CC BY 4.0 · SynOpen 2022; 06(04): 319-328
DOI: 10.1055/a-1981-9151
paper

Synthesis of α-Sulfoximino Tetrazoles via Azido-Ugi Four-Component Reaction

a   Department of Chemistry, National Institute of Technology, Tiruchirappalli-620015, Tamilnadu, India
,
b   Department of Chemistry & Centre for Advanced Studies in Chemistry, Panjab University, Chandigarh-160014, India
,
a   Department of Chemistry, National Institute of Technology, Tiruchirappalli-620015, Tamilnadu, India
› Author Affiliations
The project was supported by DST-SERB (ECR/2018/001462), CSIR-New Delhi (02(0445)/21/EMR-II), DST-FIST program. C.P.I.J. thanks CSIR-New Delhi for a Fellowship and for support of the HRMS facility (Dept. of Chemistry, NIT-Trichy). Funding provided to R.K. was due to DST-FIST (II) for the Single Crystal Facility at the Department of Chemistry, Panjab University, Chandigarh.
 


Abstract

The sulfoximine-based tetrazoles have been synthesized via azido-Ugi four-component reactions of sulfoximines, isocyanides, aldehydes, and TMS-azide in MeOH at 70 °C in the presence of InCl3. Replacement of sulfoximines with sulfonimidamides (SIA) has delivered the corresponding SIA-based tetrazole. Interestingly, SIA also acts as a surrogate amine to furnish the corresponding aminotetrazole as a by-product.


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Tetrazoles are of great importance due to their distinctive chemical and biological properties.[1] This moiety has found applications in fields such as medicine,[2] biochemistry,[3] pharmacology,[4] materials,[5] coordination chemistry,[6] and organocatalysis[7] (Figure [1]), as well as in synthetic chemistry.[8] Importantly, tetrazoles are well-established bioisosteres of carboxylic acids.[9]

Zoom Image
Figure 1 Representative tetrazole-bearing derivatives used in various fields

Sulfoximines have recently received very good attention in synthetic, medicinal, and agrochemical areas.[10] Sulfoximine-containing bioactive molecules include Atuveciclib, BAY 1251152, and AZD6738.[11] Additionally, sulfoximines have been used as chiral auxiliaries and ligands in asymmetric synthesis, and as directing groups in ortho-C–H functionalization.[12] Considering the importance of tetrazoles, together with our recent interest in sulfoximines[13] and related chemistry,[14] we herein report that sulfoximine-based tetrazoles, i.e., α-sulfoximino tetrazoles, have been prepared via four-component reaction of sulfoximines, isocyanides, aldehydes, and TMS-N3.

The classical four-component Ugi reaction utilizes carboxylic acids as one of the nucleophiles to synthesize the bis-amide.[15] Replacement of the carboxylic acid with an azide delivers the corresponding tetrazole in the Azido-Ugi tetrazole reaction (UT-4CR) (Scheme [1a]). UT-4CRs have been widely employed to construct diverse tetrazole-based systems by altering the substituents in the substrate.[16] However, most of the previous reports on UT- 4CRs employ sp3-hybridized primary or secondary amines as amine component. Hence, despite being a very well-established field, the reaction behavior with sp2 hybridized imine nucleophiles remains to be studied. In this context, we employed sulfoximines, which contain the sp2-hybridized imino group, as nucleophile in the UT-4CR to synthesize α-sulfoximino tetrazoles (Scheme [1b]).

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Scheme 1 Schematic representation of (a) general and (b) current UT-4CR

Previously, Bolm et al. prepared N-(1H)-tetrazole sulfoximines via a ZnBr2–catalyzed cycloaddition reaction (Scheme [2a]).[17] Recently, the same research group prepared 2-sulfoximidoyl acetic acids via Petasis reaction (Scheme [2b]).[18] Our α-sulfoximino tetrazoles can be considered as tetrazole isosteres of 2-sulfoximidoyl acetic acid (Scheme [2b]).

Zoom Image
Scheme 2 Previous routes to (a) sulfoximine derived tetrazoles, (b) α-sulfoximidoyl acetic acids (this work: isosteric replacement of -COOH with tetrazole to access α-sulfoximino tetrazole).

The starting NH-sulfoximines were prepared by following the reported protocol.[19a] We initiated the investigations with a four-component reaction of sulfoximine 1a, p-tolualdehyde (2a), t-butyl isocyanide (3a), and TMS-N3 (4) under conditions that are summarized in Table [1]. Initially, the reaction mixture was stirred in methanol at room temperature for 24 h, but the desired tetrazole 5a was obtained only in 10% yield, along with unreacted sulfoximine and aldehyde (entry 1). To obtain a better outcome, the Lewis acid ZnCl2 was added as mediator and a 40% yield of 5a was isolated (entry 2). Increased temperature gave a better yield of 5a (entries 3 and 4), and replacement of ZnCl2 with InCl3 resulted in a further improved yield at 70 °C (entry 6). Other Lewis acids such as Cu(OTf)2, CuBr, and Zn(OTf)2 were not as effective as InCl3 at 70 °C (entries 6–9). Other solvents, including EtOH, CH3CN, DCE, toluene, and DCM were investigated (entries 10–14), but MeOH was found to be the best solvent for the transformation. When we replaced the TMS-N3 in the reaction with NaN3 we could isolate only 41% of 5a (entry 15). It should be noted that the Lewis acids were needed in 50 mol%; the use of lesser amounts (5/10/20/30/40 mol%) InCl3 led to diminished product formation along with isolation of unreacted starting sulfoximine and aldehyde. A higher amount of InCl3 (60%) did not give a better outcome.

Table 1 Optimization of the Synthesis of Sulfoximine Derived Tetrazolesa

Entry

Solvent

Lewis acid

Temp (°C)

Time (h)

Yield (%)b

1c

MeOH

r.t.

24

10

2c

MeOH

ZnCl2

r.t.

