Palladium-Catalyzed N-Arylation of Sulfoximines with Aryl Sulfonates

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Palladium-Catalyzed N-Arylation of Sulfoximines with Aryl Sulfonates Qingjing Yang, Pui Ying Choy, Qingyang Zhao, Man Pan Leung, Hoi Shan Chan, Chau Ming So, Wing-Tak Wong, and Fuk Yee Kwong J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01599 • Publication Date (Web): 31 Jul 2018 Downloaded from http://pubs.acs.org on July 31, 2018

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The Journal of Organic Chemistry

Palladium-Catalyzed N-Arylation of Sulfoximines with Aryl Sulfonates Qingjing Yang,a Pui Ying Choy,b Qingyang Zhao,b Man Pan Leung,b Hoi Shan Chan,b Chau Ming So,a Wing-Tak Wonga and Fuk Yee Kwonga,b,* a

The Hong Kong Polytechnic University Shenzhen Research Institute (SZRI), Shenzhen, P. R. of China b

Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Email: [email protected]

Abstract:

Palladium-catalyzed C−N bond coupling reaction between NH-sulfoximines and aryl halides (e.g. −Br, −I, −Cl and pseudohalides, −OTf, −ONf) has been successfully achieved. Nevertheless, aryl tosylates/mesylates left much to be succeeded. In this report, a general N-arylation of sulfoximines with aryl sulfonates is described. Using Pd(OAc)2/MeO-CM-phos complex, the N-aryl sulfoximine products can be obtained in good-to-excellent yields (up to 99%) with good common functional group compatibility. In addition to arene moieties, alkenyl tosylates are shown to be successful coupling partners.

Keywords: sulfoximines, palladium, arylation, sulfonates, phosphine

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Sulfoximines, the monoaza analogues of sulfones, have received continuous attention over the past decades because of their unique and valuable structures.1 This privileged scaffold offers distinctive physicochemical and biologically properties2 that are favourable to medicinal chemistry (Figure 1).3 In view of synthetic chemistry, they serve as important chiral auxiliaries in resolution steps, 4 useful ligands in asymmetric catalysis, 5 and building blocks in assembling pseudopeptides. 6 Recently, they were even employed as directing groups for catalytic ortho-C-H functionalizations.

7

Considering their importance and versatility, the development of a complementary synthetic method which allows other commonly available arene reagents to be used, is thus highly desirable.

Figure 1. Examples of useful bioactive molecules with sulfoximine scaffold

Palladium-catalyzed N-arylation of sulfoximines has been successful since the pioneering work of Bolm in 1998 (Figure 2).8 Aryl bromides were well-coupled with NHsulfoximines in the presence of Pd(OAc)2/rac-BINAP complex.8,9 The same catalyst system was further extended to the corresponding aryl triflates and nonaflates in this C−N coupling process. 10 Since then, chemists have been actively searching other arene sources for this reaction, for instance, nucleophilic aryl siloxanes arylboronic acids, acyl peroxides.

16

12

hypervalent diaryliodonium salts,

13

arylsulfinates,

14

11

and

15

and

azoles

Recently, a transition metal-free N-arylation of sulfoximine using non-

regioselective aryne was also reported.17 In fact, aryl halides are attractive and more readily available coupling partners. Bolm showed that, apart from palladium catalyst system, copper and iron salts were able to catalyze this sulfoximination process (Figure 2


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2).18,19,20 In 2004, Harmata showed the cross-coupling of activated aryl chlorides with NH-sulfoximines under microwave reaction conditions.21 The same group later reported a more efficient system (Pd2dba3/RuPhos) which allowed the non-activated aryl chlorides to be coupled smoothly (Figure 2).22 Even though most of the aryl halides are commonly available, some of their arene substitution patterns may not be straightforwardly accessed from electrophilic halogenation.

Indeed, it would be

desirable having opportunity of using other complementary arene sources for expanding the scope of such coupling reactions. Rich feedstock phenol-derived coupling partners are thus complementary entities.23 Herein we report the first examples of Pd-catalyzed N-arylation of sulfoximines with aryl tosylates and mesylates.

Figure 2. Recent development for preparation of N-aryl sulfoximine using crosscoupling protocol We commenced the investigation using sulfoximine 1a and electronically neutral aryl tosylate 2a as the model substrates (Scheme 1). A number of previously found remarkable ancillary ligands were examined for their efficacy towards this N-arylation process. Poor conversions were observed with XPhos24 and Mor-DalPhos,25 whereas CataCXium PCy, 26 and Xantphos 27 were found to be ineffective.

RuPhos24 and

BrettPhos24 gave moderate product yield. CM-phos28 which formerly reported by our group, gave 89% product yield. Yet, a small amount of phenol side product (~3-4% from GC analysis) was observed due to possible competitive alkaline hydrolysis under alcoholic medium. In order to further facilitate the rate of oxidative addition of Ar−OTs bond, a more electron-rich MeO-CM-phos was employed (X-ray crystal structure, CCDC

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1851614). To our delight, no competitive phenolic side products was detected and the desired product yield was afforded in 94%. Scheme 1. An evaluation of ligand efficacy in Pd-catalyzed sulfoximinationa NH Me S O

t-Bu

t-Bu

1.5 mol% Pd(OAc)2 3.0 mol% Ligand

+

K2CO3, t-BuOH 110 °C, 18 h OTs 2a

1a

Ligands: SPhos, 0% XPhos, 5% RuPhos, 63% BrettPhos, 70%

Me O

S

N

3aa Me

Mor-DalPhos, 31% Xantphos, 0% CataCXium PCy, 0% DPPF, 0%

N

Cy2P CM-phos, 89%

Me N

OMe

Cy2P

MeO-CM-phos, 94%

a

Reaction conditions: 1a (0.4 mmol), 2a (0.48 mmol), Pd(OAc)2 (1.5 mol%), Ligand (3.0 mol%; Pd/L = 1:2),

K2CO3 (0.8 mmol) and t-BuOH (1 mL) were stirred at 110 °C under nitrogen for 18 h. GC yields with dodecane as the internal standard.

We then carried out a series of investigations to optimize the reaction conditions (Table 1). Pd(OAc)2 showed the best performance among palladium sources examined (entries 1-4). After screening of several common inorganic bases, we identified K2CO3 as the most effective base (entry 1 vs entries 5-10). When t-BuOH was replaced by CH3CN, the yield of 3aa sharply decreased to 20% (entry 13). Other commonly used solvents such as DMF and dioxane did not work well (entries 11-12, 14).

Further

reducing the Pd catalyst loading or Pd-to-ligand ratio (e.g. 1:1) resulted a slightly drop of product yield (entry 1 vs entries 16-17).

