Platinum-catalyzed 1,3-acyloxy migration/[1,5]-hydride transfer/cycloaddition sequence: synthesis of ring-fused tetrahydroquinolines

Abstract

An efficient construction of multifunctionalized ring-fused tetrahydroquinolines viaplatinum-catalyzed C–H functionalization is presented. A sequence involving 1,3-OAc migration, [1,5]-hydride shift and then cyclization takes place to produce ring-fused tetrahydroquinolines. The reaction mechanism has been confirmed by a deuterium-labeling experiment.

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Introduction

The development of methodologies for the direct functionalization of relatively less reactive C–H bonds, which provides a powerful tool for the synthesis of numerous complex molecules,¹ has now become one of the most challenging projects in organic synthesis. Various hydrogen-exchange protocols have been proposed to explain the phenomenon, which are different from oxidative C–H bond functionalization by eliminating redox adjustment steps required to generate reactive functional groups for the desired C–C bond formation.¹ Among these efficient methods, tandem [1,5]-hydride transfer/cyclization reaction is an attractive strategy, which has been recently reported by Sames and Gagosz as well as other research groups.² In particular, tertiary anilines as hydride donors (tert-amine effect³) has been exploited by the Seidel group and others to synthesize tetrahydroquinolines. On the other hand, propargylic ester as the precursor of allene has been utilized to build lots of complex molecular scaffolds in platinum chemistry from infancy to mature.⁴ However, to the best of our knowledge, there are few reports about hydrofunctionalization of allene as a hydride accepter in a 1,5-hydride transfer/cyclization reaction (Scheme 1).^5,12 Herein, we report a novel redox–neutral domino reaction using in situ formed allene to achieve multifunctionalized ring-fused tetrahydroquinoline.

Scheme 1 Hydrofunctionalization of allene.

Our group is persistently interested in C–H functionalization at the α-position of tertiary amines to prepare various functionalized heterocyclic compounds.⁶ In conjunction with our recent investigations in the field of platinum-catalyzed hydride transfers, we were intrigued by the possibility of developing a new hydrofunctionalization of the in situ formed allenes. In contrast with a traditional hydrofunctionalization,⁴ such a process would first involve the transfer of a hydride onto the C(1)-carbon of the allene intermediate 2 activated by platinum formed viaplatinum-catalyzed 1,3-OAc migration of the propargylic ester 1,⁷ which is rarely reported (Scheme 2). The resulting vinyl-platinum species would then attack the iminium ion in a final electrophilic demetalation step to furnish the ring-fused tetrahydroquinoline compound which is the key structural element in many natural products, particularly alkaloids.⁸ We report herein a successful realization of this concept and the details of our discovery.

Scheme 2 Proposed Lewis acid-catalyzed process.

Results and discussion

We started our initial study of reaction conditions using propargylic ester 1a as a model substrate (Table 1). When 1a was subjected to the reaction conditions used in our previous work (10 mol% of PtCl₂, in toluene at 80 °C), an unstable cycloadduct was afforded. But due to the lack of diastereoselectivity and chromatographic separation, the initially formed cycloadduct was then subjected to deacylation with K₂CO₃ in MeOH. To our delight, an interesting ketone derivative 2a was isolated in 22% yield. The structure of compound 2a was elucidated on the basis of one- and two-dimensional NMR data (see supporting information†). Increasing the temperature and the loading of the catalyst led to a better yield (Table 1, Scheme 3). Among the platinum catalysts tried (Table 1, entries 4–7), PtCl₂ (15 mol%) under Ar (1 atm) gave the best result (Table 1, entry 6). To further optimize the conditions, the influence of additives was investigated (Table 1, entries 8 and 9). Use of LiCl as an additive did enhance the catalytic activity of PtCl₂,⁹ and the yield was increased to 65% (Table 1, entry 8). After this, we screened the amount of additive and found that 2eq LiCl gave a better result (Table 1, entry 8). The addition of M.S. or CaO could further improve the reaction yield (Table 1, entries 10 and 11). With 15 mol% of PtCl₂ as the catalyst, 2 eq LiCl and 4 eq CaO as the additives, a better yield (78%) was obtained at 110 °C (Table 1, entry 12).

Scheme 3 Plausible mechanism leading to the formation of 2o.

