126.8, 124.5, 123.2, 118.8, 111.1; IR (KBr) ν 3502,3065, 2925, 2856, 1714, 1614, 1374, 1133, 975, 802, 754 cm−1;HRMS (quadrupole, EI) calcd for C20H12Cl2O2 [M]+ 354.0214,found 354.0213.

Experimental procedure and characterization data for theformation of 5sa

To an oven-dried sealed tube charged with phenanthren-2-ol(3sa) (43.3 mg, 0.2 mmol, 100 mol%) and IBX (2-iodoxybenzoicacid stabilized with benzoic acid and isophthalic acid,154.0 mg, 0.22 mmol, 110 mol%) was added DMF (1 mL)under air at room temperature. The reaction mixture wasallowed to stir at room temperature for 1 h. Then, o-phenylene-diamine (26.0 mg, 0.24 mmol, 120 mol%) was added to thereaction mixture and the reaction mixture was stirred at roomtemperature for 2 h. The reaction mixture was diluted withEtOAc (3 mL) and the organic layer was washed with H2O and

brine, dried over MgSO4 and concentrated in vacuo. Theresidue was purified by flash column chromatography(n-hexanes/EtOAc = 10 : 1) to afford 39.2 mg of 5sa in 70%yield.

Naphtho[2,1-a]phenazine (5sa)

39.2 mg (70%); light yellow solid; mp = 233.1–234.8 °C; 1HNMR (400 MHz, CDCl3) δ 9.47 (d, J = 8.8 Hz, 1H), 8.95 (d, J =9.6 Hz, 1H), 8.73 (d, J = 8.0 Hz, 1H), 8.40–8.36 (m, 1H),8.31–8.28 (m, 1H), 8.23 (d, J = 9.2 Hz, 1H), 8.14 (d, J = 8.8 Hz,1H), 8.04 (d, J = 7.6 Hz, 1H), 7.89–7.84 (m, 2H), 7.75–7.66 (m,2H); 13C NMR (100 MHz, CDCl3) δ 142.9, 142.8, 142.4, 142.0,133.8, 130.2, 130.0, 129.9 (two carbons overlap), 129.8, 129.5,129.2, 128.9, 128.5, 127.4, 127.3, 127.2, 127.0, 123.2, 122.4; IR(KBr) ν 3050, 2953, 2923, 2853, 1736, 1457, 1363, 1235, 1034,746 cm−1; HRMS (quadrupole, EI) calcd for C20H12N2 [M]+

280.1000, found 280.1000.

Experimental procedure and characterization data for theformation of 6a

To an oven-dried sealed tube charged with 6d (55.0 mg,0.2 mmol, 100 mol%), Zn powder (130.8 mg, 2.0 mmol,1000 mol%), acetic acid (0.24 mL), H2O (0.10 mL) and di-chloromethane (0.3 mL) were added under air at room tem-perature. The reaction mixture was allowed to stir at roomtemperature for 2 h. The reaction mixture was quenched withsaturated aqueous Na2CO3 solution and extracted with di-chloromethane. The combined organic layer was dried overMgSO4 and concentrated in vacuo. The residue was purified byflash column chromatography (n-hexanes/EtOAc = 1 : 1) toafford 41.0 mg of 6a in 74% yield.

(2R′,4R′)-Methyl 4-(tert-butylamino)-2-hydroxy-1,2,3,4-tetrahydronaphthalene-2-carboxylate (6a)

41.0 mg (74%); white solid; mp = 86.2–88.1 °C; 1H NMR(400 MHz, CDCl3) δ 7.23–7.11 (m, 4H), 4.28 (t, J = 2.8 Hz, 1H),3.80 (s, 3H), 3.25 (d, J = 17.2 Hz, 1H), 3.17 (d, J = 17.2 Hz, 1H),2.39 (dt, J = 14.0, 2.0 Hz, 1H), 2.06 (dd, J = 14.0, 3.6 Hz, 1H),1.23 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 175.6, 137.5, 133.7,130.2, 128.6, 127.8, 126.8, 74.4, 52.4, 52.0, 50.1, 40.0, 34.4,29.5; IR (KBr) ν 3313, 3064, 2955, 1732, 1433, 1099, 816,741 cm−1; HRMS (quadrupole, EI) calcd for C16H23NO3 [M]+

277.1678, found 277.1679.

