Synthesis of 2-Unsubstituted Pyrrolidines and Piperidines from Donor

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Synthesis of 2‑Unsubstituted Pyrrolidines and Piperidines from Donor−Acceptor Cyclopropanes and Cyclobutanes: 1,3,5-Triazinanes as Surrogates for Formylimines Lennart K. B. Garve,† Alexander Kreft,† Peter G. Jones,‡ and Daniel B. Werz*,† †

Institute for Organic Chemistry, TU Braunschweig, Hagenring 30, 38106 Braunschweig, Germany Institute for Inorganic and Analytical Chemistry, TU Braunschweig, Hagenring 30, 38106 Braunschweig, Germany

‡

S Supporting Information *

ABSTRACT: A synthetic procedure to access 2-unsubstituted pyrrolidines and piperidines is presented. In the presence of MgI2 as Lewis acid, donor−acceptor cyclopropanes or corresponding cyclobutanes were treated with 1,3,5-triazinanes, leading to the five- or six-membered ring systems under mild conditions in yields up to 93%. This protocol tolerates a great variety of functional groups and thus provides an efficient entry to this class of pyrrolidines and piperidines.

P

asymmetric fashion (Scheme 1b). However, 2-unsubstituted pyrrolidines were not accessible by these procedures. In recent years, D−A cyclopropanes have enjoyed a renaissance as versatile building blocks in organic synthesis.5 A wide variety of different heterocyclic systems have become accessible starting from these highly strained and polarized small ring systems. The major reaction types are easily understandable when a formal 1,3-zwitterionic relationship is taken into account. [3+n]-Cycloaddition reactions lead either to five-,6 six-,7 or seven-membered8 ring systems. Ring-opening reactions allow the attachment of substituents either in 1position9 or in 1- and 3-positions10 whereas rearrangement reactions furnish five-membered rings by insertion of an acceptor moiety.11,12 In the course of our research program aiming toward 1,3bisfunctionalization reactions of D−A cyclopropanes, we found that these strained three-membered rings undergo a formal [4+3]-cycloaddition with 1,3,5-triazinanes.13 As a result 1,3diazepanes were obtained, which were easily converted to 1,4diamines (Scheme 2a). Our initial results had shown that the seven-membered rings are easily formed. A more careful analysis of the side products has revealed that corresponding pyrrolidines are also formed. Therefore, we optimized the transformation again, this time aiming at pyrrolidines as major products. Furthermore, we tried to extend the method to corresponding D−A cyclobutanes, affording in a formal [4+2]-cycloaddition process the six-membered analogs, namely piperidines (Scheme 2b). In the search for an efficient and widely applicable protocol for the desired [3+2] annulation process, we focused especially

yrrolidines and piperidines are abundant in many natural products and pharmaceutically active compounds.1 Numerous synthetic methods have been developed to access these five- and six-membered rings. For pyrrolidines the most prominent methods are nucleophilic substitution reactions and [3+2]-cycloaddition reactions.2 Using the [3+2]-approach, various retrosynthetic cuts are possible. An alkene and an azomethine ylide can be employed as starting materials to construct the five-membered ring (Scheme 1a).3 In other Scheme 1. (a) [3+2]-Cycloaddition Reaction of Azomethine Ylides and Olefins and (b) Formal [3+2]-Cycloaddition Reaction of Donor−Acceptor Cyclopropane and Aromatic Aldimines

independent protocols Kerr, Tang, and Johnson reported that donor−acceptor (D−A) cyclopropanes could be employed as three-atom components.4 In the presence of Lewis acid with a chiral ligand, an aromatic aldimine was used to insert the fourth carbon atom and the nitrogen atom. This methodology even provided access to 2,5-cis-disubstituted pyrrolidines in an © 2017 American Chemical Society

Received: July 7, 2017 Published: August 7, 2017 9235

DOI: 10.1021/acs.joc.7b01631 J. Org. Chem. 2017, 82, 9235−9242

Note

The Journal of Organic Chemistry

An entirely different behavior was observed with Y(OTf)3, which yielded the desired pyrrolidine in 87% yield with a product ratio of 8.7:1 (entry 5). Magnesium salts as Lewis acids yielded the five-membered ring selectively, with no trace of the 1,3-diazepane. MgBr2 and Mg(OTf)2 gave moderate yields of 73% and 67%, respectively (entry 6 and 7). The most powerful Lewis acid was MgI2, which delivered the pyrrolidine in 92% yield (entry 8). Moreover the reaction time could be decreased to 1.5 h and the product was still formed in 93% yield (entry 9). With our optimized conditions in hand, a large variety of D−A cyclopropanes were investigated (Table 2). As substituent at the nitrogen, either phenyl or the more electron-rich p‑methoxyphenyl (PMP) was employed. A wide range of different donor moieties are tolerated. Methyl groups, ether, amide, halogens and even electron-withdrawing trifluoromethyl groups at the phenyl residue do not decrease the yield. The same holds true for the more bulky naphthyl unit, for thienyl, furyl, and even vinyl. Heteroatoms as donors also yield the desired pyrrolidine. With phthalimide an excellent yield of 88% (5ma) was achieved, whereas with oxygen as donor the yield dropped to 56% (5na). Besides phenyl and PMP residues as substituents at the nitrogen, o-methoxyphenyl and p-tolyl were also investigated and produced the pyrrolidine in 83% and 78% yield, respectively (Table 3). Even para-halogen substituents of the phenyl moiety were tolerated. Moreover, the trifluoromethyl group at the meta-position of the aryl group yielded the corresponding product in 81% yield. To prove the structure of the products unambiguously, we obtained single crystals of 5eg. The X-ray crystallographic analysis14,15 confirmed the generated pyrrolidine motif (SI, Figure S60). In the past few years, some of the recently developed reactions have also been investigated with D−A cyclobutanes.16,17 The ring strain of these four-membered rings is only slightly less than that of the three-membered ring analogs. Thus, we were interested to establish whether a similar transformation would also pave the way to 2-unsubstituted piperidines. Similar conditions were applied and indeed afforded the desired 6-membered ring compounds in moderate to good yields (Table 4). Next, we explored the stereospecificity of the formal [3+2]cycloaddition reaction with MgI2 and Y(OTf)3 as Lewis acids (Scheme 3). Interestingly, both Lewis acids accomplished the desired transformation with complete stereospecificity; however, different enantiomers were obtained. In the literature it is known that MgI2 reacts with net retention at the stereogenic center.18 Thus, we assume that the catalyst MgI2 interacts with the D−A cyclopropanes achieving an activated and more polarized cyclopropane (Scheme 4). Then the iodide anion opens the cyclopropane in an SN2 reaction leading to (R)-9a. Enolate (R)-9a reacts with formaldimine 10a originating from the triazinane 2a. Finally, intermediate (R)-11aa cyclizes to pyrrolidine (S)-5aa′ through an additional SN2 reaction yielding (S)-5aa′ with net retention at the stereogenic center with respect to corresponding cyclopropane (S)-1a′. In contrast to Y(OTf)3 a direct nucleophilic substitution of the nitrogen nucleophile is favored. In summary, we have developed protocols that allow the preparation of 2-unsubstituted pyrrolidines from donor− acceptor cyclopropanes and 2-unsubstituted piperidines from donor−acceptor cyclobutanes. As surrogate for formylimine, 1,3,5-triazinanes were utilized. Under the influence of MgI2 as Lewis acid, decomposition of the six-membered heterocycle

Scheme 2. (a) Synthesis of 1,3-Diazepanes and 1,4-Diamines Using 1,3,5-Triazinanes and (b) the Present Work

Table 1. Optimization of the Reaction Conditionsa

entry

Lewis acid

reaction time [h]

1b 2 3 4 5 6 7 8 9

Sc(OTf)3 Ni(ClO4)2 TiCl4 Sn(OTf)2 Y(OTf)3 MgBr2 Mg(OTf)2 MgI2 MgI2

14 14 14 14 14 14 14 14 1.5

yield 5aa [%]

yield 3aa [%]

6 45 decomposition 0 87 73 67 92 93

88 25 0 10 0 0 0 0

Reaction conditions: 1a (100 μmol), 2a (120 μmol), Lewis acid (10 mol%), CH2Cl2 (1 mL), 25 °C; yields represent isolated and purified products. bReaction was carried out in 2 mL of CH2Cl2. a

on the type of Lewis acid (Table 1). Sc(OTf)3 was the Lewis acid of choice for the synthesis of 1,3-diazepanes. A closer look at the byproducts revealed that 6% of the pyrrolidine was also formed (Table 1, entry 1). Nickel perchlorate led to a mixture of both products in a ratio of approximately 2:1 (entry 2). The harsh Lewis acid TiCl4 led to a complete decomposition of the starting materials (entry 3), whereas Sn(OTf)2 showed no conversion of the starting materials (entry 4). 9236

DOI: 10.1021/acs.joc.7b01631 J. Org. Chem. 2017, 82, 9235−9242

Note

The Journal of Organic Chemistry Table 2. Scope with Regard to the Donor−Acceptor Cyclopropanea

Reaction conditions: 1 (100 μmol), 2 (120 μmol), MgI2 (10 mol%), CH2Cl2 (1 mL), 25 °C, 1.5 h; yields represent isolated and purified products; PMP = para-methoxyphenyl a

Table 3. Scope with Regard to the 1,3,5-Triazinanea

Table 4. Synthesis of Piperidinesa

Reaction conditions: 1 (100 μmol), 2 (120 μmol), MgI2 (10 mol%), CH2Cl2 (1 mL), 25 °C, 1.5 h; yields represent isolated and purified products. a

Reaction conditions: 6 (100 μmol), 2 (120 μmol), MgI2 (10 mol%), CH2Cl2 (1 mL), 25 °C, 3 h; yields represent isolated and purified products. a

took place and allowed the formal [3+2]- or [4+2]-cycloaddition, respectively, in good to excellent yields.