15

40

3

MeOH

ZnCl2

45

12

46

4

MeOH

ZnCl2

70

12

50

5

MeOH

InCl3

45

12

55

6

MeOH

InCl3

70

12

61

7

MeOH

Cu(OTf)2

70

12

20

8

MeOH

CuBr

70

12

NR

9

MeOH

Zn(OTf)2

70

12

54

10

EtOH

InCl3

70

12

36

11

CH3CN

InCl3

70

12

21

12

DCE

InCl3

70

12

NR

13

Toluene

InCl3

70

12

12

14

DCM

InCl3

70

12

26

15d

MeOH

InCl3

45

12

41

a General conditions for the one-pot four-component reaction: 1a (1.2 equiv), 2a (1.2 equiv), 3a (1.0 equiv), 4 (1.0 equiv), Lewis acid (0.5 equiv) in 1 mL solvent unless otherwise stated.

b Isolated yield.

c 1:1:1:1 ratio of all substrates.

d NaN3 was used instead of TMSN3.

With the optimal reaction condition in hand, next we explored the scope and limitations of the method for the synthesis of sulfoximine based tetrazoles 5. Differently substituted sulfoximines, aldehydes, and isocyanides were utilized, and the results are shown in Scheme [3]. Various aromatic aldehydes with electron-poor and electron-rich substitution patterns underwent successful reaction. It was noted that electron-deficient aryl aldehydes provided better outcomes than their electron-rich counterparts. Bulky triphenylamine aldehyde and heteroaromatic benzothiophene aldehyde also delivered 5np in good yields. Several cyclic and acyclic isocyanides such as cyclohexyl, adamantyl, and t-butyl isocyanide furnished the desire products in moderate to good yields. Unfortunately, the primary alkyl isocyanide (p-toluenesulfonylmethyl isocyanide) and aromatic isocyanide (4-methoxyphenyl isocyanide) both failed to produce the desired products 5s and 5t. The modifications of the S-aryl group (phenyl to substituted phenyl) and S-alkyl group (methyl to ethyl) of the NH-sulfoximines were well tolerated in the conversion.

In addition to S-aryl S-alkyl sulfoximines, diaryl/dialkyl symmetrical sulfoximines underwent reaction smoothly to produce the corresponding products 5qr. The electronic effects induced by S-aryl substituents appeared to have only a minor influence on product formation.

Zoom Image
Scheme 3 Substrate scope for preparing sulfoximine-based tetrazoles

All the synthesized compounds were characterized by 1H and 13C NMR spectroscopy, and HRMS, and structures were unambiguously confirmed by single-crystal XRD analysis of two representative compounds (5c and 5e; see the Supporting Information).

The successful utilization of NH-sulfoximines as nucleophiles in the UT-4CR, inspired us to apply sulfonimidamide (SIA) (6) (Scheme [4]) to construct SIA derived tetrazoles via UT-4CR. SIAs, the mono-aza analogues of sulfonamides, with a stereogenic tetrahedral sulfur atom and sp2 hybridized imino group (free -NH), are considered an important emerging scaffold due to their applications in asymmetric synthesis and the medicinal and agrochemical industries.[20]

Initially, SIA (6a) was treated with aldehyde 2a, isocyanide 3a, and TMS-N3 (4) under the previously optimized reaction conditions (Table [1], entry 6), but the desired product 7a was formed in only minor amounts, accompanied by the side-product, cyclic amine-based tetrazole 8a as the major product. SIA 6 would appear to be acting as surrogate amine to yield 8. A previous report from our group had already described the surrogate nature of SIA under specific conditions.[14a] Considering that the elevated reaction temperatures may result in S–N bond cleavage, the reaction was performed at lower temperature (Table [2], entry 3) and 7a was obtained as the major product (52%) at 45 °C, along with 18% of by-product 8a. Screening of other Lewis acids, such as ZnCl2 and Zn(OTf)2 showed that they were not as effective as InCl3 (entries 4 and 5).

Table 2 Optimization of the Synthesis of Sulfonimidamide Derived Tetrazolesa

Entry

Conditions

Yield (%)b

Solvent

Lewis acid

Temp (°C)

Time (h)

7a

8a

1

MeOH

InCl3

70

10

18

65

2

MeOH

InCl3

r.t

10

0

20

3

MeOH

InCl3

45

10

52

18

4

MeOH

ZnCl2

45

10

30

40

5

MeOH

ZnCl2

45

10

34

38

a Conditions for the one-pot four-component reaction: 6a (1.2 equiv), 2a (1.2 equiv), 3a (1.0 equiv), 4 (1.0 equiv), Lewis acid (0.5 equiv), in 1 mL solvent.

b Isolated yield.

Hence, by following the optimized condition (Table [2], entry 3), we scrutinized the scope and generality of the reaction with SIA (Scheme [5]). Reaction of SIAs with various S-aryl (-Ph, 4-MePh, 4-OMePh) and S-cyclic amines (pyrrolidine and piperidine) worked equally well to deliver the corresponding product 7. Diverse substituted aromatic aldehydes, with electron-withdrawing and -donating substituents were employed successfully. The bulky triphenylamine benzaldehyde readily took part in the reaction to furnish 7e. Different secondary and tertiary isocyanides were also well tolerated to deliver the desired products in moderate yield. However, our attempts to use a primary alkyl isocyanide (p-toluenesulfonyl methyl isocyanide) and an aromatic isocyanide (4-methoxyphenyl isocyanide) were unsuccessful (7ij).

Zoom Image
Scheme 4 Synthesis of sulfonimidamide derived tetrazole
Zoom Image
Scheme 5 Substrate scope for sulfonimidamide based tetrazoles

A probable mechanistic approach based on previous literature reports[21] and the current findings is portrayed in Scheme [6]. In the presence of InCl3, sulfoximine 1 reacts with aldehyde 2 to generate 5Ia, which, on reaction with the isocyanide, yields intermediate nitrilium cation 5Ib. Subsequent cycloaddition of 5Ib with azide delivers the expected product 5 via 5Ic. SIA 6 follows a similar route to furnish the corresponding tetrazole 7. However, the surrogate nature of the SIA, which leads to 8, can be explained as in Scheme [7]. In the presence of InCl3, the sp3 amine of SIA attacks the aldehyde to generate intermediate 8Ia, which undergoes intramolecular rearrangement (transacylation) and C–O bond cleavage of 8Ib to produced iminium intermediate 8Ic via elimination. Successive reaction of isocyanide with 8Ic and further [3+2] cycloaddition of 8Id with azide leads to the formation of 8.