Table 1. Initial conditions screening of Pd-catalyzed N-arylation of sulfoximine with 2aa

4


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entry

catalyst (mol%)

solvent

base

1

Pd(OAc)2 (1.5)

t-BuOH

K2CO3

94 (93)

2

Pd2(dba)3 (1.5)

t-BuOH

K2CO3

NR

3

Pd(TFA)2 (1.5)

t-BuOH

K2CO3

91

4

PdCl2 (1.5)

t-BuOH

K2CO3

86

5

Pd(OAc)2 (1.5)

t-BuOH

Cs2CO3

55

6

Pd(OAc)2 (1.5)

t-BuOH

K3PO4

80 90

7

Pd(OAc)2 (1.5)

t-BuOH

K3PO4H2 O

8

Pd(OAc)2 (1.5)

t-BuOH

Na3PO4

33

9

Pd(OAc)2 (1.5)

t-BuOH

KOt-Bu

NR

10

Pd(OAc)2 (1.5)

t-BuOH

KF

NR

11

Pd(OAc)2 (1.5)

toluene

K2CO3

NR

12

Pd(OAc)2 (1.5)

DMF

K2CO3

NR

13

Pd(OAc)2 (1.5)

CH3CN

K2CO3

20

14

Pd(OAc)2 (1.5)

dioxane

K2CO3

NR

15

Pd(OAc)2 (2.0)

t-BuOH

K2CO3

94

16

Pd(OAc)2 (1.0)

t-BuOH

K2CO3

77

c

Pd(OAc)2 (1.5)

t-BuOH

K2CO3

79

d

18

Pd(OAc)2 (1.5)

t-BuOH

K2CO3

93

19

Pd(OAc)2 (1.5)

i-PrOH

K2CO3

8

17

a

% yieldb

Reaction conditions: 1a (0.4 mmol), 2a (0.48 mmol), Pd source (as indicated), MeO-CM-phos (2.0-4.0

mol%, Pd/Ligand = 1:2), base (0.8 mmol) and solvent (1.0 mL) were stirred at 110 °C under nitrogen for 18 h.

b

Yields were determined by GC-FID with dodecane as the internal standard. Isolated yield was c

d

shown in parentheses. Pd/Ligand = 1:1. Pd/Ligand = 1:3.

We next explored the substrate scope by first examining a series of aryl sulfonates (Scheme 2). In general, N-arylation of sulfoximine proceeded smoothly to give the desired product in good-to-excellent yields. Common functional groups such as methoxy, methyl ester, nitrile and enolizable ketone were well-tolerated under these reaction conditions (compounds 3af, 3ag, 3ai, 3aj, and 3am).

To the best of our

knowledge, there has been no successful example of aryl mesylates reported to-date in the N-arylation of sulfoximine derivatives. When 1a was treated with aryl mesylates, the N-arylation proceeded smoothly to afford the desired products. A range of functional 5



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groups were tolerated (compounds 3aa-3ag and 3al). Heteroaryl tosylates/mesylates could also be used as the coupling partners to give excellent product yields (compounds 3ac, 3al, 3an). Nevertheless, the o-tolyl and p-hydroxylphenyl tosylates were found not applicable.

Scheme 2. Palladium-catalyzed N-arylation of sulfoximine 1a with aryl sulfonatesa NH Me S O

1.5 mol% Pd(OAc)2 3.0 mol% MeO-CM-phos Me

R +

K2CO3, t-BuOH 110 °C, 18 h

OTs/OMs 1a

O

N

S

R

3

2 N

t-Bu Me

N

S

O

Me

N

S

O 3aa

Me

3ab 98% (OTs) 90% (OMs)

91% (OTs) 82% (OMs)

N

S

O

3ac 97% (OTs) 80% (OMs)

Me Me O

S

N

Me

Me

Me

N

S

O

O

O

S

Me 3af

3ae

3ad

87% (OTs) 84% (OMs)

71% (OTs) 60% (OMs)

Me

O

N

S

O S N Me

Ph

N

80% (OTs) 61% (OMs)

O

N

Me

3ag 98% (OMs)

O S Me

3ah 92% (OTs)

S

CN Me O

S

N

R

Me

Me S

O

N

3ai, 3aj, 3ak

O

S

N

N

3an

a

N

3am 62% (OTs) 84% (OMs)

89% (OTs) Me

NO2 Me

Me O

91% (OTs)

S

3al

R = COPh, 72% (OTs) R = COOMe, 85% (OTs) R = OMe, 85% (OTs)

Me

O

S

N

Me

3ao 70% (OTs)

O

S

N

3ap 52% (OTs)b

Reaction conditions: 1a (0.4 mmol), 2 (0.48 mmol), Pd(OAc)2 (1.5 mol%), MeO-CM-phos (3.0 mol%;

Pd/L = 1:2), K2CO3 (0.8 mmol) and t-BuOH (1 mL) were stirred at 110 °C under nitrogen for 18 h. Isolated yields were reported. Reaction times were not optimized for each substrate. Pd(OAc)2 and 6.0 mol% of MeO-CM-phos were used.

6


b

3.0 mol% of

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When 4-chloro-3,5-dimethylphenyl tosylate (2q) was used as the substrate, the N-arylation appeared at the chloro-position instead of the tosyl-position even there is a higher steric hindrance alongside the chloro group (Scheme 3). Scheme 3. Palladium-catalyzed N-arylation of sulfoximine 1a with 2qa

a

Reaction conditions: 1a (0.4 mmol), 2q (0.48 mmol), Pd(OAc)2 (1.5 mol%), MeO-CM-phos (3.0 mol%),

K2CO3 (0.8 mmol) and t-BuOH (1 mL) were stirred at 110 °C under nitrogen for 18 h. Isolated yield.

The Pd/MeO-CM-phos catalytic system was also found to be effective in promoting the sulfoximination of alkenyl tosylate (Scheme 4). Good-to-excellent product yields were obtained (compounds 5aa, 5ab and 5ac). Scheme 4. Palladium-catalyzed N-arylation of sulfoximine 1a with alkenyl tosylatesa

a

Reaction conditions: 1a (0.4 mmol), alkenyl tosylate 4 (0.48 mmol), Pd(OAc)2 (1.5 mol%), MeO-CM-phos

(3.0 mol%; Pd/L = 1:2), K2CO3 (0.8 mmol) and t-BuOH (1 mL) were stirred at 110 °C under nitrogen for 18 h. Isolated yields were reported. Reaction times were not optimized for each substrate.

The scope of the N-arylation reaction with respect to other substituted sulfoximines 1 and aryl tosylate 2 were next investigated (Scheme 5). An array of sulfoximines bearing different electron–donating (compounds 3ba, 3dc, 3de, and 3ee) and –withdrawing substituents (compounds 3ca and 3bc) were tested, and the corresponding N-arylated sulfoximines were furnished in excellent yields. Notably, S,S-

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dimethylsulfoximine was also found to be a feasible substrate, affording the product 3gc in 93% yield. When S,S-tetramethylenesulfoximine was treated with 2a, 70% of the product 3ha was obtained. Scheme 5. Pd-catalyzed N-arylation of substituted sulfoximine 1 with 2a

a

Reaction conditions: 1 (0.4 mmol), 2 (0.48 mmol), Pd(OAc)2 (1.5 mol%), MeO-CM-phos (3.0 mol%; Pd/L

= 1:2), K2CO3 (0.8 mmol) and t-BuOH (1 mL) were stirred at 110 °C under nitrogen for 18 h. Isolated b

yields were reported. Reaction times were not optimized for each substrate. 2.5 mol% Pd(OAc)2 was used.

