Copper Mediated Selective Mono and Sequential

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Copper Mediated Selective Mono and Sequential Organochalcogenation of C-H Bond: Synthesis of Hybrid Unsymmetrical Aryl Ferrocene Chalcogenides Moh. Sattar, Krishna Patidar, RAVIRAJ ANANDA THORAT, and Sangit Kumar J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00311 • Publication Date (Web): 10 May 2019 Downloaded from http://pubs.acs.org on May 10, 2019

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The Journal of Organic Chemistry

Copper

Mediated

Selective

Mono

and

Sequential

Organochalcogenation of C−H Bond: Synthesis of Hybrid Unsymmetrical Aryl Ferrocene Chalcogenides Moh. Sattar, Krishna Patidar, Raviraj Ananda Thorat, Sangit Kumar* Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal Bypass Road, Bhauri Bhopal, Madhya Pradesh, 462066 (India) Q NH

O

O

H

H Fe

Q NH

RSSR Cu(I) salt, CH3CN mono-thiolation

H Fe

R'EER' S R E = S, Se, and Te Cu(II) salt, DMSO

Q NH

O

R'

S

E

R

Fe

sequential chalcogenation 18 examples (46-78%)

18 examples (38-92%)

removable directing group selective alkyl/hetero/aryl-thiolation expedient ferrocene C-H chalcogenation novel sequential chalcogenation good functional group tolerance broad substrate scope

Abstract: A 8-aminoquinoline directed copper/1,10-phenanthroline-mediated selective mono-organothiolation of C−H bond in ferroceneamide has been developed using aryl/alkyldisulfide substrates. The sequential ferrocene C−H organochalcogenation (chalcogen = S, Se, and Te) has also been established for the synthesis of novel hybrid unsymmetrical aryl chalcogenides with the aid of a catalytic amount of Cu(OAc)2 under ambient reaction conditions. The developed protocol exhibits a broad functional group tolerance to allow alkyl, aryl, hetero-aryl, bromo, chloro, and nitro containing diorgano dichalcogenides as a coupling partner. Further, the 8-aminoquinoline directing group is easily removed to afford the aldehyde functionality after C−H organochalcogenation. A mechanistic understanding of the coppermediated selective mono-organothiolation reaction suggests that rigid bi-coordinated 1,10-

1 ACS Paragon Plus Environment

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phenanthroline ligand and freshly generated copper(II) from Cu(I) in the less polar solvent acetonitrile seem crucial for the selective mono-C−H functionalization of ferroceneamide.


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Introduction Ferrocene possesses unique structural features, and its derivatives offer dynamic properties in several areas such as organic synthesis and medicinal chemistry.1 Substituted ferrocene acts as a planar ligand and finds applications in enantioselective catalysis,2a metallocene containing polymers,2b electrochemical sensors, and optical applications in materials science.2c Conventionally, functionalization of ferrocene achieved via Friedel Crafts type electrophilic substitution or by stoichiometric C−H bond metalation utilizing organolithium followed by coupling with an electrophile.3 Over the past few years, transition metal (TM)-catalyzed ligand directed C−H bond functionalization reactions have become an attractive tool for the construction of C−C and C−X (X = N/O/S/Se) bonds.4,5 However, these ligand directed strategies leads to di-functionalization of the substrate unless one of the position is blocked or restricted by the group.5 Selective functionalization is difficult due to similar bond strength of both ortho C−H bonds.6,7 The selectivity in C−H bond of arenes is controlled by employing additives, acid and oxidative metal complexes, which slower the reactivity of the catalyst.8 As ferrocene based compounds are susceptible to oxidation under harsh conditions, careful optimization of the reaction conditions which include the use of additives is required. Furthermore, keeping in mind the fact that C-H bond strength in metallocenes is higher in comparison to aromatic substrates which requires more drastic conditions and hence resulting in compromise in the observed product selectivity.6 In spite of the above mentioned limitations, ligand directed selective mono C−H functionalization for C−C coupling has been accomplished exploiting Pd-catalyst with tert-butylthioketone.9 There still exists an active urge to create a strategy that can promote selective and sequential functionalization in ferrocene, in addition to dealing with the redox property and C−H bond strength of metallocenes.7



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Numerous aryl chalcogenides namely symmetrical and unsymmetrical chalcogenides have been prepared either by ortho-lithiation or TM-catalyzed approaches.10-12 The synthesis of hybrid unsymmetrical chalcogenides have not been reported till date presumably due to compatibility of aryl chalcogenides in subsequent steps as these serve as ligands for TM and thus hinder the reactivity. Also, chalcogen substituted substrates may not be compatible with Grignard and organolithiation reactions.

Scheme 1. Routes for ferrocene functionalization Previous reports DG

DG

DG H

H

Rh/Pd/Ru salts DGs, oxazoline, CH2NMe2, ferrocenylketone

Fe

R

R

pyridine, isoquinoline, 8-aminoquinoline, thioketone

Fe

Fe

or

Our approach for selective and sequential chalcogenation Q Q NH O NH O H

H Fe

RSSR (1.2 equiv) Cu(I), 1,10-Phen AgOAc, CH3CN mono thiolation

S

H

R R'EER' (1 equiv)

Fe

18 examples (46-78%)

Cu(II), AgOAc DMSO Sequential chalcogenation E = S, Se, and Te

ER

RE

Q NH

O

R'

S

E

R

Fe 18 examples (38-92%)

selective alkyl/hetero/aryl-thiolation removable directing group expedient ferrocene C-H chalcogenation good functional group tolerance broad substrate scope novel sequential chalcogenation

Earlier our group and others have reported dichalcogenation and difunctionalization of ferrocenes (Scheme 1).6,7,13 In addition to dichalcogenation, mono-aryl telluration in ferrocene was also established.13 Nonetheless, aryl ferrocene tellurides cannot be utilized for further functionalization as cleavage of carbon-tellurium bond occurs which is attributed to the presence of weak carbon-tellurium bond. The synthesis of mono-chalcogen-substituted ferroceneamides, which can be functionalized further as a strategy for sequential 4 ACS Paragon Plus Environment

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functionalization and also can be used for the removal of 8-aminoquinoline directing ligand, is worth exploring in the current situation. Here, in continuation of our work on organochalcogens,13,14 we present a novel method for selective mono-organothiolation of C−H bond of ferrocene by ligand directing approach. Furthermore, synthesized mono-thiolated ferrocenes were utilized for novel sequential organochalcogenation.

Results and discussion We chose 8-aminoquinoline directing group for selective thiolation in ferroceneamide 1a by lowering the temperature, change in stoichiometry of phenyl disulfide, and the use of one equiv of copper salt. Unfortunately, none of the variations gave desired mono-thiolated ferrocene 2a. The reaction in DMF or DMSO polar solvents failed to provide desired mono-thiolated ferrocene 2a in considerable yield and mainly dithiolated ferrocene 2a’ was observed.13 An addition of a weak acid (40 mol%), which might lower the reactivity of in-situ formed copper complex, also failed to provide 2a selectively (entries 1-4, Table 1, also see SI, Tables S1-S6). Also, low conversion of substrate 1a was realized in the presence of weak acids.



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Table 1. Optimization of reaction conditionsa Q

Fe

NH

O

NH

O

Q

Q

Ph

S

copper salt, ligand base/additive solvent, 90 oC, 18-24 h

S 2

NH

O

R

R

S

S

Fe

Fe

2a

2a'

R

N

Q 1a

entry

Cu-saltb

ligandc

additived

yielde (2a/2a’)

1f

Cu(OAc)2

(BnO)2PO2H

AgOAc

10/34

2f

Cu(OAc)2

Piv−OH

Ag2CO3

15/43

3f

Cu(OAc)2

AcOH

K2CO3

trace/28

4g

Cu(OAc)2

(BnO)2PO2H

AgOAc

NR

5

CuBr

L1

AgOAc

35/18

6

CuBr

L2

AgOAc

62/21

7

CuBr

L3

AgOAc

78/12

8h

CuBr

L3

KOAc

49/34

9

CuBr

L4

AgOAc

52/23

10

CuBr

L5

AgOAc

15/34

11

CuBr

L6

AgOAc

trace/65

t

MeO

N L1

t

Bu

OMe

N

N L2

R

Bu

N

N L3

O

R

N

N

L4 R, H L5 R, Ph

N

N L6

a Reactions

were carried at 0.2 mmol scale, phenyl disulfide (54 mg, 0.24 mmol, 1.2 equiv). b 1.5 Equiv of copper salt was used. c 0.6 Equiv of ligand was used. d 1.5 Equiv was used. e % Isolated yields, where mono and di-conversion were determined by 1H NMR. f DMSO. g DCE. h Under air.


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The reaction in less polar CH3CN solvent in the presence of an equiv of Cu(OAc)2 also failed to provide any thiolated ferrocene and substrate 1a was recovered quantitatively and this could be due to the poor solubility of Cu(OAc)2 in CH3CN. We anticipate that an in-situ generated Cu(II) salt would have better solubility in CH3CN and might be effective for C−S coupling reaction. The freshly generated Cu(II) via in-situ oxidation of CuBr by AgOAc provided the mono-thiolated ferrocene 2a in 12% yield. Next, we envisage that a suitable combination of oxidant and ligands could control the ratio of 2a/2a’. The nitrogen based ligands such as pyridine, 2,5-dimethoxy pyridine L1, dimethylaminopyridine, and 2-methylpyridine are noticed to be effective for selective mono-thiolation and gave better conversion of ferroceneamide 1a to mono-arylthiolated ferroceneamide 2a (Table 1, entry 5, see SI, Table S3). Further, better yield of 2a was observed in case of bidentate bipyridine ligand L2 as compared to monodentate ligands (entry 6, Table 1, more information is listed in SI). To our delight, a dramatic improvement in the yield of 2a (78%) vs 2a’ (12%) was observed when the conformationally restricted bidentate 1,10-phenanthroline L3 was introduced (entry 7, Table 1). The reaction afforded poor selectivity in the presence of potassium acetate base and air which suggests that the silver salt seems crucial for mono-thiolation of 1a (entry 8 vs entry 7). Substituted phenanthroline; neocuproine L4 and bathocuproine L5 ligands were also screened. However, L3 was found to be superior in terms of the yield and conversion (entries 9-10, vs 7, Table 1). On the other hand, dipyridin-5-one L6 provided only the dithiolated ferrocene 2a’ (entry 11, Table 1).