■

EXPERIMENTAL SECTION

General Experimental. All solvents were distilled before use unless otherwise stated. Air- and moisture-sensitive reactions were carried out in oven-dried or flame-dried glassware, septum-capped

under atmospheric pressure of argon. Commercially available compounds were used without further purification unless otherwise stated. 9237

DOI: 10.1021/acs.joc.7b01631 J. Org. Chem. 2017, 82, 9235−9242

Note

The Journal of Organic Chemistry

1434, 1245, 1180; HRMS (ESI) m/z: [M+Na] + Calcd for C20H21NO4Na 362.1363; Found 362.1364. Diethyl 1-(4-Methoxyphenyl)-5-(p-tolyl)pyrrolidine-3,3-dicarboxylate (5bb). Diethyl 2-(p-tolyl)cyclopropane-1,1-dicarboxylate (27.6 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-methoxyphenyl)-1,3,5triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 10:1) afforded the desired product 5bb (37.4 mg, 90.8 μmol, 91%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 1.10 (t, J = 7.1 Hz, 3 H), 1.24 (t, J = 7.1 Hz, 3 H), 2.30 (s, 3 H), 2.49 (dd, J = 13.0, 6.2 Hz, 1 H), 3.06 (dd, J = 13.0, 8.0 Hz, 1 H), 3.70 (s, 3 H), 3.83 (d, J = 9.7 Hz, 1 H), 3.94−4.15 (m, 2 H), 4.20 (qd, J = 7.1, 5.0 Hz, 2 H), 4.40 (d, J = 9.7 Hz, 1 H), 4.69 (dd, J = 7.7, 6.4 Hz, 1 H), 6.41−6.49 (m, 2 H), 6.70−6.76 (m, 2 H), 7.05−7.15 (m, 4 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 13.8, 14.0, 21.0, 43.1, 55.7, 56.3, 58.5, 61.7, 62.0, 62.7, 114.3, 114.5, 125.9, 129.2, 136.5, 140.0, 141.5, 151.5, 169.7, 170.3 ppm; IR (ATR) ṽ (cm−1): 3045, 2982, 2936, 2907, 1730, 1511, 1465, 1240, 1181; HRMS (ESI) m/z: [M+Na]+ Calcd for C24H29NO5Na 434.1938; Found 434.1941. Diethyl 1-(4-Methoxyphenyl)-5-(m-tolyl)pyrrolidine-3,3-dicarboxylate (5cb). Diethyl 2-(m-tolyl)cyclopropane-1,1-dicarboxylate (27.6 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-methoxyphenyl)-1,3,5triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 10:1) afforded the desired product 5cb (35.1 mg, 85.4 μmol, 85%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 1.10 (t, J = 7.1 Hz, 3 H), 1.24 (t, J = 7.1 Hz, 3 H), 2.30 (s, 3 H), 2.50 (dd, J = 13.0, 6.2 Hz, 1 H), 3.06 (dd, J = 13.0, 8.0 Hz, 1 H), 3.70 (s, 3 H), 3.83 (d, J = 9.8 Hz, 1 H), 3.97−4.11 (m, 2 H), 4.15−4.25 (m, 2 H), 4.41 (d, J = 9.7 Hz, 1 H), 4.67 (dd, J = 7.8, 6.3 Hz, 1 H), 6.44−6.50 (m, 2 H), 6.71− 6.76 (m, 2 H), 6.97−7.08 (m, 3 H), 7.16 (t, J = 7.5 Hz, 1 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 13.8, 14.0, 21.5, 43.1, 55.7, 56.4, 58.6, 61.7, 62.0, 63.1, 114.3, 114.5, 123.0, 126.5, 127.7, 128.4, 138.1, 141.6, 143.1, 151.5, 169.7, 170.3 ppm; IR (ATR) ṽ (cm−1): 3045, 2982, 2936, 2907, 2869, 2833, 1731, 1607, 1511, 1465, 1365, 1240, 1182; HRMS (ESI) m/z: [M+Na]+ Calcd for C24H29NO5Na 434.1938; Found 434.1939. Dimethyl 1-(4-Methoxyphenyl)-5-(o-tolyl)pyrrolidine-3,3-dicarboxylate (5db). Dimethyl 2-(o-tolyl)cyclopropane-1,1-dicarboxylate (24.8 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-methoxyphenyl)-1,3,5triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 8:1) afforded the desired product 5db (33.7 mg, 87.9 μmol, 88%) as a colorless oil. 1 H NMR (600 MHz, CDCl3): δ = 2.42 (s, 3 H), 2.46 (dd, J = 13.0, 5.4 Hz, 1 H), 3.13 (dd, J = 13.0, 8.4 Hz, 1 H), 3.57 (s, 3 H), 3.70 (s, 3 H), 3.77 (s, 3 H), 3.82 (d, J = 9.7 Hz, 1 H), 4.48 (d, J = 9.6 Hz, 1 H), 4.85 (dd, J = 8.4, 5.5 Hz, 1 H), 6.36−6.41 (m, 2 H), 6.71−6.75 (m, 2 H), 7.04−7.08 (m, 1 H), 7.11 (td, J = 7.4, 1.6 Hz, 1 H), 7.14−7.18 (m, 2 H) ppm; 13C NMR (150 MHz, CDCl3): δ = 19.2, 40.8, 52.8, 53.2, 55.7, 56.0, 58.4, 60.4, 114.1, 114.6, 125.3, 126.2, 126.8, 130.6, 134.0, 140.4, 141.3, 151.6, 170.2, 170.6 ppm; IR (ATR) ṽ (cm−1): 3004, 2998, 2953, 2834, 1733, 1511, 1435, 1365, 1241, 1212, 1179; HRMS (ESI) m/z: [M+Na]+ Calcd for C22H25NO5Na 406.1625; Found 406.1628. Dimethyl 5-(4-Methoxyphenyl)-1-phenylpyrrolidine-3,3-dicarboxylate (5ea). Dimethyl 2-(4-methoxyphenyl)cyclopropane-1,1dicarboxylate (26.4 mg, 100 μmol, 1.00 equiv), 1,3,5-triphenyl-1,3,5triazinane (37.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 20:1) afforded the desired product 5ea (27.3 mg, 74.0 μmol, 74%) as a colorless oil. 1 H NMR (600 MHz, CDCl3): δ = 2.54 (dd, J = 13.0, 5.5 Hz, 1 H), 3.08 (dd, J = 13.0, 8.0 Hz, 1 H), 3.56 (s, 3 H), 3.76 (s, 3 H), 3.77 (s, 3 H), 3.90 (d, J = 9.9 Hz, 1 H), 4.43 (d, J = 9.9 Hz, 1 H), 4.78 (dd, J = 7.9, 5.6 Hz, 1 H), 6.50 (d, J = 7.9 Hz, 2H), 6.68 (t, J = 7.3 Hz, 1 H), 6.77−6.85 (m, 2 H), 7.08−7.18 (m, 4 H) ppm; 13C NMR (150 MHz, CDCl3): δ = 43.0, 52.8, 53.2, 55.2, 55.4, 58.3, 61.8, 113.2, 113.9, 116.9,

