Metal-Free, Phosphonium Salt-Mediated Sulfoximination of Azine N-Oxides: Approach for the Synthesis of N-Azine Sulfoximines

Article abstract of DOI:10.1021/acs.joc.6b00593

Herein, we report a simple and metal-free method for the synthesis of N-azine sulfoximines by the nucleophilic substitution of azine N-oxides with NH-sulfoximines. The present method works at room temperature with wide functional group compatibility and gives several unprecedented N-azine sulfoximines. The reaction conditions were also found suitable with enantiopure substrates and furnished products without any racemization. It also finds an application in the sulfoximination of azine-based functional molecules such as 2,2′-bipyridine, 1,10-phenanthroline, and quinine.

Full text of DOI:10.1021/acs.joc.6b00593

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Article
Metal-free, Phosphonium Salt-Mediated Sulfoximination of Azine
N-oxides: Approach for the Synthesis of N-azine Sulfoximines
Sravan Kumar Aithagani, Mukesh Kumar, Mahipal Yadav, Ram A. Vishwakarma, and Parvinder Pal Singh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00593 • Publication Date (Web): 15 Jun 2016
Downloaded from http://pubs.acs.org on June 19, 2016
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Metalꢀfree, Phosphonium SaltꢀMediated Sulfoximination of Azine Nꢀoxides: Approach
for the Synthesis of Nꢀazine Sulfoximines
┴
┴
Sravan Kumar Aithagani, Mukesh Kumar, Mahipal Yadav, Ram A. Vishwakarma
*
and Parvinder Pal Singh
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Medicinal Chemistry Division, Academy of Scientific and Innovative Research, CSIRꢀIndian
Institute of Integrative Medicine, Canal Road, Jammuꢀ180001, India.
┴
These authors contributed equally
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Abstract:
Herein, we report a simple and metalꢀfree method for the synthesis of Nꢀazine
sulfoximines by the nucleophilic substitution of azine Nꢀoxides with NHꢀsulfoximines. The
present method works at room temperature with wide functional group compatibility and
gives several unprecedented Nꢀazine sulfoximines. The reaction conditions also found
suitable with enantiopure substrates and furnished products without any racemisation. It also
finds an application in the sulfoximination of azine based functional molecules such as 2,2'ꢀ
bipyridine, 1,10ꢀphenanthroline and quinine.
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Introduction:
Sulfoximines are wellꢀknown for their application as chiral auxiliaries
1
aꢀc
and
in asymmetric synthesis, as well as building blocks in pseudopeptides. However,
in recent years, their use in drug discovery have attracted the attention of medicinal
1
dꢀg
2
ligands
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3
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chemists. In drug discovery, this moiety has been used for improving specificity,
5
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stability/oral bioꢀavailability and reducing undesired toxicity. In addition, sulfoximines
have also been used as bioꢀisosters for several functional moieties such as heterocyclic
5,7
8
9
amidine, sulfones and secondary hydroxyl groups, as well as stable transitionꢀstate
10
analogue inhibitors. Keeping in view the importance of sulfoximines in drug discovery and
catalysis, several groups worldꢀwide are interested in the synthesis of sulfoximines and their
1
1,12
derivatives. There are several reports for the synthesis of NHꢀsulfoximines,
but only few
1b,13
reports are available for Nꢀsubstituted derivatives,
which involved either traditional
1b,13aꢀd
transitionꢀmetal catalysed crossꢀcoupling (Scheme 1, approach a)
or cross
1
3e,f
dehydrogenative coupling methods (Scheme 1, approach bꢀc ).
14
Our constant interest in the functionalization of electron–deficient system motivated
us to develop a simple method for the sulfoximination of electron–deficient heteroarenes.