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Table 2 Substrate scope for mono-thiolation Q NH

O

R S

Fe

S

CuBr (1.2 equiv) 1,10-Phen (0.6 equiv) AgOAc (1.2 equiv) CH3CN, 90 oC, 18-24 h

2

1a

R

Fe

2a-2r

Q NH

O

Q NH

O

Q NH

O

S

O

R

S

Fe

Q NH S

X

Fe

Fe

R 2a R, H (78%) 2b R, Me (71%) 2c R, OMe (72%)

Q NH

O

Q NH

O

S

O

2i X, F, (69%) 2j X, Cl (59%)

Q NH

Q NH

O

Fe

2m (46%)

2k (51%)

Q NH

O

2n (62%)

2l (58%)

Q NH

O

S

S S

Fe

NO2

Cl

S

N

S Fe

X

2h (60%)

S

Cl

Fe

Cl

Q NH

O

S

Fe

2g (CCDC 1589440)

Q NH

S

Fe

O

2f X, Cl (52%) 2g X, Br (54%)

2d R, Me (65%) 2e R, OMe (68%)

Fe

2o (64%)

R

Fe

2p R, Et, (69%) 2q R, nBu, (65%) 2r R, nHex, (59%) (55% at 1 g scale)

Having obtained good yield of the mono-thiolated ferrocene 2a, the substrate scope with regard to organo disulfide substrates was explored for the synthesis of selective mono thiolated ferrocenes (2a-2r, Table 2). Aryl disulfides containing methyl and methoxy groups at para and ortho positions gave the mono-thiolated ferroceneamides 2b-2e in 68-72% isolated yields.


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Noteworthy, the halide substituents such as fluoride, chloride, and even bromide could survive under the standard reaction conditions to enable halo-substituted mono-thiolated ferrocenes 2f2j in good yields (52-69%). The dichloro bearing disulfide also gave the desired monothiolated ferrocene 2k under the optimized reaction conditions. An electron withdrawing nitro group was also tolerated to give 2l in 58% yield. Heteroaryl, 2-pyridyl and 2-thiophenyl disulfides were also amenable to the selective monothiolation reaction to afford the pyridyl and thiophenyl ferroceneamide sulfides 2m and 2n (Table 2). Next, the reaction scope was extended to alkyl disulfide substrates. Generally, alkyl disulfides are labile and not compatible under the TM-catalyzed C−H functionalization reaction conditions.11 To our delight, the developed reaction conditions worked equally well with alkyl disulfides and yielded alkyl ferroceneamide sulfides 2o-2r in 64-69% yields. Moreover, a one gram-scale reaction of ferroceneamide 1a with nhexyl disulfide afforded the mono-thiolated ferroceneamide 2r in 55% yield. Interestingly, the labile benzyl disulfide also reacted smoothly to yield mono-benzyl sulfide 2s. Next, the sequential chalcogenation of C−H bond of synthesized mono-thiolated ferroceneamides was explored for the construction of hybrid unsymmetrical aryl chalcogenides (vide infra). Encouraged by the compatibility of alkyl disulfides under the selective monothiolation reaction, we set to install phenylselenium on the second C−H position of thiolated ferroceneamide 2a under standard conditions. Reaction of 2a with phenyl diselenide afforded the desired hybrid unsymmetrical chalcogenide 3a in poor yield. Further, the screening of copper salts and oxidants reveal that 20 mole % of copper(II) acetate and one equiv of silver acetate in DMSO provided good yield (88%) of 3a without any ligand.13



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Table 3 Substrate scope for sequential chalcogenation Q NH

O

Q NH

O

S

Cu(OAc)2 (20 mol%) AgOAc (1.2 equiv) DMSO, 80 oC, 10-12 h

R R E

Fe

2

S

E

R

R

Fe

E = S, Se, and Te 2

3

Q NH

O

R

Q NH

O

S

Se

S

Se

Q NH

O

S

Se

R1

Fe

Fe

Fe

X

Q NH

O

Q NH

O

S

Se

R2 3e R1, OMe, R2, H (92%) 3f R1, R2, Me (90%)

3c X, Cl (82%) 3d X, CN (79%)

3a R, H (88%) 3b R, Me (90%)

S

Se

Fe

OMe

S

Se

Fe

S

Q NH

O

Fe

R 3g (79%)

3i R, H (86%) 3j R, Me (83%)

3h (71%)

Q NH

O

O

S

Se

Q NH

O

O

S

Se Fe

Fe

Cl 3l (81%)

3k (72%)

3i (CCDC 1878231)

Q NH

O

O

S

Se

n

Bu

S

S

Fe

3l (CCDC 1878232)

a

3m R, H (83%) 3n R, OMe (85%)

3o (81%)

Q NH

O

S

S

Fe

Cl

Q NH

O

S

R

Q NH

S

Te

Q NH

O

S

Te

Fe

Fe

Fe

3p (78%)

3q (46%)a

3r (38%)a

n

Bu

1 equiv of KF was used as a additive


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Phenyl diselenides bearing both electron donating and electron-withdrawing groups were compatible with the reaction conditions and provided moderate to good yields of the hybrid unsymmetrical ferrocene chalcogenides 3a, 3c, and 3d, respectively (Table 3). Extension to other aromatics such as naphthyl and heteroaryl thiophenyl diselenides were also amenable with the catalytic reaction conditions and enabled formation of 3g and 3h in 71-79% yields. Next, 2-Methoxy mono-thiolated ferroceneamide 2e was coupled with 4-methyl, 4-chloro phenyl and 2-naphthyl diselenides to afford the desired hybrid unsymmetrical dichalcogenides 3i-3l in satisfactory yields (72-86%). Alkyl n-butyl-thiolated ferroceneamide 2q was also successfully employed for the sequential unsymmetrical chalcogenation with phenyl and 3methoxy phenyl diselenides to access unsymmetrical hybrid alkyl and aryl ferroceneamides 3m and 3n, respectively. Next, the mono-thiolated ferroceneamide underwent sequential unsymmetrical di-thiolation with 4-chlorophenyl and thiophenyl disulfides to afford the unsymmetrical dithiolated ferroceneamides 3o-3p. Furthermore, the directed telluration was also achieved for hybrid unsymmetrical thio- and tellurated ferrocene 3q and 3r in 38-46% isolated yield.

Scheme 2. Removal of directing ligand Q NH

O

S Fe 2e, 2q

H

O

S

R Cp Zr(H)Cl (2 equiv) 2 THF, rt, 5-6 h

R

Fe 4a, R, 2-MeO(C6H4), 67% 4b, R, nBu, 56%

After selective mono-thiolation, 8-aminoquinoline directing group has been removed easily from 2e and 2q by the reaction of Schwartz’s reagent to obtain substituted ferrocenealdehydes under ambient reaction condition. The 2-methoxy phenyl and butyl mono-thiolated 11 ACS Paragon Plus Environment


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ferroceneamides 2e and 2q were transformed into respective ferrocenealdehydes 4a and 4b in 56-67% yields (Scheme 2). Scheme 3. Plausible reaction mechanism

Cu(I) + Ag(I)

N

N

Ln -Ag(0)

NH

O

N

O

Cu(II)Ln

H Fe

Fe

1a

I N

L

N N

O

II

Cu Ln H OAc

CuIILn O Fe

II PhSSPh

N

AcOH

1/2 PhSSPh

N NH

O

N

Fe 3

RE-ER Cu(II) cat

N

NH

O SPh

RE

HO

N

O

CuIIILn

SPh Fe 2a

SPh reductive elimination

Fe III

In the mechanistic consideration, copper-1,10-phenanthroline Cu(I)Ln complex oxidized into Cu(II)Ln by silver acetate which subsequently undergoes substitution with ferroceneamide to form Cu(II)-amidate complex I (Scheme 3). The proton abstraction from Cp-ring and subsequent conversion of ligand acetate anion into acetic acid would provide Cu−C bond containing intermediate II. Oxidation of II by diphenyl disulfide would afford the copper(III) thiolate intermediate III.15,16 Reductive elimination would furnish the desired mono-thiolated feroceneamide 2a. Second thiolation of 2a might not be possible presumably due to the role of sterics between Cu(II)Ln and the arylthiolated ferroceneamide. Also, the introduction of the arylthio substituent makes the Cp ring electron rich which may not favour the second C−H bond activation by Cu(II)-1,10-phenanthroline complex. It is worth noticing that selectivity 12 ACS Paragon Plus Environment

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was realized in the less polar solvent acetonitrile whereas polar solvents namely DMSO and DMF lead to dithio-substituted ferroceneamide. In polar solvents, most of the copper species can act as active catalyst17 for the C−S bond formation, and therefore, could lower the monoselectivity. Sequential chalcogenation in 2a would follow established copper-catalyzed directed oxidative C−E coupling reactions.13

Conclusion In summary, a methodology has been developed for selective mono-aryl/alkyl thiolation of ferrocene with copper and 8-aminoquinoline ligand. Further, we have shown that the aryl/alkyl mono-thiolated ferroceneamides can be utilized for the construction of novel sequential hybrid chalcogenides (S, Se, and Te) under copper catalysis. Selective mono-thiolation together with sequential directed C−H bond chalcogenation enable unsymmetrical C−H bond difunctionalization through the introduction of two different functionalities in a ferroceneamide substrate. The 8-aminoquinoline directing group can be uninstalled to aldehyde functionality after ferrocene derivatization. Enantioselective delivery of mono-organothio group to ferroceneamide would open a new avenue as this would enable synthesis of chiral hybridchalcogenides, which could serve as selective Lewis base catalysts, or together with aldehyde functionality could serve as chiral ligands and will be explored in future.