In conclusion, we have demonstrated the azido-Ugi four-component reaction for the synthesis of α-sulfoximino tetrazoles. A wide range of sulfoximines, aldehydes, and isocyanides have been assembled with TMS-azide in the presence of InCl3 to form two new C–N bonds, one C–C bond, and one N–N bond in a single process. Use of SIAs instead of sulfoximines has delivered the corresponding SIA based tetrazoles. These compounds can be considered as sulfoximine/SIA-derived tetrazole isosteres of α-amino acids. Notably, SIAs can also act as surrogate amines to produce the corresponding aminotetrazoles as by-products.

Zoom Image
Scheme 6 Plausible mechanism for the formation of the UT product
Zoom Image
Scheme 7 Proposed mechanism for the formation of cyclic amine-based tetrazole 8

The starting sulfoximines/sulfonimidamides were synthesized by following reported methods.[19] The aldehydes, isocyanides, TMSN3, InCl3, and MeOH were purchased from various suppliers and used as received. 1H and 13C NMR spectra were recorded with a Bruker spectrometer operating at 500 and 125 MHz, respectively, in CDCl3 or CD6CO­ as solvents. Mass spectra were recorded with an Agilent QTOF G6545 XT spectrometer at 50,000 resolutions using ESI mode. Melting points are uncorrected.


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Sulfoximine Synthesis; General Procedure

To a stirred solution of diaryl (or alkylaryl) sulfide (1 mmol) in MeOH (5 mL), NH4CO2NH2 (1.5 equiv) and PhI(OAc)2 (2.3 equiv) were added, and the solution was stirred at r.t. for 3–4 h. After the disappearance of the sulfide (checked by TLC), the solvent was removed under reduced pressure. The crude product was purified by flash column chromatography (25–40% EtOAc/hexane).

For the gram-scale reaction, sulfide (20 mmol) and MeOH (100 mL) were used.


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One-Pot Tandem Synthesis of Tetrazole Based Sulfoximine/Sulfonimidamide (5/7); General Procedure

Precautions: We have not experienced any problems with the use of TMSN3 under the reaction conditions employed and working on small scale. However, essential precautions should be taken on scaling up this chemistry.

A solution of sulfoximine (30 mg 1.2 equiv), aldehyde (1.2 equiv), isocyanide (1.0 equiv), and InCl3 (0.5 equiv) in MeOH (1 mL) in a 20 mL sealed tube was stirred at 70 °C under argon atmosphere. After 15 min, TMS-azide (1.0 equiv) was added to the reaction mixture and the reaction was stirred for the stipulated period. Upon completion of reaction (confirmed by TLC), the reaction mixture was poured in water and extracted with EtOAc (2 × 10 mL). The organic layers were washed with sat. aq. NaHCO3, water, brine and dried over anhydrous Na2SO4. After filtration, the solvent was evaporated under reduced pressure, and the resulting crude product was purified by silica gel column chromatography with 20–30% of EtOAc in hexane as the eluent.

For sulfonimidamides, the reaction was stirred at 45 °C.

All the synthesized compounds (except 5q/5r) have more than one (generally two) stereogenic centers. Hence, mixtures of diastereomers could be expected to form. However, we isolated only single diastereomer for 5am, 5p, 5q, and 7. Another diastereomer was formed in trace amounts for 5am, 5p, 5q, and 7. For compounds 5no, two diastereomers were isolated in almost equal amounts.


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N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(p-tolyl)methyl) S-Methyl S-4-Bromophenyl Sulfoximine (5a)

Colorless viscous liquid; 61% yield. TLC (SiO2): Rf 0.25 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.63 (d, J = 8.5 Hz, 2 H), 7.57 (d, J = 8.5 Hz, 2 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 6.01 (s, 1 H), 3.08 (s, 3 H), 2.29 (s, 3 H), 1.41 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 156.2, 139.9, 138.9, 137.7, 137.4, 132.7, 130.2, 129.4, 127.5, 61.7, 52.3, 45.6, 29.9, 21.1.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H25BrN5OS: 462.0958; found: 462.0960.


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N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(phenyl)methyl) S-Methyl S-p-Tolyl Sulfoximine (5b)

Yellowish viscous liquid; 60% yield. TLC (SiO2): Rf 0.26 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.65 (d, J = 7.0 Hz, 1 H), 7.57 (d, J = 8.5 Hz, 2 H), 7.32 (d, J = 7.5 Hz, 1 H), 7.27–7.24 (m, 2 H), 7.19 (d, J = 8.0 Hz, 2 H), 7.05 (t, J = 8.0 Hz, 1 H), 6.01 (s, 1 H), 3.06 (s, 3 H), 2.34 (s, 3 H), 1.36 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 156.3, 144.5, 140.8, 137.5, 136.5, 130.1, 128.7, 127.5, 123.6, 61.7, 52.6, 45.6, 29.9, 21.6.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H26N5OS: 384.1853; found: 384.1857.


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N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Methyl S-4-Bromophenyl Sulfoximine (5c)

White solid; mp 114–116 °C; 65% yield. TLC (SiO2): Rf 0.35 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.58 (br s, 4 H), 7.28–7.27 (m, 4 H), 6.00 (s, 1 H), 3.12 (s, 3 H), 1.42 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 155.8, 139.9, 139.1, 138.5, 133.8, 132.8, 130.1, 128.9, 128.9, 61.9, 52.0, 45.6, 29.8.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H22BrClN5OS: 482.0411; found: 482.0418.