In conclusion, we reported the first general examples of palladium-catalyzed Narylation of sulfoximines using aryl(alkenyl) tosylates or mesylates as the electrophilic coupling partners. The structure of MeO-CM-phos ligand was characterized and its efficacy was found more successful than the corresponding CM-phos in dealing with sulfoximination process. The reaction conditions were compatible with methyl ester, nitrile, enolizable ketone and etc, and good-to-excellent product yields were afforded. This catalyst system would be of interest to organic chemists, as the inherently inert feature of the tosyloxy/mesyloxy group could offer its protecting characteristic in the

8


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early stage of synthetic scheme and ultimately allow post-functionalization via crosscoupling technology.

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Experimental Section General Information.

Unless otherwise noted, all reagents were purchased from

commercial suppliers and used without purification. All the reactions were performed in Rotaflo®(England) re-sealable screw-cap Schlenk tube (approx. 20 mL volume) in the presence of Teflon coated magnetic stirrer bar (4 mm × 10 mm). Dioxane and toluene were freshly distilled over sodium under nitrogen.29 N,N-Dimethylformamide (DMF) was distilled from calcium hydride under reduced pressure. Acetonitrile was distilled over calcium hydride under nitrogen. t-BuOH was first distilled over sodium and stored with calcium hydride under nitrogen. Ligand SPhos, XPhos, RuPhos, BrettPhos, MorDalPhos, Xantphos, CataCXium PCy and DPPF were purchased from commercial suppliers. CM-phos ligand was developed by Kwong and prepared according to literature.30 Thin layer chromatography was performed on precoated silica gel 60 F254 plates. Silica gel (230-400 mesh) was used for column chromatography.

1

H NMR

spectra were recorded on a 400 or 500 MHz spectrometer. Spectra were referenced internally to the residual proton resonance in CDCl3 (δ 7.26 ppm), or with TMS (δ 0.00 ppm) as the internal standard. Chemical shifts (δ) were reported as part per million (ppm) in δ scale downfield from TMS.

13

C NMR spectra were recorded on a 100 or 125

MHz spectrometer and the spectra were referenced to CDCl3 (δ 77.0 ppm, the middle peak). Coupling constants (J) were reported in Hertz (Hz). Mass spectra (EI-MS and ES-MS) were recorded on a Mass Spectrometer. High-resolution mass spectra (HRMS) were obtained on a ESI-QToF mass spectrometer which the ionization method is electrospray ionization (ESI) and the mass analyzer is a quadrupole time-of-flight mass analyzer. GC-MS analysis was conducted on a GCD system. Products described in GC yield were accorded to the authentic samples/dodecane calibration standard from GCFID system. Preparation

of

2-(2-(dicyclohexylphosphanyl)-5-methoxyphenyl)-1-methyl-1H-

indole (MeO-CM-phos) An oven-dried 500-mL single-necked round-bottomed flask equipped with a Tefloncoated magnetic stir bar is charged with 2-bromo-5-methoxyacetophenone (9.8 mL, 60

10


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mmol) and phenylhydrazine (7.1 mL, 72 mmol) via syringe. Phosphoric acid (30 mL) is added slowly and the mixture is stirred for 30 min. Polyphosphoric acid (100 g) is added to the reaction mixture slowly with continuous stirring, and is placed in a preheated oil bath (80 °C) for 15 min. The bath temperature is raised to 100 °C for 30 min. After completion of the reaction, the resulting mixture is then poured into ice water and extracted with water and dichloromethane for several times. The organic layer was separated and the aqueous layer was washed with dichloromethane. The filtrate was concentrated under rotary evaporation. The crude product was purified by flash column chromatography on silica gel to afford 2-(2-bromo-5-methoxyphenyl)-1H-indole31 ligand precursor. Pale yellow powder, 41% yield (7.43 g), hexane:EtOAc=9:1, Rf=0.26.

1

H

NMR (500 MHz, CDCl3): δ 8.68 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.5 H, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.26 (t, J = 8.0, 7.0 Hz, 1H), 7.19-7.16 (m, 2H), 6.85-6.80 (m, 2H), 3.86 (s, 3H).

13

C NMR (125 MHz, CDCl3): δ 159.0, 136.2 (overlapped), 134.6,

134.1, 128.1, 122.6, 120.8, 120.2, 116.6, 115.3, 111.7, 111.0, 103.6, 55.6. An oven-dried 100-mL three-necked round-bottomed flask is equipped with a Tefloncoated magnetic stir bar, is charged with sodium hydride (63 % dispersion in mineral oil) (0.46 g of NaH in oil, 12 mmol). The necks are fitted with pressure-equalizing dropping funnel, is charged with 2-(2-bromo-5-methoxyphenyl)-1H-indole (2.93 g, 9.7 mmol), rubber septum and nitrogen stopcock inlet. The flask is evacuated and backfilled with nitrogen three times. Anhydrous tetrahydrofuran (5 mL) is added to the reaction flask via syringe to form a suspension of sodium hydride. The suspension is cooled to 0 °C in ice-water bath.

The solution of 2-(2-bromo-5-methoxyphenyl)-1H-indole is added

dropwise via dropping funnel to the reaction mixture. Upon completion of addition, the reaction mixture is allowed to reach room temperature and stirred for 30 min. Dimethyl sulfate (1.1 mL, 11.6 mmol) are added and the mixture is stirred for overnight. Methanol is added to quench the reaction and the mixture is extracted with water and ethyl acetate. The filtrate is concentrated and purified by column chromatography to afford N-methyl-2-(2’-bromo-5’-methoxyphenyl)indole 32 ligand precursor.

Pale yellow solid,

72% yield (2.18 g), hexane:EtOAc=9:1, Rf=0.47. 1H NMR (500 MHz, CDCl3): δ 7.70 (d, J = 5.0 Hz, 1H), 7.61 (d, J = 8.5 H, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.30 (t, J = 7.5, 8.0 Hz, 1H), 7.19 (t, J = 7.5 Hz, 1H), 7.0 (s, 1H), 7.00-6.90 (m, 1H), 6.54 (s, 1H), 3.85 (s, 3H),

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3.62 (s, 3H).