Experimental section General Methods. NMR experiments were carried out on 400 MHz and 500 MHz spectrometer and NMR chemical shifts are reported in ppm referenced to the solvent peaks of CDCl3 (7.26 ppm for 1H and 77.16 (± 0.06) ppm for 13C, respectively), DMSO-d6 (3.31 ppm for H2O, 2.47 ppm for DMSO, 39.9 for carbon) ppm. High-resolution mass analysis is performed on quadruple-time of flight (Q-TOF) mass spectrometer equipped with an ESI source (+ve). Single crystal X-ray data for compounds 2g (CCDC 1589440) 3i (CCDC 13 ACS Paragon Plus Environment


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1878231) and 3l (CCDC 1878232) were collected on a Bruker D8 VENTURE diffractometer equipped with CMOS Photon 100 detector and Mo-Kα (λ = 0.71073 Å) radiation. Unless otherwise noted, materials obtained from commercial suppliers used without further purification. Substituted ferroceneamides were synthetized from the corresponding ferrocenoyl chloride and amines,6d,6g,13 aryl and alkyl disulfides derivatives were prepared by the oxidation of respective thiols by using tert-butyl hydroperoxide and aryl diselenides and aryl ditellurides were prepared by following the reported procedure.11b,18 Copper salts, silver salts, and bases were purchased from Sigma Aldrich and local company and used further without any modification. Silica gel (100-200, 230-400 mesh size) from Merck was used for column chromatography and for TLC analysis silica gel (60 F254) plates were directly purchased from Merck. General procedure and analytical data for monosulfination of ferroceneamide. The dry closed capped vial was charged with ferrocene carboxamide (71 mg, 0.2 mmol, 1 equiv), disulfide (1.2 equiv, 0.24 mmol), CuBr (1.5 equiv, 0.3 mmol, 43 mg), 1,10-Phen (0.6 equiv, 0.12 mmol, 22 mg) and AgOAc (1.5 equiv, 0.3 mmol, 50 mg) in dry CH3CN (2.5 mL). After stirring the reaction mixture at room temperature under argon atmosphere for two minutes, the reaction mixture transfer to the pre-heated oil bath at 90 oC for 18-24 h, reaction progress checked by TLC. After completion of the reaction, the resulting reaction mixture was diluted with ethyl acetate and passed through celite pad. The combined organic layers were dried with Na2SO4, filtered, concentrated and purified by column chromatography on silica gel to give the desired product. 2-(Phenylthio)-1-(N-(quinolin-8-yl) ferroceneamide (2a), dark yellow solid, yield: 72 mg (78%), Rf ~0.4 in 1:9 (ethyl acetate: hexane), mp 180−185 oC, 1H NMR (500 MHz, CDCl3) δ 11.61 (s, 1H), 8.90 (d, J = 7.6 Hz, 1H), 8.75 (dd, J = 4.1, 1.5 Hz, 1H), 8.14 (dd, J = 8.2, 1.4 Hz, 1H), 7.56 (t, J = 7.9 Hz, 1H), 7.51 (d, J = 8.1 Hz, 1H), 7.43 (dd, J = 8.2, 4.2 Hz, 1H), 7.24 (d, 14 ACS Paragon Plus Environment

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J = 7.4 Hz, 2H), 7.20 (t, J = 7.7 Hz, 2H), 7.08 (t, J = 7.2 Hz, 1H), 5.38 – 5.34 (m, 1H), 4.74 – 4.71 (m, 1H), 4.66 (t, J = 2.6 Hz, 1H), 4.41 (s, 5H), 13C {1H} NMR (126 MHz, CDCl3) δ 168.2, 148.1, 139.2, 139.1, 135.9, 135.5, 128.7, 128.1, 127.4, 126.5, 125.6, 121.4, 121.3, 117.1, 79.4, 79.1, 74.7, 73.4, 71.6, 71.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C26H20FeN2OSNa 487.0538; Found 487.0510. 2-(4-Methylphenylthio)-1-(N-(quinolin-8-yl) ferroceneamide (2b), dark yellow solid, yield: 68 mg (71%), Rf ~0.4 in 1:9 (ethyl acetate: hexane), mp 128−133 oC, 1H NMR (500 MHz, CDCl3) δ 11.68 (s, 1H), 8.93 – 8.88 (m, 1H), 8.79 (dd, J = 4.1, 1.7 Hz, 1H), 8.15 (dd, J = 8.3, 1.6 Hz, 1H), 7.56 (t, J = 7.9 Hz, 1H), 7.54 – 7.49 (m, 1H), 7.45 (dd, J = 8.2, 4.2 Hz, 1H), 7.18 (d, J = 8.2 Hz, 2H), 7.01 (d, J = 8.1 Hz, 2H), 5.33 (dd, J = 2.7, 1.6 Hz, 1H), 4.74 – 4.69 (m, 1H), 4.63 (t, J = 2.7 Hz, 1H), 4.40 (s, J = 4.3 Hz, 5H), 2.24 (s, 3H), 13C {1H} NMR (126 MHz, CDCl3) δ 168.4, 148.1, 139.2, 135.9, 135.6, 135.4, 129.6, 128.1, 127.4, 127.2, 121.5, 121.3, 117.2, 79.2, 78.8, 75.9, 73.1, 71.6, 71.3, 20.9; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H23FeN2OS 479.0875; Found 479.0893. 2-(4-Methoxyphenylthio)-1-(N-(quinolin-8-yl) ferroceneamide (2c), orange solid, yield: 71 mg (72%), Rf ~0.5 in 1:9 (ethyl acetate: hexane), mp 122−127 oC, 1H NMR (500 MHz, CDCl3) δ 11.71 (s, 1H), 8.92 (dd, J = 7.6, 1.3 Hz, 1H), 8.84 (dd, J = 4.1, 1.6 Hz, 1H), 8.18 (dd, J = 8.2, 1.5 Hz, 1H), 7.61 – 7.52 (m, 2H), 7.47 (dd, J = 8.2, 4.2 Hz, 1H), 7.34 – 7.29 (m, 2H), 6.79 – 6.73 (m, 2H), 5.28 (dd, J = 2.7, 1.7 Hz, 1H), 4.71 – 4.66 (m, 1H), 4.59 (t, J = 2.7 Hz, 1H), 4.38 (s, J = 4.3 Hz, 5H), 3.72 (s, 3H), 13C {1H} NMR (126 MHz, CDCl3) δ 168.5, 158.5, 148.2, 139.2, 136.0, 135.6, 130.1, 129.3, 128.1, 127.4, 121.5, 121.3, 117.2, 114.5, 78.7, 78.3, 77.9, 72.7, 71.6, 71.1, 55.3. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C27H22FeN2O2SNa 517.0644; Found 517.0669.



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2-(2-Methylphenylthio)-1-(N-(quinolin-8-yl) ferrocenamide (2d), yellow viscous liquid, yield: 62 mg (65%), Rf ~0.5 in 1:9 (ethyl acetate: hexane), mp 185−190 oC, 1H NMR (500 MHz, CDCl3) δ 11.46 (s, 1H), 8.91 (d, J = 7.6 Hz, 1H), 8.66 (dd, J = 4.1, 1.5 Hz, 1H), 8.12 (dd, J = 8.2, 1.5 Hz, 1H), 7.55 (t, J = 7.9 Hz, 1H), 7.51 – 7.47 (m, 1H), 7.40 (dd, J = 8.2, 4.2 Hz, 1H), 7.16 – 7.11 (m, 1H), 7.03 – 6.97 (m, 2H), 6.84 – 6.79 (m, 1H), 5.41 (dd, J = 2.6, 1.7 Hz, 1H), 4.71 – 7.66 (m, 2H), 4.43 (s, 5H), 2.54 (s, 3H), 13C {1H} NMR (126 MHz, CDCl3) δ 168.2, 147.9, 139.1, 138.8, 136.5, 135.5, 134.2, 129.6, 128.0, 127.3, 126.6, 124.9, 124.6, 121.4, 121.3, 117.2, 79.5, 79.3, 73.8, 73.6, 71.7, 71.6, 19.9. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C27H22FeN2OSNa 501.0695; Found 501.0715. 2-(2-Methoxyphenylthio)-1-(N-(quinolin-8-yl) ferrocenamide (2e), orange solid, yield: 67 mg (68%), Rf ~0.4 in 1:9 (ethyl acetate: hexane), mp 180−185 oC, 1H NMR (500 MHz, CDCl3) δ 11.50 (s, 1H), 8.88 (dd, J = 7.6, 1.1 Hz, 1H), 8.58 (dd, J = 4.1, 1.6 Hz, 1H), 8.11 (dd, J = 8.3, 1.6 Hz, 1H), 7.54 (t, J = 7.9 Hz, 1H), 7.48 (dd, J = 8.2, 1.1 Hz, 1H), 7.38 (dd, J = 8.2, 4.2 Hz, 1H), 7.09 – 7.05 (m, 1H), 6.87 (d, J = 8.1 Hz, 1H), 6.82 – 6.75 (m, 2H), 5.40 (dd, J = 2.7, 1.7 Hz, 1H), 4.70 – 4.67 (m, 2H), 4.43 (s, 5H), 3.99 (s, 3H), 13C {1H} NMR (126 MHz, CDCl3) δ 168.2, 155.3, 147.8, 139.2, 135.9, 135.6, 128.4, 128.0, 127.3, 126.1, 126.0, 121.5, 121.3, 121.2, 117.1, 110.0, 79.8, 79.6, 73.6, 73.0, 71.7, 71.6, 56.0. HRMS (ESI-TOF) m/z: [M]+ Calcd for C27H22FeN2O2S 494.0746; Found 494.0775. 2-(2-Chlorophenylthio)-1-(N-(quinolin-8-yl) ferrocenamide (2f), light yellow solid, yield: 52 mg (52%), Rf ~0.4 in 1:9 (ethyl acetate: hexane), mp 178−183 oC, 1H NMR (500 MHz, CDCl3) δ 11.42 (s, 1H), 8.91 (t, J = 10.0 Hz, 1H), 8.74 (d, J = 4.0 Hz, 1H), 8.10 (d, J = 8.2 Hz, 1H), 7.53 (t, J = 7.9 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.40 (dd, J = 8.2, 4.1 Hz, 1H), 7.36 (d, J = 7.5 Hz, 1H), 7.01 (p, J = 7.3 Hz, 2H), 6.77 (d, J = 7.4 Hz, 1H), 5.47 (s, 1H), 4.73 (s, 1H), 4.70 (s, 1H), 13C {1H} NMR (126 MHz, CDCl3) δ 167.8, 148.2, 139.1, 139.0, 135.9, 135.4, 130.0, 129.0, 128.0, 127.3, 127.2, 125.9, 125.7, 121.5, 121.4, 117.0, 79.6, 79.6, 74.3, 72.0, 16 ACS Paragon Plus Environment