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N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(p-tolyl)methyl) S-Methyl S-4-Chlorophenyl Sulfoximine (5d)

Yellowish viscous liquid; 57% yield. TLC (SiO2): Rf 0.21 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.71 (d, J = 8.5 Hz, 2 H), 7.41 (d, J = 8.5 Hz, 2 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.11 (d, J = 8.0 Hz, 2 H), 6.01 (s, 1 H), 3.08 (s, 3 H), 2.29 (s, 3 H), 1.41 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 156.3, 139.9, 138.4, 137.7, 137.5, 130.1, 129.7, 129.5, 127.5, 61.7, 52.4, 45.7, 29.9, 21.1.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H25ClN5OS: 418.1463; found: 418.1472.


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N-((1-Cyclohexyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Methyl S-4-Bromophenyl Sulfoximine (5e)

White solid; mp 117–118 °C; 68% yield. TLC (SiO2): Rf 0.45 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.67 (d, J = 8.5 Hz, 2 H), 7.57 (d, J = 8.5 Hz, 2 H), 7.38 (d, J = 8.0 Hz, 2 H), 7.29 (d, J = 8.5 Hz, 2 H), 5.91 (s, 1 H), 4.51–4.46 (m, 1 H), 3.18 (s, 3 H), 2.25–2.24 (m, 2 H), 1.96–1.93 (m, 2 H), 1.81–1.76 (m, 2 H), 1.49–1.46 (m, 2 H), 1.32–1.30 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = 155.2, 140.6, 138.1, 137.2, 133.9, 133.1, 130.1, 128.8, 128.0, 58.3, 51.5, 45.5, 33.2, 25.5, 24.9.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H24BrClN5OS: 508.0568; found: 508.0571.


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N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Ethyl S-Phenyl Sulfoximine (5f)

White solid; mp 120–122 °C; 62% yield. TLC (SiO2): Rf 0.25 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.67 (dd, J = 8.0, 1.0 Hz, 2 H), 7.56 (t, J = 7.5 Hz, 1 H), 7.44 (t, J = 8.0 Hz, 2 H), 7.29–7.26 (m, 4 H), 6.06 (s, 1 H), 3.34–3.19 (m, 2 H), 1.41 (s, 9 H), 1.26 (t, J = 8.0 Hz, 3 H).

13C NMR (125 MHz, CDCl3): δ = 156.1, 139.9, 139.7, 137.7, 133.5, 129.5, 129.4, 128.9, 128.7, 61.8, 51.8, 51.4, 30.0, 7.1.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H25ClN5OS: 418.1463; found: 418.1473.


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N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Ethyl S-4-Methoxyphenyl Sulfoximine (5g)

White solid; mp 129–130 °C; 67% yield. TLC (SiO2): Rf 0.21 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.56 (d, J = 9.0 Hz, 2 H), 7.31–7.25 (m, 4 H), 6.90 (d, J = 9.0 Hz, 2 H), 6.09 (s, 1 H), 3.84 (s, 3 H), 3.29–3.17 (m, 2 H), 1.45 (s, 9 H), 1.25 (t, J = 7.5 Hz, 3 H).

13C NMR (125 MHz, CDCl3): δ = 163.6, 156.1, 139.8, 133.3, 131.4, 128.7, 128.5, 128.3, 114.6, 61.8, 55.6, 51.7, 51.6, 29.9, 7.1.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C21H27ClN5O2S: 448.1568; found: 448.1578.


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N-((1-Adamantyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Ethyl S-Phenyl Sulfoximine (5h)

White solid; mp 132–134 °C; 66% yield. TLC (SiO2): Rf 0.25 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.66 (d, J = 8.5 Hz, 2 H), 7.55 (t, J = 7.5 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 2 H), 7.31–7.26 (m, 4 H), 6.08 (s, 1 H), 3.33–3.21 (m, 2 H), 2.07–2.01 (m, 6 H), 1.94–1.92 (m, 3 H), 1.67–1.64 (m, 3 H), 1.60–1.57 (m, 3 H), 1.27 (t, J = 7.5 Hz, 3 H).

13C NMR (125 MHz, CDCl3): δ = 156.1, 140.0, 137.9, 133.5, 133.4, 129.4, 129.3, 128.9, 128.7, 62.9, 51.9, 51.4, 42.1, 35.6, 29.6, 7.1.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H31ClN5OS: 496.1932; found: 496.1935.


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N-((1-Adamantyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Methyl S-4-Methoxyphenyl Sulfoximine (5i)

White solid; mp 179–181 °C; 70% yield. TLC (SiO2): Rf 0.24 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.63 (d, J = 9.0 Hz, 2 H), 7.29 (q, J = 8.5 Hz, 4 H), 6.91 (d, J = 9.0 Hz, 2 H), 6.04 (s, 1 H), 3.84 (s, 3 H), 3.14 (s, 3 H), 2.08–2.04 (m, 6 H), 1.98–1.96 (m, 3 H), 1.68–1.65 (m, 3 H), 1.61–1.59 (m, 3 H).

13C NMR (125 MHz, CDCl3): δ = 163.7, 156.1, 139.8, 133.5, 130.8, 130.5, 128.9, 128.7, 114.7, 63.0, 55.8, 52.2, 46.0, 42.0, 35.6, 29.6.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H30ClN5NaO2S: 534.1701; found: 534.1711.


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N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(2-bromophenyl)methyl) S-Methyl S-4-Bromophenyl Sulfoximine (5j)

White solid; mp 125–127 °C; 57% yield. TLC (SiO2): Rf 0.25 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.75 (dd, J = 8.0, 1.5 Hz, 1 H), 7.69 (d, J = 8.5 Hz, 2 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.50 (dd, J = 8.0, 1.0 Hz, 1 H), 7.27 (td, J = 7.5, 1.0 Hz, 1 H), 7.10 (td, J = 7.5, 1.5 Hz, 1 H), 6.39 (s, 1 H), 2.94 (s, 3 H), 1.46 (s, 9 H).