Page 12 of 28

13

C NMR (125 MHz, CDCl3): δ 158.6, 139.6, 137.2, 135.0, 133.3, 127.6,

121.8, 120.7, 119.58, 118.1, 116.2, 115.5, 109.5, 101.9, 55.6, 30.7. N-Methyl-2-(2’-bromo-5’-methoxyphenyl)indole (1.26 g, 4.0 mmol) is dissolved in freshly distilled THF (10 mL) at room temperature under nitrogen atmosphere. The solution is cooled to -78 °C in dry ice/acetone bath. Titrated n-BuLi (4.4 mmol) is added dropwise with

a

syringe.

After

the

reaction

mixture

is

stirred

for

30

min,

chlorodicyclohexylphosphine (1.02 mL, 4.4 mmol) in THF is added. The reaction is allowed to warm to room temperature and stirred overnight. The solvent is removed under reduced pressure. The product was recrystallized by cold ethanol and hexane to afford 2-(2-(dicyclohexylphosphanyl)-5-methoxyphenyl)-1-methyl-1H-indole (MeO-CMphos).

Off-white solid, 65% yield (1.73 g), m.p. 112.2-113.6.

1

H NMR (400 MHz,

CDCl3): δ 7.60 (d, J = 7.6 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.10 (t, J = 7.6, 7.2 Hz, 1H), 7.00 (d, J = 8.4 Hz, 1H), 6.88 (s, 1H), 6.38 (s, 1H), 3.82 (s, 3H), 3.50 (s, 3H), 1.70-7.55 (m, 11H), 7.18-1.06 (m, 11H). 13C NMR (100 MHz, CDCl3): δ 159.3, 142.6, 142.3, 141.3 (overlapped), 136.6, 133.9 (overlapped), 127.8, 127.7, 127.6, 121.1, 120.3, 119.4, 116.8, 116.7, 114.5, 109.5, 103.0, 55.2, 30.9, 30.8, 27.3, 26.4.

31

P NMR (162 MHz, CDCl3): δ -12.36. HRMS: calcd.

for C28H37NOP [M + H]+: 434.2613 found 434.2625. General Procedures for Ligand and Reaction Condition Screenings Palladium source (1.5 mol%), ligand (3.0 mol%), 4-tert-butylphenyl tosylate (2a) (145.9 mg, 0.48 mmol), and base (0.8 mmol) were loaded into a Schlenk tube equipped with a Teflon-coated magnetic stir bar. The tube was evacuated and flushed with nitrogen for three cycles. Solvent (1.0 mL) and S-methyl-S-phenylsulfoximine (1a) (54.5 µL, 0.4 mmol) were then added with stirring at room temperature for several minutes. The tube was then placed into a preheated oil bath (110 °C) and stirred for 18 hours. After completion of reaction, the reaction tube was allowed to cool to room temperature. Ethyl acetate (~10 mL), dodecane (90.8 µL, internal standard) and water (~3 ml) were added. The organic layer was subjected to GC analysis. The GC yield obtained was previously calibrated by authentic sample/dodecane calibration curve.

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General Procedures for N-arylation of Substituted Sulfoximine with Aryl Sulfonate Pd(OAc)2 (1.5 mol%, 1.4 mg, 0.006 mmol), MeO-CM-phos (3.0 mol%, 5.2 mg, 0.012 mmol), aryl sulfonate 2 or alkenyl tosylate 4 (0.48 mmol), and K2CO3 (110.5 mg, 0.8 mmol) were loaded into a Schlenk tube equipped with a Teflon-coated magnetic stir bar. The tube was evacuated and flushed with nitrogen for three cycles. t-BuOH (1.0 mL) and substituted sulfoximine 1 (0.4 mmol) were then added with stirring at room temperature for several minutes. The tube was then placed into a preheated oil bath (110 °C) and stirred for 18 hours. After completion of reaction, the reaction tube was allowed to cool to room temperature and quenched with water and diluted with ethyl acetate. The organic layer was separated and the aqueous layer was washed with ethyl acetate.

The filtrate was concentrated under reduced pressure.

The crude

product was purified by flash column chromatography on silica gel (230-400 mesh) to afford the desired product.

N-[(4-(tert-Butyl)phenyl)]-S-methyl-S-phenylsulfoximine product 3aa)9

(Scheme

1

and

2,

Yellow oil, 93% yield (106 mg) for tosyl substrate; 80% yield (92 mg) for mesyl substrate, hexane:EtOAc=2:1, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 8.02 (d, J = 7.2 Hz, 2H), 7.607.53 (m, 3H), 7.16 (d, J = 8.5 Hz, 2H), 6.96 (d, J = 8.5 Hz, 2H), 3.23 (s, 3H), 1.25 (s, 9H). 13

C NMR (100 MHz, CDCl3): δ 144.3, 142.0, 139.9, 133.1, 129.5, 128.6, 125.8, 122.7,

46.0, 34.0, 31.4.

N-(2-Naphthyl)-S-methyl-S-phenylsulfoximine (Scheme 2, product 3ab)17a White solid, 98% yield (110 mg) for tosyl substrate, 92% yield (103 mg) for mesyl substrate, m.p.=141-142°C, hexane:EtOAc=6:1, Rf=0.6. 1H NMR (400 MHz, CDCl3): δ 8.16-8.14 (m, 4H), 7.72 (t, J = 6.6 Hz, 2H), 7.67 (d, J = 8.2 Hz, 1H), 7.60 (s, 1H), 7.507.46 (m, 7H), 7.38 (t, J = 7.1 Hz, 1H), 7.33-7.28 (m, 1H).

13

C NMR (100 MHz, CDCl3): δ

142.6, 140.8, 134.5, 132.8, 129.6, 129.4, 128.7, 128.6, 127.5, 126.9, 125.9, 125.2, 123.8, 119.2. HRMS (ESI) m/z: calcd for C22H18NOS [M + H]+ 344.1109, found 344.1111.

13



Page 14 of 28

N-Quinolin-6-yl-S-methyl-S-phenylsulfoximine (Scheme 2, product 3ac) Yellow oil, 97% yield (109 mg) for tosyl substrate, 80% yield (90 mg) for mesyl substrate, hexane:EtOAc=1:3, Rf=0.3. 1H NMR (400 MHz, CDCl3): δ 8.65 (dd, J = 4.0, 1.2 Hz, 1H), 7.8 (d, J = 7.2 Hz, 2H), 7.87 (t, J = 9.0 Hz, 2H), 7.55-7.44 (m, 4H), 7.30 (d, J = 2.6 Hz, 1H), 7.20 (q, J = 4.2 Hz, 1H), 3.28 (s, 3H).

13

C NMR (100 MHz, CDCl3): δ 148.0, 144.7,

143.7, 138.9, 134.8, 133.4, 130.1, 129.6, 129.2, 128.5, 128.4, 121.0, 117.5, 46.2. HRMS (ESI) m/z: calcd for C16H15N2OS [M + H]+ 283.0905, found 283.0904.

