Synthesis of enantiomerically pure helicene-like mono 1,3-oxazines from 1,1′-binaphthyl-2,2′,7-triol and study of their chiroptical properties

Abstract

A method was developed to synthesize 1,1′-binaphthyl-2,2′,7-triol by an oxidative cross coupling reaction of 2-hydroxy naphthalene and 2,7-dihydroxy naphthalene. A process was optimized to separate the enantiomers of this compound by making its complex with S-brucine; its absolute configuration was established and it was converted into a series of helicene-like mono 1,3-oxazines. The chiroptical properties of these molecules were investigated and it was established that the helicene-like structural element contributes more to the optical rotation as compared to the stereogenic center.

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Introduction

The chemistry of optically active compounds has been extensively studied for many decades due to their well recognized applications in various fields and due to the established relationship of their chirality and specific properties. Such molecules with different elements of chirality and possessing varied shapes widen the scope of applications. Molecules of helical shape or helicene-like compounds form one such class of entities demonstrating characteristic properties associated with particular structural features. The synthesis and study of helical compounds has now been well documented in a series of excellent reviews.¹ Helical molecules have been studied in diverse areas like in molecular recognition,² as molecular devices,³ liquid crystals,⁴ optical materials,⁵ in asymmetric synthesis,⁶ medicinal chemistry or for biological interactions,⁷ etc. One of the most dramatic properties of helical compounds in enantiopure form is their very high ability to rotate plane polarized light or optical rotation (OR). Due to this unique property helical materials have been anticipated⁸ to offer many applications in modern devices.⁹ On the other hand the heterocyclic helicene shaped molecules will also add another dimension in their binding ability to biological receptors. Different kinds of heterohelicenes have been synthesized and investigated for novel applications.¹⁰ The heterohelicenes possessing a 1,3-oxazine moiety have not been much explored in the literature except for one system¹¹ other than our studies on helicene-like bis-oxazines.^12,13

Helicene like dibenzo[c]acridine with special chiroptical properties has been recently synthesized and studied (Chart 1).¹⁴ These molecules were obtained in optically pure form by the separation of helicene-like isomers following their derivatization with chiral resolving agents. The optically pure compounds were shown to have very high degree of specific OR ([α]_D) and molecular OR ([Φ]_D). In our previous studies we have synthesized binaphthalene based chiral helicene-like bis-oxazine derivatives from optically pure 2,2′,7,7′-tetrahydroxy-1,1′-binaphthalene. These molecules showed reasonable high optical rotation and interesting Circularly Polarized Luminescence (CPL) profile.

Chart 1 Helicene like molecules with notable chiroptical properties.

In this work we present synthesis, resolution of 1,1′-binaphthyl-2,2′,7-triol and its conversion to unsymmetrical chiral mono-helicene like oxazines and exploration of their optical properties.

Result and discussion

In our previous work we have started the preparation of helicene-like bis-oxazines from 2,2′,7,7′-tetrahydroxy 1,1′-binaphthyl, which is known to be easily obtained by oxidative homo-coupling of 2,7-dihydroxy naphthalene.^15,16 This set of symmetrical bis-oxazines had a single element of chirality of the helical description and the chiroptical properties were attributed to it alone.¹³ In the current set of compounds we propose to modify the helicene-like oxazines by introducing one heterocyclic ring possessing no chirality or another set with one chiral center on the oxazine ring. Also another set of helicene like compounds were prepared without the oxazine ring to compare the properties. The design of these three sets of compounds will help us to correlate the chiroptical properties with the structural elements, with and without the oxazine ring, with the chiral center on oxazine ring and finally the match-mismatched effect between the two elements of chirality.

The retrosynthetic scheme of preparation of target helicene-like mono oxazine A is presented in Scheme 1, where the first disconnection will lead to the ether precursor a diol B,¹⁴ which can easily be built from triol 1 by aromatic Mannich reaction¹⁷ with appropriate primary amine and formaldehyde.

Scheme 1 Retrosynthesis of helicene-like mono oxazine.

One can envisage the synthesis of the triol 1 by oxidative cross coupling reaction of 2-hydroxy naphthalene 2 and 2,7-dihydroxy naphthalene 3 (Scheme 2).¹⁸ The method has been widely used to synthesize useful 1,1′-binaphthayl derivatives, particularly chiral ones, in organic synthesis.¹⁹ The cross-coupling of 2-hydroxy naphthalene 2 with other substituted naphthol derivatives is a well studied reaction.²⁰ However, it is well known that the cross-coupling reaction between two naphthol units, both possessing only electron releasing groups, tend to be less selective and the cross-coupling products are accompanied by the formation of the undesired homo-coupling compounds. A good selectivity can be achieved in a cross-coupling reaction between the two coupling partners possessing considerable difference in the electron density.^20a However, in the present case we need to couple two electron rich naphthol derivatives, 2 and 3, and thus expect formation of the corresponding homocoupled products 4 and 5 (Scheme 2). The optimized condition of FeCl₃ catalyzed cross-coupling in aqueous medium is presented in Table 1. As can be seen the reaction results in formation of all three possible coupling products in considerable amounts, but were separated by careful column chromatography. We also investigated copper catalyst for the reaction, but the results were almost similar.²¹

Scheme 2 Oxidative cross-coupling reaction of 2-hydroxy naphthalene 2 and 2,7-dihydroxy naphthalene 3.

Table 1 Optimization of conditions for cross-coupling of 2-hydroxy naphthalene and 2,7-dihydroxy naphthalene

No	Conditions			Isolated yield^a (%)
	2	3	FeCl3	2^b	4	1	5
a Yields of 4 were calculated based of 2-hydroxy naphthalene while that for 1 and 5 were based on 2,7-dihydroxy naphthalene.b Based on recovered from the reaction.c All reactions were run in water at reflux for 24 h.d With benzyl amine (0.5 eq.) and piperidine (0.5 eq.).
1	1.00	0.80	2.50^c	—	31	33	50
2	1.25	1.00	2.50^c	24	30	38	59
3	1.50	1.00	2.50^c	24	34	38	51
4	2.00	1.00	2.50^c	33	30	35	49
5	1.50	1.00	1.50^c	60	12	27	64
6	1.50	1.00	0.50 (CuCl2)^d	—	46	33	30

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Axially and helically chiral molecules posses interesting properties and has been a subject of recent research. However, both the systems need to be carefully designed as to prevent the isomerisation between the two isomers arising due to prevention of an appropriate bond rotation. A derivative 7-oxa[5]helicene 6²² has been prepared from BINOL 4 by dehydration, while axially chiral bridged product 7,²³ also known as “dioxepine”^23b has been obtained by its reaction with diiodomethane (Fig. 1). The product 6 is quite flat in nature with a dihedral angle of about 12° which renderers the helical isomers to remain in equilibrium with each other.^23d On the other hand the bridged dioxepine 7 exhibits the presence of two stable helicene-like isomers, which have been established by appropriate chiral phase HPLC analysis.^23c The structure of dioxepine is more of a combination of axially chiral helicene-like structure, present as P and M configurations.