13C NMR (126 MHz, CDCl3): δ = 155.6, 139.2, 133.3, 132.5, 131.1, 129.9, 129.8, 128.6, 128.2, 125.2, 123.2, 61.7, 51.6, 46.0, 29.8.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H22Br2N5OS: 525.9901; found: 525.9912.


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N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(3-bromophenyl)methyl) S-Methyl S-4-Bromophenyl Sulfoximine (5k)

Colorless viscous liquid; 62% yield. TLC (SiO2): Rf 0.25 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.67 (d, J = 2.0 Hz, 1 H), 7.53 (brs, 4 H), 7.34–7.32 (m, 1 H), 7.17–7.16 (m, 1 H), 7.11 (t, J = 8.0 Hz, 1 H), 5.96 (s, 1 H), 3.07 (s, 3 H), 1.38 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 155.6, 142.8, 139.9, 138.5, 132.8, 131.1, 130.6, 130.2, 130.1, 126.1, 122.9, 62.0, 52.0, 45.7, 29.9.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H22Br2N5OS: 525.9906; found: 525. 9889.


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N-((1-Cyclohexyl-1H-tetrazol-5-yl)(3-bromophenyl)methyl) S-Ethyl S-4-Methoxyphenyl Sulfoximine (5l)

Colorless viscous liquid; 68% yield. TLC (SiO2): Rf 0.21 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.65 (s, 1 H), 7.47 (d, J = 9.0 Hz, 2 H), 7.30 (dt, J = 7.5, 1.5, 0.5 Hz, 1 H), 7.23 (dt, J = 7.5, 1.5, 0.5 Hz, 1 H), 7.09 (t, J = 8.0 Hz, 1 H), 6.91 (d, J = 9.0 Hz, 2 H), 5.91 (s, 1 H), 4.49–4.46 (m, 1 H), 3.80 (s, 3 H), 3.22–3.16 (m, 2 H), 2.21–2.18 (m, 1 H), 2.01–1.98 (m, 1 H), 1.94–1.92 (m, 1 H), 1.87–1.84 (m, 1 H), 1.78–1.71 (m, 1 H), 1.55–1.53 (m, 1 H), 1.31–1.26 (m, 1 H), 1.23 (t, J = 7.5 Hz, 3 H), 1.18–1.14 (m, 1 H), 1.01–0.98 (d, J = 13.1 Hz, 1 H), 0.90–0.88 (d, J = 12.4 Hz, 1 H).

13C NMR (125 MHz, CDCl3): δ = 163.9, 155.4, 142.5, 140.5, 131.4, 130.7, 129.9, 126.8, 125.3, 122.7, 114.9, 58.8, 58.1, 55.7, 51.2, 33.1, 25.5, 24.8, 7.5.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H29BrN5O2S: 518.1220; found: 518.1229.


#

N-((1-Cyclohexyl-1H-tetrazol-5-yl)(4-bromophenyl)methyl) S-Ethyl S-2-Thiophenyl Sulfoximine (5m)

Brownish viscous liquid; 67% yield. TLC (SiO2): Rf 0.30 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.69 (d, J = 6.5 Hz, 1 H), 7.42 (d, J = 8.5 Hz, 2 H), 7.32 (d, J = 3.5 Hz, 1 H), 7.29 (d, J = 8.5 Hz, 2 H), 7.12–7.10 (m, 1 H), 6.11 (s, 1 H), 4.50–4.47 (m, 1 H), 3.38–3.36 (m, 2 H), 2.26–2.23 (m, 2 H), 1.95–1.92 (m, 3 H), 1.81–1.76 (m, 2 H), 1.73–1.71 (m, 1 H), 1.48–1.45 (m, 2 H), 1.37 (t, J = 7.0 Hz, 3 H).

13C NMR (125 MHz, CDCl3): δ = 155.2, 140.7, 138.9, 137.5, 135.3, 131.6, 128.5, 128.3, 121.8, 58.9, 53.3, 51.1, 33.2, 25.5, 24.9, 7.9.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H25BrN5OS2: 494.0678; found: 494.0671.


#

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(N,N-diphenylaniline)methyl) S-methyl S-4-Methoxyphenyl Sulfoximine (5n)

Obtained as a diastereomeric mixture. Total yield 72%.

Diastereomer 1

White solid; mp 170–172 °C. TLC (SiO2): Rf 0.24 (40% EtOAc in hexane).

IR (KBr): 3059, 3038, 2937, 2835, 1735, 1587, 1508, 1487, 1405, 1375, 1317, 1259, 1215, 1154, 1078, 1025, 981, 800, 697 cm–1.

1H NMR (500 MHz, CDCl3): δ = 7.66 (d, J = 9.0 Hz, 2 H), 7.22 (t, J = 8.0 Hz, 6 H), 7.04 (dd, J = 7.5 Hz, 4 H), 7.00–6.98 (m, 4 H), 6.89 (d, J = 9.0 Hz, 2 H), 6.02 (s, 1 H), 3.83 (s, 3 H), 3.12 (s, 3 H), 1.46 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 163.5, 156.5, 147.6, 147.1, 134.6, 130.8, 130.7, 129.2, 128.4, 124.3, 123.5, 122.9, 114.5, 61.6, 55.7, 51.9, 45.9, 29.9.

HRMS (ESI-TOF): m/z [M + Na]+ calcd for C32H34N6NaO2S: 589.2356; found: 589.2356.

Diastereomer 2

White solid; mp 172–173 °C.

1H NMR (500 MHz, CDCl3): δ = 7.71 (d, J = 9.0 Hz, 2 H), 7.23–7.17 (m, 6 H), 7.01–6.99 (m, 2 H), 6.97–6.95 (m, 4 H), 6.92 (d, J = 9.0 Hz, 2 H), 6.83 (d, J = 8.5 Hz, 2 H), 6.02 (s, 1 H), 3.87 (s, 3 H), 3.10 (s, 3 H), 1.68 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 163.1, 157.0, 147.5, 147.1, 133.2, 130.3, 129.2, 128.9, 125.4, 124.3, 123.1, 122.9, 114.3, 61.5, 55.6, 52.5, 46.3, 30.1.