Table 1 Optimization of reaction conditions for tandem [1,5]-hydride transfer/cyclization^a

Entry	Catalyst (mol%)	Additive	Solvent	T/°C	Yield (%)^b
a Unless otherwise noted, all reactions were performed with 0.2 mmol of 1a in toluene (2.0 mL). b Isolated yields over two steps.
1	PtCl2(10)	—	Toluene	80	22
2	PtCl2(15)	—	Toluene	80	30
3	PtCl2(10)	—	Toluene	110	35
4	PtCl2(15)	—	Toluene	110	38
5	PtCl2(15)/O2(1 atm)	—	Toluene	110	46
6	PtCl2(15)/Ar(1 atm)	—	Toluene	110	56
7	PtCl2(15)/CO(1atm)	—	Toluene	110	40
8	PtCl2(15)/Ar(1 atm)	LiCl (2 equiv)	Toluene	110	65
9	PtCl2(15)/Ar(1 atm)	LiCl (4 equiv)	Toluene	110	57
10	PtCl2(15)/Ar(1 atm)	LiCl (2 equiv)/4 Å MS (50 mg)	Toluene	110	68
11	PtCl2(15)/Ar(1 atm)	LiCl (2 equiv)/CaO (2 equiv)	Toluene	110	70
12	PtCl2(15)/Ar(1 atm)	LiCl (2 equiv)/ CaO (4 equiv)	Toluene	110	78
13	PtCl2(15)/Ar(1 atm)	LiCl (2 equiv)/CaO (6 equiv)	Toluene	110	72

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Various substrates were prepared to test the generality of this tandem sequence under the optimal conditions (Table 1, entry 12), and the results are summarized in Table 2. We extended the scope of this transformation to a wide range of electronically and structurally diverse propargylic esters. The 1,5-hydride shift proceeded smoothly for all of the tested propargylic esters to give the ring-fused tetrahydroquinolines in moderate to good yields with moderate dr values. Firstly, we screened the effect of migratory groupR⁴. To our delight, the acetate 1a, as an excellent substrate, afforded the highest yield, while benzoate 1b behaved better than 1c. The presence of an electron-withdrawing or -donating group in R³ was well tolerated. An electron-withdrawing substituent in R³ favored products formation (entries 7–10), while an electron-donating group slightly hindered the reaction (entries 4–6). This might be due to the fact that the electron-withdrawing substituent in R³ increases the cationic character of C1 in the allene intermediate (Scheme 2). To our delight, propargylic ester 1j was found to be equally a good candidate for the process and 78% of 2g was obtained with excellent dr value (>20 : 1). Substrate 1k bearing an electron-withdrawing bromine atom on the benzene ring (R¹ = Br) gave the desired product 2h in 61% yield (entry 11). When both R¹ and R³ were electron-withdrawing groups, a better result was achieved (entry 13). When R² was methyl, the reactions also proceeded smoothly to give the corresponding products 2l and 2m in 60% and 50% yields, respectively. When propargylic ester 1r was subjected to the optimized conditions, the thienyl substituent in R³ was also tolerated and the product 2n was isolated in 63% yield. Unfortunately, sterically demanding ortho substituents could not participate in this reaction and acyclic tertiary aniline also failed to undergo this transformation (entry 19).

Table 2 Platinum-catalyzed 1,3-acyloxy migration and subsequent [1,5]-hydride transfer/cycloaddition^a