Fig. 1 Comparison of stability of isomers of 7-oxa[5]helicene (6) and naphtha[1,2,1,2-def][1,3]dioxepine (7).

Due to the stability of helicene-like isomers we focused our attention on the synthesis and study of the derivatives of dioxepine.¹³ In the present study we focus on the preparation of three types of such derivatives and study their chiroptical properties. The optically pure starting material for the synthesis was expected to be obtained by resolution of racemic 1. The hydroxyl derivatives of binaphthyl system are known to form diastereomeric complexes and can be separated by fractional crystallization.^19c Efforts were concentrated to search a suitable material which can form a complex with appropriate solubility to be able to separate the diastereomers by fractional crystallization. Different chiral basic materials were screened (Table 2) while the alkaloid (S)-brucine was found effective in separating the two axial isomers of 1 by a single crystallization (Scheme 3). The salt of one isomer of 1 was separated as solid residue when refluxed with (S)-brucine in methyl alcohol.²⁴ The free phenol was separated by treatment with aqueous mineral acid and simple extraction in organic solvent. The sample of triol 1 from the (S)-brucine salt was analyzed by chiral phase HPLC analysis to be 96% ee, while that from the solution showed moderate optical purity.

Table 2 Optimization of conditions for resolution of (R/S)-1

No	Chiral resolving agent	Solvent	Condition	Results
				Precipitate		Filtrate
				Yield (%)	% ee	Yield (%)	% ee
a Also investigated: CH3OH, CH2Cl2, EtOAc, PhCH3 and EtOH; refluxed for 12 to 30 hours.
1	L-Proline	CH3CN^a	Reflux	No precipitates observed
2	L-Phenyl glycine	CH3CN	Reflux, 12 h
3	(+)-Cinchonine	CH3CN	Reflux, 6 h
4	(−)-Quinine	CH3OH	Reflux, 6 h
5	(S)-Brucine	Acetone^a	Reflux, 6 h
6	(S)-Brucine	CH3OH	Reflux, 4 h	44	96.2	48	53.8
7	(S)-Brucine	Isopropanol	Reflux, 4 h	46	50.0	50	50.0
8	(S)-Brucine	CH3CN	Reflux, 4 h	46	18.0	49	62.3

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Scheme 3 Resolution of (R/S)-1.

Recently L-proline has been used as chiral base to separate isomers of BINOL²⁵ and 2,2′,7,7′-tetrahydroxy 1,1′-binaphthyl 5¹³ by fractional crystallization of the inclusion complexes. However, our initial efforts to use this and other amino acids or other alkaloids like cinchonine and quinine did not yield any resolution.

The triol 1 was not known in the literature till we reported its use in the synthesis of 7,12,17-trioxa[11]helicene.¹⁸ The absolute configuration of the sample obtained from the residue as salt with (S)-brucine was crystallized from methyl alcohol to get single crystal, while its X-ray diffraction analysis revealed it to be in S_a-form (Fig. 2). Two molecules of (S)-brucine formed two H-bonds with the two hydroxyl groups of 1. The brucine–N⋯H–O–Ar bond and brucine–C=O⋯H–O–Ar bond were seen to be 1.889 and 1.875 Å, growing linearly in the crystal lattice which was crystallized in P1 space group. Such supramolecular assemblies for resolution of chiral molecules by (S)-brucine are known in the literature (Fig. 3), although not for separation of isomers of chiral phenols.²⁶

Fig. 2 ORTEP diagram of the salt of (S_a)-1 and (S)-brucine (CCDC 1023827†).

Fig. 3 Crystal packing of the salt of (S)-brucine and (S_a)-1.

Having obtained the optically pure isomer of triol 1, we next embarked upon its conversion to mono methyl ether (S_a)-8, where the hydroxyl at C₇ was selectively methylated^22a (Scheme 4). Further a methylene bridge was introduced between the remaining two free hydroxyl groups by standard procedure of diiodomethane in presence of cesium carbonate to afford (P)-9, which was characterized by usual spectroscopic and analytical techniques. On crystallization this compound was obtained as a single enantiomer (>99% ee) and characterized by single crystal X-ray diffraction analysis (Fig. 4). The analysis clearly indicate presence of two molecules in the unit cell both of P-helical description, crystallized in P2₁ space group while the dihedral angle of 55.0° was observed. The other isomer (R_a)-1 was similarly converted to (M)-9, but in lower optical purity (∼62% ee). Our attempts to enrich this isomer by repeated crystallizations did not improve the optical purity. The present derivatives of methylene bridge containing helicene-like molecules have only one element of chirality.

Scheme 4 Synthesis of enantiomers (P)-9 and (M)-9.

Fig. 4 ORTEP of (P)-9 (CCDC 1453552†).

In the next sent of such derivatives we intend to introduce 1,3-oxazine moiety to increase the functionality. Optically pure (S_a)-1 was subjected to aromatic Mannich reaction^12a with benzyl amine and aqueous solution of formaldehyde to furnish (S_a)-10, which was further converted to helicene-like mono oxazine derivative (P)-11 (>99% ee). Same procedure was followed to access the other enantiomer (M)-11, but with lower optical purity (Scheme 5). Thus we have prepared another set of helicene-like compounds with a fused 1,3-oxazine ring.

Scheme 5 Synthesis of enantiomers (P)-11 and (M)-11.

In the above series further modification was introduced by adding another element of chirality where the oxazine ring was attached with chiral group. For this purpose optically pure 1-phenyl ethyl amine was chosen as the primary amine during aromatic Mannich reaction. Accordingly optically pure (S_a)-1 was treated with formaldehyde and both isomers of 1-phenyl ethyl amine followed by bridge formation to afford (P,S)-13 and (P,R)-13 (Scheme 6). Both these diastereomers were obtained in high chiral purity (up to diastereomeric ratio of 98 : 02).

Scheme 6 Synthesis of diastereomeric (P,S)-13 and (P,R)-13.