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71.9, 71.8. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H20ClFeN2OS 499.0329; Found 499.0349. 2(2-Bromophenylthio)-1-(N-(quinolin-8-yl) ferrocenamide (2g), orange solid, yield: 59 mg (54%), Rf ~0.4 in 1:9 (ethyl acetate: hexane), mp 187−193 oC, 1H NMR (400 MHz, CDCl3) δ 11.35 (s, 1H), 8.85 (dd, J = 7.5, 1.3 Hz, 1H), 8.72 (dd, J = 4.2, 1.6 Hz, 1H), 8.06 (dd, J = 8.3, 1.5 Hz, 1H), 7.52 – 7.43 (m, 3H), 7.36 (dd, J = 8.3, 4.2 Hz, 1H), 7.05 – 7.00 (m, 1H), 6.88 (td, J = 7.7, 1.4 Hz, 1H), 6.70 (dd, J = 8.0, 1.3 Hz, 1H), 5.43 (dd, J = 2.6, 1.7 Hz, 1H), 4.69 (t, J = 2.7 Hz, 1H), 4.67 – 4.64 (m, 1H), 4.41 (s, 5H); 13C {1H} NMR (101 MHz, CDCl3) δ 167.8, 148.3, 141.1, 139.1, 135.9, 135.4, 132.3, 128.0, 127.9, 127.2, 126.1, 125.7, 121.5, 121.4, 119.5, 117.0, 79.6, 79.5, 74.3, 72.5, 72.1, 71.8. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H20BrFeN2OS 542.9825; Found 542.9836. X-ray quality crystals were obtained by the slow evaporation of solution of 2g in CHCl3. 2-(3-Chlorophenylthio)-1-(N-(quinolin-8-yl) ferrocenamide (2h), brown yellow solid, yield: 60 mg (60%), Rf ~0.4 in 1:9 (ethyl acetate: hexane), mp 170−175 oC, 1H NMR (500 MHz, CDCl3) δ 11.47 (s, 1H), 8.91 – 8.88 (m, 1H), 8.75 (dd, J = 4.2, 1.7 Hz, 1H), 8.15 (dd, J = 8.3, 1.7 Hz, 1H), 7.58 – 7.50 (m, 2H), 7.45 (dd, J = 8.3, 4.2 Hz, 1H), 7.23 (t, J = 1.8 Hz, 1H), 7.12 (dd, J = 10.5, 5.1 Hz, 1H), 7.08 – 7.03 (m, 2H), 5.39 (dd, J = 2.8, 1.7 Hz, 1H), 4.72 (dd, J = 2.4, 1.7 Hz, 1H), 4.70 (t, J = 2.7 Hz, 1H), 4.42 (s, 5H), 13C {1H} NMR (126 MHz, CDCl3) δ 167.9, 148.1, 141.5, 139.1, 136.1, 135.4, 134.6, 129.8, 128.1, 127.4, 125.9, 125.6, 124.1, 121.5, 121.4, 117.2, 79.5, 79.3, 73.8, 73.2, 71.8, 71.7. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H20ClFeN2OS 499.0329; Found 499.0351. 2(4-Fluorophenylthio)-1-(N-(quinolin-8-yl) ferrocenamide (2i), brown yellow viscous liquid, yield: 67 mg (69%), Rf 0.4 in 1:9 (ethyl acetate: hexane), mp 180−185 oC, 1H NMR (500 MHz, CDCl3) δ 11.59 (s, 1H), 8.90 (d, J = 7.5 Hz, 1H), 8.80 – 8.76 (m, 1H), 8.17 (d, J = 8.2



Page 18 of 36

Hz, 1H), 7.59 – 7.52 (m, 2H), 7.46 (dd, J = 8.2, 4.1 Hz, 1H), 7.26 (dd, J = 8.6, 5.2 Hz, 2H), 6.90 (t, J = 8.7 Hz, 2H), 5.33 (s, 1H), 4.70 (s, 1H), 4.64 (t, J = 2.5 Hz, 1H), 4.40 (s, 5H); 13C {1H} NMR (126 MHz, CDCl3) δ 168.2, 162.4, 160.4, 148.1, 139.1, 136.1, 135.5, 134.0 (d, J = 3.2 Hz), 129.0 (d, J = 8.1 Hz), 128.1, 127.4, 121.5 (d, J = 12.9 Hz), 117.2, 115.9 (d, J = 22.2 Hz), 79.0, 78.9, 75.8, 73.2, 71.6, 71.4. HRMS (ESI-TOF) m/z: [M]+ Calcd for C26H19FFeN2OS 482.0546; Found 482.0570. 2-(4-Chlorophenylthio)-1-(N-(quinolin-8-yl) ferrocenamide (2j), brown yellow solid, yield: 59 mg (59%), Rf ~0.4 in 1:9 (ethyl acetate: hexane), mp 180−185 oC, 1H NMR (400 MHz, CDCl3) δ 11.51 (s, 1H), 8.89 (d, J = 7.5 Hz, 1H), 8.75 (d, J = 3.9 Hz, 1H), 8.15 (d, J = 8.2 Hz, 1H), 7.57 – 7.52 (m, 2H), 7.44 (dd, J = 7.1, 3.2 Hz, 1H), 7.30 – 7.23 (m, 2H), 7.16 (s, 2H), 5.35 (s, 1H), 4.70 (s, 1H), 4.66 (s, 1H), 4.41 (s, 5H), 13C {1H} NMR (101 MHz, CDCl3) δ 168.0, 148.1, 139.1, 137.8, 136.1, 135.4, 130.5, 129.1, 128.9, 128.1, 127.8, 127.4, 121.5, 117.2, 79.2, 75.7, 74.3, 73.5, 73.4, 71.7. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C26H20ClFeN2OS 499.0329; Found 499.0354. 2(2,4-Dichlorophenylthio)-1-(N-(quinolin-8-yl) ferrocenamide (2k), red solid, yield: 54 mg (51%), Rf ~0.3 in 1:9 (ethyl acetate: hexane), mp 157−162 oC, 1H NMR (500 MHz, CDCl3) δ 11.35 (s, 1H), 8.90 (d, J = 6.8 Hz, 1H), 8.75 (dd, J = 4.2, 1.5 Hz, 1H), 8.12 (dd, J = 8.3, 1.4 Hz, 1H), 7.57 – 7.48 (m, 2H), 7.42 (dd, J = 8.2, 4.2 Hz, 1H), 7.37 (d, J = 2.1 Hz, 1H), 7.00 (dd, J = 8.6, 2.1 Hz, 1H), 6.70 (d, J = 8.6 Hz, 1H), 5.47 (dd, J = 2.7, 1.7 Hz, 1H), 4.73 (t, J = 2.7 Hz, 1H), 4.69 – 4.67 (m, 1H), 4.45 (s, 5H),

13C

{1H} NMR (126 MHz, CDCl3) δ 167.6, 148.2,

139.0, 138.0, 136.0, 135.3, 131.0, 130.4, 128.8, 128.0, 127.6, 127.3, 126.5, 121.6, 121.5, 117.0, 79.7, 79.4, 74.4, 72.2, 71.9, 71.5. HRMS (ESI-TOF) m/z: [M+K]+ Calcd for C26H18Cl2FeN2OSK 570.9499; Found 570.9513.


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2-(4-Nitrophenylthio)-1-(N-(quinolin-8-yl) ferrocenamide (2l), orange solid, yield: 59 mg (58%), Rf ~0.3 in 1:9 (ethyl acetate: hexane), mp 178−183 oC, 1H NMR (500 MHz, CDCl3) δ 11.25 (s, 1H), 8.85 (dd, J = 7.4, 1.6 Hz, 1H), 8.69 (dd, J = 4.2, 1.7 Hz, 1H), 8.15 (dd, J = 8.3, 1.6 Hz, 1H), 8.07 – 8.03 (m, 2H), 7.57 – 7.51 (m, 2H), 7.44 (dd, J = 8.3, 4.2 Hz, 1H), 7.31 – 7.24 (m, 3H), 5.42 (dd, J = 2.8, 1.6 Hz, 1H), 4.75 (t, J = 2.7 Hz, 1H), 4.72 (dd, J = 2.5, 1.7 Hz, 1H), 4.45 (s, 5H),