Initially, we tried the coupling of isoꢀquinoline with Nꢀchlorosulfoximine in the presence of
14a
iron salt. Unfortunately, no reaction was observed (Scheme 1, approach e, path A). We
rationalized that the attempted reactions generated sulfoximinyl radical cations from Nꢀ
15
chlorosulfoximine, which represents an electronꢀdeficient system and coupling between two
15
electronꢀdeficient systems might not be possible. In this direction, Londregan et al.
established a PyBroP (bromotripyrrolidinophosphonium hexafluorophosphate) mediated
method for the functionalization of electronꢀdeficient heteroarenes with various nucleophiles
16
(
amine, phenol, sulfonamide, malonate, pyridine, thiol, silyl ketene acetal) which has
become a remarkable strategy for constructing a variety of carbon−carbon or
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carbon−heteroatom bonds under metalꢀfree conditions (Scheme 1, approach d). Considering
the nucleophilic nature of NHꢀsulfoximines, we envisioned that the same approach could be
explored for the sulfoximination of electron–deficient heteroarenes. Here, we have
successfully applied a precedented method for the sulfoximination of azines through azine Nꢀ
oxides in the presence of the NꢀO activating agent, PyBroP (Scheme 1, approach e, path B).
The method works well with substituted and unsubstituted quinolines, isoquinolines and
pyridines, and gives the corresponding Nꢀazine sulfoximines in good to excellent yields.
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Scheme 1. Previous and present reports
Reported methods
R1
X
NH
N
Z
S Me
O
Z
Pd, Cu or Fe
a)
b)
S Me
O
R1
R2
R2
X= I, Br, Cl, OTf, B(OH) , Si(OMe)
2
3
Z= CH, N
N
O
NH
R2
Cu, rt
N
Y
Z
Z
S
N O
S
R1
Y
R2
Y= O, S
Z= C, N
R1
o
O
NH
R2
Cu, 50 C
c)
S
O
S
R1
R1
N
O
N
N
R2
O
d)
PyBroP
Nucleophile
N
O
N
Nuc
Nucleophile = amine, phenol, sulfonamide, malonate,
pyridone, thiol, silyl ketene acetal
N
P
N
Our interest:
N
Br PF6
Previous work
Present work
Path A
e)
.
O
R1
PyBroP
S
FeCl2
ClN
R2
Fe
Ref. 14)
B(OH)2
N
[
N
Ph
(
Path B
O]
O
R
1
O
S
R1
N
N
S
R2
HN
R2
N-O activating agent, PyBoP
N
Metal free,
Room tempaerature
O
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Results and discussion:
Our investigation started with test substrates isoquinoline-Nꢀoxide 1a and racemic Sꢀ
methylꢀSꢀphenylsulfoximine 2a in the presence of PyBroP as Nꢀoxide activating agent using
16b,c
the conditions reported by Londregan et al,
which successfully gave desired coupled
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product 3aa in a yield of 87%. After this success, the applicability of sulfoximines was
examined, and all the results are given in Scheme 2. Various sulfoximines efficiently coupled
with isoquinolineꢀNꢀoxide 1a and gave corresponding coupled products 3aaꢀao in good to
excellent yields.
a
Scheme 2. Addition of various sulfoximines to isoquinolineꢀNꢀoxide
PyBroP
N
O
R1
i
Pr EtN
2
S
N
N
N
S
THF
O
HN R2
R2
o
2
5 C
1a
2
O
R1
3
N
N
N
N
N
N
N
N
N
Me S
O
Me S
O
Me Me S
O
Me S
O
Me S
O
OMe
Br
Cl
3aa: 87%
3ab: 80%
3ad: 78%
3ac: 82% Me
3ae: 74%
N
N
N
N
N
N
Me S
O
N
Me S
O
N
S Me
N
S Ph
N
S
Me
Ph
O
O
O
F
NO2
3aj: 70%
3af: 80%
3ag: 70%
3ah: 68%
3ai: 62%
N
N
N
N
Et S
O
N
N
N
N
N
N
nBu
Me S
nPr S
nBu S
S nBu
O
O
O
O
3ak: 65%
3al<10%
3am: 72%
3an: 70%
3ao: 69%
a
Reaction conditions: All reactions were conducted at 0.2 M concentration with 1a (0.2 mmol, 1.0 equiv),
i
o
2
(0.26 mmol, 1.3 equiv), Pr EtN (0.6 mmol, 3.0 equiv) and PyBroP (0.22 mmol, 1.1 equiv) at 25 C for 15
2
h.