Identical reaction sequence was adopted to access other two diastereomers of (M,S)-13 and (M,R)-13 starting from (R_a)-1 (Scheme 7). These diastereomers were initially obtained with moderate optical purity at the axial chirality, but eventually improved by repeated crystallizations from ethyl acetate and hexane (up to diastereomeric ratio of 89 : 11). The diastereomeric ratios of the final mono-helicene like oxazines varied slightly due to the crystallization carried out for the purification procedures.

Scheme 7 Synthesis of diastereomeric (M,S)-13 and (M,R)-13.

The structure of a representative example of (P,S)-13 was studied by its single crystal X-ray diffraction analysis (Fig. 5). The analysis clearly indicate presence of four molecules in the unit cell all with P-helical description, crystallized in P2₁2₁2₁ space group while the dihedral angle of 65.74° was observed. This mono oxazine derivative showed slightly higher dihedral angle compared to mono-methoxy derivative (P)-9, probably due to extended helicity as a result of additional heterocyclic ring.

Fig. 5 ORTEP of (P,S)-13 (CCDC 1041059†).

Having obtained optically pure samples of these four types of compounds we examined their chiroptical properties. The triol (S_a)-1 with axial chirality showed specific optical rotation, OR, of about +30° (Table 3). This compound was converted to helicene-like molecule (P)-9, as expected there was a considerable enhancement in the value of specific OR.¹³ This is in accordance with the characteristic observation for helical or helicene-like molecules.¹⁴ The third type of molecules studied contained an additional oxazine ring fused to one of the naphthalene moieties. Optically pure sample of (P)-11 with only a single chiral element in the helicene-like structure showed no significant enhancement in the OR value. In the next set of molecules we examined a combination of helicene-like basic framework in combination with oxazine containing a stereogenic center. In this part we have prepared all four possible diastereomers of 13 and compared their OR values. In this set the two enantiomers (P,S)-13 and (M,R)-13 demonstrated slightly higher degree of OR as compared to the other set of enantiomers (P,R)-13 and (M,S)-13. These two sets being diastereomeric to each other, we establish the match-mismatch effect of the two chiral elements in these helicene-like mono oxazines towards the plane polarized light.

Table 3 Correlation of the chiroptical properties of synthesized compounds

No	Compound	% ee	Ratio of d.e.^a	Specific OR ([α]D)	Molecular OR ([Φ]D)
a Determined by ^1H NMR.
1	(Sa)-1	96		+30	+90.6
2	(P)-9	>99		+1090	+3576
3	(P)-11	98		+801	+3565
4	(P,S)-13		98 : 2	+742	+3407
5	(P,R)-13		90 : 10	+638	+2929
6	(M,S)-13		89 : 11	−658	−3021
7	(M,R)-13		99 : 1	−828	−3802

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The four diastereomeric derivatives of helicene-like mono oxazines 13 showed typical UV and CD spectral features (Fig. 6 and 7).²⁷ The UV-Vis spectra of all isomers of 13 in acetonitrile exhibit absorption bands in around 320 nm. The isomers showed blue emission in the range of 410 nm with a Stokes shift of about 90 nm. Presence of two opposite bisignate couplets, one at around 214 nm and another positive one at 237 nm were attributed to the P-helical-like configuration of (P,S)-13. As expected the two pairs of enantiomers show identical but opposite CD curves.

Fig. 6 Normalized UV-Vis and fluorescence spectra of (P,S)-13, (M,R)-13 and (P,R)-13, (M,S)-13 (ext. at 318 nm).

Fig. 7 Circular dichroism spectra of enantiomer pairs (P,S)-13, (M,R)-13 (left) and (P,R)-13, (M,S)-13 (right) (c 3.81 × 10⁻⁴ M in CH₃CN, 25 °C).

Thus the CD data corroborated with the absolute configuration of the helicene-like mono-oxazines synthesized in this study.

Experimental section

Thin layer chromatography was performed on silica gel plates quoted on aluminium sheets. The spots were visualized under UV light or with iodine vapor. All the compounds were purified by column chromatography on silica gel (60–120 mesh). All reactions were carried out under an inert atmosphere (nitrogen) unless other conditions are specified. Photochemical reactions were performed in immersion well photo reactor with appropriate high pressure mercury vapor lamps. NMR spectra were recorded on Bruker Avance 400 Spectrometer (400 MHz for ¹H-NMR, 100 MHz for ¹³C-NMR) with CDCl₃ as solvent and TMS as internal standard. Mass spectra were recorded on Thermo-Fischer DSQ II GCMS instrument. ESI mass spectra and HRMS were recorded on a Thermo Scientific LCQ Fleet mass spectrometer equipped with an electrospray ion source and controlled by Xcalibur software. IR spectra were recorded on a Perkin-Elmer FTIR RXI spectrometer as KBr pallets. Fluorescence spectra were recorded on Jasco FP-6300 Fluorescence spectrometer, while UV VIS spectra were recorded at temperature on Perkin-Elmer Lambda 35 spectrometer. Melting points were recorded in Thiele's tube using paraffin oil and are uncorrected.

Representative procedure for the compound 1

A solution of FeCl₃·6H₂O (42.18 g, 156.08 mmol) in 200 mL water was added drop wise for 1 h at 100 °C to the solution of 2,7-dihydroxynaphthalene 3 (10 g, 62.43 mmol) and 2-naphthalene 2 (13.5 g, 93.65 mmol) in 500 mL of water. After the addition the reaction mixture was refluxed for 24 h, completion of the reaction the 2,7-dihydroxynaphthalene reaction mixture was cooled to room temperature and extracted with ethyl acetate (2 × 500 mL) the solvent dried over sodium sulphate and concentrated under reduced pressure to obtain the crude black mass. Purification of compound by column chromatography on silica gel using gradient petroleum ether : ethyl acetate 100 : 00 to 70 : 30 as eluent to obtained binaphthol derivatives. Yield of 1 & 4 was calculated based on 2 and yield of 1 & 5 was calculated based on 3.

2-Napthalol (2): yield = 3.20 g, 24% (recovered).

Binol (4): yield = 3.60 g, 34% (mp = 216–218 °C).

Tetrol (5): yield = 5.11 g, 51% (mp = 122–124 °C).

Triol (1): yield = 7.15 g, 38% (mp = 172–174 °C).

