Pd-Catalyzed Atroposelective C–H Allylation and Alkenylation: Access

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Pd-Catalyzed Atroposelective C−H Allylation and Alkenylation: Access to Enantioenriched Atropisomers Featuring Pentatomic Heteroaromatics Hao-Ming Chen,†,§ Shuo Zhang,‡,§ Gang Liao,‡ Qi-Jun Yao,‡ Xue-Tao Xu,† Kun Zhang,† and Bing-Feng Shi*,‡ †

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, People’s Republic of China Department of Chemistry, Zhejiang University, Hangzhou 310027, People’s Republic of China

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‡

S Supporting Information *

ABSTRACT: The development of efficient and unified synthetic methods to access enantioenriched pentatomic biaryls is extremely challenging, due to the relatively low rotational barriers of these five-membered atropisomeric species, Described herein is a Pd-catalyzed asymmetric C−H allylation and alkenylation to prepare such atropisomers. This protocol is tolerant of various five-membered biaryls containing benzothiophenes and benzofurans, providing pentatomic biaryls with good to excellent enantioselectivities (up to 99% ee).

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induction (up to 72% ee).9,10a In 2017, a Pd-catalyzed intramolecular C−H arylation to form indole-based atropisomers using a modified TADDOL-phosphoramidite ligand was developed by Gu and co-workers.10c Most recently, the Li group achieved a mild asymmetric synthesis of axially chiral biindolyls combining C−H activation with nucleophilic cyclization by employing a chiral Rh(III) catalyst.10e Despite these advances, enantioselective synthesis of these pentatomic heteroaryls via a C−H activation strategy remains challenging, probably because these motifs are conformationally less stable at the elevated temperatures that are generally employed in C− H functionalization reactions. In light of the above, we envisioned that a more general and robust strategy toward these structurally interesting motifs via asymmetric C−H activation would represent a significant synthetic advancement. Recently, Yu and co-workers disclosed the creation of point chirality via Pd-catalyzed asymmetric C−H activation employing a novel transient chiral auxiliary strategy (TDG).14 Stimulated by this seminal work, our group applied the TDG strategy to access diverse classes of axially chiral biaryls via dynamic kinetic resolution or kinetic resolution.10d,13 To overcome the limitation of the relatively low rotational barriers of five-membered heteroarenes, we previously introduced a comparatively bulky group, a TIPS-protected alkyne, into the ortho position of the rotation axis via TDG-enabled enantioselective C−H alkynylation.10d To extend this strategy

INTRODUCTION Axially chiral biaryls are very common building blocks in natural products and drugs and also play significant roles as privileged chiral catalysts/ligands in asymmetric chemistry.1 Given its importance, extensive studies on enantioselective synthesis of axially chiral biaryl compounds have been developed in the past few decades.2 Previous studies have been well established for the enantioselective synthesis of hexatomic biaryl atropisomers (6,6-ring system); in sharp contrast, the efficient construction of enantiopure atropisomers featuring pentatomic heteroaromatics is largely underdeveloped, probably due to their relatively low conformational stability (Scheme 1a).3 On the other hand, atropoisomeric fivemembered heteroaryls were found in bioactive natural products4 and might be used as superior ligands in asymmetric transformations (Scheme 1b).5 In this context, the development of facile and unified synthetic strategies to access these axially chiral heteroarenes is highly desirable. Recently, enantioselective synthesis of pentatomic biaryls has greatly attracted the attention of chemists. Diverse synthetic strategies have been employed to access these fivemembered atropisomeric species, including central to axial chirality conversion,6 the Paal−Knorr reaction,7 organocatalytic arylation,8 asymmetric addition,9 and asymmetric C−H functionalization.10 Among these, atroposelective C−H activation/functionalization is undoubtedly one of the most powerful and promising methods toward the construction of atropisomers featuring five-membered rings.2i,10−13 For example, the group of Itami and Yamaguchi first reported the Pdcatalyzed enantioselective coupling of sterically hindered naphthylboronic acid with substituted thiophenes, delivering the thiophene-naphthyl atropisomers with moderate stereo© XXXX American Chemical Society

Special Issue: Asymmetric Synthesis Enabled by Organometallic Complexes Received: July 21, 2019

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DOI: 10.1021/acs.organomet.9b00490 Organometallics XXXX, XXX, XXX−XXX

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Organometallics Table 1. Optimization of Reaction Conditionsa

Scheme 1. Importance of Axially Chiral Five-Membered Atropisomers and Our Strategy

entry

additive

1 2 3 4 5 6 7 8 9

BQ p-toluquinone duroquinone naphthoquinone 2-chloronaphthoquinone menadione 2,6-dichloquinone 2-methoxyquinone chloranil

yield (%)b

eec

44 42 47 27

97 20 5 84

33 50 52 55 (48)d

23 99 97 96

a

Reaction conditions: rac-1a (0.1 mmol), 2a (0.3 mmol), Pd(OAc)2 (10 mol %), L-tert-leucine (20 mol %), additive (1.0 equiv), HFIP:HOAc = 4:1 (1 mL), 70 °C, air, 72 h. bDetermined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as the internal standard. cThe ee value was determined by chiral HPLC. dIsolated yield.

Table 2. Scope of the Pd-Catalyzed C−H Allylationa

to more general applications, we wondered whether other synthetically useful yet relatively smaller groups, such as allyl and alkenyl, would be applicable to this protocol. Undoubtedly, the realization of such a unified strategy would enable the synthesis of axially chiral pentatomic heteroarenes featuring diverse structural characteristics. Herein, we report a Pdcatalyzed atroposelective C−H allylation and alkenylation for the synthesis of axially chiral heteroaryls (Scheme 1c). This protocol provided a facile access to a series of enantioenriched five-membered heteroarenes (up to 99% ee) containing benzothiophenes and benzofurans. The reaction is scalable, and the resulting pentaatomic heterocyclic aldehydes could be applied for further transformations.

a

Reaction conditions: rac-1a (0.1 mmol), 2a (0.3 mmol), Pd(OAc)2 (10 mol %), L-tert-leucine (20 mol %), chloranil (1.0 equiv), HFIP:HOAc = 4:1 (1.0 mL), 70 °C, air, 72 h. Isolated yields are given; the ee value was determined by chiral HPLC. s = ln[(1 − C)(1 − ee1)]/ln[(1 − C)(1 + ee1)]; C = ee1/(ee1 + ee3).

