A Bulky Disulfoxide Ligand for Pd-Catalyzed ... - ACS Publications

Apr 19, 2017 - School of Chemistry and Chemical Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei 230009, China. •S Supporting ...
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A Bulky Disulfoxide Ligand for Pd-Catalyzed Oxidative Allylic C−H Amination with 2,2,2-Trichloroethyl Tosyl Carbamate You-Gui Li,* Li Li, Ming-Yue Yang, Gang He, and Eric Assen B. Kantchev* School of Chemistry and Chemical Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei 230009, China S Supporting Information *

ABSTRACT: Challenging substrates and conditions in homogeneous catalysis pose stringent demands on the ligands used. A novel, bulky, 1-adamantyl-substituted disulfoxide ligand designed after a systematic evaluation of the electronic and steric properties of disulfoxide substituents permits the allylic oxidative C−N coupling reaction to proceed at lower catalyst loading while requiring a smaller excess of reagents. Additionally, this ligand improves the yields when TsNHCOOCH2CCl3, a novel reagent that permits deprotection of the products under both acidic and basic conditions, is used.

C

arbon-nitrogen bonds are ubiquitous in natural and manmade bioactive organic compounds. Therefore, the development of synthetic methods for C−N bond formation is an enduring theme in organic synthetic chemistry.1 In the case of amines,2 prior installation of an oxygen-containing functional group or a halogen is usually required. Subsequent introduction of amine requires labor intensive and wastegenerating functional group interconversions. Hence, the direct amination of a C−H bond is a prized alternative.3 Allylic C−H bonds are amenable to selective activation under mild conditions because of their lower bond dissociation energy.4 Since 2004, mild and functional-group tolerant allylic oxidative esterification,5 intermolecular amination,6 enolate allylation,7 and related8 reactions have been developed mainly by M. C. White’s group by using just two disulfoxide ligands. Sulfoxides are electronically and structurally similar to the ubiquitous P(III) ligands. Despite their ease of synthesis, S-center chirality, low toxicity, and tolerance to air, moisture, and long-term storage, sulfoxide ligands are still quite underrepresented9 in transition metal-catalyzed organic synthetic methods.10 It is conceivable that a systematic exploration of the disulfoxide ligand diversity space could yield ligands that lead to improvements in important parameters of the synthetic protocol such as catalyst loading or substrate scope. First, we demonstrate the effect of electronic and steric properties of the sulfoxide substituents on the allylic oxidative C−N coupling reaction. These properties can be systematically and independently investigated with a set of disulfoxides (1− 10; Figure 1) prepared (Scheme 1) by oxidation of the corresponding disulfides (1a−10a) with H2O2 or mCPBA (for 6, 7, and 9). The disulfides in turn were accessed from 1,2dibromoethane and the required thiols in the presence of KOH in MeOH. The set includes the two widely used disulfoxides developed by White’s group (3 and 8). The activity of the sulfoxide ligands 1−10 was evaluated for the C−N coupling of allylbenzene (11a) with only 1.1 equiv each of the amination reagent TsNHCOOMe (12a) and the © 2017 American Chemical Society

Figure 1. A rationally designed disulfoxide ligand set (1−10) with variable σ-donicity and steric bulk.

Scheme 1. Disulfoxide Ligand Synthesis

stoichiometic oxidant 2,6-DMBQ using 5 mol % [(1-10)Pd(OAc)2]11 and 6 mol % Et3N (Table 1).12 The yields of 13aa with 4-t-BuC6H5 (2; 65%)- and cyclohexyl (9; 69%)substituted disulfoxide ligands were the highest, and the 4MeOC6H5 (1, 52%)- and 4-t-BuC6H5 (10, 50%)-substituted Received: December 29, 2016 Published: April 19, 2017 4907

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917

Note

The Journal of Organic Chemistry Table 1. Evaluation of [(Disulfoxide)Pd(OAc)2] Catalysts for Allylic Oxidative C−N Bond Formation

ligand % 13aa

a

1

2

3

4

5

6

7

8

9

10

52

65

48

45

37

22

42

27

69

50

a

Averaged isolated yields. The reactions were performed in duplicate and combined before purification. In all cases, other possible products ((Z)13aa, N-alkenyl, and branched) were not observed at levels that permit quantification by 1H NMR.

disulfoxides were also decent performers.13 Because bulky, electron-rich disulfoxides exhibited superior activity, two such second-generation sulfoxides (14 and 15) were also synthesized (Scheme 2). Gratifyingly, 1-adamantyl-substituted ligand 14

Lowering the loading of the catalyst prepared from 14 to 2 mol % resulted in 65% yield. Evaluating a number of other Pd sources revealed that only Pd(OAc)2 was suitable. Finally, conducting the reaction under an O2 atmosphere or with an excess of 11a led to no further increase in yield. A number of oand p-substituted allylbenzenes 11b−e also gave 13ba−ea in good yields. However, yields with simple alkenes 11f−h (deactivated substrates) were low. A direct comparison of ligands 3 and 14 (Scheme 3) under previously developed

Scheme 2. Second Generation Disulfoxide Ligand Synthesis

Scheme 3. Ligand Comparison in the Oxidative C−H Allylic Amination of n-Decene

outperformed all first generation disulfoxides 1−10, giving 75% yield of 13aa; ligand 15 was much less effective (Table 2). Table 2. Oxidative C−H Allylic Amination at Lower Pd Loading (2−5 mol %) with Second Generation Ligands

R Ph (11a) Ph Ph Ph Ph Ph Ph 4-FC6H5 (11b) 4-FC6H5 4-MeOC6H5 (11c) 2-MeC6H5 (11d) 2-OAcC6H5 (11e) n-C7H15 (11f) n-C7H15 Cy (11g) Cy PhCH2 (11h) PhCH2

L

yield

Pd(OAc)2 (5) Pd(OAc)2 (5) Pd(OAc)2 (2) Pd(OAc)2 (2) Pd(TFA)2 (2) [Pd(CH3CN)4](BF4)2 (2) [Pd2(dba)3] (2) Pd(OAc)2 (5) Pd(OAc)2 (2) Pd(OAc)2 (2)

Pd (x mol %)

15 14 14 14 14 14

34% (13aa)a,b 75%a,b 65%a,b 62% (1 atm O2)a,b 17%a,c 6%a,c

14 14 14 14

24%a,b 75% (13ba)a,b 62%a,b 63% (13ca)a,b

Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2

14 14 14 14 14 14 14 14

83% (13da)a,b 80% (13ea)a,b 21% (13fa)a,c 7%a,c 30% (13ga)a,b 9%a,b 30% (13ha)a,b 9%a,b

(2) (2) (5) (2) (5) (2) (5) (2)

conditions6b using 1,4-benzoquinone (1.1 equiv) revealed that ligand 3 only gave a total of 34% of 13fa and the corresponding branched (terminal double bond) isomer 16fa (11:1:1 E/Z/B), whereas the new ligand 14 gave 59% (15:1:1.1 E/Z/B). The reaction was performed experimentally by premixing an equimolar mixture of the disulfoxide and Pd(OAc)2 in the reaction solvent for 15 min prior to adding the reactants, which simplified and accelerated the reaction procedure. However, that led to a decrease in yield for ligand 3; for comparison, the published yield of 13fa with White’s catalyst [(3)Pd(OAc)2] was 67%.6b The nitrogen substrate 12a represents NH3 that is doubly activated as well as protected by methyl carbamoyl and tosyl groups. These groups can be sequentially cleaved in the products by treatment with K2CO3/MeOH and Na·C10H8/ DME, respectively. However, if the Ts group was removed first, the carbamate could be cleaved only under aggressive basic (NaOH/H2O-EtOH, 110 °C, giving -NH2) or reducing (LiAlH4/THF, reflux, giving -NHMe) conditions.6b Thus, methyl carbamate deprotection for base-sensitive substrates or protecting groups is expected to be very challenging if not impossible, but a different carbamate should not be subject to such a limitation. White et al. have reported high yields for the amination of 11g with benzyl, tert-butyl, and 9-fluorenylmethyl carbamates using [(3)Pd(OAc)2] as the catalyst and BQ (2 equiv) as the oxidating agent.6b Liu et al. published oxidative allylic amination with methyl, benzyl, and tert-butyl tosylcarbamate as well as tert-butyl methanesulfonyl carbamate in good yields.14 We investigated the performance of ligand 14 with known (12b, c) tosylcarbamates as well as the hitherto

a

Averaged isolated yields. The reactions were performed in duplicate and combined before purification. In all cases, N-alkenyl product was not observed by 1H NMR. b(Z)-13 and branched isomer were not detected by 1H NMR. cBecause of the low yield, determination of the E/Z-branched ratio was not carried out. 4908

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917

Note

The Journal of Organic Chemistry unknown 2,2,2-trifluoroethyl (12d) and 2,2,2-trichloroethyl analogues (12e) (Table 3). In all but one case, ligand 14

Scheme 4. Oxidative C−H Allylic Amination of Terminal Alkenes with 2,2,2-Trichloroethyl Tosylcarbamate

Table 3. Oxidative C−H Allylic Amination of Various NTosylcarbamates

yield (E/Z/B)a R t-Bu (12b) Bn (12c) CH2CF3 (12d) CH2CCl3 (12e)

ligand 3 10% 39% 41% 39%

(13fb;b 12:1:0.5) (13fc;b 12:1:0.8) (13fd;b 12:1:1) (13fe;b 15:1:0.8)

ligand 14 25% 58% 64% 68%

(9:1:0.6) (17:1)c (12:1:0.9) (15:1:1)

a

Averaged isolated yields. The reactions were performed in duplicate and combined before purification. Isomer ratios were determined by 1 H NMR. In all cases, N-alkenyl and branched product were not observed at levels that permit quantification. bMajor product. cThe branched product amount was too low for quantification by 1H NMR.

outperformed 3 in terms of both yield as well as selectivity toward the desired (E)-linear products (13fb−fe). However, the improvement, although synthetically beneficial, was not dramatic. Surprisingly, t-Bu carbamate 12b reacted poorly despite the reported 69% yield using White’s catalyst [(3)Pd(OAc)2] with 10 mol % i-Pr2NEt as cocatalyst in CCl4.6b A major synthetic benefit of using 12e is that it permits deprotection with a mild reducing agent (Zn powder) in AcOH15 while retaining the facile deprotection under mildly basic conditions characteristic of the methyl analogue. Hence, this reagent permits removal of the carbamate under conditions compatible with both acid- and base-sensitive protecting groups. A range of terminal olefins (11b−p; Scheme 4) coupled in moderate to excellent yields, but the product isomer distribution depended on the nature of the alkene. As expected, p (11b, c)- and o (11d, e, i, j)-substituted allyl benzenes gave very high yields of the (E)-linear products (13ge, he) at 10% catalyst loading. We attempted lowering of the catalyst loading to 2 and 5 mol % for Pd(OAc)2 and 14, respectively. Even with 2.0 equiv of 12e, the yields of 13ce and 13de plummeted to 25 and 32%, respectively. These results confirmed that, for TsNHCOOCH2CCl3, 10 mol % of catalyst is required, underscoring the main theme of this work that demanding substrates require specialized, often novel, catalysts. However, the reaction scaled-up well: 13ce was obtained in 93% (1.14 g) yield on a 10 mmol scale. Allylpentafluorobenzene (11k) and the alkyl-substituted terminal olefins 11g, h coupled in moderate yields (52−58%), similarly giving only the (E)-linear products 13he, ge, and ke. For the remaining alkyl-substituted terminal olefins, a mixture of (E)- and (Z)-linear products (13fe, le-pe) were always observed in E/Z ratios in the range 10:1−20:1. In some cases, the linear product was accompanied by the analogous branched isomer (16fe, le-ne) in slightly larger amounts than the minor (Z)-13 product (1:2.4 to 1:1 Z/ B). For 11g, h, l, and p, 2 equiv of 12e were required for good yields. The 2,2,2-trichloroethylcarbonyl (Troc) group in products 13 was readily removed (Table 4) by heating with excess Zn in AcOH at 60 °C (conditions A) or with K2CO3 in MeOH

a Two mol % Pd(OAc)2 and 5 mol % 14 were used. bHere, 2.0 equiv of 12e was used.