13C

{1H} NMR (126 MHz, CDCl3) δ 167.4, 149.6, 148.0, 145.3, 138.9,

136.2, 135.1, 128.1, 127.4, 126.2, 125.3, 123.9, 121.6, 117.1, 79.9, 79.1, 78.2, 74.0, 72.1, 71.9. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C26H20FeN3O3S 510.0570; Found 510.0594. 2-(2-Pyridin-ylthio)-1-(N-(quinolin-8-yl) ferroceneamide (2m), brown yellow solid, yield: 43 mg (46%), Rf ~0.2 in 1:9 (ethyl acetate: hexane), mp 217−222 oC, 1H NMR (500 MHz, CDCl3) δ 11.43 (s, 1H), 8.85 (d, J = 7.5 Hz, 1H), 8.64 (dd, J = 4.1, 1.3 Hz, 1H), 8.44 (d, J = 4.7 Hz, 1H), 8.11 (dd, J = 8.2, 1.3 Hz, 1H), 7.54 (t, J = 7.9 Hz, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.45 – 7.36 (m, 2H), 6.95 (t, J = 7.1 Hz, 2H), 5.42 – 5.39 (m, 1H), 4.73 (d, J = 1.8 Hz, 1H), 4.71 (t, J = 2.6 Hz, 1H), 4.43 (s, 5H), 13C {1H} NMR (126 MHz, CDCl3) δ 167.9, 162.4, 149.2, 148.2, 139.0, 136.7, 135.9, 135.3, 127.9, 127.3, 121.4, 121.3, 119.7, 119.6, 117.0, 79.9, 79.4, 73.9, 71.9, 71.9, 71.7. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C25H19FeN3OSNa 488.0491; Found 488.0496. 2-(Thiophene-2-ylthio)-1-(N-(quinolin-8-yl) ferroceneamide (2n), brown solid, yield: 58 mg (62%), Rf ~0.4 in 1:9 (ethyl acetate: hexane), mp 220−225 oC, 1H NMR (500 MHz, CDCl3) δ 11.57 (s, 1H), 8.98 – 8.92 (m, 2H), 8.22 (dd, J = 8.3, 1.6 Hz, 1H), 7.64 – 7.57 (m, 2H), 7.51 (dd, J = 8.2, 4.2 Hz, 1H), 7.31 – 7.28 (m, 2H), 6.90 (dd, J = 5.3, 3.6 Hz, 1H), 5.18 (dd, J = 2.8, 1.6 Hz, 1H), 4.68 (dd, J = 2.5, 1.7 Hz, 1H), 4.52 (t, J = 2.7 Hz, 1H), 4.38 (s, 5H), 13C {1H} NMR (126 MHz, CDCl3) δ 168.4, 148.3, 139.1, 136.2, 136.0, 135.5, 132.5, 129.0, 128.2, 127.5, 127.3, 121.6, 121.4, 117.1, 82.0, 77.1, 73.5, 71.9, 71.6, 70.7. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C24H18FeN2OS2Na 493.0102; Found 493.0106. 19 ACS Paragon Plus Environment


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2-(Benzylthio)-1-(N-(quinolin-8-yl) ferroceneamide (2o), orange viscous liquid, yield: 61 mg (64%), Rf ~0.5 in 1:9 (ethyl acetate: hexane), 1H NMR (500 MHz, CDCl3) δ 11.74 (s, 1H), 8.94 – 8.91 (m, 1H), 8.89 (dd, J = 4.1, 1.6 Hz, 1H), 8.21 (dd, J = 8.2, 1.6 Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.56 (dd, J = 8.2, 1.2 Hz, 1H), 7.49 (dd, J = 8.2, 4.2 Hz, 1H), 7.20 – 7.15 (m, 3H), 7.15 – 7.10 (m, 2H), 5.20 (dd, J = 2.6, 1.7 Hz, 1H), 4.46 (t, J = 2.6 Hz, 1H), 4.37 – 4.34 (m, 1H), 4.30 (d, J = 4.4 Hz, 5H), 4.03 (d, J = 12.8 Hz, 1H), 3.94 (d, J = 12.8 Hz, 1H), 13C {1H} NMR (126 MHz, CDCl3) δ 168.8, 148.3, 139.3, 137.6, 136.1, 135.7, 129.1, 128.2, 128.2, 127.5, 126.9, 121.5, 121.3, 117.4, 79.0, 78.6, 77.3, 72.5, 71.4, 70.6, 43.1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C27H23FeN2OS 479.0875; Found 479.0854. 2-(Ethylthio)-1-(N-(quinolin-8-yl) ferroceneamide (2p), dark red viscous liquid, yield: 58 mg (69%), Rf ~0.5 in 1:9 (ethyl acetate: hexane), 1H NMR (500 MHz, CDCl3) δ 11.82 (s, 1H), 8.96 (dd, J = 7.6, 1.3 Hz, 1H), 8.92 (dd, J = 4.1, 1.7 Hz, 1H), 8.20 (dd, J = 8.2, 1.6 Hz, 1H), 7.60 (t, J = 7.9 Hz, 1H), 7.55 (dd, J = 8.2, 1.3 Hz, 1H), 7.51 – 7.46 (m, 1H), 5.22 (dd, J = 2.8, 1.7 Hz, 1H), 4.64 (dd, J = 2.4, 1.7 Hz, 1H), 4.53 (t, J = 2.6 Hz, 1H), 4.33 (s, J = 3.9 Hz, 4H), 2.88 – 2.75 (m, 2H), 1.30- 1.27 (m, 3H), 13C {1H} NMR (126 MHz, CDCl3) δ 169.0, 148.2, 139.3, 136.1, 135.8, 128.2, 127.5, 121.5, 121.3, 117.4, 78.9, 78.5, 77.7, 72.4, 71.4, 70.6, 32.3, 14.4. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C22H21FeN2OS 417.0719; Found 417.0733. 2-(nButylthio)-1-(N-(quinolin-8-yl) ferroceneamide (2q), dark orange viscous liquid, yield: 58 mg (65%), Rf ~0.5 in 1:9 (ethyl acetate: hexane), 1H NMR (500 MHz, CDCl3) δ 11.82 (s, 1H), 8.96 (dd, J = 7.6, 1.3 Hz, 1H), 8.91 (dd, J = 4.1, 1.7 Hz, 1H), 8.20 (dd, J = 8.2, 1.7 Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.55 (dd, J = 8.2, 1.3 Hz, 1H), 7.49 (dd, J = 8.2, 4.2 Hz, 1H), 5.21 (dd, J = 2.8, 1.7 Hz, 1H), 4.63 (dd, J = 2.4, 1.7 Hz, 1H), 4.52 (t, J = 2.6 Hz, 1H), 4.34 – 4.32 (m, 5H), 2.85 – 2.74 (m, 2H), 1.66 – 1.58 (m, 2H), 1.43 – 1.34 (m, 2H), 0.85 (t, J = 7.4 Hz, 3H),

13C

{1H} NMR (126 MHz, CDCl3) δ 169.0, 148.2, 139.4, 136.1, 135.8, 128.2, 127.5,


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121.5, 121.3, 117.4, 78.6, 78.4, 78.4, 72.3, 71.4, 70.5, 38.2, 31.3, 21.8, 13.7. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C24H25FeN2OS 445.1032; Found 445.1060. 2-(nHexylthio)-1-(N-(quinolin-8-yl) ferroceneamide (2r), yellow orange viscous liquid, yield: 56 mg (59%), Rf ~0.5 in 1:9 (ethyl acetate: hexane), 1H NMR (500 MHz, CDCl3) δ 11.82 (s, 1H), 8.96 (dd, J = 7.6, 1.3 Hz, 1H), 8.91 (dd, J = 4.2, 1.7 Hz, 1H), 8.20 (dd, J = 8.3, 1.7 Hz, 1H), 7.61 (dd, J = 10.0, 5.8 Hz, 1H), 7.55 (dd, J = 8.2, 1.3 Hz, 1H), 7.49 (dd, J = 8.2, 4.2 Hz, 1H), 5.21 (dd, J = 2.8, 1.7 Hz, 1H), 4.63 (dd, J = 2.4, 1.7 Hz, 1H), 4.52 (t, J = 2.6 Hz, 1H), 4.33 (s, J = 4.0 Hz, 5H), 2.84 – 2.73 (m, 2H), 1.66 – 1.59 (m, 2H), 1.39 – 1.31 (m, 2H), 1.23 – 1.17 (m, 4H), 0.84 – 0.80 (m, 3H), 13C {1H} NMR (126 MHz, CDCl3) δ 169.0, 148.2, 139.4, 136.1, 135.8, 128.2, 127.5, 121.5, 121.3, 117.4, 78.6, 78.5, 78.4, 72.2, 71.4, 70.5, 38.6, 31.4, 29.2, 28.4, 22.5, 14.0. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C26H29FeN2OS 473.1345; Found 473.1366. Synthesis of 2-(nHexylthio)-1-(N-(quinolin-8-yl) Ferroceneamide (2r) on Gram Scale: In an oven dried seal tube equipped with a magnetic bar was charged with ferroceneamide 1a (2.8 mmol, 1.0 g, 1 equiv), CuBr (4.2 mmol, 602 mg,1.5 equiv), AgOAc (3.6 mmol, 507 mg, 1.2 equiv), 1,10-phenanthroline (1.68 mmol, 304 mg, 0.6 equiv) and nhexyl disulfide (3.36 mmol, 786 mg, 1.2 equiv) in a dry acetonitrile (15 mL) under argon atmosphere and the resulting mixture stirred at room temperature for two minutes and transferred to the preheated oil bath at 90 oC for 24 h. The progress of the reaction was checked by thin layer chromatography. After completion of the reaction, mixture passed through celite pad and the combined organic layers were extracted using ethyl acetate and water and passed through Na2SO4, concentrated using rotary evaporator and purified by column chromatography on silica gel. Mono-thiolated ferroceneamide 2r was obtained in 730 mg, 55% yield.