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RESULTS AND DISCUSSION We began our investigation by examining the reaction of rac-1a with allylic reagent 2a in the presence of 10 mol % of Pd(OAc)2 and 20 mol % L-tert-leucine at 70 °C. To our delight, the reaction proceeded smoothly to afford the desired allylation product 3a in 44% yield with 97% ee when BQ was used as an additive (Table 1, entry 1). We then explored a range of BQ species with different substituents (entries 2−9). It was disclosed that both the reactivity and enantioselectivity could be significantly affected and the addition of chloranil gave the optimal result (entry 9). With the optimal conditions in hand, the substrate scope of asymmetric C−H allylation was explored. Biaryls bearing either the benzothiophene or benzofuran motif was compatible with this strategy, giving the corresponding products in moderate to good yields (Table 2, 3a−g). It should be noted that the

allylation of substrates rac-1a and rac-1b proceeded via kinetic resolution, though the remaining substrate had a low ee, therefore giving a moderate selectivity factor (s = 66, 1a; s = 44, 1b). When benzothiophene was positioned at the lower side of the biaryl, the desired product was obtained in 60% yield with moderate ee (3c, 88% ee). Notably, when benzothiophene was replaced with benzofuran, 3d was afforded in 83% yield, albeit with lower ee (78%). Notably, substrates with pentaatomic heteroarenes at the lower side generally have relatively lower rotational barriers, and the C− H allylation proceeded most likely through dynamic kinetic resolution (DKR) at 70 °C (3c−f). Biaryls bearing two fivemembered heteroarenes were also tested (3f,g). We were pleased to find that 3,3′-bisbenzothiophene was well tolerated, affording the desired product 3f in 77% yield with good enantiocontrol (92% ee). The enantioselectivity was dramatB

DOI: 10.1021/acs.organomet.9b00490 Organometallics XXXX, XXX, XXX−XXX

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Organometallics ically affected by the different atomic radii of sulfur and oxygen. A biaryl containing benzothiophene and benzofuran moieties gave the racemic product in 66% yield (3g). This result is consistent with the alkynylation reaction we previously reported.10d Unfortunately, an indole-based biaryl did not give the expected product under the standard conditions (3h). Inspired by these results and in order to synthesize more structurally diverse axially chiral heteroaromatics, we envisioned that alkenes could also be used as coupling partners. Therefore, we commenced our investigations with the reaction of rac-1a with butyl acrylate 4a in the presence of 10 mol % of Pd(OAc)2, 30 mol % of L-tert-leucine and 1.0 equiv of BQ at 60 °C in HOAc. As expected, the desired product 5a was afforded in 37% yield and 97% ee (Table S4, entry 1). Further optimizations revealed that the reaction proceeded more efficiently in HFIP/HOAc (4/1) at 60 °C for 48 h (51%, 98% ee, see the Supporting Information for details). To our delight, the atroposelective C−H alkenylation is applicable to various heteroatomic biaryls and alkenyl reagents, such as acrylate and styrene (Table 3). Generally, biaryls

To demonstrate the synthetic utility of the protocol, a gramscale experiment was conducted and the desired product 5h was obtained in 71% yield with 98% ee under the standard conditions (Scheme 2a). Oxidative cleavage of the alkene led to heteroatomic diarylaldehyde 6a in 70% yield without a loss of enantiomeric purity (Scheme 2b, 99% ee). Scheme 2. Synthetic Applications

Table 3. Scope of the Pd-Catalyzed C−H Alkenylationa

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CONCLUSIONS In conclusion, we have successfully synthesized a series of fivemembered axially chiral biaryls via Pd-catalyzed atroposelective C−H allylation and alkenylation. This protocol may provide a platform for the rapid construction of highly enantiopure atropisomers bearing pentatomic heteroaromatics. We believe this methodology and the obtained biaryls might find potential applications in asymmetric catalysis.

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EXPERIMENTAL SECTION

General Information. Starting materials 1a−i were prepared previously and used directly.10d NMR spectra were recorded on a Bruker NMR DRX-400 spectrometer operating for 1H NMR at 400 MHz, 13C NMR at 100 MHz, and 19F NMR at 376 MHz using TMS as internal standard. Chemical shifts are given relative to TMS (0.00 ppm), DCl3 (7.26 ppm for 1H NMR, 77.16 ppm for 13C NMR), and DMSO (2.50 ppm for 1H NMR, 39.52 ppm for 13C NMR). The following abbreviations are used to describe peak splitting patterns when appropriate: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, m = multiplet. Coupling constants, J, are reported in hertz (Hz). Optical rotations were measured using a 1 mL cell with a 1 dm path length on a PerkinElmer 341 instrument at 589 nm at 20 °C. Mass spectroscopy data of the products were collected on an HRMS-TOF instrument using ESI ionization. HPLC analyses were performed on an Shimadzu instrument using a chiral stationary phase column (Daicel Co. CHIRALPAK).The chiral HPLC measurements were calibrated with the corresponding racemic mixtures. General Procedure for Pd(II)-Catalyzed Atroposelective C− H Allylation of Pentatomic Heteroaromatics. In an oven-dried 50 mL Schlenk tube were placed rac-1 (0.10 mmol), allyl acetate 2a (0.3 mmol), Pd(OAc)2 (2.2 mg, 0.01 mmol), L-tert-leucine (2.6 mg, 0.02 mmol), and chloranil (24.6 mg, 0.1 mmol) in HFIP/HOAc = 4/ 1 (1.0 mL). The mixture was stirred for 72 h at 70 °C followed by cooling. The resulting mixture was quenched by filtering through a Celite pad and concentrated in vacuo. The residue was purified by preparative TLC using hexane/EtOAc as the eluent to afford the product 3. Ethyl 2-((1-(2-Formylbenzo[b]thiophen-3-yl)naphthalen-2-yl)methyl)acrylate (3a). The title compound 3a was prepared under the optimized conditions and purified by preparative TLC (petroleum