Entry	1	Substrates	Products	Time (h)	Yield^b (%)/d.r.^c
a Unless otherwise noted, all reactions were performed with 0.2 mmol of propargylic esters in toluene (2.0 mL) at 110 °C. b Isolated yield after two steps. c Diastereomeric ratio is determined by ^1H NMR spectroscopic analysis. d The yield is below 5%.
1	1a	R 1 = H, R2 = H, R3 = C6H5, R4 = Ac	2a	36	78 (2 : 1)
2	1b	R 1 = H, R2 = H, R3 = C6H5, R4 = PhCO	2a	36	72 (6 : 1)
3	1c	R 1 = H, R2 = H, R3 = C6H5, R4 = CH3CH2CO	2a	37	46 (4 : 1)
4	1d	R 1 = H, R2 = H, R3 = p-MeC6H4, R4 = Ac	2b	35	50 (6 : 1)
5	1e	R 1 = H, R2 = H, R3 = m-MeC6H4, R4 = Ac	2c	36	57 (13 : 1)
6	1f	R 1 = H, R2 = H, R3 = 3,4-DiMeC6H3, R4 = Ac	2d	37	40 (1 : 1)
7	1g	R 1 = H, R2 = H, R3 = p-ClC6H4, R4 = Ac	2e	38	63 (5 : 1)
8	1h	R 1 = H, R2 = H, R3 = p-BrC6H4, R4 = Ac	2f	38	64 (8 : 1)
9	1i	R 1 = H, R2 = H, R3 = p-BrC6H4, R4 = PhCO	2f	35	56 (5 : 1)
10	1j	R 1 = H, R2 = H, R3 = p-CH3COC6H4 , R4 = Ac	2g	36	78 (>20 : 1)
11	1k	R 1 = 5-Br, R2 = H, R3 = C6H5, R4 = Ac	2h	35	61 (6 : 1)
12	1l	R 1 = 5-Br, R2 = H, R3 = C6H5, R4 = PhCO	2h	35	44 (4 : 1)
13	1m	R 1 = 5-Br, R2 = H, R3 = p-BrC6H4, R4 = Ac	2i	35	73 (8 : 1)
14	1n	R 1 = 5-Br, R2 = H, R3 = p-MeC6H4, R4 = Ac	2j	35	56 (4 : 1)
15	1o	R 1 = 5-Br, R2 = H, R3 = 3,4-DiMeC6H3, R4 = Ac	2k	36	55 (3 : 1)
16	1p	R 1 = H, R2 = Me, R3 = C6H5, R4 = Ac	2l	36	60 (3 : 1)
17	1q	R 1 = H, R2 = Me, R3 = p-MeC6H4, R4 = Ac	2m	37	50 (6 : 1)
18	1r	R 1 = H, R2 = H, R3 = 2-thienyl, R4 = Ac	2n	36	63 (4 : 1)
19	1s		—	30	_^d
20	1t	R 1 = H, R2 = H, R3 = p-MeOC6H4, R4 = Ac	20	24	60

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Surprisingly, a completely different transformation occurred in the case of propargylic ester 1t bearing a strong electron-donating 4–OMeC₆H₅ group in R³ and a α,β-unsaturated ketone 2o was formed (entry 20, Scheme 3), suggesting that in this case the rate of hydration of allene intermediate is faster than that of the 1,5-hydride shift. On the basis of these facts, it is confirmed that the presence of an electron-donating group in R³ is crucial to the success of the reaction.¹⁰

To explore the mechanism of these cycloisomerizations, a deuterium-labeling experiment was performed as shown in Scheme 4. Propargylic acetate D-1a containing CD₂ produced cycloadduct D-2a in 50% yield. A mixture was isolated and the structures were assigned by ¹H NMR analysis (see supporting information†). Analysis by ¹H NMR indicated about 7 to 3 ratio of products with the compound D-2a-1 being major, in line with the previously reported deuterium isotope effect, indicating a faster rate of hydride than deuteride in the 1,5-H⁻/D⁻ shift reaction.¹¹ The deuterium atom in D-1a at the α-position of the nitrogen was transferred to the benzylic position of the D-2a, thus supporting a hydride transfer mechanism.

Scheme 4 Deuterium-labeling experiment.

Conclusions

In conclusion, we have developed a novel Lewis acid-catalyzed intramolecular redox domino reaction using 3-aryl-1-(2-(piperidin-1-yl)aryl)prop-2-ynyl esters to afford multifunctionalized ring-fused tetrahydroquinolines in moderate yields. Mechanistic studies revealed that the reaction might involve the transfer of a hydride adjacent to the nitrogen atom onto the in situ formed allene. This fascinating strategy allows the efficient conversion of tertiary sp³ C–H bonds into C–C bonds by the nucleophilic addition of a vinylplatinum species onto a zwitterionic intermediate.

Experimental

General experimental

Column chromatography was carried out on silica gel. Unless noted ¹H NMR spectra were recorded on 400 MHz or 300 MHz in CDCl_3,¹³C NMR spectra were recorded on 100 MHz or 75 MHz in CDCl₃ using TMS as internal standard. IR spectra were recorded on an FT-IR spectrometer and only major peaks are reported in cm⁻¹. Melting points were determined on a microscopic apparatus and were uncorrected. All products were further characterized by HRMS (high resolution mass spectra); copies of their ¹H NMR and ¹³C NMR spectra are provided.† Commercially available reagents and solvents were used without further purification.