Experimental procedure and characterization data for theformation of 6b

To an oven-dried sealed tube charged with 6d (55.0 mg,0.2 mmol, 100 mol%), lithium hydroxide monohydrate(25.2 mg, 0.6 mmol, 300 mol%), THF (1 mL), H2O (1 mL) andMeOH (0.5 mL) were added under air at room temperature.The reaction mixture was allowed to stir at room temperaturefor 5 h and neutralized with aqueous 1 N NaOH. The aqueouslayer was extracted with EtOAc (30 mL) and the organic layerwas washed with H2O and brine, dried over MgSO4 and con-centrated in vacuo. The residue was purified by flash column



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chromatography (DCM/MeOH = 3 : 1) to afford 18.8 mg of 6bin 36% yield.

2-(tert-Butyl)-1,2,4,5-tetrahydro-1,4-methanobenzo[d][1,2]oxazepine-4-carboxylic acid (6b)

18.8 mg (36%); white solid; mp = 286.2–288.1 °C; 1H NMR(400 MHz, CD3OD) δ 7.21–7.15 (m, 2H), 7.13–7.07 (m, 2H),4.44 (d, J = 5.2 Hz, 1H), 4.39 (d, J = 17.2 Hz, 1H), 4.21 (d, J =17.6 Hz, 1H), 2.70 (dd, J = 11.2, 5.2 Hz, 1H), 2.11 (d, J =11.6 Hz, 1H), 1.18 (s, 9H); 13C NMR (100 MHz, CD3OD)δ 178.4, 142.7, 136.0, 130.5, 128.7, 126.8, 126.7, 86.1,61.3, 60.6, 42.2, 40.8, 26.8; IR (KBr) ν 3060, 2971, 2934, 2906,2873, 1714, 1600, 1416, 1361, 1222, 1060, 737 cm−1; HRMS(quadrupole, EI) calcd for C15H19NO3 [M]+ 261.1365, found261.1364.

Experimental procedure and characterization data for theformation of 6c

To an oven-dried sealed tube charged with 6d (55.0 mg,0.2 mmol, 100 mol%), NaBH4 (11.3 mg, 0.3 mmol, 150 mol%)and EtOH (1 mL) were added under air at room temperature.The reaction mixture was allowed to stir at 60 °C for 2 h. Thereaction mixture was extracted with EtOAc (30 mL) and theorganic layer was washed with H2O and brine, dried overMgSO4 and concentrated in vacuo. The residue was purified byflash column chromatography (n-hexanes/EtOAc = 1 : 1) toafford 17.0 mg of 6c in 34% yield.

2-(tert-Butyl)-1,2,4,5-tetrahydro-1,4-methanobenzo[d][1,2]oxazepin-4-yl)methanol (6c)

17.0 mg (34%); white solid; mp = 182.2–184.8 °C; 1H NMR(400 MHz, CDCl3) δ 7.20–7.09 (m, 3H), 7.04 (d, J = 7.6 Hz, 1H),4.31 (d, J = 5.2 Hz, 1H), 3.90 (d, J = 11.6 Hz, 1H), 3.83 (d, J =12.0 Hz, 1H), 3.04 (d, J = 17.6 Hz, 1H), 2.91 (d, J = 17.2 Hz, 1H),2.54–2.53 (m, 1H), 2.03 (br s, 1H), 1.85 (d, J = 10.8 Hz, 1H),1.14 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 141.7, 133.9, 129.6,127.5, 125.8, 125.5, 82.1, 65.4, 60.2, 59.1, 39.5, 37.3, 26.6; IR(KBr) ν 3303, 3058, 2968, 2925, 2870, 1714, 1641, 1418, 1362,1220, 1039, 747 cm−1; HRMS (quadrupole, EI) calcd forC15H21NO2 [M]+ 247.1572, found 247.1572.

Experimental procedure and characterization data for theformation of 6d

To an oven-dried sealed tube charged with N-tert-butyl-1-phe-nylmethanimine oxide (1a) (35.4 mg, 0.2 mmol, 100 mol%),[RhCp*Cl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%), AgSbF6 (6.9 mg,0.02 mmol, 10 mol%), DCE (1 mL) and methyl 2-(acetoxy-methyl)acrylate (2a) (63.2 mg, 0.4 mmol, 200 mol%) wereadded under air at room temperature. The reaction mixturewas degassed with O2 gas, and the resulting mixture wasallowed to stir at 60 °C for 7 h. The reaction mixture wascooled to room temperature, diluted with EtOAc (3 mL) andconcentrated in vacuo. The residue was purified by flashcolumn chromatography (n-hexanes/EtOAc = 4 : 1) to afford54.5 mg of 6d in 99% yield.