N-[(3,4-Dimethyl)phenyl]-S-methyl-S-phenylsulfoximine (Scheme 2, product 3ad) Yellow oil, 79% yield (81 mg) for tosyl substrate, 60% yield (62 mg) for mesyl substrate, hexane:EtOAc=2:1, Rf=0.33. 1H NMR (400 MHz, CDCl3): δ 8.01 (d, J = 7.4 Hz, 2H), 7.59-7.52 (m, 3H), 6.90-6.87 (m, 2H), 6.78 (d, J = 8.0 Hz, 1H) 3.23 (s, 3H), 2.15 (s, 3H), 2.14 (s, 3H).

13

C NMR (100 MHz, CDCl3): δ 142.5, 139.7, 137.1, 133.1, 130.0, 129.8,

129.5, 128.6, 124.8, 120.5, 45.8, 19.8, 19.0. HRMS (ESI) m/z: calcd for C15H18NOS [M + H]+ 260.1109, found 260.1106.

N-(1-Naphthyl)-S-methyl-S-phenylsulfoximine (Scheme 2, product 3ae)10 Yellow solid, 88% yield (99 mg) for tosyl substrate, 80% yield (90 mg) for mesyl substrate, hexane:EtOAc=2:1, Rf=0.5. 1H NMR (400 MHz, CDCl3): δ 8.58 (d, J = 8.1 Hz, 1H), 8.03 (d, J = 7.4 Hz, 2H), 7.79 (d, J = 7.5 Hz, 1H), 7.60-7.48 (m, 5H), 7.42 (d, J = 8.1 Hz, 1H), 7.20 (t, J = 7.8 Hz, 1H), 7.13 (d, J = 7.4 Hz, 1H), 3.36 (s, 3H).

13

C NMR

(100 MHz, CDCl3): δ 141.6, 139.4, 134.6, 133.3, 130.1, 129.5, 128.4, 127.8, 126.0, 125.9, 125.0, 124.0, 121.5, 116.5, 45.9.

N-[(3-Acetyl)phenyl]-S-methyl-S-phenylsulfoximine (Scheme 2, product 3af) Yellow oil, 82% yield (90 mg) for tosyl substrate, 60% yield (66 mg) for mesyl substrate, hexane:EtOAc=1:1, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 7.2 Hz, 2H), 7.607.56 (m, 2H), 7.53-7.50 (m, 2H), 7.46-7.43 (m, 1H), 7.20-7.15 (m, 2H), 3.26 (s, 3H), 2.48 (s, 3H).

13

C NMR (100 MHz, CDCl3): δ 198.2, 145.5, 138.9, 138.0, 133.5, 129.6, 14


Page 15 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


129.1, 128.5, 127.6, 123.3, 121.4, 46.0, 26.7. HRMS (ESI) m/z: calcd for C15H16NO2S [M + H]+ 274.0902, found 274.0901.

N-(6-Benzoylnaphthalen-2-yl)-S-methyl-S-phenylsulfoximine (Scheme 2, product 3ag) Yellow solid, 92% yield (142mg), m.p.=104-105 °C, hexane:EtOAc=1:1, Rf=0.5. 1H NMR (400 MHz, CDCl3): δ 8.13 (s, 1H), 8.04 (d, J = 7.4 Hz, 2H), 7.86-7.81 (m, 3H), 7.70 (q, J = 8.8 Hz, 2H), 7.63-7.48 (m, 6H), 7.43 (d, J = 1.7 Hz, 1H), 7.33 (dd, J = 8.7, 2.1 Hz, 1H), 3.34 (s, 3H).

13

C NMR (100 MHz, CDCl3): δ 196.6, 146.0, 139.0, 138.3, 136.7, 133.5,

132.6, 132.1, 132.0, 130.4, 129.9, 129.7, 128.5, 128.3, 128.0, 127.0, 126.0, 125.6, 118.0, 46.3. HRMS (ESI) m/z: calcd for C24H20NO2S [M + H]+ 386.1215, found 386.1219.

N,N’-[Naphthalene]-2,7-bis-(S-methyl-S-phenylsulfoximine) (Scheme 2, product 3ah) White soild, 90% yield (156 mg), m.p.=140-141 °C, hexane:EtOAc=1:3, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 8.02-7.99 (m, 4H), 7.59-7.56 (m, 2H), 7.53-7.47 (m, 6H), 7.18 (dd, J = 4.7, 1.8 Hz, 2H), 7.08 (t, J = 2.4 Hz, 1H), 7.06 (t, J = 2.4 Hz, 1H), 3.29 (s, 6H).

13

C

NMR (100 MHz, CDCl3): δ 142.9, 139.2 (d, J = 8.4 Hz), 135.4, 133.2, 129.5 (d, J = 2.0 Hz), 128.6 (d, J = 3.0 Hz), 128.2, 125.6, 122.5 (d, J = 11.3 Hz), 117.6 (d, J = 10.1 Hz), 45.9 (d, J = 17.6 Hz). HRMS (ESI) m/z: calcd for C24H23N2O2S2 [M + H]+ 435.1201, found 435.1205.

N-[(4-Benzoyl)phenyl]-S-methyl-S-phenylsulfoximine (Scheme 2, product 3ai) White solid, 78% yield (105 mg), m.p.=177-178 °C, hexane:EtOAc=1:1, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 7.4 Hz, 2H), 7.72 (d, J = 7.1 Hz, 2H), 7.66-7.62 (m, 3H), 7.59-7.52 (m, 3H), 7.46-7.42 (m, 2H), 7.07 (d, J = 8.5 Hz, 2H), 3.32 (s, 3H).

13

C

NMR (100 MHz, CDCl3): δ 195.8, 150.0, 138.7, 138.4, 133.7, 131.9, 131.7, 130.5, 129.8, 129.7, 128.5, 128.1, 122.3, 46.4. HRMS (ESI) m/z: calcd for C20H18NO2S [M + H]+ 336.1058, found 336.1059.

15



Page 16 of 28

N-[4-(Methyloxycarbonyl)phenyl]-S-methyl-S-phenylsulfoximine (Scheme 2, product 3aj) White solid, 89% yield (103 mg), m.p.=126-127 °C, hexane:EtOAc=1:1, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 7.5 (d, J = 7.7 Hz, 2H), 7.80 (d, J = 8.5 Hz, 2H), 7.62-7.59 (m, 1H), 7.55-7.51 (m, 2H), 7.01 (d, J = 8.5 Hz, 2H), 3.82 (s, 3H), 3.28 (s, 3H).