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A series of alkyl aryl and diaryl sulfoximines containing electronꢀdonating groups
(
OMe and Me) and electronꢀwithdrawing groups (Br, Cl, F and NO
2
) on the aryl ring
underwent smooth reaction with isoquinolineꢀNꢀoxide 1a and gave the desired products (3abꢀ
16c,17
3
ah) in good to high yields. The high Cꢀ1 regioselectivity as observed earlier,
might be
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directed by LUMO electron density of the azine Nꢀoxide. Sulfoximines with electronꢀ
donating groups on phenyl ring have shown slightly better yields than sulfoximines with
electronꢀwithdrawing
groups.
Cyclic
and
dialkyl
sulfoximines,
S,Sꢀ
tetramethylenesulfoximine, S,Sꢀdimethylsulfoximine and S,Sꢀdibutylsulfoximine also worked
and afforded the corresponding products 3ai, 3aj and 3ak in good yields. Sterically hindered
SꢀmethylꢀSꢀnaphthyl sulfoximine didn’t give good results. To our delight, Sꢀethyl, Sꢀpropyl
and Sꢀbutyl phenyl sulfoximines also furnished high yields of corresponding products 3am,
3
an and 3ao, respectively.
Further, this reaction was successfully extended to various pyridineꢀ and quinolineꢀNꢀ
oxides (Scheme 3). Mostly, all substrates reacted smoothly and afforded the desired products
in good yields. PyridineꢀNꢀoxide gave a 1:1 mixture of separable 2ꢀ and 4ꢀsubstituted
products 4aa and 4aa' in an overall yield of 75%. Unfortunately, 2ꢀmethyl and 2,6ꢀdimethyl
pyridineꢀNꢀoxides were not good substrates for this transformation (4ab and 4ac). However,
3
ꢀmethylpyridineꢀNꢀoxide gave corresponding 2ꢀsubsituted products 4adꢀ4ae with moderate
to good yields On the other hand, 3ꢀbromopyridineꢀNꢀoxide gave a separable mixture of 2ꢀ
1
6c,17
and 6ꢀsubstituted products 4af and 4af' in the ratio of 2:1 in an overall yield of 42%.
The
2
ꢀphenylpyridineꢀNꢀoxide afforded corresponding single regiomers 4ag and 4ah in a yields
of 65% and 35%, respectively. Further, 2ꢀbromoꢀ4ꢀchloropyridineꢀNꢀoxide furnished low
yields (4ai and 4aj).
PyridineꢀNꢀoxides having electronꢀdonating (tBu) and electronꢀwithdrawing (CN,
th
CF
3
, NO
2
) groups at the 4 position furnished the single regioꢀisomeric respective products
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4akꢀ4ao in a yields of 75 %, 65%, 75%, 40% and 35%, respectively. DiazineꢀNꢀoxide such as
pyrazineꢀNꢀoxide was not found suitable substrate for this reaction. Gratifyingly, quinolineꢀ
Nꢀoxides furnished single regioꢀisomeric products with good to excellent yields. The
quinolineꢀNꢀoxide when subjected to a series of different alkyl aryl and dialkyl sulfoximines,
the corresponding coupled products 4ca, 4cb, 4cc and 4cd were obtained in a yields of 80%,
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9%, 65% and 53%, respectively. Similarly, 4ꢀmethylquinolineꢀNꢀoxide on coupling with
various sulfoximines afforded coupled products 4ce, 4cf and 4cg in yields of 72%, 60% and
5%, respectively. Furthermore, 5ꢀbromoquinolineꢀNꢀoxide and 8ꢀmethoxyquinolineꢀNꢀ
6
oxide, when tried also furnished coupled products 4ch and 4ci in 63% and 70% yields,
respectively. When 6ꢀBromoquinolineꢀNꢀoxide was employed in this reaction with Sꢀmethylꢀ
Sꢀphenylsulfoximine and S,Sꢀdibutylsulfoximine, the corresponding products 4cj and 4ck
were found in good yields of 70% and 60%, respectively. The Nꢀmethyl 8ꢀaza indoleꢀNꢀoxide
did not undergo coupling.