Methyl 2-(tert-butyl)-1,2,4,5-tetrahydro-1,4-methanobenzo[d][1,2]oxazepine-4-carboxylate (6d)

54.5 mg (99%); white solid; mp = 69.9–73.4 °C; 1H NMR(400 MHz, CDCl3) δ 7.22–7.11 (m, 3H), 7.05 (d, J = 7.6 Hz, 1H),4.39 (d, J = 4.8 Hz, 1H), 3.84 (s, 3H), 3.36 (d, J = 17.6 Hz, 1H),3.28 (d, J = 17.2 Hz, 1H), 2.78 (dd, J = 11.2, 4.8 Hz, 1H), 2.20 (d,J = 11.2 Hz, 1H), 1.18 (s, 9H); 13C NMR (100 MHz, CDCl3)δ 171.7, 140.6, 133.0, 129.6, 127.6, 126.0, 125.7, 82.2, 59.9,59.4, 52.5, 40.0, 39.8, 26.8; IR (KBr) ν 2973, 1737, 1221, 1063,749 cm−1; HRMS (quadrupole, EI) calcd for C16H21NO3 [M]+

275.1521, found 275.1521.

Experimental procedure and characterization data for theformation of deuterio-3aa

To an oven-dried sealed tube charged with 6d (55.0 mg,0.2 mmol, 100 mol%), 1 N DCl/D2O solution (0.2 mL) wasadded to the reaction mixture. The resulting mixture wasstirred at 120 °C for 16 h and neutralized with aqueous 1 NNaOH. The aqueous layer was extracted with CH2Cl2 (10 mL)and the organic layer was washed with H2O and brine, driedover MgSO4 and concentrated in vacuo. The residue was puri-fied by flash column chromatography (n-hexanes/EtOAc = 8 : 1)to afford 23.6 mg of deuterio-3aa with 85% D incorporation atthe C1-position in 72% yield.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was supported by the National Research Foundationof Korea (NRF) grant funded by the Korean government (MSIP)(Grants 2016R1A4A1011189 and 2017R1A2B2004786), and bythe Institute for Basic Science (Grant IBS-R010-G1).

Notes and references

1 (a) H. Zhao, N. Neamati, A. Mazumder, S. Sunder,Y. Pommier and T. R. Burke, J. Med. Chem., 1997, 40, 1186–1194; (b) K. Krohn and G. Zimmermann, J. Org. Chem.,1998, 63, 4140–4142; (c) M. C. Kozlowski, B. J. Morgan andE. C. Linton, Chem. Soc. Rev., 2009, 38, 3193–3207.

2 For selected reviews, see: (a) L. Pu, Chem. Rev., 1998, 98,2405–2494; (b) Y. Chen, S. Yekta and A. K. Yudin, Chem.Rev., 2003, 103, 3155–3212; (c) L. Pu, Chem. Rev., 2004, 104,1687; (d) J. M. Brunel, Chem. Rev., 2007, 107, PR1–PR45.

3 (a) H. Juteau, Y. Gareau and H. Lachance, Tetrahedron Lett.,2005, 46, 4547–4549; (b) X. X. Zhang, S. Sarkar andR. C. Larock, J. Org. Chem., 2006, 71, 236–243.

4 (a) N. Ji, B. M. Rosen and A. G. Myers, Org. Lett., 2004, 6,4551–4553; (b) H. A. Cooke, J. Zhang, M. A. Griffin,



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K. Nonaka, S. G. Van Lanen, B. Shen and S. D. Bruner,J. Am. Chem. Soc., 2007, 129, 7728–7729.

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9 M. Wu and T. P. Begle, Org. Lett., 2000, 2, 1345–1348.10 A. K. Pandey, S. H. Han, N. K. Mishra, D. Kang, S. H. Lee,

R. Chun, S. Hong, J. S. Park and I. S. Kim, ACS Catal., 2018,8, 742–746.

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15 The reaction of other heterocyclic nitrones such asN-methyl-2-pyrrolyl nitrone and N-methyl-3-indolyl nitronewith 2a provided the corresponding indole and carbazolecontaining an ester moiety through C–N bond cleavage ofthe bridged bicyclic intermediate prior to ionic decarboxyl-ative N–O bond cleavage, see ref. 11.

16 K. Wongma, N. Bunbamrung and T. Thongpanchang,Tetrahedron, 2016, 72, 1533–1540.



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one-pot synthesis of 2-naphthols from nitrones and mbh...

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