Table 4. Deprotection of the 2,2,2-Trichloroethylcarbonyl (Troc) Group

N-Troc compd

conditions

yield (product; isomer ratio)

13ee 13ie 13ie 13je 13je 13fe + 16fe 13fe + 16fe 13ge 13ge 13he 13le + 16le 13oe

A A B A B A B A B A A A

94% (17ee) 25% (17ie) + 75% (17qe) 97% (17qe) 92% (17je) 99% (17qe) 93% (17fe; 20:1:0.7 E/Z/B) 100% (17fe; 20:1:0.7 E/Z/B) 94% (17ge) 100% (17ge) 81% (17he) 91% (17le; >20:20:1 E/Z)

(conditions B; identical to those employed by White et al.6b for removal of the MeOCO group), giving γ-substituted Ntosylallylamines 17. Under conditions A, the acetate (17ee) and TBDPS phenol protecting groups (17je, le) were retained, whereas the Boc-protected phenol in 13ie gave a mixture of the 4909

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917

Note

The Journal of Organic Chemistry

bar, KOH (2.8 g, 50 mmol), and MeOH (25 mL). After stirring for 20 min at room temperature, 1,2-dibromoethane (0.86 mL, 10 mmol) and the required thiol (20.5 mmol) were added to the solution. After stirring overnight, the volatiles were removed at ∼50 °C under reduced pressure; the residue was diluted with water (30 mL) and extracted with CH2Cl2 (3 × 50 mL). The combined organic layers were dried (MgSO4) and filtered, and the volatiles were removed under reduced pressure. The products are isolated after flash chromatography (neat petrolium ether). 1,2-Bis((4-methoxyphenyl)thio)ethane (1a). From 4-methoxybenzenethiol (2.5 mL, 2.92 g, 20.5 mmol) following the general procedure, 1a (2.7 g, 88%) was isolated as a white solid. Mp 108− 109 °C. 1H NMR (CDCl3, 600 MHz): δ 7.29 (dd, J = 9.4, 2.5 Hz, 4H), 6.82 (t, J = 5.9 Hz, 4H), 3.79 (s, 6H), 2.93 (s, 4H). 13C NMR (150 MHz, CDCl3): δ 159.2, 133.6, 125.2, 114.6, 55.3, 35.2. HR-MS (APCI): m/z calcd for C16H18NaO2S2 ([M + Na] +): 329.0640; found: 329.0653 (δ 2.1 ppm). 1,2-Bis((4-(tert-butyl)phenyl)thio)ethane (2a). From 4-(tert-butyl)benzenethiol (3.5 mL, 3.4 g, 20.5 mmol) following the general procedure, 2a (2.26 g, 63%) was isolated as a white solid. Mp 107−108 °C. 1H NMR (CDCl3, 600 MHz): δ 7.33−7.28 (m, 4H), 7.27−7.23 (m, 4H), 3.06 (s, 4H), 1.32 (s, 18H). 13C NMR (CDCl3, 150 MHz): δ 149.9, 131.5, 130.2, 126.0, 34.5, 33.8, 31.3. HR-MS (APCI): m/ z calcd for C22H39NaS2 ([M + Na] +): 381.1681; found: 381.1695 (δ 3.7 ppm). 1,2-Bis(phenylthio)ethane (3a). From benzenethiol (2.1 mL, 2.3 g, 20.5 mmol) following the general procedure, 3a (2.0 g, 83%) was isolated. Spectroscopic data were identical with those from the literature.5g 1,2-Bis((4-chlorophenyl)thio)ethane (4a). From 4-chlorobenzenethiol (2.16 mL, 2.96 g, 20.5 mmol) following the general procedure, 4a (2.7 g, 87%) was isolated as a white solid. Mp 94−95 °C. 1H NMR (CDCl3, 600 MHz): δ 7.27−7.21 (m, 8H), 3.03 (s, 4H). 13C NMR (150 MHz, CDCl3): δ 133.4, 132.8, 131.5, 129.2, 33.6. HR-MS (APCI): m/z calcd for C14H12Cl2NaS2 ([M + Na] +): 336.9650; found: 336.9661 (δ 3.3 ppm). 1,2-Bis((4-(trifluoromethyl)phenyl)thio)ethane (5a). From 4(trifluoromethyl)benzenethiol (3.63 g, 20.5 mmol) following the general procedure, 5a (3.1 g, 82%) was isolated as a white solid. Mp 83−85 °C. 1H NMR (CDCl3, 600 MHz): δ 7.52 (d, J = 8.3 Hz, 4H), 7.38 (d, J = 8.2 Hz, 4H), 4.39 (s, 8H). 13C NMR (CDCl3, 150 MHz): δ 140.3, 128.6, 128.4 (q, 2JC−F = 33 Hz), 125.9 (q, 3JC−F = 4.5 Hz), 124.5 (q, 1JC−F = 270 Hz), 32.2. HR-MS (APCI): m/z calcd for C16H12F6NaS2 ([M + Na] +): 405.0177; found: 405.0187 (δ 2.5 ppm). 1,2-Bis(hexylthio)ethane (6a). From 1-hexanethiol (2.9 mL, 2.42 g, 20.5 mmol) following the general procedure, 6a (1.82 g, 80%) was isolated as a colorless liquid. 1H NMR (CDCl3, 600 MHz): δ 2.70 (s, 4H), 2.53 (t, J = 7.5 Hz, 4H), 1.57 (dt, J = 15.1, 7.5 Hz, 4H), 1.37 (dt, J = 15.0, 7.3 Hz, 4H), 1.32−1.20 (m, 8H), 0.87 (t, J = 7.0 Hz, 6H). 13C NMR (150 MHz, CDCl3): δ 32.2, 32.1, 31.4, 29.6, 28.5, 22.5, 14.0. HR-MS (APCI): m/z calcd for C14H30NaS2 ([M + Na]+): 285.1681; found: 285.1692 (δ 3.9 ppm). 1,2-Bis(isobutylthio)ethane (7a). From isobutylthiol (2.36 mL, 1.85 g, 20.5 mmol) following the general procedure, 7a (1.9 g, 92%) was isolated as a colorless liquid. 1H NMR (CDCl3, 600 MHz): δ 2.66 (s, 4H), 2.40 (d, J = 6.9 Hz, 4H), 1.76 (m, 2H), 0.96 (d, J = 6.7 Hz, 12H). 13C NMR (150 MHz, CDCl3): 41.4, 32.7, 28.6, 21.9. HR-MS (APCI): m/z calcd for C10H22NaS2 ([M + Na]+): 229.1055; found: 229.1065. (δ 4.4 ppm). 1,2-Bis(benzylthio)ethane (8a). From benzylthiol (2.34 mL, 2.55 g 20.5 mmol) following the general procedure, 8a (0.85 g, 62%) was isolated. Spectroscopic data were identical with those from the literature.16 1,2-Bis(cyclohexylthio)ethane (9a). From cyclohexylthiol (2.44 mL, 2.38 g, 20.5 mmol) following the general procedure, 9a (2.3 g, 89%) was isolated. Spectroscopic data were identical with those from the literature.7b 1,2-Bis(tert-butylthio)ethane (10a). From tert-butylthiol (1.18 mL, 1.85 g, 20.5 mmol) following the general procedure, 10a (1.78 g, 86%)

unprotected 17qe (75%) and the Boc-protected 17ie products. Overall, the yields for deprotection under conditions A ranged from 81 to 100% for both (3-arylallyl)- or (3-alkylallyl)tosylcarbamates. In particular, the Troc removal in 17oe proceeded in a very satisfying 83% without affecting the four acetates attached to the glucose moiety. The Troc removal took place in near quantitative yields under basic conditions B as expected for the relatively small and electron-poor 2,2,2trichloroethyl ester. From o-allylphenol protected with both Boc (13ie) and TPS (13je), only free phenol 17qe was isolated in contrast with conditions A. In almost all cases, the deprotection led to increasing content of (E)-linear product 17 when mixtures of (E)+(Z)-13 and 16 were used. The N-tosyl group could not be deprotected in the presence of Troc by a number of methods we tried. When clean deprotection was possible, it led to Troc removal instead of Ts (a representative example is shown on Scheme 5). Scheme 5. Attempted N-Ts Deprotection

In conclusion, a novel, electron-rich, bulky 1-adamantylsubstituted disulfoxide (ADS) showed an enhanced performance as a ligand in the Pd-catalyzed allylic oxidative amination reaction of terminal olefins compared to that of the standard Ph-substituted analogue. For activated substrates (allylbenzenes), the reaction proceeded in good yields with as low as 2 mol % Pd (vs 10 mol % typically used). Moreover, this ligand allows the use of 2,2,2-trichloroethyl tosylcarbamate. This new amination reagent is more versatile by virtue of deprotection of the Troc group in excellent yields in both acidic and basic conditions. However, removal of the Ts group in the presence of Troc was not possible.

■

EXPERIMENTAL SECTION

General. Unless otherwise noted, the allylic C−H oxidative amination reactions were performed in screw-cap glass vials (8 mL volume; used as received) without special precautions to exclude air and moisture. The reaction temperature was maintained by immersion of the vials into a silicon oil bath mounted on a commercial hot-stir plate with automatic temperature control. All reagents and solvents were purchased from a variety of commercial suppliers, used as received, and weighed on open balances in air unless otherwise specified. Thin-layer chromatography (TLC) was performed on silica gel 60 F254 precoated plates (0.25 mm) and visualized with UV and anisaldehyde stain. Flash column chromatography was performed on silica gel (60 μm; TCI). 1H and 13C NMR spectra were recorded in the specified solvents on a Varian VNMRS600 at 600 and 150 MHz, respectively, and a Bruker Avance at 300 and 75 MHz, respectively. Chemical shifts (ppm) were referenced against the residual protonated solvent peaks, and the multiplicities are described as follows: s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, m = multiplet, br = broad; the coupling constants are given in Hz. High-resolution mass spectra were recorded on a Waters XEVO G2 Q-TOF mass spectrometer. Disulfide Synthesis, General Procedure. (Caution! Stench. All operations must be conducted in a well-ventilated f ume hood.) In a flamedried 100 mL round-bottom flask was charged sequentially with a stir 4910

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917

Note

The Journal of Organic Chemistry

J = 8.4 Hz, 4H), 7.47 (d, J = 8.4 Hz, 4H), 3.04 (s, 4H), 1.34 (d, J = 7.0 Hz, 18H). 13C NMR (CDCl3, 150 MHz): δ 155.0, 138.7, 126.4, 123.8, 47.0, 35.0, 31.1. 1,2-Bis(phenylsulfinyl)ethane (3). From 3a (2.0 g, 8.3 mmol) and H2O2 (1.96 mL, 17.4 mmol) following general procedure A, 3 (1.75 g, 76%) was isolated after flash chromatography (1:2 petroleum ether/ EtOAc). Spectroscopic data were identical with those from the literature.5g 1,2-Bis((4-chlorophenyl)sulfinyl)ethane (4). From 4a (2.74 g, 8.7 mmol) and H2O2 (2.05 mL, 18.3 mmol) following general procedure A, 4 (1.51 g, 50%) was isolated as a white solid after flash chromatography (1:2 petroleum ether/EtOAc). 1H NMR (CDCl3, 600 MHz): δ 7.54−7.43 (m, 8H), 3.43−3.37 (m), 3.04−3.01 (m), 2.71−2.65 (m, total 4H). 13C NMR (CDCl3, 150 MHz): δ 140.7, 140.5, 137.8, 137.7, 129.8, 129.7, 125.3, 125.2, 47.5, 46.7. HR-MS (APCI): m/z calcd for C14H12Cl2NaO2S2 ([M + Na]+): 368.9548; found: 368.9564 (δ 4.3 ppm). 1,2-Bis((4-(trifluoromethyl)phenyl)sulfinyl)ethane (5). From 5a (3.13 g, 8.2 mmol) and H2O2 (1.94 mL, 17.2 mmol) following general procedure A, 5 (2.99 g, 88%) was isolated as a white solid after flash chromatography (1:2 petroleum ether/EtOAc). 1H NMR (CDCl3, 600 MHz): δ 7.82 (d, J = 8.2 Hz, 1H), 7.77 (d, J = 8.2 Hz, 2H), 7.70 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 8.2 Hz, 2H), 3.59−3.30 (m, 1H), 3.28−2.96 (m, 2H), 2.96−2.41 (m, 1H). 13C NMR (CDCl3, 150 MHz): δ 146.7, 146.5, 133.6 (q, 2JC−F = 33 Hz), 133.5 (q, 2JC−F = 33 Hz), 126.5 (q, 3JC−F = 8.0 Hz), 126.5 (q, 3JC−F = 8.0 Hz), 124.5, 124.4, 123.3 (q, 1JC−F = 271 Hz), 123.3 (q, 1JC−F = 271 Hz), 47.5, 46.7. HR-MS (APCI): m/z calcd for C16H12F6NaO2S2 ([M + Na]+): 437.0075; found: 437.0091 (δ 3.7 ppm). 1,2-Bis(hexylsulfinyl)ethane (6). From 6a (1.82 g, 7.0 mmol) and mCPBA (2.96 g, 14.5 mmol) following general procedure B, 6 (1.62 g, 66%) was isolated as a white solid after flash chromatography (1:1 petroleum ether/EtOAc). 1H NMR (CDCl3, 600 MHz): δ 3.24−3.16 (m, 2H), 3.02−2.93 (m, 2H), 2.83−2.78 (m, 2H), 2.74−2.67 (m, 2H), 1.82−1.71 (m, 4H), 1.51−1.39 (m, 4H), 1.35−1.29 (m, 8H), 0.91− 0.85 (m, 6H). 13C NMR (CDCl3, 150 MHz): δ 53.3, 52.8, 44.9, 44.2, 31.3, 28.4, 22.6, 22.5, 22.3 (2 carbons), 13.9 (2 carbons). HR-MS (APCI): m/z calcd for C14H30NaO2S2 ([M + Na]+): 317.1579; found: 317.1591 (δ 3.8 ppm). 1,2-Bis(isobutylsulfinyl)ethane (7). From 7a (1.83 g, 8.9 mmol) and mCPBA (3.8 g, 18.6 mmol) following general procedure B, 7 (1.1 g, 52%) was isolated as a white solid after flash chromatography (1:1 petroleum ether/EtOAc). 1H NMR (CDCl3, 600 MHz): δ 2.67 (m, 4H), 2.42−2.39 (m, 4H), 1.80−1.72 (m, 2H), 0.97−0.95 (m, 12H). 13 C NMR (CDCl3, 150 MHz): 62.5, 62.0, 45.2, 44.7, 24.0, 22.7, 21.7, 21.6. HR-MS (APCI): m/z calcd for C10H22NaO2S2 ([M + Na]+): 261.0953; found: 261.0963 (δ 3.8 ppm). 1,2-Bis(benzylsulfinyl)ethane (8). From 8a (0.85 g, 3.1 mmol) and H2O2 (0.72 mL, 6.5 mmol) following general procedure A, 8 (0.77 g, 82%) was isolated as a white solid after flash chromatography (1:2 petroleum ether/EtOAc). Spectroscopic data were identical with those from the literature.7c 1,2-Bis(cyclohexylsulfinyl)ethane (9). From 9a (0.87 g, 3.3 mmol) and mCPBA (1.41 g, 6.9 mmol) following general procedure B, 9 (0.7 g, 72%) was isolated after flash chromatography (1:1 petroleum ether/ EtOAc). Spectroscopic data were identical with those from the literature.7b 1,2-Bis(tert-butylsulfinyl)ethane (10). From 10a (1.42 g, 6.9 mmol) and H2O2 (1.6 mL, 14.5 mmol) following general procedure A, 10 (1.24 g, 76%) was isolated as a white solid after flash chromatography (1:2 petroleum ether/EtOAc). Spectroscopic data were identical with the literature.7b 1,2-Bis(adamantan-1-ylsulfinyl)ethane (14). From 14a (2.54 g, 7.0 mmol) and mCPBA (2.98 g, 14.7 mmol) following general procedure B, 14 (2.21 g, 80%) was isolated as a white solid after flash chromatography (1:1 petroleum ether/EtOAc). 1H NMR (600 MHz, CDCl3) δ 3.06−2.85 (m, 4H), 2.18 (broad s, 6H), 1.95−1.81 (m, 12H), 1.81−1.66 (m, 12H). 13C NMR (CDCl3, 150 MHz): 36.2, 36.2, 35.0, 35.0, 28.6, 28.6. HR-MS (APCI): m/z calcd for C22H34NaO2S2 ([M + Na]+): 417.1892; found: 417.1906 (δ 3.4 ppm).