a

Reaction conditions: rac-1a (0.1 mmol), alkene 4 (0.3 mmol), Pd(OAc)2 (10 mol %), L-tert-leucine (30 mol %), BQ (1.0 equiv), HFIP:HOAc = 4:1 (1 mL), 60 °C, air, 48 h. Isolated yields are given; the ee value was determined by chiral HPLC. s = ln[(1 − C)(1 − ee1)]/ln[(1 − C)(1 + ee1)], C = ee1/(ee1 + ee5).

bearing benzothiophenes gave the olefinated products in moderate yields with good to excellent enantioselectivities and selectivity factors (5a−g, 45−70% yields, 90−99% ee, s = 26− 383). An atropisomer bearing two benzothiophenes was also accessible (5h, 70%, 98% ee). Not surprisingly, when 1(benzofuran-3-yl)-2-naphthaldehyde was used in this reaction, a reduced enantioselectivity was observed, affording the corresponding product in 75% ee (5i).10d C

DOI: 10.1021/acs.organomet.9b00490 Organometallics XXXX, XXX, XXX−XXX

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Organometallics

61%). 1H NMR (400 MHz, CDCl3): δ 9.76 (s, 1H), 7.91 (d, J = 7.6 Hz, 1H), 7.58 (d, J = 7.4 Hz, 1H), 7.52 (d, J = 8.2 Hz, 1H), 7.50− 7.44 (m, 1H), 7.35−7.27 (m, 1H), 7.23−7.16 (m, 1H), 7.12 (d, J = 7.6 Hz, 1H), 6.23 (s, 1H), 5.55 (s, 1H), 4.12 (q, J = 7.1 Hz, 2H), 3.63 (s, 2H), 2.14 (s, 3H), 1.21 (t, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 192.55, 166.11, 154.32, 152.55, 139.55, 135.88, 135.83, 135.74, 134.68, 129.79, 128.70, 127.38, 125.24, 124.62, 123.34, 119.81, 113.16, 111.41, 61.15, 29.75, 19.76, 14.22. HRMS (ESITOF): calcd for C22H20O4Na (M + Na+), 371.1254; found, 371.1251. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak IC, n-hexane/2-propanol = 98/2, v = 0.5 mL min−1, λ = 254 nm, t (minor) = 14.0 min, t (major) = 15.3 min, 94% ee; [α]D20 = −38.7 (c = 0.7, CHCl3). Ethyl 2-((2′-Formyl-[3,3′-bibenzo[b]thiophen]-2-yl)methyl)acrylate (3f). The title compound 3f was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 5/1). 3f was obtained as a yellow oil (31.3 mg, 77%). 1H NMR (400 MHz, CDCl3): δ 9.76 (s, 1H), 7.98 (d, J = 8.3 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.57−7.51 (m, 1H), 7.49 (d, J = 8.1 Hz, 1H), 7.38−7.31 (m, 2H), 7.30−7.22 (m, 2H), 6.17 (d, J = 0.9 Hz, 1H), 5.72−5.15 (m, 1H), 4.28−4.00 (m, 2H), 3.88−3.36 (m, 2H), 1.20 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ 185.47, 166.03, 142.63, 142.15, 140.83, 140.68, 140.59, 139.40, 138.66, 138.21, 128.72, 127.36, 125.50, 125.44, 125.10, 125.03, 124.92, 123.59, 122.62, 122.45, 61.20, 32.00, 14.22. HRMS (ESITOF): calcd for C23H18O3S2Na (M + Na+), 429.0590; found, 429.0590. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak OD-H, n-hexane/2-propanol = 98/2, v = 0.5 mL min−1, λ = 254 nm, t (minor) = 18.7 min, t (major) = 13.1 min, 92% ee; [α]D20 = +43.0 (c = 0.8, CHCl3). Ethyl 2-((3-(2-Formylbenzo[b]thiophen-3-yl)benzofuran-2-yl)methyl)acrylate (3g). The title compound 3g was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 5/1). 3g was obtained as a yellow oil (25.8 mg, 66%). 1H NMR (400 MHz, CDCl3): δ 9.92 (s, 1H), 7.97 (d, J = 8.2 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.58−7.52 (m, 2H), 7.41−7.31 (m, 2H), 7.30−7.26 (m, 1H), 7.25−7.18 (m, 1H), 6.24 (s, 1H), 5.57 (s, 1H), 4.12−3.93 (m, 2H), 3.87−3.73 (m, 2H), 1.13 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 185.37, 165.98, 154.44, 154.23, 142.21, 140.34, 139.35, 137.46, 135.90, 129.37, 128.72, 127.55, 125.46, 125.39, 124.99, 123.62, 123.60, 119.93, 111.56, 109.82, 61.19, 30.11, 14.15. HRMS (ESI-TOF): calcd for C23H18O4SNa (M + Na+), 413.0818; found, 413.0814. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak OD-H, n-hexane/2-propanol = 98/2, v = 0.4 mL min−1, λ = 254 nm, t (minor) = 13.3 min, t (major) = 15.5 min, 0% ee. General Procedure for Pd(II)-Catalyzed Atroposelective C− H Alkenylation of Pentatomic Heteroaromatics. In an ovendried 50 mL Schlenk tube were placed rac-1 (0.10 mmol), alkene 4 (0.3 mmol), Pd(OAc)2 (2.2 mg, 0.01 mmol), L-tert-leucine (3.9 mg, 0.03 mmol), and benzoquinone (10.8 mg, 0.1 mmol) in HFIP/HOAc = 4/1 (1.0 mL). The mixture was stirred for 48 h at 60 °C followed by cooling. The resulting mixture was quenched by filtering through a Celite pad and concentrated in vacuo. The residue was purified by preparative TLC using hexane/EtOAc as the eluent to afford the product 5. Butyl (E)-3-(1-(2-Formylbenzo[b]thiophen-3-yl)naphthalen-2yl)acrylate (5a). The title compound 5a was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 15/1). 5a was obtained as a yellow oil (21.2 mg, 51%). 1H NMR (400 MHz, CDCl3): δ 9.53 (s, 1H), 8.07−8.00 (m, 2H), 7.94 (d, J = 8.2 Hz, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.58−7.51 (m, 2H), 7.43−7.35 (m, 2H), 7.33−7.27 (m, 2H), 7.25−7.20 (m, 1H), 6.51 (d, J = 15.9 Hz, 1H), 4.06 (t, J = 6.3 Hz, 2H), 1.58−1.49 (m, 2H), 1.31−1.19 (m, 2H), 0.86 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 185.20, 166.42, 143.49, 141.97, 141.48, 140.94, 140.15, 134.05, 133.49, 132.67, 131.15, 130.10, 128.88, 128.39, 127.80, 127.69, 126.74, 125.71, 125.53, 123.58, 122.93, 121.08, 64.55, 30.67, 19.22, 13.80. HRMS (ESI-TOF): calcd for C26H22O3SNa (M + Na+ ), 437.1182; found, 437.1182. Enantiomeric excess was