Scheme 3. Stereospecificity Experiment

Scheme 4. Mechanistic Proposal

Proton (1H) and carbon (13C) NMR spectra were recorded on a 400, 500, or 600 MHz instrument using residual signals from CHCl3, δ = 7.26 ppm and δ = 77.16 ppm as internal references for 1H and 13C chemical shifts, respectively. Additionally, tetramethylsilane (δ = 0.0 ppm) was added to the NMR samples. ESI-HRMS mass spectrometry was carried out on a FTICR instrument. IR spectra were measured on an ATR spectrometer. General Procedure for the Synthesis of 2-Unsubstituted Pyrrolidines (GP 1). A flask (10 mL) containing cyclopropane (1, 100 μmol, 1.00 equiv), triazinane (2, 120 μmol, 1.20 equiv), and MgI2 (10 μmol, 0.10 equiv) was evacuated and purged three times with argon. CH2Cl2 (1 mL) was added to the system, and the mixture was stirred at 25 °C for 1.5 h. The solvent was removed in vacuo, and the residue was purified by silica-gel column chromatography to give the desired compound. Dimethyl 1,5-Diphenylpyrrolidine-3,3-dicarboxylate (5aa). Dimethyl 2-phenylcyclopropane-1,1-dicarboxylate (23.4 mg, 100 μmol, 1.00 equiv), 1,3,5-triphenyl-1,3,5-triazinane (37.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (npentane:EtOAc = 20:1) afforded the desired product 5aa (31.6 mg, 93.2 μmol, 93%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 2.58 (dd, J = 13.0, 5.5 Hz, 1 H), 3.12 (dd, J = 13.0, 8.1 Hz, 1 H), 3.53 (s, 3 H), 3.77 (s, 3 H), 3.93 (d, J = 9.9 Hz, 1 H), 4.46 (d, J = 9.9 Hz, 1 H), 4.84 (dd, J = 8.0, 5.5 Hz, 1 H), 6.38−6.59 (m, 2 H), 6.69 (t, J = 7.3 Hz, 1 H), 7.12−7.17 (m, 2 H), 7.19−7.25 (m, 3 H), 7.26−7.31 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 42.8, 52.8, 53.2, 55.5, 58.4, 62.4, 113.2, 116.9, 125.8, 127.0, 128.5, 128.9, 142.5, 146.5, 170.0, 170.4 ppm. IR (ATR) ṽ (cm−1): 3040, 2985, 2930, 2911, 1729, 1516, 9238

DOI: 10.1021/acs.joc.7b01631 J. Org. Chem. 2017, 82, 9235−9242

Note

The Journal of Organic Chemistry 126.9, 128.9, 134.5, 146.6, 158.5, 170.1, 170.5 ppm; IR (ATR) ṽ (cm−1): 3060, 3027, 2954, 2838, 1733, 1598, 1504, 1434, 1364, 1345, 1244, 1211; HRMS (ESI) m/z: [M+Na]+ Calcd for C21H23NO5Na 392.1468; Found 392.1471. Dimethyl 1-(4-Methoxyphenyl)-5-(naphthalen-2-yl)pyrrolidine3,3-dicarboxylate (5fb). Dimethyl 2-(naphthalen-2-yl)cyclopropane1,1-dicarboxylate (28.4 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4methoxyphenyl)-1,3,5-triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (npentane:EtOAc = 8:1) afforded the desired product 5fb (32.0 mg, 76.2 μmol, 76%) as a colorless oil. 1H NMR (600 MHz, CDCl3): δ = 2.62 (dd, J = 13.1, 5.9 Hz, 1 H), 3.15 (dd, J = 13.1, 8.2 Hz, 1 H), 3.49 (s, 3 H), 3.68 (s, 3 H), 3.78 (s, 3 H), 3.89 (d, J = 9.7 Hz, 1 H), 4.51 (d, J = 9.7 Hz, 1 H), 4.88 (dd, J = 8.0, 6.0 Hz, 1 H), 6.44−6.58 (m, 2 H), 6.69−6.74 (m, 2 H), 7.37 (dd, J = 8.5, 1.8 Hz, 1 H), 7.41−7.48 (m, 2 H), 7.68−7.71 (m, 1 H), 7.73−7.82 (m, 3 H) ppm; 13C NMR (150 MHz, CDCl3): δ = 42.8, 52.8, 53.2, 55.7, 56.4, 58.4, 63.3, 114.4, 114.6, 124.1, 124.7, 125.6, 126.0, 127.6, 127.8, 128.6, 132.7, 133.4, 140.5, 141.4, 151.7, 170.2, 170.6 ppm; IR (ATR) ṽ (cm−1): 3333, 3089, 3050, 2984, 1733, 1666, 1516, 1467, 1313, 1237, 1207, 1187; HRMS (ESI) m/z: [M+Na]+ Calcd for C25H25NO5Na 442.1625; Found 442.1628. Diethyl 5-(4-Acetamidophenyl)-1-(4-methoxyphenyl)pyrrolidine3,3-dicarboxylate (5gb). Diethyl 2-(4-acetamidophenyl)cyclopropane-1,1-dicarboxylate (31.9 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-methoxyphenyl)-1,3,5-triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (npentane:EtOAc = 3:1) afforded the desired product 5gb (32.4 mg, 71.2 μmol, 71%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 1.11 (t, J = 7.1 Hz, 3 H), 1.23 (t, J = 7.1 Hz, 3 H), 2.13 (s, 3 H), 2.48 (dd, J = 13.1, 6.1 Hz, 1 H), 3.05 (dd, J = 13.1, 8.0 Hz, 1 H), 3.69 (s, 3 H), 3.81 (d, J = 9.8 Hz, 1 H), 3.98−4.11 (m, 2 H), 4.14−4.26 (m, 2 H), 4.39 (d, J = 9.7 Hz, 1 H), 4.63−4.71 (m, 1 H), 6.40−6.47 (m, 2 H), 6.65−6.78 (m, 2 H), 7.18 (d, J = 8.5 Hz, 2 H), 7.34 (s, 1 H), 7.40 (d, J = 8.5 Hz, 1 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 13.8, 13.9, 24.5, 42.9, 55.7, 56.3, 58.5, 61.8, 62.0, 62.6, 114.4, 114.5, 120.1, 126.6, 136.7, 139.0, 141.4, 151.6, 168.2, 169.8, 170.2 ppm; IR (ATR) ṽ (cm−1): 3308, 3192, 3046, 2983, 1731, 1667, 1511, 1467, 1312, 1242, 1207, 1182; HRMS (ESI) m/z: [M+Na]+ Calcd for C25H30N2O6Na 477.1996; Found 477.2003. Dimethyl 1-Phenyl-5-(thiophen-2-yl)pyrrolidine-3,3-dicarboxylate (5ha). Dimethyl 2-(thiophen-2-yl)cyclopropane-1,1-dicarboxylate (24.0 mg, 100 μmol, 1.00 equiv), 1,3,5-triphenyl-1,3,5-triazinane (37.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 20:1) afforded the desired product 5ea (30.6 mg, 88.6 μmol, 89%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 2.73 (dd, J = 13.1, 4.9 Hz, 1 H), 3.10 (dd, J = 13.1, 8.1 Hz, 1 H), 3.61 (s, 3 H), 3.76 (s, 3 H), 3.83 (d, J = 9.9 Hz, 1 H), 4.44 (d, J = 9.9 Hz, 1 H), 5.10 (dd, J = 8.0, 4.9 Hz, 1 H), 6.62 (dd, J = 8.8, 1.0 Hz, 2 H), 6.69−6.79 (m, 1 H), 6.86−6.93 (m, 2 H), 7.09− 7.24 (m, 3 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 43.0, 52.9, 53.2, 55.1, 58.5, 58.7, 113.3, 117.5, 123.9, 124.1, 126.6, 128.9, 146.5, 147.5, 169.9, 170.3 ppm; IR (ATR) ṽ (cm−1): 3043, 3000, 2954, 2911, 1731, 1512, 1467, 1333, 1240, 1216, 1191. HRMS (ESI) m/z: [M +Na]+ Calcd for C18H19NO4SNa 368.0927; Found 368.0926. Dimethyl 5-(Furan-2-yl)-1-(4-methoxyphenyl)pyrrolidine-3,3-dicarboxylate (5ib). Dimethyl 2-(furan-2-yl)cyclopropane-1,1-dicarboxylate (22.4 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-methoxyphenyl)1,3,5-triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 10:1) afforded the desired product 5ib (32.4 mg, 90.3 μmol, 90%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 2.82 (dd, J = 13.1, 3.9 Hz, 1 H), 2.94 (dd, J = 13.1, 8.3 Hz, 1 H), 3.62 (s, 3 H), 3.70 (d, J = 9.5 Hz, 1 H), 3.72 (s, 3 H), 3.76 (s, 3 H), 4.31 (d, J = 9.4 Hz, 1 H), 4.82 (dd, J = 8.2, 3.9 Hz, 1 H), 6.04 (dt, J = 3.2, 0.8 Hz, 1 H), 6.23 (dd, J = 3.2, 1.8 Hz, 1 H), 6.52−6.58 (m, 1 H), 6.74−6.82 (m, 2 H), 7.32 (dd, J = 1.8, 0.9 Hz, 1 H) ppm; 13C NMR (100 MHz, CDCl3): δ =