was isolated. Spectroscopic data were identical with those from the literature.7b 1,2-Bis(adamantan-1-ylthio)ethane (14a). From 1-adamanthanethiol (3.12 g, 20.5 mmol) following the general procedure, 14a (3.2 g, 88%) was isolated as a white solid. Mp 120−122 °C. 1H NMR (CDCl3, 600 MHz): δ 2.66 (s, 4H), 2.03 (broad s, 6H), 1.85 (s, 12H), 1.67 (q, J = 12.4 Hz, 12H). 13C NMR (CDCl3, 150 MHz): δ 43.7, 36.3, 29.7, 26.9. HR-MS (APCI): m/z calcd for C22H34NaS2 ([M + Na] +): 385.1994; found: 385.2009 (δ 3.9 ppm). 1,3-Bis((2-phenylpropan-2-yl)thio)ethane (15a). Caution! Stench. Use a well-ventillated fume hood for all operations). Into a 100 mL, 3necked, round-bottomed flask equipped with a reflux condenser and a 25 mL pressure-equalizing addition funnel were added ethane-1,2dithiol (0.84 mL, 0.94 g, 10 mmol), AcOH (15 mL), and concd H2SO4 (5 drops) in that order under Ar. A solution of αmethylstyrene (2.8 mL, 2.42 g, 20.5 mmol) in AcOH (10 mL) was added to the addition funnel. The reaction flask was heated to 60 °C, and α-methylstyrene solution was added dropwise to the reaction mixture under Ar. The reaction mixture was stirred at 60 °C overnight under Ar over 24 h. After cooling to room temperature, Et3N was added to adjust the pH to 7.0, and the volatiles were removed under reduced pressure. The residue was diluted with water (20 mL) and extracted with CH2Cl2 (3 × 30 mL). The combined organic layers were dried (MgSO4,) and the volatiles were removed under reduced pressure. Compound 15a (2.38 g, 72%) was isolated as a white solid after flash chromatography (neat petrolium ether). Mp 53−55 °C. 1H NMR (600 MHz, CDCl3): δ 7.44 (dd, J = 7.6, 0.7 Hz, 4H), 7.28 (d, J = 7.3 Hz, 4H), 7.17 (td, J = 7.6, 0.6 Hz, 2H), 2.17 (broad s, 4H), 1.61 (d, J = 0.9 Hz, 12H). 13C NMR (150 MHz, CDCl3): δ 146.4, 128.0, 126.5, 126.4, 47.8, 30.2, 29.5. HR-MS (APCI): m/z calcd for C20H26NaS2 ([M + Na] +): 353.1368; found: 353.1382 (δ 4.0 ppm). Disulfoxide Synthesis, General Procedure A (Disulfide Oxidation with H2O2). A 100 mL round-bottom flask was charged with a stir bar, the required amount of disulfide, and glacial acetic acid (20 mL). The mixture was stirred at room temperature until it became homogeneous. Next, it was cooled to 0 °C, and the required amount of H2O2 (30 wt % solution in water) was added dropwise. The reaction was warmed to room temperature and then stirred overnight. The acetic acid was removed at ∼60 °C under reduced pressure, and the disulfoxides were isolated after flash chromatography as (R*,S*)- and (R*,R*)-diastereomeric mixtures. Disulfoxide Synthesis, General Procedure B (Disulfide Oxidation with mCPBA). A 100 mL round-bottom flask was charged with a stir bar, the required amount of disulfide, and CH2Cl2 (20 mL). Next, the required amount of mCPBA (85 wt %) dissolved in CH2Cl2 (30 mL) was added dropwise. The mixture was stirred at 0 °C over 30 min; then, it was warmed to room temperature, and the stirring continued overnight. Next, saturated aq NaHCO3 solution (20 mL) and water (40 mL) were added carefully (Caution! Rapid evolution of CO2.), and the product was extracted into CH2Cl2 (3 × 30 mL). The organic layers were combined, dried (MgSO4), and filtered, and the volatiles were removed under reduced pressure. The disulfoxides were isolated after flash chromatography as (R*,S*)and (R*,R*)-diastereomeric mixtures. 1,2-Bis((4-methoxyphenyl)sulfinyl)ethane (1). From 1a (2.7 g, 8.8 mmol) and H2O2 (2.1 mL, 18.5 mmol) following general procedure A, 1 (1.96 g, 66%) was isolated as a white solid after flash chromatography (2:1 petroleum ether/EtOAc). 1H NMR (600 MHz, CDCl3): δ 7.28 (d, J = 8.8 Hz, 4H), 6.81 (d, J = 8.7 Hz, 4H), 3.79 (s, 6H), 2.92 (s, 4H). 13C NMR (CDCl3, 150 MHz): δ 162.2, 162.1, 133.1, 132.9, 125.8 (multiple carbons), 115.0, 114.9, 55.5, 55.5, 48.1, 47.4. HR-MS (APCI): m/z calcd for C16H18NaO4S2 ([M + Na]+): 361.0539; found: 361.0552 (δ 3.6 ppm). 1,2-Bis((4-(tert-butyl)phenyl)sulfinyl)ethane (2). From 2a (2.26 g, 6.3 mmol) and H2O2 (1.49 mL, 13.2 mmol) following general procedure A, 2 (1.30 g, 53%) was isolated as a white solid after flash chromatography (1:2 petroleum ether/EtOAc). HR-MS (APCI): m/z calcd for C22H30NaO2S2 ([M + Na]+): 413.1579; found: 413.1595 (δ 3.9 ppm). Chemical shifts for the major diastereomer (4.4:1, configuration unassigned). 1H NMR (CDCl3, 600 MHz): δ 7.53 (d, 4911

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917

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The Journal of Organic Chemistry 1,2-Bis((2-phenylpropan-2-yl)sulfinyl)ethane (15). From 15a (2.0 g, 6.0 mmol) and H2O2 (1.4 mL, 12.6 mmol) following general procedure A, 15 (1.41 g, 65%) was isolated as a white solid after flash chromatography (1:2 petroleum ether/EtOAc). HR-MS (APCI): m/z calcd for C20H26NaO2S2 ([M + Na]+): 385.1266; found: 385.1281 (δ 3.9 ppm). Chemical shifts for the major diastereomer (4.3:1, configuration unassigned). 1H NMR (CDCl3, 600 MHz): δ 7.47 (d, J = 7.6 Hz, 4H), 7.32 (t, J = 7.6 Hz, 4H), 7.21 (t, J = 7.3 Hz, 2H), 2.19 (broad s, 4H), 1.63 (s, 12H). 13C NMR (150 MHz, CDCl3): δ 138.2, 128.8, 128.2, 126.5, 40.6, 24.2, 19.1. Disulfoxide Ligand Evaluation (Table 1), General Procedure. Catalyst preparation was performed as described by White et al.5a Briefly, an equimolar mixture of a disulfoxide ligand and Pd(OAc)2 was refluxed in CH2Cl2 overnight. The solvent was evaporated to dryness, and after brief drying in high vacuum, the catalyst was used immediately. Two runs were set side by side. Each vial was charged with [(1−10)Pd(OAc)2] (12.5 μmol, 5 mol %), 2,6-dimethyl-1,4benzoquinone (37 mg, 0.275 mmol), methyl tosylcarbamate (12a; 63 mg, 0.275 mmol), and allylbenzene (11a; 33 μL, 29.5 mg, 0.25 mmol) in sequence. tert-Butyl methyl ether (1 mL) and Et3N (2 μL, 1.5 mg, 15 μmol, 6 mol %) were added via syringes. The vials were securely capped, and the reaction mixtures were stirred at 45 °C for 24 h. Next, the vials were cooled to room temperature, pooled together in CH2Cl2, and concentrated under reduced pressure. Compound 13aa was obtained as a white solid after flash chromatography (10:1 petroleum ether/EtOAc). Spectroscopic data were identical with those from the literature.17 Ligand 1: From [(1)Pd(OAc)2] (7.0 mg) following the general procedure, 13aa (44.9 mg, 52%) was obtained. Ligand 2: From [(2)Pd(OAc)2] (7.7 mg) following the general procedure, 13aa (55.7 mg, 65%) was obtained. Ligand 3: From [(3)Pd(OAc)2] (6.3 mg) following the general procedure, 13aa (41.4 mg, 48%) was obtained. Ligand 4: From [(4)Pd(OAc)2] (7.1 mg) following the general procedure, 13aa (38.8 mg, 45%) was obtained. Ligand 5: From [(5)Pd(OAc)2] (8.0 mg) following the general procedure, 13aa (31.9 mg, 37%) was obtained. Ligand 6: From [(6)Pd(OAc)2] (6.5 mg) following the general procedure, 13aa (19.0 mg, 22%) was obtained. Ligand 7: From [(7)Pd(OAc)2] (5.8 mg) following the general procedure, 13aa (36.3 mg, 42%) was obtained. Ligand 8: From [(8)Pd(OAc)2] (6.6 mg) following the general procedure, 13aa (23.3 mg, 27%) was obtained. Ligand 9: From [(9)Pd(OAc)2] (5.9 mg) following the general procedure, 13aa (59.6 mg, 69%) was obtained. Ligand 10: From [(10)Pd(OAc)2] (5.8 mg) following the general procedure, 13aa (43.2 mg, 50%) was obtained. C−H Aminations with Methyl Tosylcarbamate Mediated by Pd(OAc)2 Complexes of Ligands 14 and 15 (Table 2), General Procedure. Two runs were set side by side. Each vial was charged with Pd(OAc)2 or other Pd sources (2 or 5 mol %), ligand 14 or 15 (4.9 or 4.5 mg, respectively; 12.5 μmol, 5 mol %), and a stir bar, and tert-butyl methyl ether (1 mL) was added using a disposable syringe. Each vial was capped and stirred for 15 min. Then, 2,6-dimethyl-1,4benzoquinone (37 mg, 0.275 mmol), methyl tosylcarbamate (63 mg, 0.275 mmol), and the required alkene (0.25 mmol) were added in sequence. Et3N (2 μL, 1.5 mg, 15 μmol, 6 mol %) was added via syringe. The vials were securely capped, and the reaction mixtures were stirred at 45 °C for 24 h. Next, the vials were cooled to room temperature, pooled together in CH2Cl2, and concentrated under reduced pressure. (E)-Methyl (3-Phenylallyl)(tosyl)carbamate (13aa). Ligands/ palladium loading variation: From Pd(OAc)2 (2.8 mg, 12.5 μmol, 5 mol %) and allylbenzene (11a; 33 μL, 29.5 mg, 0.25 mmol) following the general procedure, 13aa (ligand 15: 29.3 mg, 34%; ligand 14: 64.7 mg, 75%) was obtained after flash chromatography (10:1 petroleum ether/EtOAc). From Pd(OAc)2 (1.1 mg, 5 μmol, 2 mol %), ligand 14 (4.9 mg, 12.5 μmol, 5 mol %), and allylbenzene (11a; 33 μL, 29.5 mg, 0.25 mmol) following the general procedure, 13aa (56.0 mg, 65%) was obtained. From an identical run under O2 atmosphere (rubber