ether/ethyl acetate = 5/1). 3a was obtained as a yellow oil (19.2 mg, 48%). 1H NMR (400 MHz, CDCl3): δ 9.53 (s, 1H), 8.02−7.96 (m, 2H), 7.92 (d, J = 8.2 Hz, 1H), 7.58−7.51 (m, 2H), 7.50−7.45 (m, 1H), 7.36−7.31 (m, 1H), 7.31−7.27 (m, 1H), 7.26−7.20 (m, 2H), 6.10 (s, 1H), 5.18 (s, 1H), 4.07 (q, J = 7.1 Hz, 2H), 3.61−3.42 (m, 2H), 1.17 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 185.57, 166.51, 145.20, 142.08, 140.15, 140.01, 139.43, 136.79, 133.72, 132.40, 129.54, 128.71, 128.68, 128.22, 127.77, 127.18, 126.83, 126.12, 125.76, 125.49, 125.46, 123.54, 60.96, 36.44, 14.22. HRMS (ESI-TOF): calcd for C25H20O3SNa (M + Na+), 423.1025; found, 423.1023. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak AD-H, n-hexane/2-propanol = 92/8, v = 0.5 mL min−1, λ = 254 nm, t (minor) = 12.2 min, t (major) = 13.1 min, 96% ee; [α]D20 = +43.9 (c = 0.5, CHCl3). Ethyl 2-((1-(2-Formylbenzo[b]thiophen-3-yl)-4-methylnaphthalen-2-yl)methyl)acrylate (3b). The title compound 3b was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 5/1). 3b was obtained as a yellow oil (17.0 mg, 41%). 1H NMR (400 MHz, CDCl3): δ 9.54 (s, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.56−7.43 (m, 2H), 7.38 (s, 1H), 7.32 (dd, J = 16.0, 8.7 Hz, 1H), 7.28−7.22 (m, 3H), 6.10 (s, 1H), 5.18 (d, J = 0.9 Hz, 1H), 4.07 (q, J = 7.1 Hz, 2H), 3.49 (q, J = 16.2 Hz, 2H), 2.78 (s, 3H), 1.17 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 185.70, 166.56, 145.59, 142.04, 140.20, 139.47, 136.36, 136.05, 133.81, 131.68, 128.65, 128.57, 126.85, 126.79, 126.76, 126.39, 125.93, 125.55, 125.38, 124.42, 123.50, 60.93, 36.32, 19.75, 14.22. HRMS (ESI-TOF): calcd for C26H22O3SNa (M + Na+), 437.1182; found, 437.1185. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak AD-H, n-hexane/2-propanol = 98/2, v = 0.5 mL min−1, λ = 254 nm, t (minor) = 9.6 min, t (major) = 11.2 min, 96% ee; [α]D20 = +24.6 (c = 1.0, CHCl3). Ethyl 2-((3-(2-Formylnaphthalen-1-yl)benzo[b]thiophen-2-yl)methyl)acrylate (3c). The title compound 3c was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 5/1). 3c was obtained as a colorless oil (24.0 mg, 60%). 1H NMR (400 MHz, CDCl3): δ 9.78 (s, 1H), 8.15 (d, J = 8.6 Hz, 1H), 8.03 (d, J = 8.6 Hz, 1H), 7.97 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.67−7.60 (m, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.44−7.38 (m, 1H), 7.37−7.31 (m, 1H), 7.24−7.17 (m, 1H), 7.01 (d, J = 8.0 Hz, 1H), 6.11 (s, 1H), 5.35 (s, 1H), 4.10 (q, J = 7.1 Hz, 2H), 3.68−3.43 (m, 2H), 1.20 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 192.37, 166.10, 141.64, 141.60, 139.66, 138.54, 137.98, 136.55, 132.94, 132.78, 129.35, 129.26, 128.62, 127.99, 127.49, 127.42, 127.14, 124.99, 124.83, 122.86, 122.45, 122.41, 61.15, 31.92, 14.22. HRMS (ESI-TOF): calcd for C25H20O3SNa (M + Na+), 423.1025; found, 423.1025. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak AD-H, n-hexane/2-propanol = 95/5, v = 0.7 mL min−1, λ = 254 nm, t (minor) = 16.0 min, t (major) = 14.8 min, 88% ee; [α]D20 = +35.5 (c = 0.9, CHCl3). Ethyl 2-((3-(2-Formylnaphthalen-1-yl)benzofuran-2-yl)methyl)acrylate (3d). The title compound 3d was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 5/1). 3d was obtained as a yellow oil (31.9 mg, 83%). 1H NMR (400 MHz, CDCl3): δ 9.98 (s, 1H), 8.12 (d, 1H), 8.04−7.94 (m, 2H), 7.72 (d, J = 8.5 Hz, 1H), 7.67−7.61 (m, 1H), 7.58 (d, J = 8.3 Hz, 1H), 7.48−7.41 (m, 1H), 7.37−7.31 (m, 1H), 7.20−7.15 (m, 1H), 7.07 (d, J = 7.7 Hz, 1H), 6.14 (s, 1H), 5.49 (d, 1H), 4.10−3.90 (m, 2H), 3.74−3.57 (m, 2H), 1.11 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 192.41, 166.01, 154.24, 153.97, 136.46, 136.10, 135.73, 132.91, 132.84, 130.87, 129.37, 129.19, 128.66, 127.54, 127.33, 127.12, 124.82, 123.54, 122.56, 119.96, 61.09, 29.98, 14.13. HRMS (ESI-TOF): calcd for C25H20O4Na (M + Na+), 407.1254; found, 407.1248. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak OD-H, n-hexane/2-propanol = 92/8, v = 0.2 mL min−1, λ = 254 nm, t (minor) = 15.6 min, t (major) = 14.7 min, 78% ee; [α]D20 = −10.4 (c = 1.2, CHCl3). Ethyl 2-((3-(2-Formyl-6-methylphenyl)benzofuran-2-yl)methyl)acrylate (3e). The title compound 3e was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 5/1). 3e was obtained as a yellow oil (21.3 mg, D