Specific experimental

General procedure for the preparation of product 2a–2o. To a test tube, propargylic ester derivatives (0.20 mmol), PtCl₂ (15 mol%), LiCl (2 eq) and CaO (4 eq) were added. The test tube was purged under vacuum and then refilled with argon 3 times. Toluene (2.0 mL) was then injected, and the mixture was allowed to stir at 110 °C. When the reaction was considered complete as determined by TLC analysis, ethyl acetate (20 mL) and water (20 mL) were then added to the reaction mixture. The organic layer was extracted with ethyl acetate (2 × 20 mL). The combined organic phases were washed with brine and dried over sodium sulfate. The residue was purified by flash chromatography on alkalescence silica gel to afford corresponding products. The separated product was then treated with K₂CO₃ (3 eq) and methanol (2 mL). When the reaction was considered complete as determined by TLC analysis, ethyl acetate (10 mL) and water (5 mL) were then added to the reaction mixture. The organic layer was extracted with ethyl acetate (2 × 10 mL). The combined organic phases were washed with brine and dried over sodium sulfate. The residue was purified by flash chromatography on alkalescence silica gel to afford corresponding products.

2a was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.98–8.00 (m, 2 H), 7.59 (t, J = 7.2 Hz, 1 H), 7.46–7.49 (m, 2 H), 7.12 (t, J = 7.6 Hz, 1 H), 6.94 (d, J = 7.2 Hz, 1 H), 6.86 (d, J = 8.4 Hz, 1 H), 6.65 (t, J = 7.2 Hz, 1 H), 3.99–4.02 (m, 1 H), 3.71–3.78 (m, 1 H), 3.35–3.40 (m, 1 H), 2.96–3.03 (m, 1 H), 2.80–2.86 (m, 2 H), 1.71–1.77 (m, 3 H), 1.36–1.65 (m, 3 H); ¹³C NMR (100 MHz, CDCl₃): δ 202.2, 146.1, 136.9, 133.3, 128.7, 128.6, 128.5, 128.3, 127.5, 123.1, 117.2, 112.9, 58.9, 48.5, 46.9, 32.4, 31.6, 25.4, 24.3; IR (neat, cm⁻¹) 3399, 2920, 2852, 1677, 1585, 1450, 1057, 754, 705, 590; HRMS (ESI) m/z: calcd for C₂₀H₂₁NO: M + H = 292.1696; found: 292.1694. minor diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.93 (d, J = 7.2 Hz, 2 H), 7.52–7.56 (m, 1 H), 7.43 (t, J = 8.0 Hz, 2 H), 7.06–7.12 (m, 2 H), 6.65 (t, J = 7.2 Hz, 1 H), 6.49 (d, J = 7.6 Hz, 1 H), 3.84–3.89 (m, 1 H), 3.63–3.66 (m, 1 H), 3.38 (dd, J = 9.6, 8.0 Hz, 1 H), 3.27–3.32 (m, 1 H), 3.03 (dd, J = 11.6, 6.0 Hz, 1 H), 2.56–2.63 (m, 1 H), 1.84–1.86 (m, 1 H), 1.66–1.72 (m, 2 H), 1.34–1.59 (m, 3H); ¹³C NMR (100 MHz, CDCl₃): δ 199.2, 151.5, 137.0, 133.1, 133.0, 128.5, 128.0, 127.7, 124.5, 118.1, 106.6, 67.5, 45.8, 39.1, 38.5, 26.3, 24.5, 24.4;

2b was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.90 (d, J = 8.0 Hz, 2 H), 7.25–7.29 (m, 2 H), 7.12 (t, J = 7.6 Hz, 1 H), 6.94 (d, J = 7.2 Hz, 1 H), 6.86 (d, J = 8.4 Hz, 1 H), 6.65 (t, J = 7.6 Hz, 1 H), 3.99–4.02 (m, 1 H), 3.69–3.75 (m, 1 H), 3.32–3.38 (m, 1 H), 2.96–3.02 (m, 1 H), 2.78–2.86 (m, 2 H), 2.42 (s, 3 H), 1.71–1.77 (m, 3 H), 1.56–1.62 (m, 1 H), 1.26–1.47 (m, 2 H); ¹³C NMR (100 MHz, CDCl₃): δ 201.8, 146.1, 144.2, 134.6, 129.5, 128.7, 128.5, 127.5, 123.2, 117.2, 112.9, 58.9, 48.5, 46.9, 32.6, 31.6, 25.5, 24.3, 21.6; IR (neat, cm⁻¹) 3434, 2925, 2852, 1673, 1604, 1494, 1451, 1377, 1255, 1225, 1177, 1113, 1061, 747, 574; HRMS (ESI) m/z: calcd for C₂₁H₂₃NO: M + H = 306.1852; found: 306.1848.