balloon; 1 atm), 13aa (53.5 mg, 62%) was obtained. Palladium source variation: From the required Pd source (Pd(TFA)2: 1.5 mg, [Pd(CH3CN)4](BF4)2: 2.2 mg, Pd2(dba)3: 4.6 mg; 5 μmol, 2 mol % Pd), ligand 14 (4.9 mg, 12.5 μmol, 5 mol %), and allylbenzene (11a; 33 μL, 29.5 mg, 0.25 mmol) following the general procedure, 13aa (Pd(TFA)2: 14.7 mg, 17%; [Pd(CH3CN)4](BF4)2: 5.2 mg, 6%; Pd2(dba)3: 20.7 mg, 24%) was obtained. (E)-Methyl (3-(4-Fluorophenyl)allyl)(tosyl)carbamate (13ba). From Pd(OAc)2 (2.8 mg, 12.5 μmol, 5 mol % or 1.12 mg, 5 μmol, 2 mol %), ligand 14 (4.9 mg, 12.5 μmol, 5 mol %), and 1-allyl-4fluorobenzene (11b; 35 μL, 34.0 mg, 0.25 mmol) following the general procedure, 13ba (5 mol % Pd: 68.1 mg, 75%; 2 mol % Pd: 56.3 mg, 62%) was obtained as a white solid after flash chromatography (12:1 petroleum ether/EtOAc). Mp 72−74 °C. 1H NMR (600 MHz, CDCl3): δ 7.83 (d, J = 8.1 Hz, 2H), 7.34 (dd, J = 8.3, 5.6 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H), 7.01 (t, J = 8.6 Hz, 2H), 6.64 (d, J = 15.8 Hz, 1H), 6.16 (dt, J = 15.7, 6.4 Hz, 1H), 4.60 (d, J = 6.5 Hz, 2H), 3.71 (s, 3H), 2.41 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 162.4 (d, 1JC−F = 246 Hz), 152.6, 144.6, 136.3, 132.8, 132.4, 129.3, 128.4, 128.1 (d, 3JC−F = 7.5 Hz), 123.5, 115.5 (d, 2JC−F = 21.0 Hz), 53.9, 48.7, 21.6. HR-MS (ESI): m/ z calcd for C18H18FNNaO4S ([M + Na] +): 386.0833; found: 386.0846 (d 3.4 ppm). (E)-Methyl (3-(4-Methoxyphenyl)allyl)(tosyl)carbamate (13ca). From Pd(OAc)2 (1.1 mg, 5 μmol, 2 mol %), ligand 14 (4.9 mg, 12.5 μmol, 5 mol %), and 1-allyl-4-methoxybenzene (11c; 38 μL, 30.5 mg, 0.25 mmol) following the general procedure, 13ca (59.1 mg, 63%) was obtained after flash chromatography (12:1 petroleum ether/ EtOAc). Spectroscopic data were identical with those from the literature.17 (E)-Methyl (3-(o-Tolyl)allyl)(tosyl)carbamate (13da). From Pd(OAc)2 (1.1 mg, 5 μmol, 2 mol %), ligand 14 (4.9 mg, 12.5 μmol, 5 mol %), and o-allyltoluene (11d; 37 μL, 33.1 mg, 0.25 mmol) following the general procedure, 13da (74.6 mg, 83%) was obtained as a white solid after flash chromatography (15:1 petroleum ether/ EtOAc). Mp 90−92 °C. 1H NMR (600 MHz, CDCl3): δ 7.85 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 6.8 Hz, 1H), 7.29 (d, J = 7.9 Hz, 2H), 7.17 (m, 3H), 6.92 (d, J = 15.7 Hz, 1H), 6.12 (dt, J = 15.7, 6.5 Hz, 1H), 4.64 (d, J = 6.2 Hz, 2H), 3.72 (s, 3H), 2.42 (s, 3H), 2.35 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 152.7, 144.6, 136.4, 135.6, 135.4, 132.1, 130.3, 129.3, 128.5, 127.8, 126.1, 125.7, 125.0, 53.8, 48.9, 21.6, 19.7. HR-MS (ESI): m/z calcd for C19H21NNaO4S ([M + Na] +): 382.1084; found: 382.1098 (δ 3.7 ppm). (E)-Methyl (3-(2-Acetoxyphenyl)allyl)(tosyl)carbamate (13ea). From Pd(OAc)2 (1.1 mg, 5 μmol, 2 mol %), ligand 14 (4.9 mg, 12.5 μmol, 5 mol %), and 2-allylphenyl acetate18 (11e; 44 mg, 0.25 mmol) following the general procedure, 13ea (80.6 mg, 80%) was obtained as a yellow semi-solid after flash chromatography (12:1 petroleum ether/EtOAc). 1H NMR (600 MHz, CDC3): δ 7.82 (d, J = 8.2 Hz, 2H), 7.49 (d, J = 7.7 Hz, 1H), 7.30−7.25 (m, 3H), 7.20 (t, J = 7.5 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 6.73 (d, J = 15.9 Hz, 1H), 6.23 (dt, J = 15.8, 6.3 Hz, 1H), 4.61 (d, J = 6.2 Hz, 2H), 3.69 (s, 3H), 2.39 (s, 3H), 2.30 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 169.4, 152.6, 148.1, 144.6, 136.2, 129.3, 128.8, 128.5, 127.6, 126.9, 126.2, 126.2, 122.6, 114.9, 53.9, 48.7, 21.6, 20.8. HR-MS (ESI): m/z calcd for C20H21NNaO6S ([M + Na]+): 426.0982; found: 426.0996 (δ 3.3 ppm). (E)-Methyl Dec-2-en-1-yl(tosyl)carbamate (13fa). From Pd(OAc)2 (2.8 mg, 12.5 μmol, 5 mol % or 1.1 mg, 5 μmol, 2 mol %), ligand 14 (4.9 mg, 12.5 μmol, 5 mol %), and 1-decene (11f; 50 μL, 35.1 mg, 0.25 mmol) following the general procedure, 13fa (5 mol % Pd: 19.3 mg, 21%; 2 mol % Pd: 6.4 mg, 7%) was obtained after flash chromatography (20:1 petroleum ether/EtOAc). Spectroscopic data for the product matched those reported previously.6c (E)-Methyl (3-Cyclohexylallyl)(tosyl)carbamate (13ga). From Pd(OAc)2 (2.8 mg, 12.5 μmol, 5 mol % or 1.1 mg, 5 μmol, 2 mol %), ligand 14 (4.9 mg, 12.5 μmol, 5 mol %), and allylcyclohexane (11g; 40 μL, 31.0 mg, 0.25 mmol) following the general procedure, 13ga (5 mol % Pd: 26.3 mg, 30%; 2 mol % Pd: 7.9 mg, 9%) was obtained after flash chromatography (12:1 petroleum ether/EtOAc). Spectroscopic data were identical with those from the literature.6c 4912

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917

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The Journal of Organic Chemistry (E)-Methyl (4-Phenylbut-2-en-1-yl)(tosyl)carbamate (13ha). From Pd(OAc)2 (2.8 mg, 12.5 μmol, 5 mol % or 1.1 mg, 5 μmol, 2 mol %), ligand 14 (4.9 mg, 12.5 μmol, 5 mol %), and 3butenylbenzene (11h; 38 μL, 33.1 mg, 0.25 mmol) following the general procedure, 13ha (5 mol %: 9.9 mg, 11%; 2 mol %: 5.4 mg, 6%) was obtained as a white semi-solid after flash chromatography (16:1 petroleum ether/EtOAc). 1H NMR (600 MHz, CDCl3): δ 7.78 (d, J = 8.2 Hz, 2H), 7.31 (t, J = 7.5 Hz, 2H), 7.26−7.21 (m, 3H), 7.18 (d, J = 7.4 Hz, 2H), 5.98−5.91 (m, 1H), 5.65−5.57 (m, 1H), 4.45 (d, J = 6.3 Hz, 2H), 3.68 (s, 3H), 3.39 (d, J = 6.8 Hz, 2H), 2.42 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 152.7, 144.5, 139.6, 136.4, 134.1, 129.2, 128.5, 128.5, 128.5, 126.2, 125.7, 53.7, 48.4, 38.6, 21.6. HR-MS (ESI): m/z calcd for C19H21NNaO4S ([M + Na]+): 382.1084; found: 382.1097 (δ 3.4 ppm). C−H Amination of n-Decene with Methyl Tosylcarbamate (Scheme 3): (E)- and (Z)-Methyl Dec-2-en-1-yl(tosyl)carbamate (13fa) and Methyl 2-Tosyl-3-vinyldecanoate (16fa). Two runs were set side by side. Each vial was charged with Pd(OAc)2 (5.6 mg, 25 μmol, 10 mol %), ligand 3 (6.3 mg, 25 μmol, 10 mol %) or 14 (9.8 mg, 25 μmol, 10 mol %), and a stir bar, and tert-butyl methyl ether (1 mL) was added using a disposable syringe. Each vial was capped and stirred for 15 min. Then, 1,4-benzoquinone (27 mg, 0.25 mmol), methyl tosylcarbamate (63 mg, 0.275 mmol), and 1-decene (50 μL, 35.1 mg, 0.25 mmol) were added in sequence. Finally, Et3N (2 μL, 1.5 mg, 15 μmol, 6 mol %) was added via syringe. The vials were securely capped, and the reaction mixtures were stirred at 45 °C for 72 h. Next, the vials were cooled to room temperature, pooled together in CH2Cl2, and washed sequentially with saturated aq NaHSO3 and brine. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. A mixture of (E)- and (Z)-13fa, and 16fa (ligand 3: 31.2 mg, 34%, 11:1:1 E/Z/B , ligand 14: 54.1 mg, 59%, 15:1:1 E/Z/B) was isolated as a light yellow oil after flash chromatography (20:1 petroleum ether/EtOAc). 2-Allylphenyl tert-Butyl Carbonate (11i). To a stirred solution of 2-allylphenol (0.65 mL, 0.67 g, 5 mmol) in CH2Cl2 (20 mL) was added DMAP (0.61 g, 5 mmol). The mixture was cooled to 0 °C, and (Boc)2O (2.4 g, 11 mmol) was added. Next, the mixture was warmed to room temperature and stirred for 20 min. The solution was then diluted with CH2Cl2, washed with water and brine, and dried (MgSO4), and the volatiles were removed under reduced pressure. Compound 11i (1.16 g, 98%) was obtained as a colorless oil after flash chromatography (20:1 petroleum ether/EtOAc). 1H NMR (600 MHz, CDCl3): δ 7.24 (ddd, J = 7.1, 4.1, 2.2 Hz, 2H), 7.20−7.15 (m, 1H), 7.13−7.09 (m, 1H), 5.92 (ddt, J = 16.8, 10.1, 6.7 Hz, 1H), 5.17−5.01 (m, 2H), 3.36 (d, J = 6.6 Hz, 2H), 1.55 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 151.8, 149.2, 135.8, 132.0, 130.3, 127.3, 126.1, 122.2, 116.2, 83.2, 34.3, 27.6. HR-MS (ESI): m/z calcd for C14H18NaO3 ([M + Na]+): 257.1148; found: 257.1152 (δ 1.6 ppm). (2-Allylphenoxy)(tert-butyl)diphenylsilane (11j). To a stirred solution of 2-allylphenol (2.0 mL, 2.01 g, 15 mmol) in CH2Cl2 (20 mL) was added imidazole (2.0 g, 30 mmol). The solution was cooled at 0 °C, and TBDPSCl (3.9 mL, 4.12 g, 15 mmol) was added. Then, the mixture was warmed to room temperature, stirred for 20 min, diluted with CH2Cl2, washed with water and brine, and dried (MgSO4), and the volatiles were removed under reduced pressure. Compound 11j (4.74 g, 85%) was obtained as a colorless oil after flash chromatography (20:1 petroleum ether/EtOAc). 1H NMR (600 MHz, CDCl3): δ 7.91−7.77 (m, 4H), 7.50 (t, J = 7.4, 2H), 7.45 (t, J = 7.1, 4H), 7.26 (dd, J = 7.8, 2.0, 1H), 6.91 (t, J = 7.7, 1H), 6.86 (td, J = 7.7, 1.8, 1H), 6.60−6.51 (m, 1H), 6.23 (ddt, J = 15.7, 10.7, 6.5, 1H), 5.29− 5.09 (m, 2H), 3.71 (d, J = 6.4, 2H), 1.23 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 153.1, 137.1, 135.4, 132.7, 130.1, 130.0, 129.9, 127.8, 126.8, 121.0, 118.8, 115.5, 34.7, 26.6, 19.5. HR-MS (ESI): m/z calcd for C25H29OSi ([M + H]+): 373.1988; found 373.1986 (δ 0.5 ppm). (3aR,5R,6S,6aR)-5-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)-6-(hex-5en-1-yloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole (11n). To a stirred solution of 1,2,5,6-diisopropylidene-D-glucose (0.52 g, 2 mmol) in DMF (10 mL) was added NaH (60% in oil) (96 mg, 4 mmol). The mixture was cooled to 0 °C, and 6-bromohex-1-ene (0.55 mL, 0.65 mg, 4 mmol) was added dropwise. Then, the mixture was