DOI: 10.1021/acs.organomet.9b00490 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

Daicel Chiralpak IB, n-hexane/2-propanol = 90/10, v = 0.8 mL min−1, λ = 254 nm, t (minor) = 14.8 min, t (major) = 16.4 min, 99% ee; [α]D20 = +59.7 (c = 0.8, CHCl3). Benzyl (E)-3-(1-(2-Formylbenzo[b]thiophen-3-yl)naphthalen-2yl)acrylate (5f). The title compound 5f was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 15/1). 5f was obtained as a yellow oil (24.0 mg, 54%). 1H NMR (400 MHz, CDCl3): δ 9.53 (s, 1H), 8.07−8.00 (m, 2H), 7.95 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.58−7.52 (m, 2H), 7.48 (d, J = 15.9 Hz, 1H), 7.40−7.35 (m, 1H), 7.35−7.27 (m, 5H), 7.25−7.20 (m, 3H), 6.57 (d, J = 15.9 Hz, 1H), 5.11 (s, 2H). 13 C NMR (101 MHz, CDCl3): δ 185.18, 166.12, 143.3, 142.12, 141.96, 141.00, 140.15, 135.93, 134.11, 133.48, 132.54, 131.33, 130.15, 128.92, 128.66, 128.40, 128.27, 128.01, 127.84, 127.78, 126.79, 125.76, 125.53, 123.61, 122.89, 120.63, 66.42. HRMS (ESITOF): calcd for C29H20O3SNa (M + Na+), 471.1025; found, 471.1027. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak IC, n-hexane/2-propanol = 80/20, v = 1.0 mL min−1, λ = 254 nm, t (minor) = 15.5 min, t (major) = 23.7 min, 97% ee; [α]D20 = +61.1 (c = 1.0, CHCl3). (E)-3-(2-styrylnaphthalen-1-yl)benzo[b]thiophene-2-carbaldehyde (5g). The title compound 5g was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/acetone = 15/1). 5g was obtained as a yellow solid (17.3 mg, 45%). 1H NMR (400 MHz, CDCl3): δ 9.61 (s, 1H), 8.08−7.99 (m, 3H), 7.95−7.91 (m, 1H), 7.58−7.53 (m, 1H), 7.51−7.46 (m, 1H), 7.37−7.27 (m, 4H), 7.25−7.16 (m, 6H), 6.81 (d, J = 16.2 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 185.74, 145.02, 141.99, 140.51, 140.26, 136.94, 135.36, 133.74, 132.95, 131.68, 129.78, 128.81, 128.77, 128.29, 128.19, 127.89, 127.43, 126.80, 126.48, 126.22, 126.01, 125.81, 125.62, 123.56, 122.91. HRMS (ESI-TOF): calcd for C27H18OSNa (M + Na+), 413.0971; found, 413.0971. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak IB, n-hexane/2propanol = 90/10, v = 0.8 mL min−1, λ = 254 nm, t (minor) = 9.9 min, t (major) = 16.0 min, 96% ee; [α]D20 = +71.8 (c = 0.8, CHCl3). (E)-2′-Styryl-[3,3′-bibenzo[b]thiophene]-2-carbaldehyde (5h). The title compound 5h was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/acetone = 20/1). 5h was obtained as a yellow solid (27.7 mg, 70%). 1H NMR (400 MHz, CDCl3): δ 9.83 (s, 1H), 8.04−7.99 (m, 1H), 7.91−7.87 (m, 1H), 7.61−7.54 (m, 2H), 7.44−7.34 (m, 2H), 7.34−7.28 (m, 5H), 7.26−7.21 (m, 2H), 7.16 (d, J = 16.0 Hz, 1H), 6.99 (d, J = 16.0 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 185.59, 142.86, 142.17, 140.97, 140.20, 139.47, 137.89, 136.15, 133.43, 128.86, 128.79, 128.68, 126.92, 125.87, 125.59, 125.55, 125.29, 123.56, 122.97, 122.48, 120.04. HRMS (ESI-TOF): calcd for C25H16OS2Na (M + Na+), 419.0535; found, 419.0535. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak IB, n-hexane/2-propanol = 90/10, v = 0.8 mL min−1, λ = 254 nm, t (minor) = 9.1 min, t (major) = 10.6 min, 98% ee; [α]D20 = +54.7 (c = 0.9, CHCl3). (E)-1-(2-Styrylbenzofuran-3-yl)-2-naphthaldehyde (5i). The title compound 5i was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 15/1). 5i was obtained as a yellow oil (18.9 mg, 50%). 1H NMR (400 MHz, CDCl3): δ 10.04 (d, J = 0.7 Hz, 1H), 8.19 (d, J = 8.6 Hz, 1H), 8.07 (d, J = 8.7 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 8.5 Hz, 1H), 7.69−7.62 (m, 2H), 7.51−7.44 (m, 2H), 7.43−7.37 (m, 1H), 7.37− 7.32 (m, 2H), 7.29−7.25 (m, 2H), 7.25−7.17 (m, 2H), 7.11 (d, J = 7.7 Hz, 1H), 6.58 (d, J = 16.1 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 192.43, 154.28, 153.79, 136.55, 136.19, 135.84, 133.15, 132.84, 132.63, 131.28, 129.54, 129.33, 128.81, 128.68, 128.65, 127.51, 127.40, 127.04, 125.83, 123.76, 122.73, 120.21, 114.07, 112.55, 111.34. HRMS (ESI-TOF): calcd for C27H18O2Na (M + Na+ ), 397.1199; found, 397.1197. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak IB, n-hexane/2propanol = 90/10, v = 0.8 mL min−1, λ = 254 nm, t (minor) = 7.2 min, t (major) = 7.7 min, 75% ee; [α]D20 = +109.5 (c = 0.8, CHCl3). Gram-Scale Synthesis of 5h. In an oven-dried 250 mL Schlenk tube were placed substrate rac-1b (1.47 g, 5.0 mmol), styrene 4b (15 mmol), Pd(OAc)2 (110.0 mg, 0.5 mmol), L-tert-leucine (195.0 mg,