2c was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.78–7.80 (m, 2 H), 7.34–7.41 (m, 2 H), 7.12 (t, J = 7.6 Hz, 1 H), 6.94 (d, J = 7.2 Hz, 1 H), 6.86 (d, J = 8.4 Hz, 1 H), 6.65 (t, J = 7.2 Hz, 1 H), 3.99–4.02 (m, 1 H), 3.71–3.77 (m, 1 H), 3.33–3.39 (m, 1 H), 2.95–3.02 (m, 1 H), 2.79–2.86 (m, 2 H), 2.41 (s, 3 H), 1.71–1.77 (m, 3 H), 1.55–1.65 (m, 1 H), 1.23–1.49 (m, 2 H); ¹³C NMR (100 MHz, CDCl₃): δ 202.5, 146.1, 138.6, 137.1, 134.1, 128.9, 128.7, 128.6, 127.5, 125.6, 123.2, 117.2, 112.9, 58.9, 48.5, 47.1, 32.6, 31.6, 25.5, 24.3, 21.3; IR (neat, cm⁻¹) 3336, 2929, 2851, 1675, 1601, 1494, 1451, 1370, 1253, 1161, 1050, 744, 550; HRMS (ESI) m/z: calcd for C₂₁H₂₃NO: M + H = 306.1852; found: 306.1850.

2d was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.73–7.77 (m, 2 H), 7.14–7.26 (m, 1 H), 7.10–7.14 (m, 1 H), 6.94 (d, J = 7.6 Hz, 1 H), 6.87 (d, J = 8.4 Hz, 1 H), 6.63–6.67 (m, 1 H), 3.99–4.03 (m, 1 H), 3.69–3.76 (m, 1 H), 3.32–3.37 (m, 1 H), 2.96–3.02 (m, 1 H), 2.77–2.86 (m, 2 H), 2.33 (s, 3 H), 2.32 (s, 3 H), 1.71–1.77 (m, 3 H), 1.56–1.62 (m, 1 H), 1.24–1.47 (m, 2 H); ¹³C NMR (100 MHz, CDCl₃): δ 202.1, 146.1, 143.0, 137.2, 135.0, 130.0, 129.5, 128.8, 127.4, 126.1, 123.3, 117.1, 112.9, 59.0, 48.5, 46.8, 32.6, 31.6, 25.6, 24.3, 20.0, 19.8; IR (neat, cm⁻¹) 3400, 2923, 2851, 1671, 1602, 1494, 1451, 1378, 1253, 1115, 1054, 793, 749, 708; HRMS (ESI) m/z: calcd for C₂₂H₂₅NO: M + H = 320.2009; found: 320.2006.

2e was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.91–7.94 (m, 2 H), 7.44–7.46 (m, 2 H), 7.12 (t, J = 7.6 Hz, 1 H), 6.93 (d, J = 7.6 Hz, 1 H), 6.85 (d, J = 8.4 Hz, 1 H), 6.66 (t, J = 7.2 Hz, 1 H), 3.98–4.01 (m, 1 H), 3.65–3.71 (m, 1 H), 3.32–3.38 (m, 1 H), 2.95–3.01 (m, 1 H), 2.78–2.86 (m, 2 H), 1.55–1.76 (m, 4 H), 1.38–1.49 (m, 1 H), 1.19–1.29 (m, 1 H); ¹³C NMR (100 MHz, CDCl₃): δ 200.9, 146.0, 139.9, 135.3, 129.7, 129.1, 128.7, 127.6, 122.9, 117.3, 112.9, 58.8, 48.5, 47.1, 32.3, 31.6, 25.4, 24.3; IR (neat, cm⁻¹) 3436, 2929, 2851, 1677, 1590, 1493, 1451, 1253, 1092, 1008, 839, 747, 534; HRMS (ESI) m/z: calcd for C₂₀H₂₀ClNO: M + H = 326.1306; found: 326.1301.

2f was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.84 (d, J = 8.4 Hz, 2 H), 7.62 (d, J = 8.4 Hz, 2 H), 7.12 (t, J = 7.6 Hz, 1 H), 6.93 (d, J = 7.6 Hz, 1 H), 6.85 (d, J = 8.4 Hz, 1 H), 6.65 (t, J = 7.2 Hz, 1 H), 3.98–4.01 (m. 1 H), 3.64–3.69 (m, 1 H), 3.33–3.38 (m, 1 H), 2.95–3.01 (m, 1 H), 2.78–2.86 (m, 2 H), 1.56–1.76 (m, 4 H), 1.20–1.49 (m, 2 H); ¹³C NMR (100 MHz, CDCl₃): δ 201.1, 146.0, 135.7, 132.1, 129.8, 128.7, 128.6, 127.6, 122.9, 117.3, 112.9, 58.8, 48.5, 47.1, 32.3, 31.6, 25.4, 24.3; IR (neat, cm⁻¹) 3403, 2923, 2853, 1764, 1681, 1452, 1381, 1243, 1061, 913, 746; HRMS (ESI) m/z: calcd for C₂₀H₂₀NOBr: M + H = 370.0801; found: 370.0806.