38.9, 52.9, 53.2, 55.0, 55.7, 57.0, 58.6, 106.8, 110.1, 114.0, 114.6, 141.0, 141.7, 151.9, 154.8, 170.0, 170.4 ppm; IR (ATR) ṽ (cm−1): 3045, 2999, 2953, 2907, 2835, 1734, 1511, 1435, 1338, 1240, 1210, 1178; HRMS (ESI) m/z: [M+Na]+ Calcd for C19H21NO6Na 382.1261; Found 382.1264. Dimethyl 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)pyrrolidine3,3-dicarboxylate (5jb). Dimethyl 2-(4-chlorophenyl)cyclopropane1,1-dicarboxylate (26.9 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4methoxyphenyl)-1,3,5-triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (npentane:EtOAc = 10:1) afforded the desired product 5jb (31.9 mg, 79.0 μmol, 79%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 2.49 (dd, J = 13.1, 5.8 Hz, 1 H), 3.07 (dd, J = 13.1, 8.2 Hz, 1 H), 3.58 (s, 3 H), 3.70 (s, 3 H), 3.75 (s, 3 H), 3.81 (d, J = 9.7 Hz, 1 H), 4.42 (d, J = 9.7 Hz, 1 H), 4.68 (dd, J = 8.1, 5.8 Hz, 1 H), 6.32−6.50 (m, 2 H), 6.69−6.81 (m, 2 H), 7.10−7.23 (m, 2 H), 7.21−7.29 (m, 2 H) ppm; 13 C NMR (100 MHz, CDCl3): δ = 42.8, 52.9, 53.2, 55.7, 56.4, 58.3, 62.4, 114.4, 114.6, 127.4, 128.7, 132.6, 141.0, 141.5, 151.9, 170.1, 170.4 ppm; IR (ATR) ṽ (cm−1): 3045, 2998, 2953, 2835, 1733, 1511, 1487, 1435, 1408, 1241, 1210, 1179; HRMS (ESI) m/z: [M+Na]+ Calcd for C21H22ClNO5Na 426.1079; Found 426.1081. Dimethyl 5-(4-Bromophenyl)-1-(4-methoxyphenyl)pyrrolidine3,3-dicarboxylate (5kb). Dimethyl 2-(4-bromophenyl)cyclopropane1,1-dicarboxylate (31.3 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4methoxyphenyl)-1,3,5-triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (npentane:EtOAc = 10:1) afforded the desired product 5kb (32.8 mg, 73.1 μmol, 73%) as a colorless oil. 1H NMR (600 MHz, CDCl3): δ = 2.49 (dd, J = 13.1, 5.8 Hz, 1 H), 3.07 (dd, J = 13.1, 8.2 Hz, 1 H), 3.58 (s, 3 H), 3.70 (s, 3 H), 3.76 (s, 3 H), 3.81 (d, J = 9.7 Hz, 1 H), 4.41 (d, J = 9.7 Hz, 1 H), 4.66 (dd, J = 8.1, 5.8 Hz, 1 H), 6.39−6.45 (m, 2 H), 6.70−6.76 (m, 2 H), 7.09−7.13 (m, 2 H), 7.36−7.44 (m, 2 H) ppm; 13 C NMR (150 MHz, CDCl3): δ = 42.7, 52.9, 53.2, 55.7, 56.3, 58.3, 62.4, 114.4, 114.6, 120.7, 127.7, 131.7, 141.0, 142.0, 151.9, 170.1, 170.4 ppm; IR (ATR) ṽ (cm−1): 3054, 3011, 3000, 2954, 1733, 1515, 1503, 1434, 1322, 1257; HRMS (ESI) m/z: [M+Na] + Calcd for C21H22BrNO5Na 470.0574; Found 470.0575. Dimethyl 1-Phenyl-5-(4-(trifluoromethyl)phenyl)pyrrolidine-3,3dicarboxylate (5la). Dimethyl 2-(4-(trifluoromethyl)phenyl)cyclopropane-1,1-dicarboxylate (30.2 mg, 100 μmol, 1.00 equiv), 1,3,5-triphenyl-1,3,5-triazinane (37.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (npentane:EtOAc = 20:1) afforded the desired product 5la (31.7 mg, 77.7 μmol, 78%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 2.56 (dd, J = 13.1, 5.4 Hz, 1 H), 3.15 (dd, J = 13.1, 8.3 Hz, 1 H), 3.53 (s, 3 H), 3.77 (s, 3 H), 3.93 (d, J = 9.9 Hz, 1 H), 4.48 (d, J = 9.9 Hz, 1 H), 4.89 (dd, J = 8.2, 5.4 Hz, 1 H), 6.48 (dd, J = 8.7, 0.9 Hz, 2 H), 6.68−6.77 (m, 1 H), 7.07−7.23 (m, 2 H), 7.35 (d, J = 8.6 Hz, 2 H), 7.55 (d, J = 8.1 Hz, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 42.5, 52.8, 53.3, 55.6, 58.3, 62.1, 110.9, 113.3, 115.1, 117.5, 118.5, 124.1 (q, 1J = 272.0 Hz), 125.6 (q, 3J = 3.8 Hz), 126.3, 128.1, 129.0, 129.4 (q, 2J = 32.3 Hz), 146.2, 146.8, 169.8, 170.2 ppm; 19F-NMR (400 MHz, CDCl3): δ = −62.8 ppm; IR (ATR) ṽ (cm−1): 3063, 3031, 3009, 2955, 1735, 1599, 1503, 1435, 1323, 1254, 1212; HRMS (ESI) m/z: [M+Na]+ Calcd for C21H20F3NO4Na 430.1237; Found 430.1239. Dimethyl 5-(1,3-Dioxoisoindolin-2-yl)-1-phenylpyrrolidine-3,3-dicarboxylate (5ma). Dimethyl 2-(1,3-dioxoisoindolin-2-yl)cyclopropane-1,1-dicarboxylate (30.3 mg, 100 μmol, 1.00 equiv), 1,3,5-triphenyl-1,3,5-triazinane (37.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (npentane:EtOAc = 4:1) afforded the desired product 5ma (35.9 mg, 88.4 μmol, 88%) as a colorless oil. 1H NMR (600 MHz, CDCl3): δ = 2.97 (dd, J = 14.0, 4.9 Hz, 1 H), 3.23 (dd, J = 13.9, 8.3 Hz, 1 H), 3.77 (s, 3 H), 3.84 (s, 3 H), 4.16 (d, J = 9.5 Hz, 1 H), 4.40 (d, J = 9.5 Hz, 1 H), 6.33 (dd, J = 8.2, 4.9 Hz, 1 H), 6.65 (d, J = 7.9 Hz, 2 H), 6.71 (t, J = 7.3 Hz, 1 H), 7.16 (td, J = 7.4, 1.9 Hz, 2 H), 7.66 (dd, J = 5.5, 3.0 9239