warmed to room temperature, stirred for 1 h, quenched with MeOH, and washed with H2O (3 × 10 mL), and the aqueous rinses were backextracted with ether (3 × 20 mL). The combined organic extracts were dried over MgSO4 and filtered, and the volatiles were removed under reduced pressure. Compound 11n (671.8 mg, 98%) was obtained as a light yellow oil after flash chromatography (16:1 petroleum ether/ EtOAc). 1H NMR (600 MHz, CDCl3): δ 5.85−5.80 (m, 1H), 5.80− 5.70 (m, 1H), 4.96 (ddd, J = 17.1, 3.3, 1.6 Hz, 1H), 4.92−4.88 (m, 1H), 4.48 (dd, J = 4.1, 2.3 Hz, 1H), 4.29−4.22 (m, 1H), 4.11−4.00 (m, 2H), 3.93 (ddd, J = 8.4, 6.0, 3.1 Hz, 1H), 3.84−3.77 (m, 1H), 3.62−3.53 (m, 1H), 3.51−3.44 (m, 1H), 2.02 (s, 2H), 1.58−1.49 (m, 2H), 1.46−1.44 (m, 3H), 1.43−1.39 (m, 2H), 1.39−1.37 (m, 3H), 1.31−1.29 (m, 3H), 1.28−1.26 (m, 3H). 13C NMR (150 MHz, CDCl3): δ 138.5, 114.5, 111.6, 108.8, 105.2, 82.4, 82.0, 81.1, 72.4, 70.3, 67.2, 33.3, 29.0, 26.7, 26.67, 26.1, 25.3, 25.2. HR-MS (ESI): m/z calcd for C18H30NaO6 ([M + Na]+): 365.1935; found: 365.1948 (δ 3.6 ppm). 2,2,2-Trifluoroethyl Tosylcarbamate (12d). Following the procedure for 12e from 2,2,2-trifluoroethanol (1.1 mL, 1.5 g, 15 mmol) and tosyl isocyanate (1.5 mL, 2.0 g, 10 mmol), 12d (2.22 g, 75%) was obtained as a white solid after flash chromatography (2:1 petroleum ether/EtOAc). Mp 126−128 °C. 1H NMR (300 MHz, CDCl3): δ 7.93 (d, J = 8.3 Hz, 2H), 7.80 (s, 1H), 7.37 (d, J = 8.1 Hz, 2H), 4.43 (q, J = 8.2 Hz, 2H), 2.46 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 148.9, 145.7, 134.7, 129.8, 128.4, 121.2 (q, 1JC−F = 276 Hz), 61.9 (q, 2JC−F = 36.0 Hz), 21.7. HR-MS (ESI): m/z calcd for C10H10F3NNaO4S ([M + Na] +): 320.0175; found: 320.0188 (δ 4.1 ppm). 2,2,2-Trichloroethyl Tosylcarbamate (12e). To a stirred solution of 2,2,2-trichloroethanol (1.4 mL, 2.24 g, 15 mmol) in CH2Cl2 (20 mL), after cooling the mixture to 0 °C, tosyl isocyanate (1.5 mL, 2.0 g, 10 mmol) was added dropwise. Then, the mixture was warmed to room temperature, stirred for 3 h, diluted with CH2Cl2, washed with water and brine, dried (MgSO4), and filtered, and the volatiles were removed under reduced pressure; 12e (1.47 g, 85%) was obtained as a white solid after flash chromatography (2:1 petroleum ether/EtOAc). Mp 95−97 °C. 1H NMR (600 MHz, CDCl3): δ 8.19 (s, 1H), 7.95 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 4.69 (s, 2H), 2.45 (s, 3H). 13 C NMR (150 MHz, CDCl3): δ 149.1, 145.5, 134.9, 129.7, 128.5, 126.4, 93.9, 75.2, 21.7. HR-MS (ESI): m/z calcd for C10H10Cl3NNaO4S ([M + Na] +): 367.9288; found: 367.9301 (δ 3.5 ppm). C−H Amination of Various Tosyl Carbamates: (Table 3), General Procedure. Two runs were set side by side. Each vial was charged with Pd(OAc)2 (5.6 mg, 25 μmol, 10 mol %), ligand 3 (6.3 mg, 25 μmol, 10 mol %) or 14 (9.8 mg, 25 μmol, 10 mol %), and a stir bar, and tert-butyl methyl ether (1 mL) was added using a disposable syringe. Each vial was capped and stirred for 15 min; then, 1,4benzoquinone (54 mg, 0.5 mmol), the required tosyl carbamate (0.275 mmol), and 1-decene (50 μL, 35.1 mg, 0.25 mmol) were added in sequence. Finally, Et3N (2 μL, 1.5 mg, 15 μmol, 6 mol %) was added via syringe. The vials were securely capped, and the reaction mixtures were stirred at 45 °C for 72 h. Next, the vials were cooled to room temperature, pooled together in CH2Cl2, and washed sequentially with saturated aq NaHSO3 and brine. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. (E)- and (Z)-tert-Butyl Dec-2-en-1-yl(tosyl)carbamate (13fb) and tert-Butyl Dec-1-en-3-yl(tosyl)carbamate (16fb). From tert-butyl tosylcarbamate (74.2 mg, 0.275 mmol) following the general procedure, a mixture of (E)- and (Z)-13fb and 16fb (ligand 3: 10.3 mg, 10%, 12:1:0.5 E/Z/B; ligand 14: 25.7 mg, 25%, 9:1:0.6 E/Z/B) was isolated after flash chromatography (20:1 petroleum ether/ EtOAc). Spectroscopic data were identical with those from the literature.19 (E)- and (Z)-Benzyl Dec-2-en-1-yl(tosyl)carbamate (13fc) and Benzyl Dec-1-en-3-yl(tosyl)carbamate (16fc). From benzyl tosylcarbamate (83.9 mg, 0.275 mmol) following the general procedure, a mixture of (E)- and (Z)-13fc and 16fc (ligand 3: 43.3 mg, 39%, 12:1:0.8 E/Z/B; ligand 14: 64.3 mg, 58%, 17:1:0 E/Z/B) was isolated as a yellow semi-solid after flash chromatography (20:1 petroleum ether/EtOAc). HR-MS (ESI): m/z calcd for C25H33NNaO4S ([M + 4913

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917

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The Journal of Organic Chemistry

petroleum ether/EtOAc). Mp 157−159 °C. 1H NMR (600 MHz, CDCl3): δ 7.89 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.7 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 6.68 (d, J = 15.8 Hz, 1H), 6.16 (dt, J = 15.7, 6.7 Hz, 1H), 4.73 (s, 2H), 4.68 (d, J = 6.7 Hz, 2H), 3.82 (s, 3H), 2.41 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 159.6, 150.9, 145.0, 135.8, 134.5, 129.4, 128.8, 128.7, 127.8, 120.8, 114.0, 94.1, 75.7, 55.3, 49.4, 21.6. HR-MS (ESI): m/z calcd for C20H20Cl3NNaO5S ([M + Na] +): 514.0020; found: 514.0040 (δ 3.9 ppm). Low catalyst loading run: From 1-allyl-4-methoxybenzene (11c; 38 μL, 30.5 mg, 0.25 mmol), Pd(OAc)2 (1.1 mg, 5 μmol, 2 mol %), 14 (4.9 mg, 12.5 μmol, 5 mol %), and 12e (172.5 mg, 0.5 mmol) following the general procedure, 13ce (30.7 mg, 25%) was isolated as above. Larger scale run: From 1-allyl-4-methoxybenzene (11c; 380 μL, 305 mg, 2.5 mmol), Pd(OAc)2 (56 mg, 0.25 mmol, 10 mol %), 14 (98 mg, 0.25 mmol, 10 mol %), Et3N (20 μL, 15 mg, 0.15 mmol, 6 mol %), and 12e (950 mg, 2.75 mmol) following the general procedure, 13ce (1.14 g, 93%) was isolated as above. (E)-2,2,2-Trichloroethyl (3-(o-tolyl)allyl)(tosyl)carbamate (13de). From 1-allyl-2-methylbenzene (11d; 37 μL, 33.1 mg, 0.25 mmol) following the general procedure, 13de (114.4 mg, 96%) was isolated as a white solid after flash chromatography (16:1 petroleum ether/ EtOAc). Mp 110−112 °C. 1H NMR (600 MHz, CDCl3): δ 7.90 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 6.5 Hz, 1H), 7.30 (d, J = 8.1 Hz, 2H), 7.22−7.15 (m, 3H), 6.97 (d, J = 15.7 Hz, 1H), 6.19 (dt, J = 15.6, 6.5 Hz, 1H), 4.74 (s, 2H), 4.73 (d, J = 7.3 Hz, 2H), 2.42 (s, 3H), 2.35 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 150.8, 145.0, 135.7, 135.2, 132.7, 130.3, 129.4, 128.6, 127.9, 126.4, 126.1, 125.7, 124.4, 94.1, 75.7, 49.4, 21.6, 19.7. HR-MS (ESI): m/z calcd for C20H20Cl3NNaO4S ([M + Na] +): 498.0071; found: 498.0086 (δ 3.0 ppm). Low catalyst loading run: From 1-allyl-2-methylbenzene (11d; 37 μL, 33.1 mg, 0.25 mmol), Pd(OAc)2 (1.1 mg, 5 μmol, 2 mol %), 14 (4.9 mg, 12.5 μmol, 5 mol %), and 12e (172.5 mg, 0.5 mmol) following the general procedure, 13de (38.2 mg, 32%) was isolated as above. (E)-2-(3-(4-Methyl-N-((2,2,2-trichloroethoxy)carbonyl)phenylsulfonamido)prop-1-en-1-yl)phenyl Acetate (13ee). From 2allylphenyl acetate18 (11e; 44 mg, 0.25 mmol) following the general procedure, 13ee (104.8 mg, 83%) was isolated as a white solid after flash chromatography (12:1 petroleum ether/EtOAc). Mp 92−94 °C. 1 H NMR (600 MHz, CDCl3): δ 7.87 (d, J = 8.2 Hz, 2H), 7.49 (d, J = 7.7 Hz, 1H), 7.32−7.29 (m, 3H), 7.22 (t, J = 7.5 Hz, 1H), 7.07 (d, J = 8.1 Hz, 1H), 6.81 (d, J = 15.9 Hz, 1H), 6.30 (dt, J = 15.8, 6.4 Hz, 1H), 4.72 (s, 2H), 4.70 (d, J = 6.4 Hz, 2H), 2.41 (s, 3H), 2.32 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 169.3, 150.7, 148.1, 145.0, 135.6, 129.5, 129.0, 128.8, 128.7, 128.2, 126.8, 126.2, 125.6, 122.7, 94.1, 75.7, 49.1, 21.6, 20.8. HR-MS (ESI): m/z calcd for C21H20Cl3NNaO6S ([M + Na] +): 541.9969; found: 541.9986. (E)-2,2,2-Trichloroethyl (3-(2-((tert-Butoxycarbonyl)oxy)phenyl)allyl)(tosyl)carbamate (13ie). From 2-allylphenyl tert-butyl carbonate (11i; 58.5 mg, 0.25 mmol) following the general procedure, 13ie (125.7 mg, 87%) was isolated as a white solid after flash chromatography (12:1 petroleum ether/EtOAc). Mp 100−102 °C. 1 H NMR (600 MHz, CDCl3): δ 7.89 (d, J = 8.2 Hz, 2H), 7.48 (d, J = 7.7 Hz, 1H), 7.31−7.27 (m, 3H), 7.21 (t, J = 7.5 Hz, 1H), 7.15 (d, J = 8.1 Hz, 1H), 6.88 (d, J = 15.9 Hz, 1H), 6.33 (dt, J = 15.7, 6.7 Hz, 1H), 4.72 (s, 2H), 4.71 (d, J = 6.8 Hz, 2H), 2.40 (s, 3H), 1.55 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 151.7, 150.7, 148.4, 145.0, 135.5, 129.4, 129.0, 128.7, 128.7, 128.4, 126.9, 126.1, 125.5, 122.5, 94.0, 83.8, 75.7, 49.2, 27.6, 21.6. HR-MS (ESI): m/ z calcd for C24H26Cl3NNaO7S ([M + Na] +): 600.0388; found: 600.0413 (δ 4.2 ppm). (E)-2,2,2-Trichloroethyl (3-(2-((tert-Butyldiphenylsilyl)oxy)phenyl)allyl)(tosyl)carbamate (13je). From (2-allylphenoxy)(tertbutyl)diphenylsilane (11j; 93 mg, 0.25 mmol) following the general procedure, 13je (157.3 mg, 88%) was isolated as a white solid after flash chromatography (16:1 petroleum ether/EtOAc). Mp 118−120 °C. 1H NMR (600 MHz, CDCl3): δ 7.92 (d, J = 8.2 Hz, 2H), 7.74 (d, J = 7.0 Hz, 4H), 7.45−7.41 (m, 4H), 7.39 (t, J = 7.3 Hz,4H), 7.27 (d, J = 8.1 Hz, 2H), 6.84 (m, 2H), 6.46 (m, 1H), 6.32 (dt, J = 15.9, 6.7 Hz, 1H), 4.78 (d, J = 6.7 Hz, 2H), 4.74 (s, 2H), 2.41 (s, 3H), 1.12 (s, 9H). 13 C NMR (150 MHz, CDCl3): δ 152.9, 150.9, 144.8, 135.9, 135.4, 132.5, 130.1, 129.9, 129.4, 128.7, 128.7, 127.8, 126.9, 126.5, 123.2,