2g was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 8.05 (m, 4 H), 7.13 (t, J = 7.6 Hz, 1 H), 6.94 (d, J = 7.2 Hz, 1 H), 6.86 (d, J = 8.4 Hz, 1 H), 6.66 (t, J = 7.2 Hz, 1 H), 3.99–4.02 (m, 1 H), 3.72–3.78 (m, 1 H), 3.35–3.41 (m, 1 H), 2.96–3.03 (m, 1 H), 2.80–2.86 (m, 2 H), 2.65 (s, 3 H), 1.73–1.79 (m, 3 H), 1.28–1.69 (m, 3 H); ¹³C NMR (100 MHz, CDCl₃): δ 201.7, 197.4, 146.0, 140.2, 140.1, 128.7, 128.6, 128.5, 127.6, 122.8, 117.3, 113.0, 58.8, 48.5, 47.6, 32.2, 31.6, 26.9, 25.3, 24.3; IR (neat, cm⁻¹) 2927, 2852, 1683, 1601, 1495, 1259, 910, 748; HRMS (ESI) m/z: calcd for C₂₂H₂₃NO₂: M + H = 334.1802; found: 334.1812.

2h was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.96–7.98 (m, 2 H), 7.59 (t, J = 7.2 Hz, 1 H), 7.47–7.50 (m, 2 H), 7.17–7.19 (m, 1 H), 7.03 (d, J = 2.0 Hz, 1 H), 6.69 (d, J = 8.8 Hz, 1H); 3.89–3.93 (m, 1 H), 3.67–3.72 (m, 1 H), 3.34–3.39 (m, 1 H), 2.91–2.97 (m, 1 H), 2.76–2.86 (m, 2 H), 1.70–1.79 (m, 3 H), 1.54–1.63 (m, 1 H), 1.39–1.49 (m, 1 H), 1.20–1.30 (m, 1 H); ¹³C NMR (100 MHz, CDCl₃): δ 201.6, 145.1, 136.8, 133.4, 130.9, 130.1, 128.8, 128.3, 125.3, 114.5, 108.8, 58.7, 48.4, 46.8, 31.8, 31.5, 25.2, 24.2; IR (neat, cm⁻¹) 3436, 2927, 2851, 1676, 1592, 1489, 1445, 1370, 1254, 1219, 793, 705, 546; HRMS (ESI) m/z: calcd for C₂₀H₂₀NOBr: M + H = 370.0801; found: 370.0795.

2i was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.83 (d, J = 8.4 Hz, 2 H), 7.63 (d, J = 8.8 Hz, 2 H), 7.17–7.19 (m, 1 H), 7.03 (d, J = 2.0 Hz, 1 H), 6.69 (d, J = 8.8 Hz, 1 H), 3.89–3.93 (m, 1 H), 3.60–3.66 (m, 1 H), 3.31–3.36 (m, 1 H), 2.90–2.97 (m, 1 H), 2.74–2.85 (m, 2 H), 1.66–1.79 (m, 3 H), 1.28–1.63 (m, 3 H); ¹³C NMR (100 MHz, CDCl₃): δ 200.6, 145.0, 135.4, 132.2, 130.9, 130.1, 129.8, 128.8, 125.0, 114.5, 108.9, 58.7, 48.4, 46.8, 31.7, 31.5, 25.1, 24.2; IR (neat, cm⁻¹) 3433, 2923, 2851, 1764, 1676, 1584, 1488, 1387, 1251, 1066, 1009, 746; HRMS (ESI) m/z: calcd for C₂₀H₁₉NOBr₂: M + H = 447.9906; found: 447.9914.