HRMS (ESI-TOF): m/z [M + Na]+ calcd for C32H34N6NaO2S: 589.2356; found: 589.2357.


#

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(N,N-diphenylaniline)methyl)S-Methyl S-Phenyl Sulfoximine (5o)

Obtained as a diastereomeric mixture. Total yield 70%.

Diastereomer 1

White solid; mp 169–170 °C. TLC (SiO2): Rf 0.26 (40% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.76 (d, J = 7.5 Hz, 2 H), 7.54 (t, J = 7.5 Hz, 1 H), 7.43 (t, J = 8.0 Hz, 2 H), 7.24–7.20 (m, 6 H), 7.04 (d, J = 7.5 Hz, 4 H), 7.00–6.97 (m, 4 H), 6.01 (s, 1 H), 3.14 (s, 3 H), 1.43 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 156.4, 147.7, 147.3, 139.9, 134.5, 133.4, 129.5, 129.3, 128.6, 128.5, 124.5, 123.6, 123.0, 61.6, 52.0, 45.6, 30.0.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C31H32N6NaOS: 559.2251; found: 559.2257.

Diastereomer 2

White solid; mp 167–168 °C.

1H NMR (500 MHz, CDCl3): δ = 7.79 (d, J = 7.5 Hz, 2 H), 7.57 (t, J = 7.5 Hz, 1 H), 7.45 (t, J = 8.0 Hz, 2 H), 7.23–7.19 (m, 4 H), 7.17 (d, J = 8.5 Hz, 2 H), 7.00 (t, J = 7.5 Hz, 2 H), 6.95 (d, J = 7.5 Hz, 4 H), 6.80 (d, J = 8.5 Hz, 2 H), 6.04 (s, 1 H), 3.13 (s, 3 H), 1.68 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 157.0, 147.6, 140.2, 132.9, 129.7, 129.3, 129.2, 129.1, 128.3, 127.2, 124.4, 123.3, 123.0, 61.7, 52.7, 46.1, 30.3.

HRMS (ESI-TOF): m/z [M + Na]+ calcd for C31H32N6NaOS: 559.2251; found: 559.2259.


#

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(benzo[b]thiophen-3-yl)methyl) S-Ethyl S-4-Methoxyphenyl Sulfoximine (5p)

Brown viscous liquid; 58% yield. TLC (SiO2): Rf 0.18 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 8.18 (d, J = 8.0 Hz, 1 H), 7.83 (d, J = 8.0 Hz, 1 H), 7.66 (d, J = 9.0 Hz, 2 H), 7.43–7.34 (m, 2 H), 7.20 (s, 1 H), 6.87 (d, J = 9.0 Hz, 2 H), 6.46 (s, 1 H), 3.83 (s, 3 H), 3.29–3.22 (m, 1 H), 3.18–3.13 (m, 1 H), 1.34 (s, 9 H), 1.20 (t, J = 7.5 Hz, 3 H).

13C NMR (125 MHz, CDCl3): δ = 163.4, 156.1, 140.9, 137.2, 134.9, 131.4, 129.0, 125.7, 124.5, 124.3, 122.7, 122.3, 114.3, 61.2, 55.6, 51.7, 46.4, 29.6, 6.8.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H28N5O2S2: 470.1679; found: 470.1689.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-bromophenyl)methyl) S-Diisopropyl Sulfoximine (5q)

Off-white solid; mp 87–88 °C; 44% yield. TLC (SiO2): Rf 0.20 (30% EtOAc in hexane).

IR (KBr): 3343, 2997, 2981, 2879, 2136, 1907, 1673, 1586, 1511, 1484, 1460, 1393, 1314, 1297, 1261, 1251, 1147, 1127, 1042, 1009, 950, 829, 783, 665 cm–1.

1H NMR (500 MHz, CDCl3): δ = 7.42 (d, J = 8.5 Hz, 2 H), 7.26 (d, J = 8.5 Hz, 2 H), 6.32 (s, 1 H), 3.35–3.31 (m, 2 H), 1.62 (s, 9 H), 1.30 (d, 7.0 Hz,3 H), 1.28 (d, J = 6.5 Hz, 3 H), 1.21 (d, 7.0 Hz, 3 H), 1.18 (d, 7.0 Hz, 3 H),

13C NMR (125 MHz, CDCl3): δ = 156.9, 141.3, 131.5, 129.1, 121.4, 61.9, 52.7, 51.8, 51.0, 30.1, 16.1, 15.7, 15.5, 15.4.

HRMS (ESI-TOF): m/z [M + Na]+ calcd for C18H28BrN5NaOS: 442.1271; found: 442.1273.


#

N-((1-Cyclohexyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) Di-S-4-methoxyphenyl Sulfoximine (5r)

Yellowish viscous liquid; 47% yield. TLC (SiO2): Rf 0.28 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.87 (d, J = 9.0 Hz, 2 H), 7.62 (d, J = 9.0 Hz, 2 H), 7.53 (d, J = 9.0 Hz, 2 H), 7.38 (d, J = 8.5 Hz, 2 H), 6.95 (d, J = 6.5 Hz, 2 H), 6.85 (d, J = 9.0 Hz, 2 H), 4.60 (s, 1 H), 4.30–4.27 (m, 1 H), 3.83 (s, 3 H), 3.81 (s, 3 H), 1.98–1.95 (m, 2 H), 1.83–1.79 (m, 1 H), 1.60–1.56 (m, 3 H), 1.34–1.31 (m, 2 H), 1.19 (br s, 2 H).

13C NMR (125 MHz, CDCl3): δ = 171.5, 163.3, 163.2, 133.0, 132.2, 130.6, 130.4, 128.7, 128.4, 127.0, 114.9, 114.7, 114.6, 61.8, 58.9, 55.8, 48.0, 33.1, 25.7, 24.8.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C28H31ClN5O3S: 552.1831; found: 552.1840.