¹H NMR (CDCl₃, 400 MHz) δ 7.96 (d, J = 9.2 Hz, 1H), 7.91–7.87 (d, J = 8.4 Hz, 2H merged), 7.78 (d, J = 8.8 Hz, 1H), 7.42–7.39 (m, 1H), 7.37 (d, J = 9.2 Hz, 1H), 7.34–7.28 (m, 1H), 7.22 (d, J = 8.8 Hz, 1H), 7.18 (d, J = 8.4 Hz, 1H), 6.97 (dd, J = 8.8, 2.4 Hz, 1H), 6.41 (d, J = 2.4 Hz, 1H), 5.13 (s, 1H), 5.05 (s, 1H), 4.83 (s, 1H).

¹³C NMR (CDCl₃, 100.6 MHz) δ 154.9, 153.5, 152.7, 134.9, 133.3, 131.5, 131.3, 130.5, 129.5, 128.4, 127.6, 124.8, 124.2, 124.1, 117.7, 115.6, 115.3, 110.9, 109.4, 106.4.

IR (KBr) ν 3492 (OH), 3391 (OH), 1620, 1593, 1560, 1470, 1216, 1150, 838, 820.

Mass (EI) m/z, (%) 301.88 (100) and (ESI) [M + 1] 303.4.

HRMS (ESI⁺) calcd for C₂₀H₁₄O₃ (M + 1)⁺ 303.1012, found 303.1022.

Resolution of 1,1′-binaphthyl-2,2′,7-triol (1)

Racemic triol 1 (1 g, 3.31 mmol) and (S)-brucine (0.76 g, 3.31 mmol) were taken in MeOH (30 mL). The mixture was refluxed for 4 h, and then cooled to room temperature to give white precipitates, which were filtered and crystallized in methanol to furnish colourless crystals of the molecular complex. The crystals was added to a mixture of ethyl acetate–HCl (1 M, 1 : 1) and stirred at room temperature for 10 min. The solid crystals were completely dissolved, the organic layer was separated, and the water phase extracted with ethyl acetate (2 × 50 mL). The organic layer was dried over anhydrous Na₂SO₄, concentrated at reduced pressure, to give (S)-1,1′-binaphthyl-2,2′,7-triol (0.440 g, 48%), mp 172–174 °C, [α]²⁸_D = +30 (c = 0.30, acetonitrile) [96.2% ee based on HPLC on Chiralpak OD-H].

The mother liquor MeOH was evaporated under reduced pressure to get residue then treated with a mixture of ethyl acetate–HCl (1 M, 1 : 1) and stirred at room temperature for 10 min. The residue was completely dissolved, the organic layer was separated, and the water phase extracted with ethyl acetate (2 × 50 mL). The organic layer was dried over anhydrous Na₂SO₄, concentrated at reduced pressure, to give (R)-1,1′-binaphthyl-2,2′,7-triol as off white powder (0.480 g, 48%), mp 172–174 °C. This sample was 54.0% optically pure, [α]²⁸_D = −12 (c = 0.30, acetonitrile).

(±)7-Methoxy-[1,1′-binaphthalene]-2,2′-diol (8)

To a solution of triol (0.25 g, 0.83 mmol) in MeOH (10 mL) was added concentrated H₂SO₄ (0.04 mL, 0.83 mmol). The reaction mixture was allowed to gently reflux for 3 days. After quenching with saturated potassium carbonate solution, the crude product was extracted with ethyl acetate. The crude product was purified by column chromatography over silica gel using light petroleum ether/ethyl acetate as eluent (100 : 00 to 90 : 20) furnishing a white solid (0.19 g, 74%).

Mp 90–92 °C.

¹H NMR (CDCl₃, 400 MHz) δ 8.01–7.98 (d, J = 8.8 Hz, 1H), 7.93–7.90 (d, J = 8.8 Hz, 2H), 7.82–7.80 (d, J = 8.8 Hz, 1H), 7.42–7.40 (d, J = 8.8 Hz, 1H), 7.39–7.33 (m, 2H), 7.26–7.24 (d, J = 8.8 Hz, 1H), 7.23–7.21 (d, J = 8.8 Hz, 1H), 7.06–7.04 (dd, J = 2.8 & 8.8 Hz, 1H), 6.46–6.45 (d, J = 2.8 Hz, 1H), 3.57 (s, 3H).

¹³C NMR (CDCl₃, 100.6 MHz): δ 159.1, 153.2, 152.7, 134.9, 133.2, 131.4, 131.1, 130.0, 129.5, 128.4, 127.5, 124.7, 124.2, 124.0, 117.8, 116.0, 115.1, 110.9, 109.9, 103.2, 55.1.

IR (KBr) ν 3470, 3058, 2951, 1657, 1620, 1512, 1466, 1374, 1273, 1222, 1178, 1031, 838, 749 cm⁻¹.

MS (EI): m/z, (%) 316 (100).

HRMS (ESI⁺) calcd for C₂₁H₁₆O₃ [M + 1]⁺ 317.1177, found 317.1171.

(S_a) 7-Methoxy-[1,1′-binaphthalene]-2,2′-diol [(S_a)-8]

Compound (S_a)-8 was prepared by same procedure as that of (±)-8.

Yield = 71%.

Mp 92–94 °C.

(R_a) 7-Methoxy-[1,1′-binaphthalene]-2,2′-diol [(R_a)-8]

Compound (R_a)-8 was prepared by same procedure as that of (±)-8.

Yield = 74%.

Mp 90–92 °C.

(±) 10-Methoxydinaphtho[2,1-d:1′,2′-f][1,3]dioxepine (9)

A solution of pure 7-methoxy-[1,1′-binaphthalene]-2,2′-diol (0.10 g, 0.32 mmol) and anhydrous Cs₂CO₃ (0.52 g, 1.58 mmol) in dry DMF (5 mL) and CH₂I₂ (0.13 g, 0.47 mmol) was added and the mixture was stirred 48 h at room temperature under nitrogen atmosphere. After the completion of the reaction (tlc) the reaction mixture was poured in ice cold water. The aqueous layer was extracted with chloroform (3 × 100 mL) combine the extract and washed with water (2 × 100 mL) and the organic layer was dried over Na₂SO₄ and evaporated to obtained crude solid. The crude product was purified by column chromatography over silica gel using petroleum ether/ethyl acetate as eluent (100 : 00 to 90 : 10) furnishing a white solid (0.08 g, 83%).

Mp 138 °C.

¹H NMR (CDCl₃, 400 MHz) δ 8.00 (d, J = 8.8 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.85 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.49–7.45 (m, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.13 (dd, J = 8.8 & 2.4 Hz, 1H), 6.80 (d, J = 2.4 Hz, 2H), 5.72 (s, 2H), 3.44 (s, 3H).