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General procedure and analytical data for sequential chalcogenation of ferroceneamide. The dry closed capped vial was charged with mono-thiolated ferroceneamide (2, 0.1 mmol, 1 equiv), dichalcogenides (1.1 equiv, 0.11 mmol), Cu(OAc)2 (20 mol%, 4 mg) and AgOAc (1.2 equiv, 0.12 mmol, 20 mg) in dry DMSO (2 mL) under air and stirred at room temperature for 2-5 minutes and transferred to the pre-heated oil bath at 80 oC for 8-12h. The progress of reaction was checked by TLC and after completion of the reaction, the resulting reaction mixture was diluted with ethyl acetate and passed through celite pad. The combined organic layers were dried with Na2SO4, filtered, concentrated and purified by column chromatography on silica gel to give the desired product. 2-(Phenylselanyl)-5-(phenylthio)-1-(N-(quinolin-8-yl) ferroceneamide (3a), dark yellow solid, yield: 55 mg (88%), Rf ~0.4 in 1:20 (ethyl acetate: hexane), mp 194−199 oC, 1H NMR (500 MHz, CDCl3) δ 11.73 (s, 1H), 8.97 (dd, J = 7.5, 1.3 Hz, 1H), 8.74 (dd, J = 4.1, 1.6 Hz, 1H), 8.16 (dd, J = 8.3, 1.5 Hz, 1H), 7.80 (dd, J = 6.3, 3.0 Hz, 2H), 7.59 – 7.52 (m, 2H), 7.45 – 7.41 (m, 4H), 7.30 – 7.27 (m, 2H), 7.21 (t, J = 7.7 Hz, 2H), 7.11 (t, J = 7.3 Hz, 1H), 4.61 (d, J = 2.6 Hz, 1H), 4.39 (s, 5H), 4.27 (d, J = 2.6 Hz, 1H);. 13C {1H} NMR (126 MHz, CDCl3) δ 168.8, 148.1, 139.2, 138.6, 136.0, 135.9, 135.3, 129.9, 129.3, 128.8, 128.4, 128.0, 127.4, 127.1, 125.9, 121.5, 121.4, 117.5, 85.9, 77.9, 76.1, 73.4, 73.3, 72.6. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C32H24FeN2OSSeNa 643.0019; Found 643.0014. 2-(phenylthio)-N-(quinolin-8-yl)-5-(o-tolylselanyl)ferroceneamide (3b), orange solid, yield: 57 mg (90%), Rf ~0.4 in 1:20 (ethyl acetate: hexane), mp 171-176 oC, 1H NMR (500 MHz, CDCl3) δ 11.66 (s, 1H), 8.98 (dd, J = 7.5, 1.4 Hz, 1H), 8.69 (dd, J = 4.1, 1.6 Hz, 1H), 8.15 (dd, J = 8.3, 1.6 Hz, 1H), 7.71 (d, J = 7.4 Hz, 1H), 7.57 – 7.51 (m, 2H), 7.43 (dd, J = 8.3, 4.1 Hz, 1H), 7.35 – 7.29 (m, 3H), 7.26 – 7.19 (m, 3H), 7.15 – 7.11 (m, 1H), 4.62 (d, J = 2.6 Hz, 1H), 4.40 (s, 5H), 4.25 (d, J = 2.6 Hz, 1H), 2.56 (s, 3H), 13C {1H} NMR (126 MHz, CDCl3) δ 168.6, 148.0, 141.4, 139.2, 138.5, 135.9, 135.9, 135.3, 131.5, 130.2, 128.8, 128.6, 128.0, 22 ACS Paragon Plus Environment

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127.4, 127.3, 126.7, 125.9, 121.4, 121.4, 117.5, 84.4, 77.9, 76.6, 73.5, 73.4, 73.3, 22.9. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C33H27FeN2OSSe 635.0356; Found 635.0379. 2-((4-Chlorophenyl)selanyl)-5-(phenylthio)-N-(quinolin-8-yl)ferroceneamide (3c), yellow solid, yield: 54 mg (82%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 170−175 oC, 1H NMR (500 MHz, CDCl3) δ 11.71 (s, 1H), 8.95 (dd, J = 7.3, 1.6 Hz, 1H), 8.74 (dd, J = 4.1, 1.7 Hz, 1H), 8.16 (dd, J = 8.3, 1.6 Hz, 1H), 7.72 – 7.69 (m, 2H), 7.57 – 7.52 (m, 2H), 7.44 (dd, J = 8.3, 4.2 Hz, 1H), 7.40 – 7.36 (m, 2H), 7.27 – 7.24 (m, 2H), 7.22 – 7.19 (m, 2H), 7.14 – 7.09 (m, 1H), 4.63 (d, J = 2.6 Hz, 1H), 4.39 (s, 5H), 4.26 (d, J = 2.6 Hz, 1H), 13C {1H} NMR (126 MHz, CDCl3) δ 168.7, 148.1, 139.2, 138.4, 137.0, 136.0, 135.2, 134.8, 129.5, 128.9, 128.3, 128.0, 127.4, 127.2, 125.9, 121.6, 121.5, 117.5, 85.1, 78.0, 77.3, 76.4, 73.5, 72.7. HRMS (APCI-TOF) m/z: [M+H]+ Calcd for C32H24ClFeN2OSSe 654.9807; Found 654.9793. 2-((4-cyanophenyl)selanyl)-5-(phenylthio)-N-(quinolin-8-yl)ferroceneamide (3d), yellow solid, yield: 51 mg (79%), Rf ~0.3 in 1:20 (ethyl acetate: hexane), mp 170−175 oC, 1H NMR (500 MHz, CDCl3) δ 11.48 (s, 1H), 8.88 (dd, J = 6.0, 3.0 Hz, 1H), 8.73 (dd, J = 4.2, 1.7 Hz, 1H), 8.17 (dd, J = 8.3, 1.6 Hz, 1H), 7.70 – 7.65 (m, 2H), 7.59 – 7.53 (m, 4H), 7.46 (dd, J = 8.3, 4.2 Hz, 1H), 7.32 – 7.29 (m, 2H), 7.26 (dd, J = 10.4, 5.0 Hz, 2H), 7.20 – 7.15 (m, 1H), 4.71 (d, J = 2.6 Hz, 1H), 4.50 (d, J = 2.6 Hz, 1H), 4.48 (s, 5H). 13C {1H} NMR (126 MHz, CDCl3) δ 167.3, 148.2, 139.7, 139.0, 137.9, 136.1, 134.9, 132.7, 132.4, 128.9, 128.0, 128.0, 127.4, 126.4, 121.7, 121.5, 118.8, 117.3, 110.6, 81.0, 79.3, 77.9, 77.8, 75.5, 73.4. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C33H24FeN3OSSe 646.0152; Found 646.0140. 2-((3-methoxyphenyl)selanyl)-5-(phenylthio)-N-(quinolin-8-yl)ferroceneamide (3e), red brown solid, yield: 60 mg (92%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 102−107 oC, 1H NMR (500 MHz, CDCl3) δ 11.69 (s, 1H), 8.96 (dd, J = 7.4, 1.0 Hz, 1H), 8.74 (dd, J = 4.1, 1.3 Hz, 1H), 8.16 (d, J = 8.2 Hz, 1H), 7.58 – 7.52 (m, 2H), 7.44 (dd, J = 8.3, 4.1 Hz, 1H), 7.38 –



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7.31 (m, 3H), 7.27 (d, J = 7.6 Hz, 2H), 7.28 – 7.25 (m, 2H), 7.13 – 7.09 (m, 1H), 6.95 (dd, J = 8.0, 2.2 Hz, 1H), 4.63 (d, J = 2.5 Hz, 1H), 4.41 (s, 5H), 4.36 (d, J = 2.5 Hz, 1H), 3.85 (s, 3H). 13C

{1H} NMR (126 MHz, CDCl3) δ 168.6, 159.9, 148.1, 139.2, 138.6, 136.0, 135.3, 131.1,

130.0, 128.8, 128.0, 127.6, 127.4, 127.1, 125.9, 121.5, 121.4, 120.6, 117.5, 114.3, 85.0, 77.8, 77.6, 76.2, 73.4, 73.0, 55.4. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C33H27FeN2O2SSe 651.0305; Found 651.0327. 2-((3,5-Dimethylphenyl)selanyl)-5-(phenylthio)-N-(quinolin-8-yl)ferroceneamide (3f), red brown viscous solid, yield: 58 mg (90%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 127−132 oC, 1H

NMR (500 MHz, CDCl3) δ 11.70 (s, 1H), 8.97 (dd, J = 7.5, 1.5 Hz, 1H), 8.74 (dd, J =

4.1, 1.7 Hz, 1H), 8.15 (dd, J = 8.3, 1.7 Hz, 1H), 7.59 – 7.51 (m, 2H), 7.44 (dd, J = 8.2, 4.1 Hz, 1H), 7.41 (s, 2H), 7.28 – 7.24 (m, 2H), 7.23 – 7.18 (m, 2H), 7.12 – 7.08 (m, 1H), 7.04 (s, 1H), 4.62 (d, J = 2.6 Hz, 1H), 4.40 (s, 5H), 4.31 (d, J = 2.6 Hz, 1H), 2.37 (s, 6H). 13C {1H} NMR (126 MHz, CDCl3) δ 168.8, 148.1, 139.2, 138.8, 138.7, 135.9, 135.3, 133.4, 130.1, 129.4, 128.7, 128.0, 127.3, 127.0, 125.8, 121.4, 121.4, 117.5, 86.1, 77.9, 77.17, 75.9, 73.4, 72.7, 21.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C34H29FeN2OSSe 649.0513; Found 649.0515. 2-(Naphthalen-1-ylselanyl)-5-(phenylthio)-N-(quinolin-8-yl)ferroceneamide (3g), brown solid, yield: 53 mg (79%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 190−195 oC, 1H NMR (500 MHz, CDCl3) δ 11.80 (s, 1H), 9.04 (dd, J = 7.6, 1.3 Hz, 1H), 8.68 (dd, J = 4.1, 1.7 Hz, 1H), 8.62 (d, J = 8.2 Hz, 1H), 8.15 (dd, J = 8.3, 1.6 Hz, 1H), 8.11 (dd, J = 7.0, 1.1 Hz, 1H), 7.97 (d, J = 8.2 Hz, 1H), 7.95 – 7.92 (m, 1H), 7.64 – 7.56 (m, 3H), 7.55 – 7.50 (m, 2H), 7.42 (dd, J = 8.3, 4.1 Hz, 1H), 7.29 – 7.27 (m, 2H), 7.24 – 7.20 (m, 2H), 7.15 – 7.10 (m, 1H), 4.51 (d, J = 2.6 Hz, 1H), 4.37 (s, 5H), 3.96 (d, J = 2.6 Hz, 1H). 13C {1H} NMR (126 MHz, CDCl3) δ 169.2, 148.1, 139.2, 138.6, 135.9, 135.9, 135.4, 135.2, 134.1, 129.9, 129.5, 128.8, 128.6, 128.6, 128.0, 127.4, 127.0, 126.9, 126.4, 126.0, 125.9, 121.5, 121.4, 117.6, 87.2, 78.1, 76.2, 75.3, 73.5, 72.8. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C36H27FeN2OSSe 671.0356; Found 671.0370.