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(p-tolyl)methyl) S-Pyrrolidyl S-Phenyl Sulfonimidamide (7a)

Yellowish solid; mp 110–112 °C; 52% yield. TLC (SiO2): Rf 0.45 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.97 (d, J = 7.5 Hz, 2 H), 7.57–7.54 (m, 1 H), 7.51–7.48 (m, 2 H), 7.45 (d, J = 7.5 Hz, 2 H), 7.14 (d, J = 7.5 Hz, 2 H), 6.53 (s, 1 H), 3.09–3.07 (m, 2 H), 2.96–2.94 (m, 2 H), 2.33 (s, 3 H), 1.72 (brs, 4 H), 1.59 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 157.1, 137.9, 137.2, 136.7, 132.4, 129.1, 128.9, 127.8, 127.4, 61.9, 51.1, 48.4, 30.2, 25.2, 21.2.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H31N6OS: 439.2275; found: 439.2281.


#

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Pyrrolidyl S-Phenyl Sulfonimidamide (7b)

Off-white solid; mp 107–108 °C; 56% yield. TLC (SiO2): Rf 0.45 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.94 (d, J = 8.0 Hz, 2 H), 7.54–7.51 (m, 5 H), 7.31 (d, J = 8.0 Hz, 2 H), 6.52 (s, 1 H), 3.09–3.08 (m, 2 H), 2.95–2.93 (m, 2 H), 1.72 (brs, 4 H), 1.59 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 156.6, 139.5, 136.5, 133.5, 132.6, 129.1, 128.9, 128.7, 127.8, 62.2, 50.9, 48.5, 30.2, 25.2.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C22H28ClN6OS: 459.1728; found: 459.1733.


#

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-bromophenyl)methyl) S-Pyrrolidyl S-p-Tolyl Sulfonimidamide (7c)

White solid; mp 89–91 °C; 59% yield. TLC (SiO2): Rf 0.44 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.80 (d, J = 8.0 Hz, 2 H), 7.45 (brs, 4 H), 7.29 (d, J = 8.0 Hz, 2 H), 6.48 (s, 1 H), 3.08–3.06 (m, 2 H), 2.93–2.91 (m, 2 H), 2.41 (s, 3 H), 1.71 (brs, 4 H), 1.58 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 156.6, 143.4, 140.2, 133.5, 131.5, 129.6, 129.2, 127.8, 121.5, 62.2, 51.0, 48.4, 30.2, 25.2, 21.5.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H30BrN6OS: 517.1380; found: 517.1385.


#

N-((1-Adamantyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Pyrrolidyl S-4-Methoxyphenyl Sulfonimidamide (7d)

White solid; mp 83–95 °C; 61% yield. TLC (SiO2): Rf 0.42 (30% EtOAc in hexane).

IR (KBr): 3357, 3259, 3085, 2960, 2839, 2581, 2037, 1898, 1727, 1590, 1494, 1390, 1325, 1261, 1154, 1098, 1059, 1017, 892, 833, 753, 677 cm–1.

1H NMR (500 MHz, CDCl3): δ = 7.87 (d, J = 9.0 Hz, 2 H), 7.50 (d, J = 8.0 Hz, 2 H), 7.31 (d, J = 8.5 Hz, 2 H), 6.97 (d, J = 9.0 Hz, 2 H), 6.50 (s, 1 H), 3.86 (s, 3 H), 3.09–3.07 (m, 2 H), 2.96–2.94 (m, 2 H), 2.31–2.28 (m, 3 H), 2.21–2.19 (m, 4 H), 2.11 (br s, 4 H), 1.64–1.61 (m, 8 H).

13C NMR (125 MHz, CDCl3): δ = 162.8, 156.6, 139.8, 133.2, 129.9, 128.8, 128.4, 128.3, 114.0, 63.0, 55.5, 51.2, 48.3, 41.9, 35.6, 29.6, 25.1.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C29H36ClN6O2S: 567.2303; found: 567.2307.


#

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(N,N-diphenylaniline)methyl)S-Pyrrolidyl S-p-Tolyl Sulfonimidamide (7e)

Yellow solid; mp 189–191 °C; 58% yield. TLC (SiO2): Rf 0.45 (30% EtOAc in hexane).

IR (KBr): 3033, 2972, 2849, 1588, 1504, 1485, 1402, 1317, 1272, 1254, 1194, 1006, 789, 754, 699 cm–1.

1H NMR (500 MHz, CDCl3): δ = 7.82 (d, J = 8.0 Hz, 2 H), 7.45 (d, J = 8.5 Hz, 2 H), 7.27 (d, J = 8.0 Hz, 2 H), 7.24–7.21 (m, 4 H), 7.05–7.04 (m, 5 H), 7.02–6.98 (m, 3 H), 6.48 (s, 1 H), 3.10–3.06 (m, 2 H), 2.98–2.93 (m, 2 H), 2.41 (s, 3 H), 1.65 (s, 9 H), 1.63–1.61 (m, 4 H).

13C NMR (125 MHz, CDCl3): δ = 157.1, 147.8, 147.2, 143.1, 135.0, 133.8, 129.5, 129.3, 128.6, 127.9, 124.4, 123.6, 123.0, 61.9, 51.1, 48.4, 30.3, 25.2, 21.5.

HRMS (ESI-TOF): m/z [M + Na]+ calcd for C35H39N7NaOS: 628.2829; found: 628.2825.