¹³C NMR (CDCl₃, 100.6 MHz): δ 157.9, 152.0, 151.2, 133.8, 131.7, 130.3, 129.9, 128.5, 127.3, 127.3, 126.3, 125.9, 125.1, 121.1, 118.4, 117.9, 105.5, 103.6, 55.0 (OCH₃).

IR (KBr) ν 3062, 3005, 2946, 2829, 1659, 1625, 1581, 1524, 1464, 1361, 1260, 1223, 1132, 1033, 828, 744 cm⁻¹.

MS (ESI)⁺ 329.2 m/z.

HRMS (ESI⁺) calcd for C₂₂H₁₆O₃ [M + 1]⁺ 329.1178, found 329.1172.

(P) 10-Methoxydinaphtho[2,1-d:1′,2'-f][1,3]dioxepine [(P)-9]

Compound (P)-9 was prepared by same procedure as that of (±)-9.

Yield = 60%.

Mp 136–138 °C.

[α]²⁸_D = +1090 (c = 0.65, CHCl₃).

(M) 10-Methoxydinaphtho[2,1-d:1′,2′-f][1,3]dioxepine [(M)-9]

Compound (M)-9 was prepared by same procedure as that of (±)-9.

Yield = 66%.

Mp 137–138 °C.

[α]²⁸_D = −319 (c = 0.65, CHCl₃).

(±) 2-Benzyl-10-(2-hydroxynaphthalen-1-yl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-9-ol (10)

A solution of formaldehyde (0.24 g, 37% w/v, 0.79 mL, 7.95 mmol) and benzylamine (0.43 g, 3.97 mmol) in methanol (10 mL) was stirred for 30 min under nitrogen atmosphere, to this solution [1,1′-binaphthalene]-2,2′,7-triol (1 g, 3.31 mmol) was added in one portion. The solution was stirred for 48 h at 60 °C. After the completion of the reaction the mixture was concentrated and the crude product was purified by column chromatography on silica gel using light petroleum ether : ethyl acetate (100 : 0 to 70 : 30) as eluent to obtain a yellow solid which was dried in vacuum (1.3 g, 92%).

Mp 92–94 °C.

¹H NMR (CDCl₃, 400 MHz) δ 7.89–7.86 (d, J = 8.8 Hz, 2H), 7.82–7.79 (d, J = 9.2 Hz, 1H), 7.73–7.71 (d, J = 9.2 Hz, 1H), 7.36–7.29 (m, 3H), 7.23–7.21 (d, J = 8.8 Hz, 1H), 7.20–7.15 (m, 4H), 6.99–6.97 (m, 3H), 5.09–5.03 (broad singlet, 2H, OH), 4.70–4.68 (d, J = 9.6 Hz, 1H), 4.60–4.58 (d, J = 9.6 Hz, 1H), 3.62–3.59 (d, J = 13.2 Hz, 1H), 3.52–3.48 (d, J = 16.8 Hz, 1H), 3.49–3.46 (d, J = 13.2 Hz, 1H), 2.96–2.92 (d, J = 16.8 Hz, 1H).

¹³C NMR (CDCl₃, 100.6 MHz): δ 154.1, 153.7, 152.5, 137.6, 133.6, 133.2, 132.8, 131.6, 129.5, 128.9, 128.6, 128.5, 128.3, 127.9, 127.1, 125.9, 124.2, 123.9, 117.4, 116.9, 114.7, 113.8, 111.9, 108.9, 80.7 (NCH₂O), 55.3 (ArCH₂N), 48.1 (NCH₂Ph).

IR (KBr) ν 3469 (OH), 3052, 2951, 2897, 1668, 1620, 1522, 1515, 1456, 1374, 1273, 1219, 1169, 1031, 838, 749.

MS (ESI)⁺ [M+1]⁺ 434.2.

HRMS (ESI⁺) calcd for C₂₉H₂₃NO₃ [M + 1]⁺ 434.1756, found 434.1750.

(S_a) 2-Benzyl-10-(2-hydroxynaphthalen-1-yl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-9-ol [(S_a)-10]

Compound (S_a)-10 was prepared by same procedure as that of (±)-10.

Yield = 73%.

Mp 90–92 °C.

(R_a) 2-Benzyl-10-(2-hydroxynaphthalen-1-yl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-9-ol [(R_a)-10]

Compound (R_a)-10 was prepared by same procedure as that of (±)-10.

Yield = 89%.

Mp 92–94 °C.

(±) 10-Benzyl-10,11-dihydro-9H-naphtho[1′′,2′′:6′,7′][1,3]dioxepino[4′,5′:7,8]naphtho[1,2-e][1,3]oxazine (11)

A solution of pure 2-benzyl-10-(2-hydroxynaphthalen-1-yl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-9-ol (0.30 g, 0.69 mmol) and anhydrous Cs₂CO₃ (1.13 g, 3.46 mmol) in dry DMF (5 mL) and CH₂I₂ (0.28 g, 1.04 mmol) was added and the mixture was stirred 48 h at room temperature under nitrogen atmosphere. After the completion of the reaction (tlc) the reaction mixture was poured in ice cold water. The aqueous layer was extracted with chloroform (3 × 100 mL) combine the extract and washed with water (2 × 100 mL) and the organic layer was dried over Na₂SO₄ and evaporated to obtained crude solid. The crude product was purified by column chromatography over silica gel using petroleum ether/ethyl acetate as eluent (100 : 00 to 80 : 20) furnishing a white solid (0.18 g, 61%).

Mp 162–164 °C.

¹H NMR (CDCl₃, 400 MHz) δ 7.93–7.91 (d, J = 8.8 Hz, 1H), 7.91–7.89 (d, J = 8.8 Hz, 1H), 7.89–7.87 (d, J = 8.4 Hz, 1H), 7.83–7.81 (d, J = 8.8 Hz, 1H), 7.42–7.40 (d, J = 8.8 Hz, 1H), 7.40–7.36 (dt, J = 8 & 1.2 Hz, 1H), 7.33–7.31 (d, J = 8.4 Hz, 1H), 7.26–7.18 (m, 5H), 7.10–7.08 (d, J = 8.8 Hz, 1H), 7.06–7.04 (m, 2H), 5.71–5.67 (two doublet, J = 10 Hz, 2H), 4.51–4.50 (broad singlet, 2H), 3.48–3.45 (d, J = 12.8 Hz, 1H), 3.33–3.30 (d, J = 12.8 Hz, 1H), 3.05–2.99 (m, 2H).