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2-(Phenylthio)-N-(quinolin-8-yl)-5-(thiophen-2-ylselanyl)ferroceneamide

(3h),

orange

solid, yield: 44 mg (71%), Rf ~0.4 in 1:20 (ethyl acetate: hexane), mp 290−295 oC, 1H NMR (500 MHz, CDCl3) δ 11.87 (s, 1H), 8.96 (d, J = 7.3 Hz, 1H), 8.79 – 8.75 (m, 1H), 8.16 (d, J = 8.2 Hz, 1H), 7.61 – 7.53 (m, 3H), 7.47 (d, J = 3.3 Hz, 1H), 7.44 (dd, J = 8.2, 4.2 Hz, 1H), 7.25 – 7.22 (m, 2H), 7.21 – 7.16 (m, 3H), 7.10 – 7.16 (m, 1H), 4.63 (d, J = 2.5 Hz, 1H), 4.38 (s, 5H), 4.24 (d, J = 2.5 Hz, 1H). 13C {1H} NMR (126 MHz, CDCl3) δ 169.6, 148.2, 139.2, 138.7, 137.9, 135.9, 135.3, 132.3, 128.8, 128.4, 128.0, 127.4, 126.6, 125.7, 123.7, 121.5, 121.4, 117.7, 89.9, 78.3, 75.4, 74.4, 73.7, 70.8. HRMS (APCI-TOF) m/z: [M+H]+ Calcd for C30H23FeN2OS2Se 626.9762; Found 626.9748. 2-((2-Methoxyphenyl)thio)-5-(phenylselanyl)-N-(quinolin-8-yl)ferroceneamide (3i), red solid, yield: 56 mg (86%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 177−182 oC, 1H NMR (500 MHz, CDCl3) δ 11.60 (s, 1H), 8.96 (d, J = 7.5 Hz, 1H), 8.59 (dd, J = 4.1, 1.4 Hz, 1H), 8.12 (dd, J = 8.3, 1.4 Hz, 1H), 7.82 (dt, J = 7.1, 3.6 Hz, 2H), 7.54 (t, J = 7.9 Hz, 1H), 7.50 (d, J = 8.1 Hz, 1H), 7.44 – 7.41 (m, 3H), 7.39 (dd, J = 8.2, 4.1 Hz, 1H), 7.11 – 7.06 (m, 1H), 6.90 – 6.84 (m, 2H), 6.80 (t, J = 7.6 Hz, 1H), 4.60 (d, J = 2.5 Hz, 1H), 4.41 (s, 5H), 4.28 (d, J = 2.6 Hz, 1H), 3.94 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 168.7, 155.4, 147.8, 139.2, 135.9, 135.8, 135.3, 129.9, 129.3, 128.4, 127.9, 127.8, 127.3, 126.6, 126.4, 121.4, 121.3, 121.3, 117.4, 110.1, 86.3, 78.3, 77.7, 74.1, 73.5, 73.4, 72.7, 55.9. HRMS (APCI-TOF) m/z: [M+H]+ Calcd for C33H27FeN2O2SSe 651.0305; Found 651.0294. X-ray quality orange colored crystals were obtained by the slow evaporation of solution of 3i in CH2Cl2 and hexane (1:1). 2-((2-Methoxyphenyl)thio)-N-(quinolin-8-yl)-5-(p-tolylselanyl)ferroceneamide (3j), red brown solid, yield: 55 mg (83%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 177−183 oC, 1H NMR (500 MHz, CDCl3) δ 11.62 (s, 1H), 8.96 (dd, J = 7.6, 1.3 Hz, 1H), 8.59 (dd, J = 4.1, 1.7 Hz, 1H), 8.12 (dd, J = 8.3, 1.6 Hz, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.55 (t, J = 7.9 Hz, 1H), 7.50 (dd, J = 8.2, 1.3 Hz, 1H), 7.39 (dd, J = 8.3, 4.2 Hz, 1H), 7.24 (d, J = 7.8 Hz, 2H), 7.08 (td, J = 8.2, 1.6 Hz, 1H), 6.89 - 6.83 (m, 2H), 6.79 (td, J = 7.7, 1.0 Hz, 1H), 4.58 (d, J = 2.6 Hz, 1H), 25 ACS Paragon Plus Environment


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4.39 (s, 5H), 4.24 (d, J = 2.6 Hz, 1H), 3.95 (s, 3H), 2.43 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 168.9, 155.3, 147.8, 139.2, 138.7, 136.4, 135.8, 135.8, 135.4, 130.2, 127.9, 127.3, 126.5, 126.3, 125.9, 121.4, 121.3, 121.3, 117.5, 110.0, 87.4, 78.3, 77.2, 73.6, 73.5, 72.3, 55.9, 21.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C34H29FeN2O2SSe 665.0462; Found 665.0472. 2-((4-Chlorophenyl)selanyl)-5-((2-methoxyphenyl)thio)-N-(quinolin-8-yl)ferroceneamide (3k), red brown solid, yield: 49 mg (72%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 190−195 oC, 1H


4.1, 1.6 Hz, 1H), 8.13 (dd, J = 8.3, 1.5 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.57 – 7.49 (m, 2H), 7.41 – 7.37 (m, 3H), 7.11 – 7.08 (m, 1H), 6.89 – 6.84 (m, 2H), 6.83 – 6.78 (m, 1H), 4.62 (d, J = 2.6 Hz, 1H), 4.42 (s, 5H), 4.27 (d, J = 2.6 Hz, 1H), 3.94 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 168.6, 155.5, 147.9, 139.2, 137.1, 135.9, 135.3, 134.7, 129.5, 128.4, 127.9, 127.7, 127.3, 126.7, 126.5, 121.4, 121.4, 121.3, 117.4, 110.1, 85.4, 78.3, 78.0, 74.4, 73.5, 72.8, 55.9. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C33H26ClFeN2O2SSe 684.9913; Found 684.9896. 2-((2-Methoxyphenyl)thio)-5-(naphthalen-1-ylselanyl)-N-(quinolin-8-yl)ferroceneamide (3l), brown solid, yield: 57 mg (81%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 178−183 oC, 1H

NMR (500 MHz, CDCl3) δ 11.64 (s, 1H), 9.02 (d, J = 7.6 Hz, 1H), 8.63 (d, J = 8.2 Hz, 1H),

8.56 – 8.51 (m, 1H), 8.16 – 8.10 (m, 2H), 7.97 (d, J = 8.2 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.64 – 7.55 (m, 3H), 7.52 (t, J = 7.6 Hz, 2H), 7.38 (dd, J = 8.3, 4.1 Hz, 1H), 7.12 – 7.07 (m, 1H), 6.91 – 6.85 (m, 2H), 6.81 (t, J = 7.5 Hz, 1H), 4.48 (d, J = 2.5 Hz, 1H), 4.39 (s, 5H), 3.98 – 3.94 (m, 4H), 13C {1H} NMR (126 MHz, CDCl3) δ 169.0, 155.4, 147.8, 139.2, 136.0, 135.8, 135.4, 135.3, 134.1, 129.9, 129.6, 128.7, 128.6, 127.9, 127.9, 127.3, 126.8, 126.5, 126.4, 126.0, 121.5, 121.4, 121.3, 117.5, 110.1, 87.5, 78.4, 76.9, 73.5, 73.3, 72.9, 55.9. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C37H29FeN2O2SSe 701.0462; Found 701.0433. X-ray quality crystals were obtained by the slow evaporation of solution of 3l in CH2Cl2 and hexane (1:1). 2-(Butylthio)-5-(phenylselanyl)-N-(quinolin-8-yl)ferroceneamide (3m), yellow solid, yield: 50 mg (83%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 100−105 oC, 1H NMR (500 MHz, 26 ACS Paragon Plus Environment

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CDCl3) δ 11.91 (s, 1H), 9.03 (dd, J = 7.5, 1.1 Hz, 1H), 8.89 (dd, J = 4.1, 1.5 Hz, 1H), 8.21 (dd, J = 8.3, 1.5 Hz, 1H), 7.78 – 7.74 (m, 2H), 7.63 – 7.56 (dt, J = 8.1, 7.5 Hz, 2H), 7.49 (dd, J = 8.2, 4.1 Hz, 1H), 7.41 – 7.37 (m, 3H), 4.55 (d, J = 2.5 Hz, 1H), 4.33 (s, 5H), 4.16 (d, J = 2.5 Hz, 1H), 2.83 – 2.73 (m, 2H), 1.69 – 1.59 (m, 2H), 1.41 – 1.36 (m, 2H), 0.86 (t, J = 6.3 Hz, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 169.4, 148.2, 139.4, 136.1, 135.6, 135.54, 130.2, 129.2, 128.2, 128.1, 127.5, 121.5, 121.4, 117.8, 84.5, 79.5, 77.2, 76.9, 73.2, 71.9, 38.0, 31.3, 21.8, 13.6. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C30H29FeN2OSSe 601.0512; Found 601.0544. 2-(Butylthio)-5-((3-methoxyphenyl)selanyl)-N-(quinolin-8-yl)ferroceneamide (3n), red brown viscous liquid, yield: 53 mg (85%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 131−136 oC, 1H