DOI: 10.1021/acs.joc.7b01631 J. Org. Chem. 2017, 82, 9235−9242

Note

The Journal of Organic Chemistry Hz, 2 H), 7.76 (dd, J = 5.5, 3.0 Hz, 2 H) ppm; 13C NMR (150 MHz, CDCl3): δ = 37.5, 53.2, 53.5, 54.2, 58.8, 63.8, 113.3, 118.2, 123.4, 129.3, 131.6, 134.1, 143.4, 167.9, 169.5, 170.9 ppm; IR (ATR) ṽ (cm−1): 3030, 2954, 2887, 1735, 1708, 1599, 1504, 1354, 1307, 1258, 1203, 1124; HRMS (ESI) m/z: [M+Na]+ Calcd for C22H20N2O6Na 431.1214; Found 431.1216. Dimethyl 5-Phenoxy-1-phenylpyrrolidine-3,3-dicarboxylate (5na). Dimethyl 2-phenoxycyclopropane-1,1-dicarboxylate (25.0 mg, 100 μmol, 1.00 equiv), 1,3,5-triphenyl-1,3,5-triazinane (37.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 10:1) afforded the desired product 5na (20.0 mg, 56.4 μmol, 56%) as a colorless oil. 1H NMR (600 MHz, CDCl3): δ = 3.32 (dd, J = 11.9, 4.4 Hz, 1 H), 3.42 (dd, J = 11.9, 7.9 Hz, 1 H), 3.43 (s, 3 H), 3.65 (d, J = 10.6 Hz, 1 H), 3.74 (s, 3 H), 4.21 (d, J = 10.6 Hz, 1 H), 5.10 (d, J = 8.3 Hz, 1 H), 6.62 (t, J = 7.6 Hz, 1 H), 6.74−6.81 (m, 2 H), 6.89 (ddt, J = 8.3, 5.7, 1.0 Hz, 1 H), 7.02 (dd, J = 8.7, 1.0 Hz, 1 H), 7.08 (d, J = 7.6 Hz, 1 H), 7.23−7.32 (m, 4 H) ppm; 13C NMR (150 MHz, CDCl3): δ = 45.9, 50.5, 52.6, 53.1, 54.4, 56.7, 60.7112.9, 116.5, 118.4, 120.1, 120.1, 124.2, 126.3, 129.2, 129.3, 141.4, 147.9, 148.7, 169.6, 170.9 ppm; IR (ATR) ṽ (cm−1): 3063, 3025, 2959, 2987, 2856, 1733, 1519, 1249, 1233, 1177; HRMS (ESI) m/z: [M+Na]+ Calcd for C20H21NO5Na 378.1312; Found 378.1315. Dimethyl 1-(4-Methoxyphenyl)-5-vinylpyrrolidine-3,3-dicarboxylate (5ob). Dimethyl 2-vinylcyclopropane-1,1-dicarboxylate (18.4 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-methoxyphenyl)-1,3,5-triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 10:1) afforded the desired product 5ob (29.1 mg, 91.1 μmol, 91%) as a colorless oil. 1H NMR (600 MHz, CDCl3): δ = 2.45 (dd, J = 13.1, 5.1 Hz, 1 H), 2.82 (dd, J = 13.1, 8.3 Hz, 1 H), 3.68 (d, J = 9.7 Hz, 1 H), 3.74 (s, 6 H), 3.75 (s, 3 H), 4.15−4.21 (m, 2 H), 5.11 (dt, J = 10.2, 1.3 Hz, 1 H), 5.19 (dt, J = 17.2, 1.4 Hz, 1 H), 5.72 (ddd, J = 17.1, 10.2, 6.2 Hz, 1 H), 6.54−6.64 (m, 2 H), 6.79−6.83 (m, 2 H) ppm; 13C NMR (150 MHz, CDCl3): δ = 39.6, 52.9, 53.1, 55.6, 55.8, 58.3, 61.4, 114.3, 114.6, 115.8, 139.3, 141.5, 151.7, 170.4, 170.6 ppm; IR (ATR) ṽ (cm−1): 3043, 2999, 2954, 2909, 2836, 1734, 1511, 1435, 1241, 1213, 1180; HRMS (ESI) m/z: [M+Na]+ Calcd for C17H21NO5Na 342.1312; Found 342.1314. Dimethyl 1-(4-Methoxyphenyl)-5-phenylpyrrolidine-3,3-dicarboxylate (5ab). Dimethyl 2-phenylcyclopropane-1,1-dicarboxylate (23.4 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-methoxyphenyl)-1,3,5triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 10:1) afforded the desired product 5ab (33.8 mg, 91.6 μmol, 92%) as a colorless oil. 1 H NMR (600 MHz, CDCl3): δ = 2.54 (dd, J = 13.1, 5.9 Hz, 1 H), 3.08 (dd, J = 13.0, 8.1 Hz, 1 H), 3.56 (s, 3 H), 3.70 (s, 3 H), 3.76 (s, 3 H), 3.84 (d, J = 9.7 Hz, 1 H), 4.42 (d, J = 9.7 Hz, 1 H), 4.72 (dd, J = 7.9, 6.0 Hz, 1 H), 6.35−6.50 (m, 2 H), 6.66−6.78 (m, 2 H), 7.18−7.24 (m, 3 H), 7.26−7.30 (m, 2 H) ppm; 13C NMR (150 MHz, CDCl3): δ = 43.0, 52.8, 53.2, 55.7, 56.3, 58.4, 62.9, 114.3, 114.6, 125.9, 127.0, 128.6, 141.3, 142.9, 151.6, 170.2, 170.6 ppm; IR (ATR) ṽ (cm−1): 3059, 3030, 2954, 2826, 1731, 1594, 1516, 1452, 1425, 1187; HRMS (ESI) m/z: [2 M+Na]+ Calcd for C42H46N2O10Na 761.2693; Found 761.2694. Dimethyl 1-(2-Methoxyphenyl)-5-phenylpyrrolidine-3,3-dicarboxylate (5ac). Dimethyl 2-phenylcyclopropane-1,1-dicarboxylate (23.4 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(2-methoxyphenyl)-1,3,5triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 5:1) afforded the desired product 5ac (30.7 mg, 83.0 μmol, 83%) as a colorless oil; 1 H NMR (600 MHz, CDCl3): δ = 2.36 (dd, J = 13.0, 9.9 Hz, 1 H), 2.99 (dd, J = 13.0, 6.5 Hz, 1 H), 3.66 (d, J = 10.7 Hz, 1 H), 3.76 (s, 3 H), 3.76 (s, 3 H), 3.82 (s, 3 H), 4.69 (d, J = 10.8 Hz, 1 H), 4.83 (dd, J = 9.9, 6.5 Hz, 1 H), 6.57−6.61 (m, 1 H), 6.68 (ddd, J = 8.0, 6.5, 2.3 Hz, 1 H), 6.74−6.82 (m, 2 H), 7.11−7.17 (m, 1 H), 7.19−7.24 (m, 2

H), 7.28 (dd, J = 8.1, 1.1 Hz, 2 H) ppm; 13C NMR (150 MHz, CDCl3): δ = 43.1, 52.9, 53.0, 55.6, 58.3, 58.6, 62.9, 112.0, 117.7, 120.8, 120.8, 126.4, 127.0, 128.4, 137.4, 142.1, 151.2, 170.7, 171.4 ppm; IR (ATR) ṽ (cm−1): 3062, 3029, 2953, 2836, 1732, 1595, 1501, 1453, 1435, 1250; HRMS (ESI) m/z: [M+Na]+ Calcd for C21H23NO5Na 392.1468; Found 392.1472. Dimethyl 5-Phenyl-1-(p-tolyl)pyrrolidine-3,3-dicarboxylate (5ad). Dimethyl 2-phenylcyclopropane-1,1-dicarboxylate (23.4 mg, 100 μmol, 1.00 equiv), 1,3,5-tri-p-tolyl-1,3,5-triazinane (42.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 15:1) afforded the desired product 5ad (27.5 mg, 77.9 μmol, 78%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 2.19 (s, 3 H), 2.54 (dd, J = 13.0, 5.7 Hz, 1 H), 3.09 (dd, J = 13.0, 8.1 Hz, 1 H), 3.52 (s, 3 H), 3.74 (s, 3 H), 3.88 (d, J = 9.8 Hz, 1 H), 4.43 (d, J = 9.8 Hz, 1 H), 4.77 (dd, J = 8.0, 5.8 Hz, 1 H), 6.35−6.48 (m, 2 H), 6.87−6.99 (m, 2 H), 7.12−7.32 (m, 5 H) ppm; 13C NMR (125 MHz, CDCl3): δ = 20.2, 42.9, 52.7, 53.1, 55.8, 58.3, 62.5, 113.2, 125.8, 126.0, 126.9, 128.5, 129.4, 142.8, 144.4, 170.0, 170.5 ppm; IR (ATR) ṽ (cm−1):3062, 3028, 3009, 2861, 1733, 1618, 1518, 1450, 1343, 1249; HRMS (ESI) m/z: [M+Na]+ Calcd for C21H23NO4Na 376.1519; Found 376.1522. Dimethyl 1-(4-Fluorophenyl)-5-phenylpyrrolidine-3,3-dicarboxylate (5ae). Dimethyl 2-phenylcyclopropane-1,1-dicarboxylate (23.4 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-fluorophenyl)-1,3,5-triazinane (44.3 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 12:1) afforded the desired product 5ae (24.0 mg, 67.1 μmol, 67%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 2.56 (dd, J = 13.1, 5.9 Hz, 1 H), 3.10 (dd, J = 13.1, 8.1 Hz, 1 H), 3.55 (s, 3 H), 3.77 (s, 3 H), 3.88 (d, J = 9.7 Hz, 1 H), 4.41 (d, J = 9.7 Hz, 1 H), 4.75 (dd, J = 7.9, 6.0 Hz, 1 H), 6.28−6.49 (m, 2 H), 6.73−6.90 (m, 2 H), 7.19−7.23 (m, 3 H), 7.27− 7.31 (m, 2 H) ppm; 13C NMR (125 MHz, CDCl3): δ = 43.0, 52.8, 53.2, 56.1, 58.4, 62.8, 113.9 (d, 3J = 7.3 Hz), 115.3 (d, 2J = 22.2 Hz), 125.8, 127.1, 128.6, 142.4, 143.1, 155.5 (d, 1J = 235.4 Hz), 170.0, 170.5 ppm; 19F-NMR (283 MHz, CDCl3): δ = −133.0 ppm; IR (ATR) ṽ (cm−1): 3056, 3028, 2954, 2848, 1734, 1506, 1451, 1365, 1254, 1210; HRMS (ESI) m/z: [M+Na]+ Calcd for C20H20FNO4Na 380.1269; Found 380.1271. Dimethyl 1-(4-Chlorophenyl)-5-phenylpyrrolidine-3,3-dicarboxylate (5af). Dimethyl 2-phenylcyclopropane-1,1-dicarboxylate (23.4 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-chlorophenyl)-1,3,5-triazinane (50.2 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (n-pentane:EtOAc = 15:1) afforded the desired product 5af (29.6 mg, 79.2 μmol, 79%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 2.44−2.69 (m, 1 H), 3.11 (dd, J = 13.1, 8.0 Hz, 1 H), 3.54 (s, 3 H), 3.76 (s, 3 H), 3.91 (d, J = 9.9 Hz, 1 H), 4.38 (d, J = 9.9 Hz, 1 H), 4.78 (dd, J = 7.8, 6.0 Hz, 1 H), 6.29−6.50 (m, 2 H), 7.00−7.12 (m, 2 H), 7.15−7.23 (m, 3 H), 7.24−7.34 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 42.9, 52.9, 53.3, 55.7, 58.4, 62.5, 114.3, 122.0, 125.8, 127.2, 128.7, 128.7, 142.0, 145.0, 169.8, 170.4 ppm; IR (ATR) ṽ (cm−1):3028, 3004, 2953, 2848, 1733, 1599, 1496, 1450, 1434, 1364, 1251, 1211; HRMS (ESI) m/z: [M+Na]+ Calcd for C20H20ClNO4Na 396.0973; Found 396.0976. Dimethyl 1-(4-Bromophenyl)-5-(4-methoxyphenyl)pyrrolidine3,3-dicarboxylate (5eg). Dimethyl 2-(4-methoxyphenyl)cyclopropane-1,1-dicarboxylate (26.4 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-bromophenyl)-1,3,5-triazinane (66.2 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (npentane:EtOAc = 10:1) afforded the desired product 5eg (35.9 mg, 80.0 μmol, 80%) as a colorless solid. mp = 80−83 °C; 1H NMR (600 MHz, CDCl3): δ = 2.52 (dd, J = 13.1, 6.0 Hz, 1 H), 3.07 (dd, J = 13.1, 7.9 Hz, 1 H), 3.57 (s, 3 H), 3.76 (s, 3 H), 3.77 (s, 3 H), 3.88 (d, J = 9.9 Hz, 1 H), 4.36 (d, J = 9.9 Hz, 1 H), 4.72 (dd, J = 7.6, 6.2 Hz, 1 H), 6.32−6.38 (m, 2 H), 6.78−6.84 (m, 2 H), 7.07−7.11 (m, 2 H), 7.17− 7.23 (m, 2 H) ppm; 13C NMR (150 MHz, CDCl3): δ = 43.1, 52.9, 53.3, 55.2, 55.5, 58.3, 61.9, 109.1, 114.0, 114.8, 126.9, 131.6, 133.8, 9240