2j was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.88 (d, J = 8.4 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 2 H), 7.18 (dd, J = 6.8, 2.0 Hz, 1 H), 7.03 (d, J = 2.0 Hz, 1 H), 6.70 (d, J = 8.8 Hz, 1 H), 3.90–3.93 (m, 1 H), 3.64–3.70 (m, 1 H), 3.32–3.38 (m, 1 H), 2.91–2.98 (m, 1 H), 2.74–2.86 (m, 2 H), 2.43 (s, 3 H), 1.69–1.79 (m, 3 H), 1.26–1.59 (m, 3 H); ¹³C NMR (100 MHz, CDCl₃): δ 201.2, 145.2, 144.4, 134.4, 130.9, 130.1, 129.5, 128.5, 125.4, 114.5, 108.8, 58.8, 48.5, 46.7, 31.9, 31.5, 25.2, 24.2, 21.6; IR (neat, cm⁻¹) 3400, 2922, 2852, 2332, 1764, 1674, 1489, 1380, 1248, 1058, 913, 771, 747, 669; HRMS (ESI) m/z: calcd for C₂₁H₂₂NOBr: M + H = 384.0958; found: 384.0962.

2k was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.67–7.76 (m, 2 H), 7.10–7.25 (m, 3 H), 6.28–6.34 (m, 1 H), 3.81–3.87 (m, 1 H), 3.59–3.56 (m, 1 H), 3.23–3.37 (m, 2 H), 2.95–3.01 (m, 1 H), 2.57–2.64 (m, 1 H), 2.32 (s, 3 H), 2.31 (s, 3 H), 1.83–1.85 (m, 1 H), 1.31–1.69 (m, 5 H); ¹³C NMR (100 MHz, CDCl₃): δ 198.5, 150.5, 142.7, 136.9, 135.6, 134.7, 130.2, 129.9, 129.8, 129.2, 127.5, 127.1, 125.8, 125.7, 109.5, 107.8, 67.5, 45.7, 38.9, 38.1, 26.0, 24.2, 24.1, 20.0, 19.8; IR (neat, cm⁻¹) 2930, 2852, 1679, 1602, 1477, 1448, 1382, 1249, 1122, 803; HRMS (ESI) m/z: calcd for C₂₂H₂₄BrNO: M + H = 398.1114; found: 398.1111.

2l was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.99–8.01 (m, 2 H), 7.59 (t, J = 7.6 Hz, 1 H), 7.49 (t, J = 7.6 Hz, 2 H), 7.12 (t, J = 7.8 Hz, 1 H), 6.94 (d, J = 7.2 Hz, 1 H), 6.86 (d, J = 8.4 Hz, 1 H),6.65 (t, J = 7.2 Hz, 1 H), 3.99–4.04 (m, 1 H), 3.70–3.76 (m, 1 H), 3.38–3.43 (m, 1 H), 2.94–3.00 (m, 1 H), 2.81–2.88 (m, 2 H), 1.70–1.76 (m, 2 H), 1.21–1.64 (m, 3 H), 0.87 (d, J = 6.4 Hz, 3 H); ¹³C NMR (100 MHz, CDCl₃): δ 202.2, 145.9, 136.9, 133.3, 128.8, 128.6, 128.4, 127.5, 123.1, 117.2, 112.9, 58.3, 48.0, 47.1, 39.9, 33.8, 32.6, 30.9, 21.9; IR (neat, cm⁻¹) 3440, 2923, 2849, 1677, 1600, 1495, 1452, 1373, 1239, 1210, 750, 702, 665; HRMS (ESI) m/z: calcd for C₂₁H₂₃NO: M + H = 306.1852; found: 306.1855.

2m was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.89–7.92 (m, 2 H), 7.25–7.30 (m, 2 H), 7.12 (t, J = 7.8 Hz, 1 H), 6.94 (d, J = 7.2 Hz, 1 H), 6.86 (d, J = 8.4 Hz, 1 H), 6.65 (t, J = 7.2 Hz, 1 H), 3.99–4.04 (m, 1 H), 3.68–3.74 (m, 1 H), 3.36–3.41 (m, 1 H), 2.94–3.01 (m, 1 H), 2.79–2.88 (m, 2 H), 2.43 (s, 3 H), 1.69–1.77 (m, 2 H), 1.53–1.63 (m, 2 H), 1.24–1.28 (m, 1 H), 0.87 (d, J = 6.4 Hz, 3 H); ¹³C NMR (100 MHz, CDCl₃): δ 201.8, 145.9, 144.3, 134.5, 129.5, 128.7, 128.5, 127.5, 123.2, 117.2, 112.9, 58.4, 48.1, 46.9, 39.9, 33.9, 32.7, 30.9, 21.9, 21.6; IR (neat, cm⁻¹) 3399, 2019, 2850, 1672, 1603, 1494, 1453, 1374, 1241, 1045, 748, 610; HRMS (ESI) m/z: calcd for C₂₂H₂₅NO: M + H = 320.2009; found: 320.2001.