13

C NMR (100

MHz, CDCl3): δ 167.1, 150.2, 138.7, 133.6, 130.8, 129.7, 128.5, 122.9, 122.5, 51.7, 46.3. HRMS (ESI) m/z: calcd for C15H16NO3S [M + H]+ 290.0851, found 290.0852. N-[(3-Methoxy)]phenyl-S-phenyl-S-methylsulfoximine (Scheme 2, product 3ak)17a Yellow oil, 82% yield (75 mg), hexane:EtOAc=2:1, Rf=0.25. 1H NMR (400 MHz, CDCl3): δ 7.97 (d, J = 7.4 Hz, 2H), 7.59-7.49 (m, 3H), 7.00 (t, J = 8.3 Hz, 1H), 6.63-6.61 (m, 2H), 6.44 (dd, J = 8.2, 2.2 Hz, 1H), 3.69 (s, 3H), 3.23 (s, 3H).

13


160.2, 146.3, 139.4, 133.2, 129.6, 129.5, 128.6, 115.7, 109.0, 107.7, 55.1, 46.0. N-[3-(5-Methyl-thiophen-2-yl)]phenyl-S-phenyl-S-methylsulfoximine product 3al)

(Scheme 2,

Yellow oil, 92% yield (120 mg), hexane:EtOAc=3:1, Rf=0.5. 1H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 7.1 Hz, 2H), 7.57-7.50 (m, 3H), 7.28 (s, 1H), 7.10-7.08 (m, 2H), 7.03 (d, J = 3.5 Hz, 1H), 6.94-6.92 (m, 1H), 6.69 (d, J = 4.5 Hz, 1H), 3.25 (s, 3H), 2.48 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 145.6, 142.1, 139.3, 139.2, 135.4, 133.3, 129.6, 129.4, 128.6, 126.1, 122.8, 121.7, 120.5, 119.0, 45.9, 15.5. HRMS (ESI) m/z: calcd for C18H18NOS2 [M + H]+ 328.0830, found 328.0834. N-[4-(Cyano)phenyl]-S-methyl-S-phenylsulfoximine (Scheme 2, product 3am)9 Yellow oil, 70% yield (72 mg) for tosyl substrate, 86% yield (88 mg) for mesyl substrate, hexane:EtOAc=2:1, Rf=0.3. 1H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 7.9 Hz, 2H), 7.667.62 (m, 1H), 7.58-7.54 (m, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.5 Hz, 2H), 3.29 (s, 3H).

13

C NMR (100 MHz, CDCl3): δ 150.2, 138.4, 133.8, 133.2, 129.8, 128.4, 123.2,

119.6, 103.9, 46.5.

16


Page 17 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


N-[3-(1H-pyrrol-1-yl)]phenyl-S-(4-methylphenyl)-S-methylsulfoximine product 3an)

(Scheme 2,

Yellow oil, 90% yield (106 mg), hexane:EtOAc=3:1, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.17-7.13 (m, 2H), 7.04 (t, J = 1.8 Hz, 2H), 6.94-6.91 (m, 2H), 6.32 (t, J = 1.8 Hz, 2H), 3.26 (s, 3H), 2.41 (s, 3H).

13

C NMR

(100 MHz, CDCl3): δ 146.7, 144.4, 141.3, 135.9, 130.4, 129.9, 128.6, 120.2, 119.2, 115.3, 113.5, 110.1, 46.3, 21.6. HRMS (ESI) m/z: calcd for C18H19N2OS [M + H]+ 311.1218, found 311.1221.

N-[(3,5-Dimethyl)phenyl]-S-methyl-S-phenylsulfoximine (Scheme 2, product 3ao)10 White solid, 72% yield (75 mg), hexane:EtOAc=2:1, Rf=0.35. 1H NMR (400 MHz, CDCl3): δ 8.01 (d, J = 7.3 Hz, 2H), 7.62-7.52 (m, 3H), 6.70 (s, 2H), 6.56 (s, 1H), 3.23 (s, 3H), 2.20 (s, 6H).

13

C NMR (100 MHz, CDCl3): δ 144.6, 139.7, 138.5, 133.1, 129.5, 128.6,

123.7, 121.1, 45.9, 21.3.

N-[(4-Nitro)]phenyl-S-phenyl-S-methylsulfoximine (Scheme 2, product 3ap) Pale yellow solid, 52% yield (57 mg), m.p.=131-134 °C, hexane:EtOAc=1:1, Rf=0.45. 1H NMR (500 MHz, CDCl3): δ 8.00-7.94 (m, 4H), 7.65 (t, J = 7.5 Hz, 1H), 7.57 (t, J = 7.5 Hz, 2H), 7.03-7.00 (td, J = 9.0, 2.0 Hz, 2H), 3.32 (s, 3H).

13


152.6, 141.6, 138.2, 133.9, 129.9, 128.3, 125.1, 122.4, 46.5. HRMS (ESI) m/z: calcd for C13H13N2O3S [M + H]+ 277.0641, found 277.0644. 3,5-Dimethyl-4-((methyl(oxo)(phenyl)-λ6-sulfanylidene)amino)phenyl 4methylbenzenesulfonate (Scheme 3, product 3aq) Yellow oil, 93% yield (159 mg), hexane:EtOAc=2:1, Rf=0.25. 1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 7.4 Hz, 2H), 7.69 (d, J = 8.3 Hz, 2H), 7.63-7.61 (m, 1H), 7.58-7.54 (m, 2H), 7.8 (d, J = 8.1 Hz, 2H), 6.64 (s, 2H), 3.05 (s, 3H), 2.43 (s, 3H), 2.26 (s, 6H).

17


13

C NMR


Page 18 of 28

(100 MHz, CDCl3): δ 145.1, 144.8, 140.9, 139.7, 135.4, 133.2, 132.6, 129.6, 129.3, 128.5, 127.6, 121.6, 43.8, 21.8, 20.1. HRMS (ESI) m/z: calcd for C22H24NO4S2 [M + H]+ 430.1147, found 430.1144. 1-Methyl-4-((methyl(oxo)(phenyl)-λ6-sulfanylidene)amino)quinolin-2(1H)-one (Scheme 4, product 5aa) White solid, 91% yield (114 mg), m.p.=168-169 °C, hexane:EtOAc=2:1, Rf=0.2. 1H NMR (400 MHz, CDCl3): δ 8.30 (dd, J = 7.9, 1.1 Hz, 1H), 7.91 (d, J = 7.7 Hz, 2H), 7.61-7.55 (m, 1H), 7.55-7.49 (m, 3H), 7.27-7.21 (m, 2H), 6.15 (s, 1H), 3.56 (s, 3H), 3.36 (s, 3H). 13

C NMR (100 MHz, CDCl3): δ 163.0, 151.5, 140.0, 137.7, 133.9, 130.7, 129.8, 128.1,

125.2, 121.4, 120.4, 113.9, 106.2, 46.3, 28.9. HRMS (ESI) m/z: calcd for C17H17N2O2S [M + H]+ 313.1011, found 313.1009.

4-[(S-Methyl-S-phenylsulfoximin)-yl]product 5ab)

6-methyl-2H-pyran-2-one

(Scheme

4,

Yellow oil, 82% yield (86 mg), hexane:EtOAc=2:1, Rf=0.2. 1H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 7.7 Hz, 2H), 7.64-7.63 (m, 1H), 7.57-7.53 (m, 2H), 5.79 (s, 1H), 5.37 (s, 1H), 3.24 (s, 3H), 2.07 (s, 3H).