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a
Scheme 3. Substrate scope of azineꢀNꢀoxides
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Considering the mildness of the reaction conditions, isoquinolineꢀNꢀoxide 1a, was
treated with enantiopure sulfoximine (S)ꢀ(+)ꢀSꢀmethylꢀSꢀphenylsulfoximine, (Scheme 4), the
corresponding product (S)ꢀ(ꢀ)ꢀ3aa was obtained in 85% yield with high enantiomeric excess
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(>99% ee, see SI), respectively suggested that chiral substrates are also tolerated under
reaction conditions.
a
Scheme 4. Reaction with enantiopure sulfoximine
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After exploring the feasibility of the present method with various substrates, its
application towards the diversification of azineꢀbased functional molecules were also
explored. Azineꢀbased functional molecules, such as 1,10ꢀphenanthroline and 2,2'ꢀbipyridine,
are well known ligands and in many instances their substituted versions provide additional
18
advantages in terms of reactivity and selectivity. On the other hand, sulfoximines are also
1aꢀc
1dꢀg
wellꢀknown for their application as chiral auxiliaries and ligands,
and sulfoximination
of the above mentioned ligands may provide some advantages. Towards this end,
sulfoximidoyl containing 1,10ꢀphenanthroline 6aa and 2,2'ꢀbipyridine 6ab were successfully
synthesized on reaction with SꢀmethylꢀSꢀphenylsulfoximine (Scheme 5).
a
Scheme 5. Sulfoximination of ligands
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Furthermore, a notable example for the present method is the direct sulfoximination
of quinine. The reaction of quinine analogue 7a with racemic SꢀmethylꢀSꢀphenylsulfoximine
2
a (Scheme 6), provided the corresponding coupled product 8aa as an unseparable
diasteromeric mixture in a 1:1.2 ratio (predicted through NMR). The sulfoximination of azine
based functional molecules proved the utility of the present method in the functionalization
and diversification.
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Scheme 6. Sulfoximination of quinine
Conclusions:
In summary, we have developed a nucleophilic substitution reaction of azine Nꢀoxides
with sulfoximines. The present metalꢀfree method provides a simple and mild approach for
the synthesis of Nꢀazine sulfoximines. This protocol works very well with various azines,
such as substituted and unsubstituted isoquinoline, pyridine and quinolines and gives a
diverse range of several novel and unprecedented Nꢀazine sulfoximines. This reaction
proceeds at room temperature, operationally simple, and has broad functional group
compatibility and substrate scope. Moreover, by utilizing the present method, direct
sulfoximination of functional molecules, such as 1,10ꢀphenanthroline, 2,2'ꢀbipyridine and
quinine was also achieved.
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EXPERIMENTAL SECTION:
General Information:
All the reactions were performed under nitrogen atmosphere. Analytical thin layer
chromatography was performed using TLC preꢀcoated silica gel 60 F254 (20 x 20 cm). TLC
plates were visualized by exposing UV light. Organic solvents were concentrated by rotary
evaporation. Column chromatography was performed on flash silica gel 230ꢀ400 mesh size
and ethyl acetate/hexane mixture used for elution. Melting points were recorded on melting
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point instrument and are uncorrected. H NMR (400 MHz or 500 MHz) and C NMR (101
MHz or 126 MHz) recorded on FTꢀNMR instruments. Chemical shift data for protons are
reported in parts per million (ppm, scale) downfield from tetramethylsilane and are
referenced to the residual proton in the NMR solvent (CDCl
3
: δ 7.26). The coupling constant
(J) are in Hz. ESIꢀMS and HRMS spectra were recorded on LCꢀQꢀTOF machines. FTꢀIR was
recorded in chloroform using NaCl plate. Optical rotations were measured at room
temperature in 10 cm cells. Analytical HPLC was performed using a chiral stationary phase
(flow rate: 1.0 mL/min, column type and eluent is given for the corresponding compound)
and UV detection (λ = 210 nm or 254 nm) at 20 °C.
19,20
General procedure for the preparation of sulfoximines:
StepꢀI. Oxidation of sulfides to sulfoxides: To a stirred solution of CuBr
sulfide (1.0 equiv) in CH CN (2.0 mL/1mmol) was added 70% tꢀBuOOH (in water, 5.0
equiv). The reaction mixture was heated to reflux and the progress was monitored by TLC
until all sulfide was found consumed. After completion, CH CN was evaporated and the
crude mixture was washed with NaHCO and extracted with ethyl acetate. The ethyl acetate
2
(0.05 equiv) and
3
3
3
was evaporated and the crude sulfoxides were subsequently used for the imination reaction.