¹³C NMR (CDCl₃, 100.6 MHz): δ 153.2, 152.4, 149.7, 137.6, 133.3, 132.7, 131.2, 130.1, 129.4, 129.2, 128.8, 128.7, 128.3, 127.9, 127.2, 126.6, 125.0, 124.5, 123.5, 120.5, 118.2, 117.8, 112.5, 102.8 (O–CH₂–O), 79.7 (NCH₂O), 54.6 (ArCH₂N), 51.2 (NCH₂Ph).

IR (KBr) ν 3033, 2951, 2891, 2848, 1611, 1508, 1456, 1362, 1323, 1268, 1233, 1135, 1045, 996, 912, 830, 807, 746, 722.

MS (EI) m/z, (%): [M]⁺ 445.2 (100) and (ESI)⁺ [M + 1]⁺ 446.2.

HRMS (ESI⁺) calcd for C₃₀H₂₃NO₃ [M + 1]⁺ 446.1756, found 446.1750.

(P)-10-Benzyl-10,11-dihydro-9H-naphtho[1′′,2′′:6′,7′][1,3]dioxepino[4′,5′:7,8]naphtha[1,2-e][1,3]oxazine [(P)-11]

Yield = 61%.

Mp 164–166 °C.

[α]²⁸_D = +800 (c = 0.8, CHCl₃).

¹H-NMR (CDCl₃, 400 MHz) δ 7.93–7.91 (d, J = 8.8 Hz, 1H), 7.92–7.90 (d, J = 8.8 Hz, 1H), 7.89–7.88 (d, J = 8.4 Hz, 1H), 7.83–7.81 (d, J = 8.8 Hz, 1H), 7.43–7.41 (d, J = 8.8 Hz, 1H), 7.40–7.36 (dt, J = 8 & 1.2 Hz, 1H), 7.34–7.32 (d, J = 8.4 Hz, 1H), 7.27–7.19 (m, 5H), 7.11–7.09 (d, J = 8.8 Hz, 1H), 7.06–7.04 (m, 2H), 5.71–5.68 (two doublet, J = 10 Hz, 2H), 4.54–4.48 (broad singlet, 2H), 3.49–3.46 (d, J = 12.8 Hz, 1H), 3.34–3.31 (d, J = 12.8 Hz, 1H), 3.09–3.00 (AB splitting, J = 16.8 Hz, 2H).

MS (EI) m/z, (%): [M]⁺ 445.2 (100), 354 (11), 327 (12), 326 (65), 325 (38), 296 (35), 295 (61), 278 (38), 238 (38).

MS (ESI⁺): [M + 1] 446 m/z.

IR (KBr) ν 3024, 2905, 2842, 1609, 1508, 1451, 1356, 1322, 1280, 1235, 1138, 1043, 1010, 909, 830, 806, 751, 722.

(M)-10-Benzyl-10,11-dihydro-9H-naphtho[1′′,2′′:6′,7′][1,3]dioxepino[4′,5′:7,8]naphtha[1,2-e][1,3]oxazine [(M)-11]

Yield = 63%.

Mp 164–166 °C.

[α]²⁸_D = −195 (c = 0.8, CHCl₃).

¹H NMR (CDCl₃, 400 MHz) δ 7.93–7.91 (d, J = 8.8 Hz, 1H), 7.92–7.90 (d, J = 8.8 Hz, 1H), 7.89–7.88 (d, J = 8.4 Hz, 1H), 7.83–7.81 (d, J = 8.8 Hz, 1H), 7.43–7.41 (d, J = 8.8 Hz, 1H), 7.40–7.36 (dt, J = 8 & 1.2 Hz, 1H), 7.34–7.32 (d, J = 8.4 Hz, 1H), 7.27–7.19 (m, 5H), 7.11–7.09 (d, J = 8.8 Hz, 1H), 7.06–7.04 (m, 2H), 5.71–5.68 (two doublet, J = 10 Hz, 2H), 4.54–4.48 (broad singlet, 2H), 3.49–3.46 (d, J = 12.8 Hz, 1H), 3.34–3.31 (d, J = 12.8 Hz, 1H), 3.09–3.00 (AB splitting, J = 16.8 Hz, 2H).

MS (EI) m/z, (%): [M]⁺ 445.2 (100), 354 (11), 327 (12), 326 (65), 325 (38), 296 (35), 295 (61), 278 (38), 238 (38).

MS (ESI⁺): [M + 1] 446 m/z.

IR (KBr) ν 3033, 2951, 2891, 2848, 1611, 1508, 1456, 1362, 1323, 1268, 1233, 1200, 1135, 1045, 1009, 996, 912, 830, 807, 751, 722 cm⁻¹.

(±) 10-(2-Hydroxynaphthalen-1-yl)-2-((S)-1-phenylethyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-9-ol (12)

A solution of formaldehyde (0.36 g, 37% w/v, 1.19 mL, 11.9 mmol) and (S)-α-phenyl ethyl amine (0.72 g, 5.96 mmol) in methanol (10 mL) was stirred for 30 min under nitrogen atmosphere, to this solution [1,1′-binaphthalene]-2,2′,7-triol (1.5 g, 4.96 mmol) was added in one portion. The solution was stirred for 48 h at 60 °C. After the completion of the reaction the mixture was concentrated and the crude product was purified by column chromatography on silica gel using light petroleum ether : ethyl acetate (100 : 0 to 70 : 30) as eluent to obtain a mixture of diastereomers as a yellow solid which was dried in vacuum (1.92 g, 86%).

¹H NMR (CDCl₃, 400 MHz) δ 7.88–7.84 (m, 3H), 7.79–7.77 (d, J = 8.8 Hz, 1H), 7.70–7.68 (d, J = 8.8 Hz, 2H), 7.37–7.28 (m, 5H), 7.26–7.19 (m, 9H), 7.08–7.01 (m, 7H), 6.96–6.94 (two doublets, J = 8.8 Hz, 2H), 6.91–6.88 (m, 1H), 4.79–4.71 (m, 2H), 4.57–4.45 (two doublets, J = 9.6 Hz, 2H), 3.69–3.56 (m, 2H), 3.45–3.41 (m, 2H), 3.07–2.82 (two doublets, J = 16.8 Hz, 2H), 0.91–0.89 (m, 6H).

MS (EI⁺): m/z, (%) 447 (21), 446 (13), 445 (13), 430 (7), 316 (27), 315 (30), 312 (33), 297 (98), 284 (14), 105 (100) and (ESI⁺): 448.3 m/z [M + 2].

HRMS (ESI⁺) calcd for C₃₀H₂₆O₃N [M + 1]⁺ 448.19127, found 448.19073.