determined by HPLC with a Daicel Chiralpak IB, n-hexane/2propanol = 85/15, v = 0.9 mL min−1, λ = 254 nm, t (minor) = 9.9 min, t (major) = 11.5 min, 98% ee; [α]D20 = +62.0 (c = 0.9, CHCl3). Butyl (E)-3-(3-(2-Formylnaphthalen-1-yl)benzo[b]thiophen-2yl)acrylate (5b). The title compound 5b was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 15/1). 5b was obtained as a colorless oil (24.1 mg, 58%). 1H NMR (400 MHz, CDCl3): δ 9.75 (d, J = 0.8 Hz, 1H), 8.16 (d, J = 8.6 Hz, 1H), 8.08 (d, J = 8.7 Hz, 1H), 7.99 (d, J = 8.3 Hz, 1H), 7.95−7.90 (m, 1H), 7.69−7.59 (m, 1H), 7.49−7.37 (m, 3H), 7.29 (d, J = 15.6 Hz, 1H), 7.26−7.21 (m, 1H), 7.09−7.04 (m, 1H), 6.38 (d, J = 15.6 Hz, 1H), 4.07 (t, J = 6.6 Hz, 2H), 1.61−1.52 (m, 2H), 1.36−1.23 (m, 2H), 0.87 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 191.64, 166.19, 141.47, 138.78, 138.77, 137.96, 136.50, 135.31, 134.51, 133.19, 132.80, 129.98, 129.44, 128.67, 127.77, 127.24, 127.07, 125.65, 124.11, 122.71, 122.52, 121.47, 64.75, 30.71, 19.20, 13.78. HRMS (ESI-TOF): calcd for C26H22O3SNa (M + Na + ), 437.1182; found, 437.1183. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak IB, n-hexane/2propanol = 90/10, v = 0.8 mL min−1, λ = 254 nm, t (minor) = 8.5 min, t (major) = 9.1 min, 90% ee; [α]D20 = +132.4 (c = 1.0, CHCl3). Butyl (E)-3-(3-(2-Formyl-6-methylphenyl)benzo[b]thiophen-2yl)acrylate (5c). The title compound 5c was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 15/1). 5c was obtained as a yellow oil (19.6 mg, 52%). 1H NMR (400 MHz, CDCl3): δ 9.54 (d, J = 0.8 Hz, 1H), 7.98−7.94 (m, 1H), 7.89−7.85 (m, 1H), 7.64−7.60 (m, 1H), 7.57− 7.52 (m, 1H), 7.46−7.40 (m, 1H), 7.36 (d, J = 15.6 Hz, 1H), 7.32− 7.27 (m, 1H), 7.16−7.11 (m, 1H), 6.34 (d, J = 15.6 Hz, 1H), 4.13 (t, J = 6.6 Hz, 2H), 2.04 (s, 3H), 1.67−1.58 (m, 2H), 1.43−1.31 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 191.68, 166.39, 140.41, 139.15, 139.06, 137.13, 136.69, 136.20, 136.16, 135.81, 135.36, 129.30, 127.14, 125.71, 125.54, 123.74, 122.76, 121.04, 64.77, 30.78, 19.57, 19.26, 13.83. HRMS (ESI-TOF): calcd for C23H22O3SNa (M + Na+), 401.1182; found, 401.1186. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak IB, n-hexane/2-propanol = 90/10, v = 0.8 mL min−1, λ = 254 nm, t (minor) = 7.2 min, t (major) = 7.7 min, 90% ee; [α]D20 = −7.5 (c = 0.9, CHCl3). Methyl (E)-3-(1-(2-Formylbenzo[b]thiophen-3-yl)naphthalen-2yl)acrylate (5d). The title compound 5d was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 12/1). 5d was obtained as a white solid (18.3 mg, 49%). 1H NMR (400 MHz, CDCl3): δ 9.53 (s, 1H), 8.06−8.00 (m, 2H), 7.94 (d, J = 8.1 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.59− 7.51 (m, 2H), 7.41 (d, J = 16.0 Hz, 1H), 7.39−7.33 (m, 1H), 7.32− 7.26 (m, 2H), 7.23 (d, J = 8.1 Hz, 1H), 6.52 (d, J = 15.9 Hz, 1H), 3.67 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 185.19, 166.81, 143.47, 141.98, 141.70, 140.94, 140.15, 134.06, 133.46, 132.64, 131.17, 130.13, 128.91, 128.38, 127.80, 127.72, 126.75, 125.74, 125.52, 123.64, 123.00, 120.76, 51.88. HRMS (ESI-TOF): calcd for C23H16O3SNa (M + Na+), 395.0712; found, 395.0710. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak IB, nhexane/2-propanol = 90/10, v = 0.8 mL min−1, λ = 254 nm, t (minor) = 17.6 min, t (major) = 20.5 min, 99% ee; [α]D20 = +45.1 (c = 0.9, CHCl3). Ethyl (E)-3-(1-(2-Formylbenzo[b]thiophen-3-yl)naphthalen-2-yl)acrylate (5e). The title compound 5e was prepared under the optimized conditions and purified by preparative TLC (petroleum ether/ethyl acetate = 12/1). 5e was obtained as a yellow oil (19.2 mg, 50%). 1H NMR (400 MHz, CDCl3): δ 9.53 (s, 1H), 8.05−8.00 (m, 2H), 7.94 (d, J = 8.1 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.58−7.51 (m, 2H), 7.41 (d, J = 15.9 Hz, 1H), 7.39−7.32 (m, 1H), 7.32−7.27 (m, 2H), 7.25−7.21 (m, 1H), 6.52 (d, J = 15.9 Hz, 1H), 4.13 (q, J = 7.1 Hz, 2H), 1.21 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 185.20, 166.38, 143.49, 141.98, 141.53, 140.95, 140.15, 134.04, 133.47, 132.71, 131.13, 130.10, 128.88, 128.37, 127.78, 127.68, 126.75, 125.71, 125.53, 123.61, 123.00, 121.15, 60.69, 14.27. HRMS (ESI-TOF): calcd for C24H18O3SNa (M + Na+), 409.0869; found, 409.0870. Enantiomeric excess was determined by HPLC with a E