StepꢀII. Imination of sulfoxides: A solution of crude sulfoxide (1.0 equiv) and sodium azide
(
1.2 equiv) in CHCl (~8ꢀ10 mL for 5 mmol of sulfoxide) was stirred in an ovenꢀdried threeꢀ
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necked round bottom flask equipped with a reflux condenser and an addition funnel.
Concentrated sulphuric acid (~2.0 mL for 1.0 g of sulfoxide) was introduced over 5ꢀ10
o
o
minutes at 0 C. The resulting mixture was slowly warmed up to 45 C and the same
temperature was maintained until nitrogen gas evolution subsides. The reaction was
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continued for an additional 12 h at 45 C. The reaction mixture was cooled and the pastyꢀ
mass was dissolved with iceꢀwater. The organic layer was decanted and the aqueous layer
was washed with minimum amount of CHCl
using 20% NaOH solution and extracted with CHCl
combined organic extracts were dried over Na SO . Solvent was filtered and evaporated
3
. The aqueous layer was made slightly alkaline
3
(3 × 5 mL, for 5 mmol sulfoxide). The
2
4
under reduced pressure. The crude residue was purified using column chromatography on
silica gel to afford the desired sulfoximines in good yields.
21
General procedure for the preparation of azine Nꢀoxides: To a 0 °C solution of the
2 2
appropriate azine in CH Cl (0.5 M) is added mꢀCPBA (2.0 equiv) and the reaction is allowed
to stir at room temperature overnight. The reaction mixture is diluted with CH Cl and
2
2
washed with aq. KOH (6N, 3x), the organic layer is dried over Na SO and the solvent is
2
4
evaporated under reduced pressure. The azine Nꢀoxides are obtained as white solids and used
without further purification.
22
Synthesis of 1,10ꢀphenanthroline Nꢀoxide (5a): Hydrogen peroxide (30%, 1.4 mL) was
added into the solution of the phenanthroline (10 mmol) in acetic acid (10 mL). The reaction
o
mixture was stirred at 70 C for 72 h. The solvent was evaporated under vacuum, and the
residue was basified with aqueous solution of sodium carbonate until pH = 9. The resulting
mixture was extracted with chloroform (3x20 mL). The organic phase were combined and
dried over anhydrous sodium sulphate, filtered and evaporated under vacuum. The residue
was purified by flash chromatography (silica gel, EtOAc: methanol 8:1).
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Synthesis of 2,2´ꢀbipyridyl Nꢀoxide (5b): 2,2’ꢀBipyridine (1.248 g, 8.00 mmol) was added
to a 50 mL roundꢀbottomed flask with stir bar, followed by dissolution in trifluoroacetic acid
(
2 2
6.0 mL). This was cooled to room temperature, followed by slow addition of 30% H O (1.2
mL, 12 mmol). Reaction was stirred at room temperature for 2 h, followed by addition of
chloroform (25 mL). This was washed with 6M aqueous NaOH (3 x 10 mL), followed by
back extraction of the combined aqueous phase with dichloromethane (4 x 20 mL). The
combined organic phase was dried over MgSO4, followed by evaporation in vacuo to give
oil. This was dried under vacuum overnight to obtain required compound as a white solid.
Synthesis of Nꢀoxide quinine analogue (7a):
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2
4
Step I: Oꢀbenzylation: To a solution of quinine (4.0 g, 12.4 mmol) in DMF (40 mL) under
nitrogen atmosphere, NaH (1.36 g, 57 % suspension in mineral oil, 32.3 mmol) was added
and the resulted mixture was stirred at room temperature for 2 h. Then BnCl (1.56 mL, 13.6
mmol) was added dropwise via a syringe over 10 minutes. The resulting mixture was stirred
overnight. After the starting material was completely consumed, brine was added carefully
(
40 mL) and the resulting mixture was extracted with ethyl acetate (200 mL). The organic
phase was washed with H O (5 x 100 mL), brine (100 mL) and dried over Na SO . The
2
2
4
solvent was removed in vacuo to afford light yellow oil (5.1 g, 99%). This crude product was
used for next reaction without further purification.