2n was obtained according to the above method as an oil. major diastereomer: ¹H NMR (400 MHz, CDCl₃): δ 7.77 (d, J = 3.6 Hz, 1 H), 7.68 (d, J = 4.8 Hz, 1 H), 7.10–7.17 (m, 2 H), 6.96 (d, J = 7.2 Hz, 1 H), 6.87 (d, J = 8.4 Hz, 1 H), 6.67 (t, J = 7.2 Hz, 1 H), 3.99–4.02 (m, 1 H), 3.50–3.56 (m, 1 H), 3.28–3.34 (m, 1 H) 3.05–3.12 (m, 1 H), 2.78–2.87 (m, 2 H), 1.76–1.78 (m, 3 H), 1.57–1.66 (m, 1 H), 1.28–1.47 (m, 2 H); ¹³C NMR (100 MHz, CDCl₃): δ 194.9, 146.1, 144.9, 134.5, 132.2, 128.6, 128.4, 127.5, 123.0, 117.3, 113.1, 58.8, 49.1, 48.5, 32.6, 31.6, 25.5, 24.1; IR (neat, cm⁻¹) 3399, 2925, 2851, 1653, 1494, 1413, 1253, 1057, 789, 744, 661; HRMS (ESI) m/z: calcd for C₁₈H₁₉NOS: M + H = 298.1260; found: 298.1254.

2o ¹H NMR (400 MHz, CDCl₃): δ 8.17 (d, J = 15.6 Hz, 1 H), 8.05 (d, J = 8.8 Hz, 2 H), 7.66 (d, J = 8.4 Hz, 1 H), 7.52 (d, J = 16.0 Hz, 1 H), 7.32–7.37 (m, 1 H), 7.05 (d, J = 7.6 Hz, 2 H), 6.98 (d, J = 8.8 Hz, 2 H), 3.89 (s, 3 H), 2.91–2.94 (m, 4 H), 1.73–1.78 (m, 4 H), 1.57–1.60 (m, 2 H); ¹³C NMR (100 MHz, CDCl₃): δ 189.4, 163.2, 154.4, 142.0, 131.4, 130.9, 130.8, 130.7, 129.2, 127.9, 122.3, 121.4, 119.0, 113.7, 113.6, 55.4, 54.4, 26.4, 24.2; IR (neat, cm⁻¹): 2928, 1655, 1599, 1449, 1380, 1332, 1257, 1219, 1167, 1021, 835, 757, 575; HRMS (ESI) m/z: calcd for C₂₁H₂₃NO₂: M + H = 322.1802; found: 322.1808.

D–2a¹H NMR (400 MHz, CDCl₃): δ 7.99 (d, J = 7.2 Hz, 2 H), 7.59 (t, J = 7.6 Hz, 1 H), 7.49 (t, J = 8.0 Hz, 2 H), 7.13 (t, J = 7.6 Hz, 1 H), 6.94 (d, J = 7.2 Hz, 1 H), 6.86 (d, J = 8.0 Hz, 1 H), 6.65 (t, J = 7.2 Hz, 1 H), 3.99–4.02 (m, 0.3 H), 3.71–3.78 (m, 1 H), 3.35–3.40 (m, 0.7 H), 2.96–3.03 (m, 1 H), 2.80–2.88 (m, 1.2 H), 1.38–1.79 (m, 6 H); ¹³C NMR (100 MHz, CDCl3): δ 202.2, 146.1, 137.1, 133.3, 128.8, 128.7, 128.4, 127.5, 123.1, 117.2, 112.9, 58.9, 47.1, 32.5, 31.6, 25.3, 24.3; HRMS (ESI) m/z: calcd for C₂₀H₁₉NOD₂: M + H = 294.1821; found: 294.1825.

Acknowledgements

We thank the National Science Foundation (NSF 21072080), and the Fundamental Research Funds for the Central Universities (lzujbky-2011-151 and lzujbky-2010-k09) for financial support. We acknowledge National Basic Research Program of China (973 Program) 2010CB833203 and “111” program of MOE.

References

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12. One of the reviewers of this manuscript is of the view that this work is an extension of our previous work.^5c However, we have excluded this because when we treated 1a with a palladium catalyst, we observed no reaction. The present reaction is completely different from that reported previously in terms of substrate structure, reaction conditions, catalyst and most importantly by mechanism.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c1ra00789k

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