DOI: 10.1021/acs.organomet.9b00490 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics 1.5 mmol), and benzoquinone (540 mg, 5.0 mmol) in HFIP/HOAc = 4/1 (50 mL). The mixture was stirred for 48 h at 60 °C followed by cooling. The resulting mixture was diluted with EtOAc, filtered through a Celite pad, and concentrated in vacuo. The reaction mixture was quenched with saturated NaHCO3 (60 mL) and extracted with EtOAc (3 × 40 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated, and the residue was purified by silica gel column chromatography. 5h was obtained in 71% yield (1.40 g, 98% ee). Oxidative Cleavage of Alkene. In an oven-dried 50 mL flask were placed substrate 5d (74.5 mg, 0.2 mmol), K2OsO4·2H2O (3.7 mg, 0.01 mmol), and NaIO4 (213.9 mg, 1.0 mmol) in THF/H2O = 1/1 (2 mL). The mixture was stirred at room temperature overnight. The resulting mixture was quenched with saturated NH4Cl (5 mL) and extracted with EtOAc (3 × 5 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated, and the residue was purified by preparative TLC using hexane/EtOAc as the eluent to afford 6a. 3-(2-Formylnaphthalen-1-yl)benzo[b]thiophene-2-carbaldehyde (6a). 6a was obtained as a colorless solid (44.3 mg, 70%). 1H NMR (400 MHz, CDCl3): δ 9.82 (d, J = 0.8 Hz, 1H), 9.60 (s, 1H), 8.19 (d, J = 8.6 Hz, 1H), 8.12 (d, J = 8.6 Hz, 1H), 8.07−7.99 (m, 2H), 7.71− 7.64 (m, 1H), 7.61−7.55 (m, 1H), 7.50−7.43 (m, 2H), 7.37−7.31 (m, 1H), 7.31−7.27 (m, 1H). 13C NMR (101 MHz, CDCl3): δ 190.90, 184.57, 141.67, 141.60, 140.99, 140.91, 136.25, 136.17, 133.42, 133.12, 130.40, 129.68, 129.17, 128.74, 128.21, 126.91, 126.14, 125.31, 123.65, 122.57. HRMS (ESI-TOF): calcd for C20H12O2SNa (M + Na+), 339.0450; found, 339.0446. Enantiomeric excess was determined by HPLC with a Daicel Chiralpak IA, nhexane/2-propanol = 85/15, v = 1.0 mL min−1, λ = 254 nm, t (minor) = 9.6 min, t (major) = 14.1 min, 99% ee; [α]D20 = +77.5 (c = 0.8, CHCl3).