DOI: 10.1021/acs.joc.7b01631 J. Org. Chem. 2017, 82, 9235−9242

Note

The Journal of Organic Chemistry 145.5, 158.7, 169.9, 170.4 ppm; IR (ATR) ṽ (cm−1): 3001, 2954, 2838, 1733, 1591, 1509, 1494, 1434, 1366, 1245, 1211, 1170; HRMS (ESI) m/z: [M+Na]+ Calcd for C21H22BrNO5Na 470.0574; Found 470.0572. Dimethyl 5-Phenyl-1-(3-(trifluoromethyl)phenyl)pyrrolidine-3,3dicarboxylate (5ah). Dimethyl 2-phenylcyclopropane-1,1-dicarboxylate (23.4 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(3-(trifluoromethyl)phenyl)-1,3,5-triazinane (62.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 1. Silica gel column chromatography (npentane:EtOAc = 15:1) afforded the desired product 5ah (33.2 mg, 81.4 μmol, 81%) as a colorless oil. 1H NMR (500 MHz, CD3CN): δ = 2.51 (dd, J = 13.2, 6.5 Hz, 1 H), 3.10 (ddd, J = 13.2, 7.8, 0.6 Hz, 1 H), 3.56 (s, 3 H), 3.72 (s, 3 H), 4.01 (d, J = 10.2 Hz, 1 H), 4.34 (d, J = 10.2 Hz, 1 H), 4.85−4.92 (m, 1 H), 6.67−6.76 (m, 2 H), 6.87−6.92 (m, 1 H), 7.20−7.27 (m, 4 H), 7.28−7.34 (m, 2 H) ppm; 13C NMR (125 MHz, CD3CN): δ = 43.5, 53.6, 53.9, 56.2, 59.4, 62.9, 110.1 (q, 3J = 4.1 Hz), 113.8 (q, 3J = 3.9 Hz), 117.6, 125.6 (d, 1J = 271.6 Hz) 127.0, 128.3, 129.7, 130.5, 131.4 (q, 2J = 31.3 Hz), 143.3, 147.8, 170.6, 171.2 ppm; 19F-NMR (283 MHz, CD3CN): δ = −62.3 ppm; IR (ATR) ṽ (cm−1): 3062, 3031, 3006, 2956, 1735, 1611, 1586, 1498, 1456, 1371, 1254; HRMS (ESI) m/z: [M+Na] + Calcd for C21H20F3NO4Na 430.1237; Found 430.1241. General Procedure 2 for the Synthesis of 2-Unsubstituted Piperidines. A flask (10 mL) containing cyclobutane (6; 100 μmol, 1.00 equiv), triazinane (2, 120 μmol, 1.20 equiv) and MgI2 (0.10 μmol, 0.10 equiv) was evacuated and purged three times with argon. CH2Cl2 (1 mL) was added to the system, and the mixture was stirred at 25 °C for 3 h. The solvent was removed in vacuo, and the residue was purified by silica-gel column chromatography to give the desired compound. Dimethyl 1,6-Diphenylpiperidine-3,3-dicarboxylate (7aa). Dimethyl 2-phenylcyclobutane-1,1-dicarboxylate (24.8 mg, 100 μmol, 1.00 equiv), 1,3,5-triphenyl-1,3,5-triazinane (37.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 2. Silica gel column chromatography (npentane:EtOAc = 20:1) afforded the desired product 7aa (19.9 mg, 56.3 μmol, 56%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 2.03−2.16 (m, 3 H), 2.21−2.36 (m, 1 H), 3.72 (s, 3 H), 3.75 (d, J = 13.1 Hz, 1 H), 3.84 (s, 3 H), 3.92 (dd, J = 13.1, 1.1 Hz, 1 H), 4.40 (t, J = 5.9 Hz, 1 H), 6.80 (tt, J = 7.5, 1.1 Hz, 1 H), 6.90−6.96 (m, 2 H), 7.09−7.17 (m, 3 H), 7.17−7.25 (m, 4 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 28.4, 30.7, 52.6, 52.7, 54.8, 55.5, 60.3, 120.0, 120.8, 126.6, 127.1, 128.3, 128.7, 141.9, 150.8, 170.6, 170.7 ppm; IR (ATR) ṽ (cm−1): 3084, 3060, 3027, 3003, 2953, 1730, 1597, 1493, 1434, 1391, 1374, 1234; HRMS (ESI) m/z: [M+Na]+ Calcd for C21H23NO4Na 376.1519; Found 376.1521. Dimethyl 6-(3,4-Dimethoxyphenyl)-1-phenylpiperidine-3,3-dicarboxylate (7ba). Dimethyl 2-(3,4-dimethoxyphenyl)cyclobutane-1,1dicarboxylate (30.8 mg, 100 μmol, 1.00 equiv), 1,3,5-triphenyl-1,3,5triazinane (37.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 2. Silica gel column chromatography (n-pentane:EtOAc = 4:1) afforded the desired product 7ba (27.8 mg, 67.2 μmol, 67%) as a colorless oil. 1 H NMR (400 MHz, CDCl3): δ = 2.07 (tq, J = 8.4, 3.7 Hz, 3 H), 2.23−2.36 (m, 1 H), 3.71 (s, 3 H), 3.73 (s, 3 H), 3.77 (d, J = 6.2 Hz, 1 H), 3.80 (s, 3 H), 3.83 (s, 3 H), 3.86 (d, J = 6.2 Hz, 1 H), 4.33 (t, J = 5.9 Hz, 1 H), 6.67−6.73 (m, 3 H), 6.77−6.83 (m, 1 H), 6.89−6.97 (m, 2 H), 7.12 (tt, J = 7.4, 2.1 Hz, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 28.4, 30.6, 52.6, 54.8, 55.6, 55.7, 55.7, 60.0, 110.4, 110.8, 119.3, 120.2, 120.9, 128.7, 134.5, 147.5, 148.8, 151.0, 170.6, 170.7 ppm; IR (ATR) ṽ (cm−1): 3058, 3000, 2953, 2836, 1731, 1593, 1513, 1436, 1255, 1231, 1136; HRMS (ESI) m/z: [M+Na]+ Calcd for C23H27NO6Na 436.1731; Found 436.1731. Dimethyl 6-(4-Methoxyphenyl)-1-phenylpiperidine-3,3-dicarboxylate (7ca). Dimethyl 2-(4-methoxyphenyl)cyclobutane-1,1-dicarboxylate (27.8 mg, 100 μmol, 1.00 equiv), 1,3,5-triphenyl-1,3,5-triazinane (37.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 2. Silica gel column chromatography (n-pentane:EtOAc = 8:1) afforded the desired product 7ca (28.6 mg, 74.7 μmol, 75%) as a colorless oil.