13

C NMR (100 MHz, CDCl3): δ 164.6, 161.3, 160.3, 137.4,

134.3, 130.0, 127.9, 104.7, 96.0, 46.4, 19.8. HRMS (ESI) m/z: calcd for C13H14NO3S [M + H]+ 264.0694, found 264.0695.

4-[(S-Methyl-S-phenylsulfoximin)-yl]-2H-chromen-2-one (Scheme 4, product 5ac) White solid, 60% yield (71 mg), m.p.=164-165 °C, hexane:EtOAc=2:1, Rf=0.2. 1H NMR (400 MHz, CDCl3): δ 8.12 (dd, J = 7.9, 1.1 Hz, 1H), 7.4 (d, J = 8.1 Hz, 2H), 7.71-7.67 (m, 1H), 7.61-7.51 (m, 2H), 7.52-7.49 (m, 1H), 7.30-7.23 (m, 2H), 5.71 (s, 1H), 3.42 (s, 3H). 13

C NMR (100 MHz, CDCl3): δ 162.4, 156.0, 153.7, 137.0, 134.5, 131.7, 130.1, 127.9,

124.6, 123.6, 119.3, 116.6, 98.3, 46.4. HRMS (ESI) m/z: calcd for C16H14NO3S [M + H]+ 300.0694, found 300.0694.

18


Page 19 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


((3,4-Dihydronaphthalen-2-yl)imino)(methyl)(phenyl)-λ6-sulfanone product 5ad)

(Scheme

4,

Yellow oil, 86% yield (97 mg), hexane:EtOAc=2:1, Rf=0.2. 1H NMR (500 MHz, CDCl3): δ 7.98 (d, J = 7.5 Hz, 2H), 7.65-7.56 (m, 3H), 7.05-7.00 (q, J = 7.5, 6.5 Hz, 2H), 6.94 (t, J = 6.5 Hz, 1H), 5.92 (s, 1H), 3.24 (s, 3H), 2.86-2.75 (m, 2H), 2.43 (t, J = 8.0 Hz, 2H).

13

C

NMR (125 MHz, CDCl3): δ 144.6, 139.3, 136.1, 133.3, 132.3, 129.5, 128.3, 126.8, 126.2, 124.6, 124.4, 110.9, 45.8, 30.4, 28.6 HRMS (ESI) m/z: calcd for C17H18NOS [M + H]+ 284.1104, found 284.1107.

N-(4-(tert-Butyl)phenyl)-S-methyl-S-(4-methylphenyl)sulfoximine (Scheme 5, product 3ba)13 Yellow oil, 96% yield (116 mg). hexane:EtOAc=5:1, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.6 Hz, 2H), 6.95 (d, J = 8.6 Hz, 2H), 3.21 (s, 3H), 2.41 (s, 3H), 1.25 (s, 9H).

13


144.1, 144.0, 142.2, 136.8, 130.2, 128.6, 125.8, 122.7, 46.1, 34.0, 31.4, 21.5.

N-(4-(tert-Butyl)phenyl)-S-methyl-S-(4-fluorophenyl)sulfoximine (Scheme 5, product 3ca) White solid, 90% yield (110 mg), m.p.=109-110 °C, hexane:EtOAc=5:1, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 8.02-7.99 (m, 2H), 7.19-7.15 (m, 4H), 6.95-6.93 (d, J = 8.8 Hz, 2H), 3.23 (s, 3H), 1.25 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 165.5 (d, J = 253.6 Hz), 144.5, 141.8, 135.7, 131.4 (d, J = 9.4 Hz), 125.9, 122.7, 116.8 (d, J = 22.5 Hz), 46.1, 34.0, 31.4. HRMS (ESI) m/z: calcd for C17H21FNOS [M + H]+ 306.1328, found 306.1326.

N-Quinolin-6-yl-S-methyl-S-(4-fluorophenyl)sulfoximine (Scheme 5, product 3bc) Yellow oil, 99% yield (118 mg), hexane:EtOAc=1:2, Rf=0.5. 1H NMR (400 MHz, CDCl3): δ 8.66 (dd, J = 4.2, 1.5 Hz, 1H), 7.99-7.96 (m, 2H), 7.89-7.86 (m, 2H), 7.44 (dd, J = 9.0, 2.4 Hz, 1H), 7.29-7.28 (m, 1H), 7.21 (q, J = 4.2 Hz, 1H), 7.17-7.12 (m, 2H), 3.28 (s, 3H). 13

C NMR (100 MHz, CDCl3): δ 165.6 (d, J = 254.6 Hz), 148.1, 144.7, 143.4, 134.9,

19



Page 20 of 28

134.7, 131.4 (d, J = 9.5 Hz), 130.1, 129.1, 128.3, 121.1, 117.0 (d, J = 22.4 Hz), 116.8, 46.3. HRMS (ESI) m/z: calcd for C16H14FN2OS [M + H]+ 301.0811, found 301.0800.

N-Quinolin-6-yl-S-(4-methoxylphenyl)-S-methylsulfoximine (Scheme 5, product 3dc) Yellow oil, 87% yield (109 mg), hexane:EtOAc=2:1, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 8.61-8.60 (m, 1H), 7.87-7.82 (m, 4H), 7.43 (dd, J = 8.9, 2.3 Hz, 1H), 7.27 (d, J = 2.2 Hz, 1H), 7.16 (q, J = 4.1 Hz, 1H), 6.90-6.88 (m, 2H), 3.71 (s, 3H), 3.24 (s, 3H). 13C NMR (100 MHz, CDCl3): δ163.5, 147.7, 144.4, 144.0, 134.9, 130.7, 129.8, 129.7, 129.2, 128.6, 120.9, 117.4, 114.9, 55.6, 46.5. HRMS (ESI) m/z: calcd for C17H17N2O2S [M + H]+ 313.1011, found 331.0988.

N-(1-Naphthyl)-S-methyl-S-(4-methoxyphenyl)sulfoximine 3de)

(Scheme 5, product

White solid, 89% yield (111 mg), m.p.=145-146 °C, hexane:EtOAc=2:1, Rf=0.5. 1H NMR (400 MHz, CDCl3): δ 8.62 (d, J = 8.3 Hz, 1H), 7.91 (d, J = 8.9 Hz, 2H), 7.79 (d, J = 7.9 Hz, 1H), 7.58-7.48 (m, 2H), 7.41 (d, J = 8.0 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 6.7 Hz, 1H), 6.89 (d, J = 8.9 Hz, 2H), 3.75 (s, 3H), 3.32 (s, 3H).