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C. Total Synthesis of Chiral Biaryl Natural Products by Asymmetric Biaryl Coupling. Chem. Soc. Rev. 2009, 38, 3193−3207. (d) Privileged Chiral Ligands and Catalysts; Zhou, Q.-L., Ed.; Wiley-VCH: Weinheim, Germany, 2011. (e) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley: New York, 1994. (2) For recent reviews on the synthesis of axially chiral biaryls, see: (a) Baudoin, O. The Asymmetric Suzuki Coupling Route to Axially Chiral Biaryls. Eur. J. Org. Chem. 2005, 2005, 4223−4229. (b) Bringmann, G.; Price Mortimer, A. J.; Keller, P. A.; Gresser, M. J.; Garner, J.; Breuning, M. Atroposelective Synthesis of Axially Chiral Biaryl Compounds. Angew. Chem., Int. Ed. 2005, 44, 5384−5427. (c) WencelDelord, J.; Panossian, A.; Leroux, F. R.; Colobert, F. Recent Advances and New Concepts for the Synthesis of Axially Stereoenriched Biaryls. Chem. Soc. Rev. 2015, 44, 3418−3430. (d) Ma, G.; Sibi, M. P. Catalytic Kinetic Resolution of Biaryl Compounds. Chem. - Eur. J. 2015, 21, 11644−11657. (e) Kumarasamy, E.; Raghunathan, R.; Sibi, M. P.; Sivaguru, J. Nonbiaryl and Heterobiaryl Atropisomers: Molecular Templates with Promise for Atropselective Chemical Transformations. Chem. Rev. 2015, 115, 11239−11300. (f) Mori, K.; Itakura, T.; Akiyama, T. Enantiodivergent Atroposelective Synthesis of Chiral Biaryls by Asymmetric Transfer Hydrogenation: Chiral Phosphoric Acid Catalyzed Dynamic Kinetic Resolution. Angew. Chem., Int. Ed. 2016, 55, 11642−11646. (g) Zilate, B.; Castrogiovanni, A.; Sparr, C. Catalyst-Controlled Stereoselective Synthesis of Atropisomers. ACS Catal. 2018, 8, 2981−2988. (h) Wang, Y.-B.; Tan, B. Construction of Axially Chiral Compounds via Asymmetric Organocatalysis. Acc. Chem. Res. 2018, 51, 534−547. (i) Liao, G.; Zhou, T.; Yao, Q.-J.; Shi, B.-F. Recent Advance in the Synthesis of Axially Chiral Biaryls via Transition Metal-catalysed Asymmetric C−H Functionalization. Chem. Commun. 2019, 55, 8514−8523. (3) (a) Zhang, S.; Liao, G.; Shi, B.-F. Enantioselective Synthesis of Atropisomers Featuring Pentatomic Heteroaromatics. Youji Huaxue 2019, 39, 1522−1528. (b) Bonne, D.; Rodriguez, J. A Bird’s Eye View of Atropisomers Featuring a Five-Membered Ring. Eur. J. Org. Chem. 2018, 2018, 2417−2431. (c) Bonne, D.; Rodriguez, J. Enantioselective Syntheses of Atropisomers Featuring a Five-Membered Ring. Chem. Commun. 2017, 53, 12385−12393. (d) Kumarasamy, E.; Raghunathan, R.; Sibi, M. P.; Sivaguru, J. Nonbiaryl and Heterobiaryl Atropisomers: Molecular Templates with Promise for Atropselective Chemical Transformations. Chem. Rev. 2015, 115, 11239−11300. (4) (a) Norton, R. S.; Wells, R. J. A Series of Chiral Polybrominat-ed Biindoles From the Marine Blue-Green Alga Rivularia f irma. Application of 13C NMR Spin-Lattice Relaxation Data and 13C-1H Coupling Constants to Structure Elucidation. J. Am. Chem. Soc. 1982, 104, 3628−3635. (b) Ito, C.; Thoyama, Y.; Omura, M.; Kajiura, I.; Furukawa, H. Alkaloidal Constituents of Murraya koenigii. Isolation and Structural Elucidation of Novel Binary Carbazolequinones and Carbazole Alkaloids. Chem. Pharm. Bull. 1993, 41, 2096−2100. (c) Bringmann, G.; Tasler, S.; Endress, H.; Kraus, J.; Messer, K.; Wohlfarth, M.; Lobin, W. Murrastifoline-F: First Total Synthesis, Atropo-Enantiomer Resolution, and Stereoanalysis of an Axially Chiral N, C-Coupled Biaryl Alkaloid. J. Am. Chem. Soc. 2001, 123, 2703−2711. (d) Hughes, C. C.; Prieto-Davo, A.; Jensen, P. R.; Fenical, W. The Marinopyrroles, Antibiotics of an Unprecedented Structure Class from a Marine Streptomyces sp. Org. Lett. 2008, 10, 629−631. (5) (a) Benincori, T.; Brenna, E.; Sannicolò, F.; Trimarco, L.; Antognazza, P.; Cesarotti, E.; Demartin, F.; Pilati, T. New Class of Chiral Diphosphine Ligands for Highly Efficient Transition Metal Catalyzed Stereoselective Reactions: The Bis(diphenylphosphino) Five-membered Biheteroaryls. J. Org. Chem. 1996, 61, 6244−6251. (b) Benincori, T.; Cesarotti, E.; Piccolo, O.; Sannicolo, F. 2,2’,5,5′Tetramethyl-4,4’-bis(diphenylphoshino)-3,3′-bithiophene: A New, Very Efficient, Easily Accessible, Chiral Biheteroaromatic Ligand for Homogeneous Stereoselective Catalysis. J. Org. Chem. 2000, 65, 2043−2047. (c) Andersen, N.; Parvez, M.; Keay, B. A. Synthesis, Resolution, and Applications of 2,2’-Bis(diphenylphosphino)-3,3′binaphtho[2,1-b]furan. Org. Lett. 2000, 2, 2817−2820.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.9b00490. Experimental details and characterization data of the products (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (B.-F. Shi). ORCID

Bing-Feng Shi: 0000-0003-0375-955X Author Contributions §

H.-M.C. and S.Z. contributed equally.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support from the NSFC (21772170, 21572201), the China Postdoctoral Science Foundation (2019M650135), the National Basic Research Program of China (2015CB856600), and Zhejiang Provincial NSFC (LR17B020001) is gratefully acknowledged.

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REFERENCES

(1) For selected reviews, see: (a) Smyth, J. E.; Butler, N. M.; Keller, P. A. A Twist of Nature -The Significance of Atropisomers in Biological Systems. Nat. Prod. Rep. 2015, 32, 1562−1583. (b) Bringmann, G.; Gulder, T.; Gulder, T. A. M.; Breuning, M. Atroposelective Total Synthesis of Axially Chiral Biaryl Natural Products. Chem. Rev. 2011, 111, 563−639. (c) Kozlowski, M. C.; Morgan, B. J.; Linton, E. F

DOI: 10.1021/acs.organomet.9b00490 Organometallics XXXX, XXX, XXX−XXX

Article

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DOI: 10.1021/acs.organomet.9b00490 Organometallics XXXX, XXX, XXX−XXX