4.1, 1.6 Hz, 1H), 8.21 (dd, J = 8.3, 1.5 Hz, 1H), 7.62 – 7.56 (m, 2H), 7.49 (dd, J = 8.2, 4.2 Hz, 1H), 7.34 – 7.27 (m, 4H), 6.95 – 6.90 (m, 1H), 4.56 (d, J = 2.5 Hz, 1H), 4.34 (s, 5H), 4.24 (d, J = 2.5 Hz, 1H), 3.83 (s, 3H), 2.82 – 2.74 (m, 2H), 1.64 – 1.59 (m, 2H) 1.43 – 1.36 (m, 2H), 0.86 (t, J = 7.4 Hz, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 169.3, 159.9, 148.2, 139.3, 136.1, 135.5, 131.2, 129.9, 128.2, 127.5, 127.4, 121.4, 121.4, 120.5, 117.7, 114.1, 83.9, 79.6, 77.3, 77.2, 73.2, 72.2, 55.3, 37.9, 31.3, 21.8, 13.6. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C31H31FeN2O2SSe 631.0618; Found 631.0592. 2-((4-Chlorophenyl)thio)-5-(phenylthio)-N-(quinolin-8-yl)ferroceneamide (3o), red brown solid, yield: 49 mg (81%), Rf ~0.4 in 1:20 (ethyl acetate: hexane), mp 165−170 oC, 1H NMR (500 MHz, CDCl3) δ 11.47 (s, 1H), 8.93 (dd, J = 7.1, 1.9 Hz, 1H), 8.75 (dd, J = 4.2, 1.6 Hz, 1H), 8.17 (dd, J = 8.3, 1.6 Hz, 1H), 7.57 – 7.52 (m, 2H), 7.40 – 7.36 (m, 1H), 7.38 (dd, J = 8.2, 1.0 Hz, 2H), 7.32 – 7.28 (m, 4H), 7.27 – 7.21 (m, 3H), 4.59 – 4.56 (m, 2H), 4.50 (s, 5H); 13C {1H} NMR (126 MHz, CDCl3) δ 167.0, 148.1, 139.0, 137.2, 136.2, 136.1, 135.1, 132.5, 130.4, 129.5, 129.1, 129.0, 128.0, 127.4, 126.8, 121.5, 121.5, 117.3, 83.2, 81.8, 80.6, 75.6, 75.5, 73.4. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C32H23ClFeN2OS2Na 629.0183; Found 629.0158. 2-(Phenylthio)-N-(quinolin-8-yl)-5-(thiophen-2-ylthio)ferroceneamide (3p), red solid, yield: 45 mg (78%), Rf ~0.4 in 1:20 (ethyl acetate: hexane), mp 172−177 oC, 1H NMR (500 MHz, CDCl3) δ 11.73 (s, 1H), 8.99 (dd, J = 7.4, 1.3 Hz, 1H), 8.78 (dd, J = 4.1, 1.6 Hz, 1H), 27 ACS Paragon Plus Environment


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8.17 (dd, J = 8.3, 1.6 Hz, 1H), 7.59 – 7.51 (m, 3H), 7.45 (dd, J = 8.3, 4.2 Hz, 1H), 7.38 (dd, J = 3.5, 1.0 Hz, 1H), 7.28 – 7.24 (m, 2H), 7.21 (t, J = 7.7 Hz, 2H), 7.13 – 7.09 (m, 2H), 4.56 (d, J = 2.6 Hz, 1H), 4.44 (s, 5H), 4.37 (d, J = 2.6 Hz, 1H), 13C {1H} NMR (126 MHz, CDCl3) δ 168.4, 148.1, 139.2, 138.3, 136.0, 135.7, 135.3, 132.4, 130.8, 128.8, 128.0, 127.7, 127.4, 125.9, 121.5, 121.4, 117.5, 94.2, 76.8, 76.4, 76.4, 73.4, 73.4, 70.8. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C30H22FeN2OS3Na 601.0136; Found 601.0126. 2-(Phenyltellanyl)-5-(phenylthio)-N-(quinolin-8-yl)ferroceneamide (3q), red solid, yield: 31 mg (46%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 210−215 oC, 1H NMR (500 MHz, CDCl3) δ 11.95 (s, 1H), 8.94 (dd, J = 7.4, 1.5 Hz, 1H), 8.75 (dd, J = 4.1, 1.6 Hz, 1H), 8.18 – 8.11 (m, 3H), 7.59 – 7.52 (m, 2H), 7.51 – 7.47 (m, 1H), 7.46 – 7.39 (m, 3H), 7.27 – 7.23 (m, 2H), 7.21 – 7.16 (m, 2H), 7.08 (t, J = 7.3 Hz, 1H), 4.70 (d, J = 2.5 Hz, 1H), 4.30 (s, 5H), 4.16 (d, J = 2.5 Hz, 1H). 13C {1H} NMR (126 MHz, CDCl3) δ 170.2, 148.2, 141.5, 139.3, 138.8, 135.9, 135.3, 129.4, 128.7, 128.6, 128.0, 127.3, 126.5, 125.7, 121.6, 121.4, 117.7, 116.1, 80.8, 76.7, 74.5, 74.0, 73.9, 64.9. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C32H25FeN2OSTe 671.0094; Found 671.0099. 2-Butylthio-5-(phenyltellanyl)-N-(quinolin-8-yl)ferroceneamide (3r), red brown solid, yield: 25 mg (38%), Rf ~0.5 in 1:20 (ethyl acetate: hexane), mp 112−117 oC, 1H NMR (500 MHz, CDCl3) δ 12.19 (s, 1H), 9.01 (dd, J = 7.4, 1.4 Hz, 1H), 8.91 (dd, J = 4.1, 1.6 Hz, 1H), 8.22 (dd, J = 8.3, 1.6 Hz, 1H), 8.13 – 8.09 (m, 2H), 7.64 – 7.58 (m, 2H), 7.52 – 7.46 (m, 2H), 7.38 (t, J = 7.5 Hz, 2H), 4.59 (d, J = 2.5 Hz, 1H), 4.22 (s, 5H), 4.01 (d, J = 2.4 Hz, 1H), 2.84 – 2.77 (m, 1H), 2.76 – 2.70 (m, 1H), 1.69 – 1.52 (m, 4H), 0.85 (t, J = 7.4 Hz, 3H), 13C {1H} NMR (126 MHz, CDCl3) δ 170.9, 148.2, 141.5, 139.5, 136.1, 135.6, 129.3, 128.5, 128.2, 127.4, 121.7, 121.4, 118.0, 116.1, 80.3, 78.1, 76.2, 73.6, 72.9, 63.9, 38.5, 31.3, 21.8, 13.6. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C30H29FeN2OSTe 651.0410; Found 651.0407.


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Removal of the directing group. The thiolated ferrocenamide (0.1 mmol) was dissolved in dry THF (2 mL) under argon. Then, Cp2Zr(H)Cl (77 mg, 0.3 mmol) was added portion wise at room temperature under argon. After 30 minutes, the reaction mixture was concentrated under vacuo. The resulted crude mixture was purified by column chromatography using silica gel and hexane and ethyl acetate as eluents. 2-((2-Methoxyphenyl)thio-1-ferrocenealdehyde (4a), dark brown viscous liquid, yield: 24 mg (67%), Rf ~0.7 in 1:20 (ethyl acetate: hexane), 1H NMR (500 MHz, CDCl3) δ 10.21 (s, 1H), 7.11 (td, J = 8.1, 1.3 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H), 6.79 (t, J = 7.6 Hz, 1H), 6.68 (dd, J = 7.8, 1.4 Hz, 1H), 5.12 (dd, J = 2.5, 1.4 Hz, 1H), 4.81 (dd, J = 5.8, 2.2 Hz, 2H), 4.40 (s, 5H), 3.95 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 194.2, 155.2, 128.2, 126.5, 126.4, 121.3, 110.1, 80.4, 80.3, 79.3, 73.5, 71.4, 69.5, 55.8. HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C18H16FeO2SNa 375.011; Found 375.0100. 2-(nButylthio)-1-ferrocenealdehyde (4b), dark brown viscous liquid, yield: 17 mg (56%), Rf ~0.7 in 1:20 (ethyl acetate: hexane),1H NMR (500 MHz, CDCl3) δ 10.29 (s, 1H), 4.96 (s, 1H), 4.73 (s, 1H), 4.67 (t, J = 2.6 Hz, 1H), 4.31 (s, 5H), 2.61 (t, J = 7.4 Hz, 2H), 1.53 – 1.48 (m, 2H), 1.39 (dd, J = 14.0, 6.4 Hz, 2H), 1.42 – 1.35 (m, 3H), 13C {1H} NMR (126 MHz, CDCl3) δ 194.2, 84.5, 79.0, 72.7, 71.1, 70.1, 68.8, 38.0, 31.6, 21.7, 13.6. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C15H18FeOSNa 325.0320; Found 325.0341.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website



1H, 13C

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and mass spectra of synthesized mono-thiolated ferroceneamides and hybrid

chalcogenides and crystallographic details (PDF) Crystallographic data for 2g (CIF, CCDC 1589440) Crystallographic data for 3i (CIF, CCDC 1878231) Crystallographic data for 3l (CIF, CCDC 1878232)

AUTHOR INFORMATION Corresponding Author Fax: +91-755-669-2392. E-mail: [email protected] ORCID Moh. Sattar: 0000-0001-6529-4255 Sangit Kumar: 0000-0003-0658-8709 Notes The authors declare no competing financial interest.

ACKNOWLEDGMENTS SK thanks DST-SERB (EMR/2015/000061), New Delhi, and IISER Bhopal for generous funding. MS and KP kindly acknowledge IISER Bhopal and RT [09/1020(0113)/2017-EMRI] acknowledges CSIR New Delhi, for fellowships. SK kindly acknowledges Professor Deepak Chopra, IISER Bhopal for proof reading of the manuscript.


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