13

C NMR (100 MHz,

CDCl3): δ 163.4, 142.0, 134.6, 130.6, 130.4, 130.2, 127.8, 126.1, 125.9, 125.0, 124.1, 121.4, 116.5, 114.8, 55.6, 46.3. HRMS (ESI) m/z: calcd for C18H18NO2S [M + H]+ 312.1058, found 312.1059.

N-[3-(1H-Pyrrol-1-yl)]phenyl-S-(4-methylphenyl)-S-methylsulfoximine (Scheme 5, product 3bm) Yellow oil, 90% yield (111 mg), hexane:EtOAc=3:1, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.17-7.13 (m, 2H), 7.04 (t, J = 1.8 Hz, 2H), 6.94-6.91 (m, 2H), 6.32 (t, J = 1.8 Hz, 2H), 3.26 (s, 3H), 2.41 (s, 3H).

13

C NMR

(100 MHz, CDCl3): δ 146.7, 144.4, 141.3, 135.9, 130.4, 129.9, 128.6, 120.2, 119.2, 115.3, 113.5, 110.1, 46.3, 21.6. HRMS (ESI) m/z: calcd for C18H19N2OS [M + H]+ 311.1218, found 311.1221. 20


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N-[3-(1H-pyrrol-1-yl)]phenyl-S-(4-methoxylphenyl)-S-methylsulfoximine (Scheme 5, product 3dm) Yellow oil, 84% yield (109 mg), hexane:EtOAc=2:1, Rf=0.4. 1H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.8 Hz, 2H), 7.15 (t, J = 8.0 Hz, 1H), 7.11 (t, J = 2.0 Hz, 1H), 7.04 (t, J = 2.1 Hz, 2H), 6.99 (d, J = 8.9 Hz, 2H), 6.93-6.91 (m, 2H), 6.31 (t, J = 2.1 Hz, 2H), 3.84 (s, 3H), 3.26 (s, 3H).

13

C NMR (100 MHz, CDCl3): δ 163.6, 146.7, 141.3, 130.7, 130.1,

129.8, 120.2, 119.2, 115.3, 114.9, 113.5, 110.1, 55.7, 46.5. HRMS (ESI) m/z: calcd for C18H19N2O2S [M + H]+ 327.1167, found 327.1170.

N-(1-Naphthyl)-S,S-(di-4-methylphenyl)sulfoximine (Scheme 5, product 3ee) White solid, 95% yield (140 mg), m.p.=153-154 °C, hexane:EtOAc=4:1, Rf=0.5. 1H NMR (400 MHz, CDCl3): δ 8.78 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 8.2 Hz, 4H), 7.80 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 7.3 Hz, 1H), 7.52 (d, J = 7.5 Hz, 1H), 7.41 (d, J = 7.7 Hz, 1H), 7.277.18 (m, 6H), 2.36 (s, 6H).

13

C NMR (100 MHz, CDCl3): δ 143.4, 141.5, 138.3, 134.6,

130.5, 130.0, 128.4, 127.8, 126.1, 125.8, 125.0, 124.1, 121.3, 116.9, 21.5. HRMS (ESI) m/z: calcd for C24H22NOS [M + H]+ 372.1422, found 372.1425.

N-(4-(tert-Butyl)phenyl)-S,S-diphenylsulfoximine (Scheme 5, product 3fa) White solid, 90% yield (125 mg), m.p.=158-159 °C, hexane:EtOAc=8:1, Rf=0.5. 1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 7.4 Hz, 4H), 7.52-7.44 (m, 6H), 7.19 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.6 Hz, 2H), 1.27 (s, 9H).

13

C NMR (100 MHz, CDCl3): δ 144.2, 141.7,

141.2, 132.6, 129.3, 128.5, 125.8, 123.1, 34.1, 31.4. HRMS (ESI) m/z: calcd for C22H24NOS [M + H]+ 350.1579, found 350.1581.

N-(2-Naphthyl)-S,S-diphenylsulfoximine (Scheme 5, product 3fb) White solid, 90% yield (123 mg), m.p.=141-142 °C, hexane:EtOAc=6:1, Rf=0.6. 1H NMR (400 MHz, CDCl3): δ 8.16-8.14 (m, 4H), 7.72 (t, J = 6.6 Hz, 2H), 7.67 (d, J = 8.2 Hz, 1H), 7.60 (s, 1H), 7.50-7.46 (m, 7H), 7.38 (t, J = 7.1 Hz, 1H), 7.33-7.28 (m, 1H).

13

C NMR

(100 MHz, CDCl3): δ 142.6, 140.8, 134.5, 132.8, 129.6, 129.4, 128.7, 128.6, 127.5,

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Page 22 of 28

126.9, 125.9, 125.2, 123.8, 119.2. HRMS (ESI) m/z: calcd for C22H18NOS [M + H]+ 344.1109, found 344.1111.

N-Quinolin-6-yl-S,S-dimethylsulfoximine (Scheme 5, product 3gc) Yellow oil, 93% yield (81 mg), hexane:EtOAc=1:2, Rf=0.25. 1H NMR (400 MHz, CDCl3): δ 8.69-8.68 (m, 1H), 7.93 (t, J = 8.4 Hz, 2H), 7.40-7.38 (m, 2H), 7.24 (q, J = 4.2 Hz, 1H), 3.13 (s, 6H).

13

C NMR (100 MHz, CDCl3): δ 148.2, 144.9, 143.8, 134.8, 130.2, 129.3,

128.5, 121.2, 127.2, 42.0. HRMS (ESI) m/z: calcd for C11H13N2OS [M + H]+ 221.0749, found 221.0748.

N-(4-(tert-Butyl)phenyl)-S,S-tetramethylenesulfoximine (Scheme 5, product 3ha) Yellow oil, 70% yield (70 mg), hexane:EtOAc=2:1, Rf=0.35. 1H NMR (400 MHz, CDCl3): δ 7.26 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 3.45-3.38 (m, 2H), 3.19-3.12 (m, 2H), 2.32-2.21 (m, 4H), 1.31 (s, 9H).

13

C NMR (100 MHz, CDCl3): δ 144.4, 143.2, 126.1,

122.2, 52.4, 34.1, 31.5, 23.9. HRMS (ESI) m/z: calcd for C14H22NOS [M + H]+ 252.1427, found 252.1424.

Supporting Information Available: Copies of 1H NMR and

13

C NMR spectra, as well

as X-ray crystallographic data and HRMS spectrum of MeO-CM-phos. This material is available free of charge via the Internet at http://pubs.acs.org.

Acknowledgements We thank the National Natural Science Foundation of China (NSFC: 2015-21572193), Research Grants Council of Hong Kong, Collaborative Research Fund (CRF: C502314G), General Research Fund (GRF: 153034/15P) and CUHK Direct Fund (4053269) for financial support. We are grateful to Dr. Pui Kin So (University research facilities in Life Science, PolyU) for HRMS analysis.

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Palladium-Catalyzed N-Arylation of Sulfoximines with Aryl Sulfonates

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