2
5
o
Step II: Oxidation: At 0 C, mꢀchloroperoxybenzoic acid (77%, 9.20 g, 37.5 mmol) was
added in portions to a solution of above compound (4.89 g, 15.0 mmol) in chloroform (90
mL). The resulting suspension was allowed to warm to rt and stirred for 3 h at that
temperature, during which time the reaction mixture became a clear yellow solution. The
2
reaction was quenched with NaOH (aq) (10% in H O) until pH = 10. The resulting twoꢀphase
mixture was extracted with a mixed solvent of CHCl /MeOH (10/1, 50 mL×6). The organic
3
phase was collected and the combined organic phase was dried over Na SO , filtered and
2
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evaporated in vacuo to give the crude product as light yellow foam (5.30 g, 99% yield). This
crude product was used in the next step without further purification.
25
Step III: Deoxygenation: To the solution of above intermediate (5.30 g, 15.0 mmol) in
o
acetone (60 mL) at 0 C was added dropwise an aqueous solution of sulfurous acid (6% wt,
0
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24 mL, 18 mmol). The resulting mixture was warmed to rt. The resulting mixture was stirred
overnight. Then, the acetone was removed under vacuum and ammonium hydroxide was
added to make the solution alkaline. Chloroform (50 mL×5) was used to extract the aqueous
2 4
layer. The organic layers were combined, washed with brine (50 mL), dried over Na SO and
concentrated in vacuo. The residue was subjected to silica gel column chromatography
1
(CHCl /MeOH = 20/1 + 1% Et N) to afford 7a as a viscous liquid (4.51 g, 86% yield). H
3
3
NMR (400 MHz, CDCl
3
) δ 8.75 (d, J = 9.6 Hz, 1H), 8.37 (d, J = 6.3 Hz, 1H), 7.46 – 7.28 (m,
8
H), 5.78 (ddd, J = 17.5, 10.3, 7.6 Hz, 1H), 5.00 – 4.91 (m, 2H), 4.44 (dd, J = 29.2, 11.5 Hz,
H), 3.90 (s, 3H), 3.27 (s, 1H), 3.14 (d, J = 5.0 Hz, 1H), 3.10 – 2.85 (m, 2H), 2.71 – 2.53 (m,
2
2H), 2.26 (s, 1H), 1.78 (dd, J = 33.4, 4.6 Hz, 3H), 1.49 (d, J = 7.8 Hz, 1H).
General procedure for the synthesis of Nꢀazine sulfoximines: To a solution of sulfoximine
(
0.26 mmol, 1.3 equiv) in THF (1 mL) was added i-Pr
temperature. After stirring for 5 minutes, azine Nꢀoxide (0.2 mmol, 1.0 equiv) and PyBroP
0.22 mmol, 1.1 equiv) were added sequentially. Then the reaction mixture was stirred at
2
EtN (0.6 mmol, 3 equiv) at room
(
room temperature. After completion of the reaction (by TLC analysis), reaction mixture was
diluted with CHCl and washed with aqueous NaHCO solution. The combined organic layers
3
3
were dried over anhydrous NaSO4, filtered and concentrated in vacuo. The crude compounds
were purified through column chromatography and pure compounds were characterized by
NMR and Mass analysis.
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀmethylphenylsulfoximine (3aa):
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o
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TLC (Hexane/EtOAc, 7:3) R
f
= 0.30; Yield 87% (49 mg);White solid; m.p.: 161ꢀ163 C; H
NMR (400 MHz, CDCl ) δ 8.53 (d, J = 8.3 Hz, 1H), 8.11 (d, J = 7.6 Hz, 2H), 7.96 (d, J = 5.8
3
13
1
Hz, 1H), 7.59 (m, 6H), 7.11 (d, J = 5.8 Hz, 1H), 3.52 (s, 3H); C{ H} NMR (126 MHz,
CDCl ) δ 157.8, 141.0, 140.2, 137.4, 133.1, 130.0, 129.4, 127.7, 126.1, 126.0, 126.0, 123.7,
3
10
11
12
13
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44
45
46
47
48
49
50
51
52
53
54
55
56
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58
59
60
+
114.0, 45.0; HRMS (ESIꢀTOF) calc. for C H N OS [M + H] 283.0905; found 283.0900.