(S_a) 10-(2-Hydroxynaphthalen-1-yl)-2-((S)-1-phenylethyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-9-ol [(S_a,S)-12]

Compound (S_a,S)-12 was prepared by same procedure as that of (±)-12.

Yield = 87%.

(S_a) 10-(2-Hydroxynaphthalen-1-yl)-2-((R)-1-phenylethyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-9-ol [(S_a,R)-12]

Compound (S_a,R)-12 was prepared by same procedure as that of (±)-12.

Yield = 87%.

(R_a) 10-(2-Hydroxynaphthalen-1-yl)-2-((S)-1-phenylethyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-9-ol [(S_a,R)-12]

Compound (R_a,S)-12 was prepared by same procedure as that of (±)-12.

Yield = 86%.

(R_a) 10-(2-Hydroxynaphthalen-1-yl)-2-((R)-1-phenylethyl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-9-ol [(R_a,R)-12]

Compound (R_a,R)-12 was prepared by same procedure as that of (±)-12.

Yield = 83%.

(±)-10-((S)-1-Phenylethyl)-10,11-dihydro-9H-naphtho[1′′,2′′:6′,7′][1,3]dioxepino [4′,5′:7,8]naphtho[1,2-e][1,3]oxazine (13)

A solution of pure 2-benzyl-10-(2-hydroxynaphthalen-1-yl)-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazin-9-ol (0.7 g, 1.57 mmol) and anhydrous Cs₂CO₃ (2.55 g, 7.83 mmol) in dry DMF (5 mL) and CH₂I₂ (0.63 g, 2.35 mmol) was added and the mixture was stirred 48 h at room temperature under nitrogen atmosphere. After the completion of the reaction (tlc) the reaction mixture was poured in ice cold water. The aqueous layer was extracted with chloroform (3 × 100 mL) combine the extract and washed with water (2 × 100 mL) and the organic layer was dried over Na₂SO₄ and evaporated to obtained crude solid. The crude product was purified by column chromatography over silica gel using petroleum ether/ethyl acetate as eluent (100 : 00 to 80 : 20) furnished mixture of diastereomers as a yellow solid (0.38 g, 53%).

¹H NMR (CDCl₃, 400 MHz) δ 7.99–7.97 (d, J = 8.8 Hz, 1H), 7.94–7.77 (m, 7H), 7.49–7.47 (d, J = 8.8 Hz, 1H), 7.43–7.04 (m, 19H, including CDCl₃), 6.83–6.81 (m, 2H), 5.71–5.70 (m, 1.5H), 5.62–5.56 (AB splitting, J = 20.8 Hz, 2H), 4.94–4.91 (d, J = 9.6 Hz, 1H), 4.59–4.57 (dd, J = 9.6 & 0.8 Hz, 1H), 4.47–4.44 (d, J = 9.6 Hz, 0.6H), 4.36–4.33 (dd, J = 9.6 Hz, 1H), 3.52–3.37 (m, 3H), 2.96–2.92 (d, J = 16.8 Hz, 1H), 2.68–2.63 (d, J = 16.8 Hz, 1H), 2.33–2.30 (d, J = 9.6 Hz, 1H), 1.9–1.18 (d, J = 6.4 Hz, 3H), 0.98–0.96 (d, J = 6.4 Hz, 2H).

IR (KBr) ν 3058, 2968, 2894, 1611, 1509, 1463, 1449, 1326, 1268, 1233, 1200, 1155, 1129, 1104, 1039, 997, 927, 838, 807, 754, 700.

MS (ESI⁺): 460.2 m/z.

HRMS (ESI⁺) calcd for C₃₁H₂₆O₃N [M + 1]⁺ 460.1913, found 460.1907.

(M)-10-((R)-1-Phenylethyl)-10,11-dihydro-9H-naphtho[1′′,2′′:6′,7′][1,3]dioxepino [4′,5′:7,8]naphtho[1,2-e][1,3]oxazine [(M,R)-13]

Compound (M,R)-13 was prepared by same procedure as that of (±)-13.

Yield = 57%.

Mp 180–182 °C.

[α]²⁸_D = −828 (c = 0.1, CHCl₃).

¹H NMR (CDCl₃, 400 MHz) δ 7.87 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.8 Hz, 2H), 7.36–7.34 (m, 1H), 7.29–7.14 (m, 7H), 7.05 (d, J = 8.8 Hz, 1H), 6.82 (dd, J = 8.4 & 1.6 Hz, 2H), 5.62 (d, J = 3.6 Hz, 1H), 5.56 (d, J = 3.2 Hz, 1H), 4.92 (dd, J = 9.6 & 2.4 Hz, 1H), 4.57 (d, J = 9.6 Hz, 1H), 3.39 (q, J = 6.8 Hz, 1H), 2.85 (dd, J = 16.4 & 2 Hz, 1H), 2.66 (d, J = 16.4 Hz, 1H), 1.18 (d, J = 6.8 Hz, 3H).

¹³C NMR (CDCl₃, 100.6 MHz): δ 153.7, 152.2, 149.4, 143.5, 133.3, 132.7, 131.0, 130.9, 129.5, 129.1, 128.6, 128.5, 128.2, 127.9, 126.9, 126.4, 124.9, 124.6, 123.5, 120.2, 117.9, 117.7, 113.1, 102.5 (O–CH₂–O), 78.7 (NCH₂O), 57.1 (ArCH₂N), 48.8 (NCH₂Ph), 20.3 (CH₃).

IR (KBr) ν 3054, 3019, 2973, 2909, 2851, 1610, 1509, 1454, 1323, 1274, 1140, 1007, 989, 890, 757, 700.

MS (ESI⁺): m/z, (%) 460 [M + 1].

HRMS (ESI⁺) calcd for C₃₁H₂₆NO₃ [M + 1]⁺ 460.1913, found 460.1915.

(M)-10-((S)-1-Phenylethyl)-10,11-dihydro-9H-naphtho[1′′,2′′:6′,7′][1,3]dioxepino [4′,5′:7,8]naphtho[1,2-e][1,3]oxazine [(M,S)-13]

Compound (M,S)-13 was prepared by same procedure as that of (±)-13.

Yield = 65%.

Mp 80–82 °C.

[α]²⁸_D = −658 (c = 0.4, CHCl₃).