Na]+): 466.2023; found: 466.2038 (δ 3.2 ppm). The peaks for the major isomer (13fc) are as follows. 1H NMR (600 MHz, CDCl3): δ 7.75 (d, J = 8.2 Hz, 2H), 7.36−7.30 (m, 3H), 7.24−7.18 (m, 4H), 5.80−5.76 (m, 1H), 5.58−5.53 (m, 1H), 5.10 (s, 2H), 4.45 (d, J = 6.4 Hz, 2H), 2.42 (s, 3H), 2.05 (q, J = 7.1 Hz, 2H), 1.39−1.33 (m, 2H), 1.33−1.29 (m, 8H), 0.91 (t, J = 7.0 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 152.1, 144.2, 136.6, 136.1, 134.6, 129.1, 128.4, 128.4, 128.4, 128.7, 124.1, 68.8, 48.7, 32.2, 31.8, 29.1, 29.1, 28.9, 22.6, 21.6, 14.1. (E)- and (Z)-2,2,2-Trifluoroethyl Dec-2-en-1-yl(tosyl)carbamate (13fd) and 2,2,2-Trifluoroethyl Dec-1-en-3-yl(tosyl)carbamate (16fd). From 2,2,2-trifluoroethyl tosylcarbamate (81.7 mg, 0.275 mmol) following the general procedure, a mixture of (E)- and (Z)13fd and 16fd (ligand 3: 44.6 mg, 41%, 12:1:1 E/Z/B; ligand 14: 69.7 mg, 64%, 12:1:0.9E/Z/B) was isolated as a yellow semi-solid after flash chromatography (20:1 petroleum ether/EtOAc). HR-MS (ESI): m/z calcd for C20H28F3NNaO4S ([M + Na]+): 458.1583; found: 458.1601 (δ 3.9 ppm). The peaks for the major isomer (13fd) are as follows. 1H NMR (600 MHz, CDCl3): δ 7.82 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 5.81−5.77 (m, 1H), 5.53−5.49 (m, 1H), 4.44−4.40 (m, 4H), 2.42 (s, 3H), 2.03 (q, J = 7.0 Hz, 2H), 1.38−1.33 (m, 2H), 1.30−1.26 (m, 8H), 0.87 (t, J = 6.9 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 150.8, 144.9, 136.8, 135.9, 129.3, 128.5, 123.4, 122.4 (q, 1JC−F = 276 Hz), 62.1 (q, 2JC−F = 37.5 Hz), 49.1, 32.1, 31.7, 29.1, 29.1, 28.8, 22.6, 21.6, 14.0. (E)- and (Z)-2,2,2-Trichloroethyl Dec-2-en-1-yl(tosyl)carbamate (13fe) and 2,2,2-Trichloroethyl Dec-1-en-3-yl(tosyl)carbamate (16fe). From 2,2,2-trichloroethyl tosylcarbamate (95 mg, 0.275 mmol) following the general procedure, a mixture of (E)- and (Z)13fe and 16fe (ligand 3: 47.9 mg, 39%, 15:1:0.8 E/Z/B; ligand 14: 82.4 mg, 68%, 15:1:1 E/Z/B) was isolated as a white solid after flash chromatography (20:1 petroleum ether/EtOAc). HR-MS (ESI): m/z calcd for C20H28Cl3NNaO4S ([M + Na]+): 506.0702; found: 506.0712. The peaks for the major isomer (13fe) are as follows. 1H NMR (600 MHz, CDCl3): δ 7.87 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 5.88−5.81 (m, 1H), 5.62−5.54 (m, 1H), 4.69 (s, 2H), 4.48 (d, J = 6.5 Hz, 2H), 2.43 (s, 3H), 2.04 (q, J = 7.1 Hz, 2H), 1.38−1.33 (m, 2H), 1.32−1.24 (m, 8H), 0.88 (t, J = 7.0 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 150.9, 144.8, 136.8, 136.0, 129.3, 128.6, 123.7, 94.1, 75.7, 49.1, 32.2, 31.8, 29.1, 29.1, 28.9, 22.6, 21.6, 14.1. C−H Amination with 2,2,2-Trichloroethyl Tosylcarbamate (Scheme 4), General Procedure. Two runs were set side by side. Each vial was charged with Pd(OAc)2 (5.6 mg, 25 μmol, 10 mol %), ligand 14 (9.8 mg, 25 μmol, 10 mol %), and a stir bar, and tert-butyl methyl ether (1 mL) was added using a disposable syringe. Each vial was capped and stirred for 15 min; then, 1,4-benzoquinone (54 mg, 0.05 mmol), 2,2,2-trichloroethyl tosylcarbamate (95 mg, 0.275 mmol), and the required alkene (0.25 mmol) were added in sequence. Finally, Et3N (2 μL, 1.5 mg, 15 μmol, 6 mol %) was added via syringe. The vials were securely capped, and the reaction mixtures were stirred at 45 °C for 72 h. Next, the vials were cooled to room temperature, pooled together in CH2Cl2, and washed sequentially with saturated aq NaHSO3 and brine. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. (E)-2,2,2-Trichloroethyl (3-(4-Fluorophenyl)allyl)(tosyl)carbamate (13be). From 1-allyl-4-fluorobenzene (11b; 35 μL, 34.0 mg, 0.25 mmol) following the general procedure, 13be (117.8 mg, 98%) was isolated as a white solid after flash chromatography (16:1 petroleum ether/EtOAc). Mp 107−108 °C. 1H NMR (600 MHz, CDCl3): δ 7.88 (d, J = 8.2 Hz, 2H), 7.34 (dd, J = 8.4, 5.5 Hz, 2H), 7.29 (d, J = 8.1 Hz, 2H), 7.02 (t, J = 8.6 Hz, 2H), 6.69 (d, J = 15.8 Hz, 1H), 6.22 (dt, J = 15.7, 6.6 Hz, 1H), 4.73 (s, 2H), 4.68 (d, J = 6.6 Hz, 2H), 2.42 (s, 3H). 13 C NMR (150 MHz, CDCl3): δ 162.6 (d, 1JC−F = 246 Hz), 150.8, 145.1, 135.7, 133.6, 132.2, 132.2, 129.4, 128.6, 128.2 (d, 3JC−F = 7.5 Hz), 122.9, 122.9, 115.6 (d, 2JC−F = 21 Hz), 94.1, 75.8, 49.7, 21.6. HRMS (ESI): m/ z calcd for C19H17Cl3FNNaO4S ([M + Na] +): 501.9826; found: 501.9837 (δ 2.2 ppm). (E)-2,2,2-Trichloroethyl (3-(4-Methoxyphenyl)allyl)(tosyl)carbamate (13ce). From 1-allyl-4-methoxybenzene (11c; 38 μL, 30.5 mg, 0.25 mmol) following the general procedure, 13ce (114.6 mg, 93%) was isolated as a white solid after flash chromatography (16:1 4914

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917

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The Journal of Organic Chemistry 121.1, 119.5, 94.1, 75.7, 49.6, 26.6, 21.6, 19.6. HR-MS (ESI): m/ z calcd for C35H36Cl3NNaO5SSi ([M + Na] +): 738.1041; found: 738.1072 (δ 4.2 ppm). (E)-2,2,2-Trichloroethyl (3-(Perfluorophenyl)allyl)(tosyl)carbamate (13ke). From 1-allyl-2,3,4,5,6-pentafluorobenzene (11k; 39 μL, 52.0 mg, 0.25 mmol) following the general procedure, 13ke (73.2 mg, 53%) was isolated as a white solid after flash chromatography (20:1 petroleum ether/EtOAc). Mp 106−108 °C. 1 H NMR (600 MHz, CDCl3): δ 7.90 (d, J = 7.9 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 6.68−6.60 (m, 2H), 4.73 (broad s, 4H), 2.44 (s, 3H). 13C NMR (150 MHz, CDCl3): δ (C6F5 carbon signals are hidden in the noise) 150.6, 145.4, 135.5, 132.7, 129.5, 128.6, 118.4, 93.9, 75.8, 49.4, 21.7. HR-MS (ESI): m/z calcd for C19H13Cl3F5NNaO4S ([M + Na] + ): 573.9443; found: 573.9467 (δ 4.2 ppm). (E)-2,2,2-Trichloroethyl (3-Cyclohexylallyl)(tosyl)carbamate (13ge). From allylcyclohexane (11g; 40 μL, 31.0 mg, 0.25 mmol) and 2,2,2-trichloroethyl tosylcarbamate (173 mg, 0.50 mmol) following the general procedure, 13ge (60.8 mg, 52%) was isolated as a white solid after flash chromatography (16:1 petroleum ether/ EtOAc). Mp 119−121 °C. 1H NMR (600 MHz, CDCl3): δ 7.87 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 5.80 (dd, J = 15.5, 6.6 Hz, 1H), 5.54 (dt, J = 15.5, 6.5 Hz, 1H), 4.69 (s, 2H), 4.48 (d, J = 6.5 Hz, 2H), 2.43 (s, 3H), 1.98 (m, 1H), 1.72 (m, 4H), 1.66 (d, J = 12.6 Hz, 1H), 1.31−1.22 (m, 2H), 1.20−1.13 (m, 1H), 1.11−1.03 (m, 2H). 13C NMR (150 MHz, CDCl3): δ 150.9, 144.8, 142.3, 135.9, 129.3, 128.7, 121.3, 94.1, 75.7, 49.2, 40.3, 32.6, 26.1, 25.9, 21.6. HR-MS (ESI): m/z calcd for C19H24Cl3NNaO4S ([M + Na] +): 490.0384; found: 490.0402 (δ 3.7 ppm). (E)-2,2,2-Trichloroethyl (4-Phenylbut-2-en-1-yl)(tosyl)carbamate (13he). From 3-butenylbenzene (11h; 38 μL, 33.1 mg, 0.25 mmol) and 2,2,2-trichloroethyl tosylcarbamate (173 mg, 0.50 mmol) following the general procedure, 13he (68.9 mg, 58%) was isolated as a white solid after flash chromatography (16:1 petroleum ether/ EtOAc). Mp 103−105 °C. 1H NMR (600 MHz, CDCl3): δ 7.83 (d, J = 8.3 Hz, 2H), 7.30 (t, J = 7.5 Hz, 2H), 7.27−7.21 (m, 3H), 7.17 (d, J = 7.5 Hz, 2H), 6.02 (m, 1H), 5.65 (m, 1H), 4.67 (s, 2H), 4.52 (d, J = 6.4 Hz, 2H), 3.40 (d, J = 6.7 Hz, 2H), 2.43 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 150.8, 144.9, 139.4, 135.7, 135.0, 129.3, 128.6, 128.6, 128.5, 126.2, 125.1, 94.0, 75.6, 48.7, 38.6, 21.7. HR-MS (ESI): m/z calcd for C20H20Cl3NNaO4S ([M + Na] +): 498.0071; found: 498.0087 (δ 3.2 ppm). (E)- and (Z)-2,2,2-Trichloroethyl (5-((tert-Butyldiphenylsilyl)oxy)pent-2-en-1-yl)(tosyl)carbamate (13le) and 2,2,2-Trichloroethyl (5((tert-Butyldiphenyl-silyl)oxy)pent-1-en-3-yl)(tosyl)carbamate (16le). From 5-((tert-butyldipehylsilyl)-oxy)pent-1-ene (11l; 81 mg, 0.25 mmol) and 2,2,2-trichloroethyl tosylcarbamate (173 mg, 0.50 mmol) following the general procedure, a mixture of (E)- and (Z)13le and 16le (98.6 mg, 58%, 10:1:1.4 E/Z/B) was isolated as a yellow oil after flash chromatography (20:1 petroleum ether/EtOAc). HR-MS (ESI): m/z calcd for C31H36Cl3NNaO5SSi ([M + Na]+): 690.1041; found: 690.1066 (δ 3.6 ppm). The peaks for the major isomer (13le) are as follows. 1H NMR (600 MHz, CDCl3): δ 7.89 (d, J = 7.4 Hz, 2H), 7.70 (d, J = 6.8 Hz, 4H), 7.46−7.40 (m, 6H), 7.26 (d, J = 8.0 Hz, 2H), 5.89 (m, 1H), 5.68 (m, 1H), 4.70 (s, 2H), 4.51 (d, J = 6.0 Hz, 2H), 3.75 (t, J = 6.6 Hz, 2H), 2.41 (s, 3H), 2.36 (m, 2H), 1.09 (d, J = 1.7 Hz, 9H). 13C NMR (150 MHz, CDCl3): δ 150.8, 144.8, 135.5, 135.5, 133.8, 132.8, 129.6, 129.3, 128.6, 127.6, 125.8, 94.1, 75.6, 63.2, 49.0, 35.6, 26.8, 21.6, 19.2. (E)- and (Z)-2,2,2-Trichloroethyl (6-(1,3-Dioxoisoindolin-2-yl)hex2-en-1-yl)(tosyl)carbamate (13me) and 2,2,2-Trichloroethyl (6-(1,3Dioxoisoindolin-2-yl)hex-1-en-3-yl)(tosyl)carbamate (16me). From 2-(hex-5-en-1-yl)isoindoline-1,3-dione (11m; 57.3 mg, 0.25 mmol) following the general procedure, a mixture of (E)- and (Z)-13me and 16me (85.8 mg, 60%, 11:1:2.4 E/Z/B) was isolated as a white solid after flash chromatography (5:1 petroleum ether/EtOAc). HR-MS (ESI) m/z calcd for C24H23Cl3N2NaO6S ([M + Na]+): 595.0235; found: 595.0258 (δ 3.9 ppm). The peaks for the major isomer (13me) are as follows. 1H NMR (600 MHz, CDCl3): δ 7.87−7.81 (m, 4H), 7.73−7.69 (m, 2H), 7.30 (d, J = 7.8 Hz, 2H), 5.83 (m, 1H), 5.63 (m, 1H), 4.70 (d, J = 0.9 Hz, 2H), 4.45 (d, J = 6.2 Hz, 2H), 3.68 (t, J = 6.6