H NMR (400 MHz, CDCl3): δ = 2.02−2.13 (m, 3 H), 2.21−2.32 (m, 1 H), 3.72 (s, 3 H), 3.73 (s, 3 H), 3.75 (d, J = 12.9 Hz, 1 H), 3.83 (s, 3 H), 3.88 (dd, J = 13.1, 1.0 Hz, 1 H), 4.36 (t, J = 5.8 Hz, 1 H), 6.72− 6.77 (m, 2 H), 6.80 (tt, J = 7.6, 1.1 Hz, 1 H), 6.89−6.95 (m, 2 H), 7.06−7.19 (m, 4 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 28.4, 30.6, 52.6, 52.7, 54.8, 55.1, 55.4, 59.6, 113.7, 120.0, 120.7, 128.2, 128.7,, 133.8, 150.9, 158.1, 170.6, 170.7 ppm; IR (ATR) ṽ (cm−1): 3011, 3001, 2955, 2865, 1728, 1592, 1502, 1497, 1265, 1223; HRMS (ESI) m/z: [M+Na]+ Calcd for C22H25NO5Na 406.1625; Found 406.1629. Dimethyl 1-(4-Chlorophenyl)-6-(4-methoxyphenyl)piperidine3,3-dicarboxylate (7cb). Dimethyl 2-(4-methoxyphenyl)cyclobutane1,1-dicarboxylate (27.8 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4chlorophenyl)-1,3,5-triazinane (50.2 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 2. Silica gel column chromatography (npentane:EtOAc = 8:1) afforded the desired product 7cb (28.8 mg, 68.9 μmol, 69%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 1.98−2.11 (m, 3 H), 2.28 (td, J = 10.8, 6.6 Hz, 1 H), 3.65 (d, J = 13.0 Hz, 1 H), 3.72 (s, 3 H), 3.73 (s, 3 H), 3.83 (s, 3 H), 3.88 (d, J = 13.1 Hz, 1 H), 4.27 (t, J = 4.8 Hz, 1 H), 6.71−6.78 (m, 2 H), 6.81−6.86 (m, 2 H), 7.03−7.09 (m, 4 H) ppm; 13C NMR (100 MHz, CDCl3): δ = 28.4, 30.8, 52.7, 54.8, 55.1, 55.6, 60.0, 68.7, 113.8, 119.0, 121.5, 125.8, 128.1, 128.6, 129.0, 129.2, 133.5, 149.5, 158.2, 170.4, 170.6 ppm; IR (ATR) ṽ (cm−1): 3033, 2999, 2953, 2837, 1731, 1594, 1510, 1492, 1278, 1234; HRMS (ESI) m/z: [M+Na] + Calcd for C22H24ClNO5Na 440.1235; Found 440.1237. Dimethyl 1,6-Bis(4-methoxyphenyl)piperidine-3,3-dicarboxylate (7cc). Dimethyl 2-(4-methoxyphenyl)cyclobutane-1,1-dicarboxylate (27.8 mg, 100 μmol, 1.00 equiv), 1,3,5-tris(4-methoxyphenyl)-1,3,5triazinane (48.6 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 2. Silica gel column chromatography (n-pentane:EtOAc = 5:1) afforded the desired product 7cc (29.2 mg, 70.6 μmol, 71%) as a colorless oil. 1 H NMR (500 MHz, CD3CN): δ = 1.84 (ddd, J = 7.8, 4.6, 2.7 Hz, 3 H), 2.38−2.44 (m, 1 H), 3.12 (d, J = 12.2 Hz, 1 H), 3.64 (s, 3 H), 3.65 (s, 3 H), 3.66 (s, 3 H), 3.75 (dd, J = 12.2, 2.2 Hz, 1 H), 3.85 (s, 3 H), 3.98−4.02 (m, 1 H), 6.63−6.72 (m, 4 H), 6.88−6.93 (m, 2 H), 7.06− 7.12 (m, 2 H) ppm; 13C NMR (125 MHz, CD3CN): δ = 30.7, 34.1, 53.2, 53.3, 55.7, 55.8, 56.1, 61.6, 63.6, 114.3, 114.7, 126.3, 129.5, 137.1, 146.3, 156.7, 159.2, 171.3, 171.8 ppm; IR (ATR) ṽ (cm−1): 3034, 2997, 2952, 2835, 1730, 1611, 1507, 1437, 1278, 1233; HRMS (ESI) m/z: [M+Na]+ Calcd for C23H27NO6Na 436.1731; Found 436.1733. Dimethyl 6-(4-Methoxyphenyl)-1-(p-tolyl)piperidine-3,3-dicarboxylate (7cd). Dimethyl 2-(4-methoxyphenyl)cyclobutane-1,1-dicarboxylate (27.8 mg, 100 μmol, 1.00 equiv), 1,3,5-tri-p-tolyl-1,3,5triazinane (42.8 mg, 120 μmol, 1.20 equiv), and MgI2 (2.78 mg, 10.0 μmol, 0.10 equiv) in CH2Cl2 (1 mL) were reacted according to GP 2. Silica gel column chromatography (n-pentane:EtOAc = 5:1) afforded the desired product 7cd (29.0 mg, 72.9 μmol, 73%) as a colorless oil. 1 H NMR (500 MHz, CD3CN): δ = 1.85−1.91 (m, 3 H), 2.15 (s, 3 H), 2.34 (ddt, J = 8.5, 3.9, 2.3 Hz, 1 H), 3.27 (d, J = 12.4 Hz, 1 H), 3.65 (s, 3 H), 3.67 (s, 3 H), 3.79 (dd, J = 12.4, 1.9 Hz, 1 H), 3.83 (s, 3 H), 4.14 (dd, J = 8.4, 4.6 Hz, 1 H), 6.66−6.73 (m, 2 H), 6.82−6.88 (m, 2 H), 6.92 (ddt, J = 9.0, 2.5, 1.3 Hz, 2 H), 7.07−7.12 (m, 2 H) ppm; 13C NMR (125 MHz, CD3CN): δ = 20.6, 30.2, 33.4, 53.3, 53.3, 55.7, 55.9, 59.9, 62.2, 114.4, 123.7, 129.4, 130.2, 132.7, 136.7, 150.4, 159.2, 171.3, 171.7 ppm; IR (ATR) ṽ (cm−1): 2999, 2952, 2857, 2836, 1731, 1612, 1510, 1435, 1237; HRMS (ESI) m/z: [M+Na] + Calcd for C23H27NO5Na 420.1781; Found 420.1784. 1

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01631. Copies of 1H and 13C NMR spectra of all new compounds (PDF) X-ray crystallographic data of compound 5eg (CIF) 9241