¹H NMR (CDCl₃, 400 MHz) δ 7.99 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.43–7.39 (m, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.27–7.19 (m, 5H), 7.11–7.06 (m, 3H), 5.72–5.69 (broad singlet, 2H), 4.45 (d, J = 9.6 Hz, 1H), 4.35 (dd, J = 9.6 & 2.8 Hz, 1H), 3.53 (q, J = 6.4 Hz, 1H), 3.47 (dd, J = 9.6 & 2.8 Hz, 1H), 2.93 (d, J = 16.8 Hz, 1H), 0.95 (d, J = 6.8 Hz, 1H).

¹³C NMR (CDCl₃, 100.6 MHz): δ 153.5, 152.4, 149.7, 143.4, 133.2, 132.6, 131.3, 131.1, 130.1, 129.4, 129.1, 128.6, 128.4, 128.3, 128.2, 127.8, 127.5, 127.2, 126.9, 126.6, 126.4, 125.3, 125.1, 124.6, 123.3, 120.4, 118.1, 117.7, 112.8, 102.8 (O–CH₂–O), 79.9 (NCH₂O), 56.3 (ArCH₂N), 47.5 (NCH₂Ph), 21.1 (CH₃).

IR (KBr) ν 3058, 2968, 2894, 1611, 1509, 1463, 1449, 1326, 1268, 1233, 1200, 1155, 1129, 1104, 1039, 997, 927, 838, 754, 700.

MS (ESI⁺): m/z, (%) 460 [M + 1].

HRMS (ESI⁺) calcd for C₃₁H₂₆NO₃ [M + 1]⁺ 460.1913, found 460.1938.

(P)-10-((S)-1-Phenylethyl)-10,11-dihydro-9H-naphtho[1′′,2′′:6′,7′][1,3]dioxepino [4′,5′:7,8]naphtho[1,2-e][1,3]oxazine [(P,S)-13]

Compound (P,S)-13 was prepared by same procedure as that of 13.

Yield = 68%.

Mp 182–184 °C.

[α]²⁸_D = +742 (c = 0.1, CHCl₃).

¹H NMR (CDCl₃, 400 MHz) δ 7.87 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.36–7.34 (m, 1H), 7.29–7.14 (m, 7H), 7.05 (d, J = 8.8 Hz, 1H), 6.82 (dd, J = 8 & 1.6 Hz, 2H), 5.62 (d, J = 3.2 Hz, 1H), 5.56 (d, J = 3.2 Hz, 1H), 4.93 (dd, J = 9.6 & 2.4 Hz, 1H), 4.57 (d, J = 10 & 0.8 Hz, 1H), 3.39 (q, J = 6.8 Hz, 1H), 2.85 (dd, J = 16.8 & 1.6 Hz, 1H), 2.65 (d, J = 16.4 Hz, 1H), 1.18 (d, J = 6.8 Hz, 3H).

¹³C NMR (CDCl₃, 100.6 MHz): δ 153.7, 152.2, 149.4, 143.5, 133.3, 132.7, 131.9, 130.9, 129.5, 129.1, 128.6, 128.5, 128.2, 127.8, 126.9, 126.4, 124.9, 124.5, 123.5, 120.1, 117.9, 117.7, 113.1, 102.5 (O–CH₂–O), 78.7 (NCH₂O), 57.1 (ArCH₂N), 48.8 (NCH₂Ph), 20.2 (CH₃).

IR (KBr): ν 3054, 3020, 2974, 2911, 2850, 1610, 1509, 1454, 1323, 1275, 1246, 1140, 1007, 989, 891, 757, 700.

MS (ESI⁺): m/z, (%) 460 [M + 1].

HRMS (ESI⁺) calcd for C₃₁H₂₆NO₃ [M + 1]⁺ 460.1913, found 460.1907.

(P) 10-((R)-1-Phenylethyl)-10,11-dihydro-9H-naphtho[1′′,2′′:6′,7′][1,3]dioxepino [4′,5′:7,8]naphtho[1,2-e][1,3]oxazine [(P,R)-13]

Compound (P,R)-13 was prepared by same procedure as that of (±)-13.

Yield = 53%.

Mp 80–82 °C.

[α]²⁸_D = +638 (c = 0.4, CHCl₃).

¹H NMR (CDCl₃, 400 MHz) δ 7.98 (d, J = 8.8 Hz, 1H), 7.92 (m, 2H), 7.82 (d, J = 9.2 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.44–7.39 (m, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.27–7.16 (m, 5H), 7.11–7.06 (m, 3H), 5.72–5.69 (broad singlet, 2H), 4.45 (d, J = 9.6 Hz, 1H), 4.35 (dd, J = 9.6 & 2.8 Hz, 1H), 3.53 (q, J = 6.4 Hz, 1H), 3.42 (d, J = 9.6 Hz, 1H), 2.93 (d, J = 16.8 Hz, 1H), 0.95 (d, J = 6.8 Hz, 1H).

¹³C NMR (CDCl₃, 100.6 MHz): δ 153.5, 152.4, 149.7, 143.4, 133.2, 132.6, 131.3, 131.1, 130.1, 129.4, 129.1, 128.7, 128.4, 128.3, 128.2, 127.8, 127.5, 127.2, 126.9, 126.6, 125.1, 124.6, 123.3, 120.4, 118.1, 117.7, 112.3, 102.8 (O–CH₂–O), 79.9 (NCH₂O), 56.3 (ArCH₂N), 47.5 (NCH₂Ph), 21.1 (CH₃).

IR (KBr) ν 3058, 2968, 2894, 1611, 1509, 1463, 1449, 1326, 1268, 1233, 1200, 1155, 1129, 1104, 1039, 997, 927, 838, 754, 700.

MS (ESI⁺): m/z, (%) 460 [M + 1].

HRMS (ESI⁺) calcd for C₃₁H₂₆NO₃ [M + 1]⁺ 460.1913, found 460.1927.

Conclusion

Hence in this account we have presented our studies in the synthesis and characterization of a series of helicene-like molecules and established their chiroptical properties. The absolute configuration of the compound was established by the single crystal X-ray analysis, which was in agreement with the chiroptical data. The effect of helicene-like structural arrangement was more influencing the chiroptical properties as compared to the stereogenic center of the diastereomeric compounds.

Acknowledgements

We wish to thank Science and Engineering Research Board (SERB), India for the financial assistance for this work [No. SR/S1/OC-74/2012]. We thank Council of Scientific and Industrial Research (CSIR), India for the award of Senior Research Fellowship to MSS and Department of Science and Technology (DST), India for the PURSE project under which the X-Ray Diffraction Machine was acquired in the Faculty of Science.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. CCDC 1023827, 1453552 and 1041059. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra10496g

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