Hz, 2H), 2.41 (s, 3H), 2.12 (q, J = 7.0 Hz, 2H), 1.77 (p, J = 7.0 Hz, 2H). 13C NMR (150 MHz, CDCl3): δ 168.3, 150.8, 144.9, 135.8, 134.7, 133.9, 132.1, 129.4, 128.6, 124.8, 123.2, 94.1, 75.7, 48.9, 37.5, 29.4, 27.7, 21.6. (E)- and (Z)-2,2,2-Trichloroethyl (6-(((3aR,5R,6S,6aR)-5-((S)-2,2Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl)oxy)hex-2-en-1-yl)(tosyl)carbamate (13ne) and 2,2,2Trichloroethyl (6-(((3aR,5R,6S,6aR)-5-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl)oxy)hex1-en-3-yl)(tosyl)carbamate (16ne). From 11n (85.5 mg, 0.25 mmol) following the general procedure, a mixture of 13ne and 16ne (115.1 mg, 67%, 18:1:2 E/Z/B) was isolated as a yellow oil after flash chromatography (8:1 petroleum ether/EtOAc). HR-MS (ESI): m/z calcd for C28H38Cl3NNaO10S ([M + Na]+): 708.1174; found: 708.1199 (δ 3.5 ppm). The peaks for the major isomer (13ne) are as follows. 1H NMR (600 MHz, CDCl3): δ 7.85 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 5.86 (d, J = 3.6 Hz, 1H), 5.82 (m, 1H), 5.61 (m, 1H), 4.69 (s, 2H), 4.52 (d, J = 3.7 Hz, 1H), 4.47 (d, J = 6.3 Hz, 2H), 4.29 (dd, J = 13.5, 6.1 Hz, 1H), 4.09 (ddd, J = 14.8, 8.0, 4.5 Hz, 2H), 3.97 (dd, J = 8.5, 5.9 Hz, 1H), 3.84 (d, J = 2.9 Hz, 1H), 3.63− 3.59 (m, 1H), 3.50 (dt, J = 9.4, 6.2 Hz, 1H), 2.42 (s, 3H), 2.15 (s, 1H), 2.13 (q, J = 7.1 Hz, 1H), 1.70−1.64 (m, 2H), 1.48 (s, 3H), 1.41 (s, 3H), 1.34 (s, 3H), 1.30 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 150.8, 144.9, 135.4, 135.4, 129.4, 128.5, 124.5, 111.7, 108.9, 105.2, 94.1, 82.4, 82.1, 81.1, 75.6, 72.4, 69.5, 67.2, 49.0, 28.9, 28.6, 26.8, 26.7, 26.2, 25.4, 21.6. (E)- and (Z)-(2R,3R,4R,5S,6R)-2-(Acetoxymethyl)-6-3-(4-methyl-N((trichloromethoxy)carbonyl)phenylsulfonamido)prop-1-en-1-yl)tetrahydro-2H-pyran-3,4,5-triyl Triacetate (13oe). From 11o20 (93.1 mg, 0.25 mmol) following the general procedure, 13oe (121.6 mg, 68%, E/Z = 14:1) was isolated as a white solid after flash chromatography (6:1 petroleum ether/EtOAc). HR-MS (ESI) m/z calcd for C27H32Cl3NNaO13S ([M + Na]+): 738.0552; found: 738.0579 (δ 3.7 ppm). The peaks for the major isomer (13oe) are as follows. 1H NMR (600 MHz, CDCl3): δ 7.87 (d, J = 8.1 Hz, 2H), 7.33 (d, J = 8.2 Hz, 2H), 6.05−6.01 (m, 2H), 5.26 (t, J = 9.6 Hz, 1H), 5.08 (dd, J = 10.0, 6.3 Hz, 1H), 5.03 (t, J = 9.5 Hz, 1H), 4.79 (m, 1H), 4.73 (s, 2H), 4.59 (d, J = 3.5 Hz, 2H), 4.20 (dd, J = 12.3, 4.9 Hz, 1H), 4.07 (dd, J = 10.6, 1.5 Hz, 1H), 3.96 (m, 1H), 2.44 (s, 3H), 2.08 (s, 3H), 2.03 (s, 3H), 2.02 (s, 3H), 2.01 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 170.7, 170.0, 169.7, 169.5, 150.7, 145.3, 135.6, 131.3, 129.6, 128.6, 126.6, 94.0, 77.2, 77.0, 76.8, 75.7, 69.5, 68.9, 62.3, 48.5, 21.7, 20.7, 20.7, 20.7, 20.6. (E)- and (Z)-2,2,2-Trichloroethyl (4-(oxiran-2-yl)but-2-en-1-yl)(tosyl)carbamate (13pe). From 2-(but-3-en-1-yl)oxirane (11p; 28 μL, 24.5 mg, 0.25 mmol) and 2,2,2-trichloroethyl tosylcarbamate (173 mg, 0.50 mmol) following the general procedure, 13pe (75.3 mg, 68%, E/Z = 14:1) was isolated as a yellow oil after flash chromatography (10:1 petroleum ether/EtOAc). HR-MS (ESI) m/z calcd for C16H18Cl3NNaO5S ([M + Na]+): 463.9864; found: 463.9883 (δ 4.1 ppm). The peaks for the major isomer (13pe) are as follows. 1H NMR (600 MHz, CDCl3): δ 7.87 (d, J = 7.8 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 5.86 (m, 1H), 5.74 (dt, J = 15.2, 6.0 Hz, 1H), 4.69 (broad s, 2H), 4.50 (d, J = 6.2 Hz, 2H), 2.99 (m, 1H), 2.76 (t, J = 4.3 Hz, 1H), 2.51 (dd, J = 4.2, 2.8 Hz, 1H), 2.42 (s, 3H), 2.38−2.28 (m, 2H). 13C NMR (150 MHz, CDCl3): δ 150.7, 145.0, 135.7, 130.4, 129.4, 128.5, 127.0, 94.0, 75.7, 50.9, 48.8, 46.5, 34.9, 21.6. Troc Removal (Table 4), General Procedure A (Reductive Cleavage with Zn/AcOH). The required amount of C−N coupling product (13be−pe) was added to a 25 mL flame-dried roundbottomed flask charged with a stir bar; AcOH (1−2 mL) and Zn (10 equiv) were added, and the reaction mixture was stirred at 60 °C over 4 h. The solution was then cooled to room temperature and filtered over a short pad of Celite. The volatiles were removed under reduced pressure. Troc Removal (Table 4), General Procedure B.6b The required amount of C−N coupling product (13be−pe) was added to a 10 mL flame-dried round-bottomed flask charged with a stir bar; MeOH (1− 2 mL) and K2CO3 (1.9 equiv) were added, and the reaction was vigorously stirred for 3 h at 25 °C. The volatiles were removed under reduced pressure. 4915

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917

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The Journal of Organic Chemistry (E)-2-(3-(Tosylamido)prop-1-en-1-yl)phenyl Acetate (17ee). From 13ee (52.8 mg, 0.1 mmol), AcOH (1 mL), and Zn (65 mg, 1 mmol) following general procedure A, 17ee (32.3 mg, 94%) was isolated as a white solid after flash chromatography (5:1 petroleum ether/EtOAc). Mp 73−75 °C. 1H NMR (600 MHz, CDCl3): δ 7.76 (d, J = 7.8 Hz, 2H), 7.33 (d, J = 7.8 Hz, 1H), 7.29 (d, J = 7.5 Hz, 2H), 7.25 (dd, J = 9.1, 6.3 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 8.1 Hz, 1H), 6.49 (d, J = 15.9 Hz, 1H), 6.02 (m, 1H), 4.75 (m, 1H), 3.73 (t, J = 6.2 Hz, 2H), 2.40 (s, 3H), 2.31 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 169.3, 147.9, 143.5, 137.1, 129.7, 128.7, 128.7, 127.1, 126.8, 126.8, 126.2, 126.1, 122.6, 45.5, 21.4, 20.9. HR-MS (ESI) m/z calcd for C18H18NNaO4S ([M + Na] +): 368.0927; found: 368.0941 (δ 3.8 ppm). (E)-tert-Butyl (2-(3-(Tosylamido)prop-1-en-1-yl)phenyl)carbonate (17ie) and (E)-N-(3-(2-Hydroxyphenyl)allyl)tosylamide (17qe). From 13ie (57.9 mg, 0.1 mmol), AcOH (1 mL), and Zn (65.0 mg, 1 mmol) following general procedure A, 17ie (10.1 mg, 25%) and 17qe (22.8 mg, 75%) were isolated sequentially after flash chromatography (5:1 and 2:1 petroleum ether/EtOAc, respectively). 17ie: light yellow oil. 1 H NMR (600 MHz, CDCl3): δ 7.77 (d, J = 8.1 Hz, 2H), 7.33 (d, J = 7.7 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.25 (t, J = 7.5 Hz, 1H), 7.16 (t, J = 7.5 Hz, 1H), 7.10 (d, J = 8.1 Hz, 1H), 6.56 (d, J = 15.9 Hz, 1H), 6.04 (dt, J = 15.7, 6.4 Hz, 1H), 4.54 (m, 1H), 3.75 (t, J = 6.2 Hz, 2H), 2.41 (s, 3H), 1.54 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 151.6, 148.2, 143.6, 137.0, 129.8, 128.8, 128.7, 127.2, 126.8, 126.6, 126.5, 126.1, 122.4, 83.8, 45.7, 27.7, 21.5. HR-MS (ESI) m/z calcd for C21H25NNaO5S ([M + Na]+): 426.1346; found: 426.1361 (δ 3.5 ppm). 17qe: white solid. Mp 130−132 °C. 1H NMR (600 MHz, acetone-d6): δ 7.78 (d, J = 8.1 Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 7.7 Hz, 1H), 7.05 (t, J = 7.7 Hz, 1H), 6.85 (d, J = 8.1 Hz, 1H), 6.79−6.74 (m, 2H), 6.11 (dt, J = 15.9, 6.4 Hz, 1H), 3.69 (d, J = 6.5 Hz, 2H), 2.40 (s, 3H). 13C NMR (150 MHz, acetone-d6): δ 157.1, 145.5, 141.0, 132.2, 131.1, 129.9, 129.7, 129.7, 129.5, 127.4, 122.2, 118.3, 48.3, 23.1. HR-MS (ESI) m/z calcd for C16H17NNaO3S ([M + Na] +): 326.0821; found: 326.0833 (δ 3.7 ppm). (E)-N-(3-(2-((tert-Butyldiphenylsilyl)oxy)phenyl)allyl)tosylamide (17je). From 13je (50.2 mg, 0.07 mmol), AcOH (1 mL), and Zn (45.5 mg, 0.7 mmol) following general procedure A, 17je (35.4 mg, 92%) was isolated as a pale yellow semi-solid after flash chromatography (8:1 petroleum ether/EtOAc). 1H NMR (600 MHz, CDCl3): δ 7.84 (d, J = 8.2 Hz, 2H), 7.71 (d, J = 7.8 Hz, 4H), 7.44 (t, J = 7.4 Hz, 2H), 7.38 (t, J = 7.4 Hz, 4H), 7.33−7.28 (m, 3H), 7.08 (d, J = 16.0 Hz, 1H), 6.82 (tt, J = 13.0, 6.4 Hz, 2H), 6.47 (d, J = 7.9 Hz, 1H), 6.02 (dt, J = 15.8, 6.5 Hz, 1H), 4.76 (m, 1H), 3.80 (t, J = 6.3 Hz, 2H), 2.42 (s, 3H), 1.12 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 152.6, 143.5, 137.2, 135.4, 132.5, 130.0, 129.7, 128.6, 128.5, 127.8, 127.2, 126.9, 126.3, 124.0, 121.2, 119.6, 46.0, 26.6, 21.5, 19.6. HR-MS (ESI) m/z calcd for C32H35NNaO3SSi ([M + Na]+): 564.1999; found: 564.2018 (δ 3.4 ppm). (E)-N-(3-(2-Hydroxyphenyl)allyl)tosylamide (17qe). From 13je (28.6 mg, 0.04 mmol), MeOH (1 mL), and K2CO3 (10.5 mg, 0.076 mmol) following general procedure B, 17qe (12.0 mg, 99%) was isolated after flash chromatography (2:1 petroleum ether/EtOAc). From 13ie (57.9 mg, 0.1 mmol), MeOH (1 mL), and K2CO3 (26 mg, 0.19 mmol) following general procedure B, 17qe (29.4 mg, 97%) was isolated after flash chromatography (2:1 petroleum ether/EtOAc). (E)- and (Z)-N-(Dec-2-en-1-yl)tosylamide (17fe). From the mixture of (E)- and (Z)-13fe and 16fe (48.3 mg, 0.1 mmol), AcOH (1 mL), and Zn (65 mg, 1 mmol) following general procedure A, a mixture of (E)- and (Z)-17fe (28.6 mg, 93%) was isolated as a light yellow oil as the major product after flash chromatography (10:1 petroleum ether/ EtOAc). From the same mixture (48.3 mg, 0.1 mmol), MeOH (1 mL), and K2CO3 (26.2 mg, 0.19 mmol) following general procedure B, a mixture of (E)- and (Z)-17fe (30.9 mg, 100%) was isolated as a pale yellow semi-solid as the major product after flash chromatography (10:1 petroleum ether/EtOAc). HR-MS (ESI) m/z calcd for C17H27NNaO2S ([M + Na]+): 332.1655; found: 332.1667 (δ 3.6 ppm). The E/Z/B ratio changed from 15:1:1 to 20:1:0.7 after both procedures. The peaks for the major isomer (17fe) are as follows. 1H NMR (600 MHz, CDCl3): δ 7.75 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 8.0