DOI: 10.1021/acs.joc.7b01631 J. Org. Chem. 2017, 82, 9235−9242

Note

The Journal of Organic Chemistry

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T. J. Am. Chem. Soc. 2016, 138, 6598. (e) Wallbaum, J.; Garve, L. K. B.; Jones, P. G.; Werz, D. B. Org. Lett. 2017, 19, 98. (f) Ilchenko, N. O.; Hedberg, M.; Szabó, K. J. Chem. Sci. 2017, 8, 1056. (11) (a) Reissig, H.-U.; Hirsch, E. Angew. Chem., Int. Ed. Engl. 1980, 19, 813. (b) Brückner, C.; Reissig, H.-U. Angew. Chem., Int. Ed. Engl. 1985, 24, 588. (12) (a) Schneider, T. F.; Kaschel, J.; Awan, S. I.; Dittrich, B.; Werz, D. B. Chem. - Eur. J. 2010, 16, 11276. (b) Schneider, T. F.; Werz, D. B. Org. Lett. 2011, 13, 1848. (c) Kaschel, J.; Schneider, T. F.; Kratzert, D.; Stalke, D.; Werz, D. B. Angew. Chem., Int. Ed. 2012, 51, 11153. (d) Kaschel, J.; Schmidt, C. D.; Mumby, M.; Kratzert, D.; Stalke, D.; Werz, D. B. Chem. Commun. 2013, 49, 4403. (13) Garve, L. K. B.; Jones, P. G.; Werz, D. B. Angew. Chem., Int. Ed. 2017, 56, 9226. (14) (a) CrysAlisPro, Agilent Technologies: Oxford, U.K., 2013. (b) . Sheldrick, G. M. SHELXL-97; University of Göttingen: Germany, 1997. (c) Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112−122. (15) The CIF File has been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-1556214 (5eg). (16) (a) Parsons, A. T.; Johnson, J. S. J. Am. Chem. Soc. 2009, 131, 14202. (b) Moustafa, M. M. A. R.; Pagenkopf, B. L. Org. Lett. 2010, 12, 4732. (c) Stevens, A. C.; Palmer, C.; Pagenkopf, B. L. Org. Lett. 2011, 13, 1528. (d) de Nanteuil, F.; Waser, J. Angew. Chem., Int. Ed. 2013, 52, 9009. (e) Shenje, R.; Martin, M. C.; France, S. Angew. Chem., Int. Ed. 2014, 53, 13907. (f) Vemula, N.; Stevens, A. C.; Schon, T. B.; Pagenkopf, B. L. Chem. Commun. 2014, 50, 1668. (17) (a) Hu, J.-L.; Wang, L.; Xu, H.; Xie, Z.; Tang, Y. Org. Lett. 2015, 17, 2680. (b) Perrotta, D.; Racine, S.; Vuilleumier, J.; de Nanteuil, F.; Waser, J. Org. Lett. 2015, 17, 1030. (c) Reissig, H.-U.; Zimmer, R. Angew. Chem., Int. Ed. 2015, 54, 5009. (d) Vemula, N.; Pagenkopf, B. L. Eur. J. Org. Chem. 2015, 2015, 4900. (e) Levens, A.; Ametovski, A.; Lupton, D. W. Angew. Chem., Int. Ed. 2016, 55, 16136. (f) Feng, L.-W.; Ren, H.; Xiong, H.; Wang, P.; Wang, L.; Tang, Y. Angew. Chem., Int. Ed. 2017, 56, 3055. (18) Chakrabarty, S.; Chatterjee, I.; Wibbeling, B.; Daniliuc, C. G.; Studer, A. Angew. Chem., Int. Ed. 2014, 53, 5964.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] ORCID

Daniel B. Werz: 0000-0002-3973-2212 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Studienstiftung des deutschen Volkes (Ph.D. fellowship to L.K.B.G.) and CaSuS program (Catalysis for Sustainable Synthesis) of the State of Lower Saxony (Lichtenberg fellowship to A.K.).

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REFERENCES

(1) Buckingham, J.; Baggaley, K. H.; Roberts, A. D.; Szabó, L. F. Dictionary of Alkaloids; CRC Press: Boca Raton, 2010. (2) Li, J.; Zhao, H.; Zhang, Y. Synlett 2015, 26, 2745. (3) For reviews see: (a) Pandey, G.; Banerjee, P.; Gadre, S. R. Chem. Rev. 2006, 106, 4484. (b) Hashimoto, T.; Maruoka, K. Chem. Rev. 2015, 115, 5366. (c) Narayan, R.; Potowski, M.; Jia, Z.-J.; Antonchick, A.; Waldmann, H. Acc. Chem. Res. 2014, 47, 1296. (d) Adrio, J.; Carretero, J. C. Chem. Commun. 2014, 50, 12434. (4) (a) Carson, C. A.; Kerr, M. A. J. Org. Chem. 2005, 70, 8242. (b) Kang, Y.-B.; Tang, Y.; Sun, X.-L. Org. Biomol. Chem. 2006, 4, 299. (c) Parsons, A. T.; Smith, A. G.; Neel, A. J.; Johnson, J. S. J. Am. Chem. Soc. 2010, 132, 9688. (5) For selected reviews see: (a) Reissig, H.-U.; Zimmer, R. Chem. Rev. 2003, 103, 1151. (b) Cavitt, M. A.; Phun, L. H.; France, S. Chem. Soc. Rev. 2014, 43, 804. (c) Schneider, T. F.; Kaschel, J.; Werz, D. B. Angew. Chem., Int. Ed. 2014, 53, 5504. (6) (a) Kaicharla, T.; Roy, T.; Thangaraj, M.; Gonnade, R. G.; Biju, A. T. Angew. Chem., Int. Ed. 2016, 55, 10061. (b) Sabbatani, J.; Maulide, N. Angew. Chem., Int. Ed. 2016, 55, 6780. (c) Curiel Tejeda, J. E.; Irwin, L. C.; Kerr, M. A. Org. Lett. 2016, 18, 4738. (d) Wang, D.-C.; Xie, M.-S.; Guo, H.-M.; Qu, G.-R.; Zhang, M.-C.; You, S.-L. Angew. Chem., Int. Ed. 2016, 55, 14111. (e) Dey, R.; Banerjee, P. Org. Lett. 2017, 19, 304. (7) (a) Zhou, Y.-Y.; Li, J.; Ling, L.; Liao, S.-H.; Sun, X.-L.; Li, Y.-X.; Wang, L.-J.; Tang, Y. Angew. Chem., Int. Ed. 2013, 52, 1452. (b) Talukdar, R.; Tiwari, D. P.; Saha, A.; Ghorai, M. K. Org. Lett. 2014, 16, 3954. (c) Cheng, Q.-Q.; Qian, Y.; Zavalij, P. Y.; Doyle, M. P. Org. Lett. 2015, 17, 3568. (d) Liu, Q.-J.; Yan, W.-G.; Wang, L.; Zhang, X. P.; Tang, Y. Org. Lett. 2015, 17, 4014. (e) Ma, W.; Fang, J.; Ren, J.; Wang, Z. Org. Lett. 2015, 17, 4180. (f) Garve, L. K. B.; Petzold, M.; Jones, P. G.; Werz, D. B. Org. Lett. 2016, 18, 564. (g) Chidley, T.; Vemula, N.; Carson, C. A.; Kerr, M. A.; Pagenkopf, B. L. Org. Lett. 2016, 18, 2922. (h) Das, S.; Chakrabarty, S.; Daniliuc, C. G.; Studer, A. Org. Lett. 2016, 18, 2784. (i) Mondal, K.; Pan, S. C. Eur. J. Org. Chem. 2017, 2017, 534. (8) (a) Ivanova, O. A.; Budynina, E. M.; Grishin, Y. K.; Trushkov, I. V.; Verteletskii, P. V. Angew. Chem., Int. Ed. 2008, 47, 1107. (b) Xu, H.; Hu, J.-L.; Wang, L.; Liao, S.; Tang, Y. J. Am. Chem. Soc. 2015, 137, 8006. (c) Garve, L. K. B.; Pawliczek, M.; Wallbaum, J.; Jones, P. G.; Werz, D. B. Chem. - Eur. J. 2016, 22, 521. (d) Zhang, C.; Tian, J.; Ren, J.; Wang, Z. Chem. - Eur. J. 2017, 23, 1231. (9) (a) Kang, Q.-K.; Wang, L.; Liu, Q.-J.; Li, J. F.; Tang, Y. J. Am. Chem. Soc. 2015, 137, 14594. (b) Xia, Y.; Lin, L.; Chang, F.; Fu, X.; Liu, X.; Feng, X. Angew. Chem., Int. Ed. 2015, 54, 13748. (c) Budynina, E. M.; Ivanov, K. L.; Chagarovskiy, A. O.; Rybakov, V. B.; Trushkov, I. V.; Melnikov, M. Y. Chem. - Eur. J. 2016, 22, 3692. (d) Nguyen, T. N.; Nguyen, T. S.; May, J. A. Org. Lett. 2016, 18, 3786. (10) (a) Sparr, C.; Gilmour, R. Angew. Chem., Int. Ed. 2011, 50, 8391. (b) Garve, L. K. B.; Barkawitz, P.; Jones, P. G.; Werz, D. B. Org. Lett. 2014, 16, 5804. (c) Das, S.; Daniliuc, C. G.; Studer, A. Org. Lett. 2016, 18, 5576. (d) Pitts, C. R.; Ling, B.; Snyder, J. A.; Bragg, A. E.; Lectka, 9242

DOI: 10.1021/acs.joc.7b01631 J. Org. Chem. 2017, 82, 9235−9242