#

N-((1-Cyclohexyl-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Piperidyl S-p-Tolyl Sulfonimidamide (7f)

Yellowish solid; mp 112–113 °C; 55% yield. TLC (SiO2): Rf 0.44 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 7.74 (d, J = 8.0 Hz, 2 H), 7.55 (d, J = 8.5 Hz, 2 H), 7.35–7.32 (m, 4 H), 6.23 (s, 1 H), 4.72–4.67 (m, 1 H), 2.90–2.85 (m, 2 H), 2.80–2.76 (m, 2 H), 2.44 (s, 3 H), 1.99–1.97 (m, 1 H), 1.93–1.87 (m, 1 H), 1.76–1.74 (m, 1 H), 1.68–1.66 (m, 5 H), 1.49–1.47 (m, 2 H), 1.42–1.39 (m, 2 H), 1.33–1.25 (m, 3 H), 1.18–1.16 (m, 1 H).

13C NMR (125 MHz, CDCl3): δ = 155.7, 143.4, 138.7, 133.7, 132.7, 129.7, 128.8, 128.4, 127.7, 58.0, 49.8, 47.7, 32.4, 25.5, 25.3, 25.0, 23.6, 21.6.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C26H34ClN6OS: 513.2198; found: 513.2193.


#

N-((1-(tert-Butyl)-1H-tetrazol-5-yl)(4-chlorophenyl)methyl) S-Piperidyl-S-4-Methoxyphenyl Sulfonimidamide (7g)

Yellowish viscous liquid; 57% yield. TLC (SiO2): Rf 0.42 (30% EtOAc in hexane).

1H NMR (500 MHz, acetone-d 6): δ = 7.84 (d, J = 9.0 Hz, 2 H), 7.69 (d, J = 8.5 Hz, 2 H), 7.39 (d, J = 8.5 Hz, 2 H), 7.09 (d, J = 9.0 Hz, 2 H), 6.45 (s, 1 H), 3.87 (s, 3 H), 2.78–2.77 (m, 4 H), 1.67 (s, 9 H), 1.43–1.39 (m, 4 H), 1.33–1.31 (m, 2 H).

13C NMR (125 MHz, Acetone): δ = 163.9, 157.6, 141.6, 133.6, 130.7, 130.2, 129.2, 128.1, 114.9, 62.5, 56.1, 51.3, 48.3, 25.9, 24.2.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H32ClN6O2S: 503.1990; found: 503.2001.


#

N-((1-Cyclohexyl-1H-tetrazol-5-yl)(2-bromophenyl)methyl) S-Piperidyl S-4-Bromophenyl Sulfonimidamide (7h)

Yellowish viscous liquid; 45% yield. TLC (SiO2): Rf 0.44 (30% EtOAc in hexane).

1H NMR (500 MHz, CDCl3): δ = 8.11 (dd, J = 8.0, 1.5 Hz, 1 H), 7.74 (d, J = 8.5 Hz, 2 H), 7.64 (d, J = 8.5 Hz, 2 H), 7.54 (dd, J = 8.0, 1.0 Hz, 1 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.22–7.18 (m, 1 H), 6.52 (s, 1 H), 4.79–4.73 (m, 1 H), 2.82–2.79 (m, 2 H), 2.67–2.62 (m, 2 H), 1.99–1.88 (m, 5 H), 1.81–1.78 (m, 1 H), 1.71–1.69 (m, 1 H), 1.37–1.32 (m, 3 H), 1.29–1.25 (m, 3 H), 1.21–1.18 (m, 3 H).

13C NMR (125 MHz, CDCl3): δ = 155.0, 139.5, 134.5, 132.7, 132.2, 131.3, 129.7, 129.2, 128.1, 127.7, 122.8, 57.8, 48.8, 48.0, 33.1, 32.8, 25.6, 25.4, 25.2, 23.5.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C25H31Br2N6OS: 621.0641; found: 621.0644.


#
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Conflict of Interest

The authors declare no conflict of interest.

Supporting Information

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  • 16 Neochoritis CG, Zhao T, Domling A. Chem. Rev. 2019; 119: 1970
  • 17 Mancheño OG, Bolm C. Org. Lett. 2007; 9: 2951
  • 18 Hommelsheim R, Ponce HM. N, Truong K.-N, Rissanen K, Bolm C. Org. Lett. 2021; 23: 3415
    • 19a Xie Y, Zhou B, Zhou S, Zhou S, Wei W, Liu J, Zhan Y, Cheng D, Li Y, Wang B, Xue X, Li Z. ChemistrySelect 2017; 2: 1620
    • 19b Izzo F, Schafer M, Stockman R, Lucking U. Chem. Eur. J. 2017; 23: 15189
    • 20a Worch C, Bolm C. Synlett 2009; 2425
    • 20b Steurer M, Bolm C. J. Org. Chem. 2010; 75: 3301
    • 20c Nandi GC, Arvidsson PI. Adv. Synth. Catal. 2018; 360: 2976
    • 20d Chinthakindi PK, Naicker T, Thota N, Govender T, Kruger HG, Arvidsson PI. Angew. Chem. Int. Ed. 2017; 56: 4100
    • 20e Boulard E, Zibulski V, Oertel L, Lienau P, Schäfer M, Ganzer U, Lücking U. Chem. Eur. J. 2020; 26: 4378

Corresponding Author

Ganesh Chandra Nandi
Department of Chemistry, National Institute of Technology
Tiruchirappalli-620015, Tamilnadu
India   

Publication History

Received: 12 October 2022

Accepted after revision: 17 November 2022

Accepted Manuscript online:
17 November 2022

Article published online:
12 December 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by/4.0/)

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Figure 1 Representative tetrazole-bearing derivatives used in various fields
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Scheme 1 Schematic representation of (a) general and (b) current UT-4CR
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Scheme 2 Previous routes to (a) sulfoximine derived tetrazoles, (b) α-sulfoximidoyl acetic acids (this work: isosteric replacement of -COOH with tetrazole to access α-sulfoximino tetrazole).
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Scheme 3 Substrate scope for preparing sulfoximine-based tetrazoles
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Scheme 4 Synthesis of sulfonimidamide derived tetrazole
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Scheme 5 Substrate scope for sulfonimidamide based tetrazoles
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Scheme 6 Plausible mechanism for the formation of the UT product
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Scheme 7 Proposed mechanism for the formation of cyclic amine-based tetrazole 8