Hz, 2H), 5.53 (m, 1H), 5.29 (m, 1H), 4.49 (m, 1H), 3.51 (t, J = 6.2 Hz, 2H), 2.42 (s, 3H), 1.91 (dd, J = 13.6, 6.7 Hz, 2H), 1.32−1.1 (m, 10H), 0.87 (t, J = 7.0 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 143.3, 137.1, 135.1, 129.6, 127.1, 124.3, 45.3, 32.0, 31.7, 29.1, 29.0, 28.9, 22.6, 21.5, 14.0. (E)-N-(3-Cyclohexylallyl)tosylamide (17ge). From 13ge (46.9 mg, 0.1 mmol), AcOH (1 mL), and Zn (65 mg, 1 mmol) following general procedure A, 17ge (27.6 mg, 94%) was isolated as a white solid after flash chromatography (8:1 petroleum ether/EtOAc). From 13ge (46.9 mg, 0.1 mmol), MeOH (1 mL), and K2CO3 (27.4 mg, 0.19 mmol) following general procedure B, 17ge (29.3 mg, 100%) was isolated as a white solid after flash chromatography (8:1 petroleum ether/EtOAc). Mp 82−84 °C. 1H NMR (600 MHz, CDCl3): δ 7.74 (d, J = 8.1 Hz, 2H), 7.29 (d, J = 8.1 Hz, 2H), 5.46 (dd, J = 15.5, 6.6 Hz, 1H), 5.23 (dt, J = 15.5, 5.6 Hz, 1H), 4.57 (broad s, 1H), 3.50 (t, J = 5.1 Hz, 2H), 2.42 (s, 3H), 1.83 (m, 1H), 1.68−1.63 (m, 2H), 1.63−1.55 (m, 3H), 1.26− 1.15 (m, 2H), 1.09 (ddt, J = 16.0, 12.6, 6.1 Hz, 1H), 0.92 (qd, J = 12.5, 3.3 Hz, 2H). 13C NMR (150 MHz, CDCl3): δ 143.3, 140.6, 137.1, 129.6, 127.1, 121.8, 45.5, 40.1, 32.5, 26.0, 25.8, 21.5. HR-MS (ESI) m/ z calcd for C16H23NNaO2S ([M + Na] +): 316.1342; found: 316.1353 (δ 3.5 ppm). (E)-N-(4-Phenylbut-2-en-1-yl)tosylamide (17he). From 13he (76.3 mg, 0.16 mmol), AcOH (2 mL), and Zn (104 mg, 1.6 mmol) following general procedure A, 17he (38.8 mg, 81%) was isolated as a light yellow oil after flash chromatography (6:1 petroleum ether/ EtOAc). 1H NMR (600 MHz, CDCl3): δ 7.75 (d, J = 8.0 Hz, 2H), 7.30−7.24 (m, 4H), 7.24−7.17 (m, 1H), 7.09 (d, J = 7.5 Hz, 2H), 5.72 (m, 1H), 5.39 (m, 1H), 4.75 (broad s, 1H), 3.55 (broad s, 2H), 3.27 (d, J = 6.7 Hz, 2H), 2.42 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 143.3, 139.4, 136.9, 133.3, 133.2, 129.6, 128.4, 128.4, 126.1, 125.8, 45.1, 38.4, 21.5. HR-MS (ESI) m/z calcd for C17H19NNaO2S ([M + Na]+): 324.1029; found: 324.1040 (δ 3.4 ppm). (E)-N-(5-((tert-Butyldiphenylsilyl)oxy)pent-2-en-1-yl)tosylamide (17le). From the mixture of (E)- and (Z)-13le and 16le (133.4 mg, 0.2 mmol), AcOH (2 mL), and Zn (130 mg, 2 mmol) following general procedure A, 17le (89.8 mg, 91%) was isolated as a pale yellow oil as the major product after flash chromatography (6:1 petroleum ether/ EtOAc). The E/Z/B ratio changed from 10:1:1.4 to >20:20:1. HR-MS (ESI) m/ z calcd for C24H31NNaO11S ([M + Na]+): 564.1510; found: 564.1530 (δ 3.5 ppm). The peaks for the major isomer (17oe) are as follows. 1H NMR (600 MHz, CDCl3): δ 7.75 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 5.81 (dd, J = 6.1, 4.2 Hz, 2H), 5.21 (t, J = 9.6 Hz, 1H), 5.06− 4.96 (m, 2H), 4.87 (broad s, 1H), 4.65 (t, J = 5.5 Hz, 1H), 4.17 (dd, J = 12.3, 4.6 Hz, 1H), 4.01 (dd, J = 12.3, 1.7 Hz, 1H), 3.90−3.84 (m, 1H), 3.67−3.59 (m, 2H), 2.43 (s, 3H), 2.07 (s, 3H), 2.01 (s, 6H). 2.00 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 170.7, 170.1, 169.6, 169.5, 143.7, 136.6, 132.4, 129.8, 127.1, 125.0, 72.1, 70.5, 70.1, 69.3, 68.8, 62.2, 44.8, 21.5, 20.7, 20.7, 20.6, 20.6. Troc Removal during Attempted Ts Deprotection (Scheme 5): (E)-N-(3-(4-Metoxyphenyl)allyl)tosylamide (17ce). The sodiumnaphthalene reagent was prepared in dry DME as described.6d A flame-dried, 10 mL pear-shape flask was charged with a stir bar, 13ce (59.2 mg, 0.12 mmol), and dry oxygen-free DME (1 mL). The 4916

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917

Note

The Journal of Organic Chemistry reaction mixture was cooled to −78 °C, and sodium-naphthalene reagent (1.1 mL, ∼0.9 mmol, ∼8 equiv) was added dropwise over ∼5 min. After an additional 10 min at −78 °C, the solution was diluted with saturated NH4Cl solution (4 mL), allowed to warm to room temperature, and extracted with EtOAc (10 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (2 × 10 mL). The combined organic fractions were dried (MgSO4), and the volatiles were removed at reduced pressure. Compound 17ce (22.9 mg, 60%) was isolated as a light yellow oil after flash chromatography (10:1 petroleum ether/EtOAc). Spectroscopic data were identical with those from the literature.21

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(c) Young, A. J.; White, M. C. J. Am. Chem. Soc. 2008, 130, 14090− 14091. (d) Lin, S.; Song, C.-X.; Cai, G.-X.; Wang, W.-H.; Shi, Z.-J. J. Am. Chem. Soc. 2008, 130, 12901−12903 and refs cited therein. (8) Major contributions: (a) Braun, M.-G.; Doyle, A. G. J. Am. Chem. Soc. 2013, 135, 12990−12993. (b) Delcamp, J. H.; Gormisky, P. E.; White, M. C. J. Am. Chem. Soc. 2013, 135, 8460−8463. (c) Bigi, M. A.; White, M. C. J. Am. Chem. Soc. 2013, 135, 7831−7834. (d) Stang, E. M.; White, M. C. J. Am. Chem. Soc. 2011, 133, 14892−14895 and refs cited therein. (9) Sipos, G.; Drinkel, E.; Dorta, R. Chem. Soc. Rev. 2015, 44, 3834− 3860. (10) (a) Trost, B. M.; Rao, M. Angew. Chem., Int. Ed. 2015, 54, 5026−5043. (b) Mellah, M.; Voituriez, A.; Schulz, E. Chem. Rev. 2007, 107, 5133−5209. (11) The catalyst was prepared by complexation of equimolar amounts of the required sulfoxide and Pd(OAc)2 in refluxing CH2Cl2 over 24 h as described by White et al.5a and used immediately to ensure consistent results. (12) Engelin, C.; Jensen, T.; Rodriguez-Rodriguez, S.; Fristrup, P. ACS Catal. 2013, 3, 294−302. (13) All disulfoxides were tested as an equimolar mixture of mesoand dl-diastereomers. However, for three of them (2, 3, and 5), the diastereomers proved relatively easy to separate; hence, we also evaluated their activity separately. The sulfoxide stereochemistry had little effect on reaction yields. (14) Yin, G.; Wu, Y.; Liu, G. J. Am. Chem. Soc. 2010, 132, 11978− 11987. (15) Montzka, T. A.; Matiskella, J. D.; Partyka, R. A. Tetrahedron Lett. 1974, 15, 1325−1327. (16) Li, J. R.; Bu, X. H.; Jiao, J.; Du, W. P.; Xu, X. H.; Zhang, R. H. Dalton Trans. 2005, 34, 464−474. (17) Liu, G.; Yin, G.; Wu, L. Angew. Chem., Int. Ed. 2008, 47, 4733− 4736. (18) Gresser, M. J.; Wales, S. M.; Keller, P. A. Tetrahedron 2010, 66, 6965−6976. (19) Millán, A.; Á lvarez de Cienfuegos, L.; Miguel, D.; Campaña, A. G.; Cuerva, J. M. Org. Lett. 2012, 14, 5984−5987. (20) McGarvey, G. J.; LeClair, C. A.; Schmidtmann, B. A. Org. Lett. 2008, 10, 4727−4730. (21) Prediger, P.; Barbosa, L. F.; Génisson, Y.; Correia, C. R. D. J. Org. Chem. 2011, 76, 7737−7749.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.6b03089. Plots of 1H and 13C NMR spectra for all new compounds (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*Fax: +86-551-62901450. Phone: ++86-551-62901450. E-mail: [email protected]. *E-mail: [email protected]; [email protected]. ORCID

Eric Assen B. Kantchev: 0000-0002-0607-9288 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors thank Hefei University of Technology (China) for financial support. ABBREVIATIONS mCPBA, m-chloroperbenzoic acid; 2,6-DMBQ, 2,6-dimethyl1,4-benzoquinone; Ad, 1-adamantyl; BQ, 1,4-benzoquinone; Troc, ((2,2,2-trichloroethyl)oxy)carbonyl

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REFERENCES

(1) Hili, R.; Yudin, A. K. Nat. Chem. Biol. 2006, 2, 284−287. (2) Ricci, A., Ed. Amino Group Chemistry: From Synthesis to the Life Sciences, 1st ed.; Wiley-VCH: Weinheim, 2008. (3) Jeffrey, J. L.; Sarpong, R. Chem. Sci. 2013, 4, 4092−4106. (4) Blanksby, S. J.; Ellison, G. B. Acc. Chem. Res. 2003, 36, 255−263. (5) Seminal reports of disulfoxide-Pd catalysts for oxidative allylic C− H functionalization: (a) Chen, M. S.; White, M. C. J. Am. Chem. Soc. 2004, 126, 1346−1347. (b) Chen, M. S.; Prabagaran, N.; Labenz, N. A.; White, M. C. J. Am. Chem. Soc. 2005, 127, 6970−6971. Major contributions: (c) Covell, D. J.; White, M. C. Tetrahedron 2013, 69, 7771−7778. (d) Vermeulen, N. A.; Delcamp, J. H.; White, M. C. J. Am. Chem. Soc. 2010, 132, 11323−11328. (e) Covell, D. J.; White, M. C. Angew. Chem., Int. Ed. 2008, 47, 6448−6451. (f) Delcamp, J. H.; White, M. C. J. Am. Chem. Soc. 2006, 128, 15076−15077. (g) Fraunhoffer, K. J.; Prabagaran, N.; Sirois, L. E.; White, M. C. J. Am. Chem. Soc. 2006, 128, 9032−9033 and refs cited therein. (6) Major contributions: (a) Pattillo, C. C.; Strambeanu, I. I.; Calleja, P.; Vermeulen, N. A.; Mizuno, T.; White, M. C. J. Am. Chem. Soc. 2016, 138, 1265−1272. (b) Reed, S. A.; Mazzotti, A. R.; White, M. C. J. Am. Chem. Soc. 2009, 131, 11701−11706. (c) Reed, S. A.; White, M. C. J. Am. Chem. Soc. 2008, 130, 3316−3318. (d) Fraunhoffer, K. J.; White, M. C. J. Am. Chem. Soc. 2007, 129, 7274−7276 and refs cited therein. (7) Major contributions: (a) Howell, J. M.; Liu, W.; Young, A. J.; White, M. C. J. Am. Chem. Soc. 2014, 136, 5750−5754. (b) Young, A. J.; White, M. C. Angew. Chem., Int. Ed. 2011, 50, 6824−6827. 4917

DOI: 10.1021/acs.joc.6b03089 J. Org. Chem. 2017, 82, 4907−4917