16
14
2
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀmethyl(4ꢀmethoxyphenyl)sulfoximine
(3ab):
TLC
= 0.25; Yield 80% (50 mg); White solid; m.p.: 121ꢀ122 C; H NMR
) δ 8.52 (d, J = 8.3 Hz, 1H), 8.02 (d, J = 8.9 Hz, 2H), 7.98 (d, J = 5.9 Hz,
H), 7.67 (d, J = 8.0 Hz, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.11 (d, J =
o
1
(
Hexane/EtOAc, 7:3) R
500 MHz, CDCl
f
(
3
1
1
3
1
5.8 Hz, 1H), 7.01 (d, J = 8.9 Hz, 2H), 3.85 (s, 3H), 3.49 (s, 3H); C{ H} NMR (126 MHz,
CDCl
3
) δ 163.3, 158.0, 141.1, 137.4, 131.5, 130.0, 129.9, 126.1, 126.0, 126.0, 123.8, 114.6,
+
1
13.9, 55.7, 45.2; HRMS (ESIꢀTOF) calc. for C17
13.1019.
H
17
N
2
O
2
S [M + H] 313.1011; found
3
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀmethyl(3,5ꢀdimethylphenyl)sulfoximine(3ac):
TLC
o
1
(
Hexane/EtOAc, 7:3) R = 0.50; Yield 82% (50 mg); White solid; m.p.: 102ꢀ105 C; H NMR
f
(500 MHz, CDCl
3
) δ 8.53 (d, J = 8.2 Hz, 1H), 7.98 (d, J = 5.8 Hz, 1H), 7.72 – 7.65 (m, 3H),
7
.62 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 7.23 (s, 1H), 7.11 (d, J = 5.8 Hz, 1H), 3.49
13
1
(
3
s, 3H), 2.39 (s, 6H); C{ H} NMR (126 MHz, CDCl ) δ 158.0, 141.1, 140.0, 139.5, 137.4,
134.8, 130.0, 126.1, 126.0, 125.9, 125.1, 123.8, 113.9, 45.0, 21.3; HRMS (ESIꢀTOF) calc. for
+
C H N OS [M + H] 311.1218; found 311.1212.
18
18
2
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀmethyl(4ꢀbromophenyl)sulfoximine (3ad): TLC (Hexane/EtOAc,
o
1
7
:3) R
CDCl ) δ 8.49 (d, J = 8.2 Hz, 1H), 7.95 (t, J = 5.5 Hz, 3H), 7.73 – 7.66 (m, 3H), 7.62 (t, J =
.4 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 7.12 (d, J = 5.8 Hz, 1H), 3.49 (s, 3H); C{ H} NMR
f
= 0.35; Yield 78% (56 mg); White solid; m.p.: 137ꢀ138 C; H NMR (400 MHz,
3
1
3
1
7
(
126 MHz, CDCl ) δ 157.5, 140.9, 139.3, 137.4, 132.7, 130.1, 129.4, 128.2, 126.2, 126.1,
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4
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5
5
5
5
5
5
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8
1
+
125.9, 123.6, 114.3, 45.1; HRMS (ESIꢀTOF) calc. for C16
found 362.9988.
2
H13 BrN OS [M + H] 362.9990;
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀmethyl(4ꢀchlorophenyl)sulfoximine (3ae): TLC (Hexane/EtOAc,
o
1
7
:3) R = 0.50; Yield 74% (46 mg); White solid; m.p.: 139ꢀ142 C; H NMR (500 MHz,
f
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
CDCl ) δ 8.49 (d, J = 8.3 Hz, 1H), 8.03 – 7.99 (m, 2H), 7.96 – 7.92 (m, 1H), 7.67 (d, J = 8.0
3
Hz, 1H), 7.62 (t, J = 7.5 Hz, 1H), 7.52 (dd, J = 7.5, 6.3 Hz, 3H), 7.12 (d, J = 5.8 Hz, 1H),
13
1
3
3
.48 (s, 3H); C{ H} NMR (126 MHz, CDCl ) δ 157.5, 140.9, 139.7, 138.8, 137.4, 130.1,
1
29.7, 129.3, 126.2, 126.1, 125.9, 123.6, 114.3, 45.2; HRMS (ESIꢀTOF) calc. for
+
C H ClN OS [M + H] 317.0515; found 317.0510.
16 13
2
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀmethyl(4ꢀfluorophenyl)sulfoximine (3af): TLC (Hexane/EtOAc,
1
7:3) R
f
= 0.40; Yield 80% (48 mg); Gummy solid; H NMR (400 MHz, CDCl
3
) δ 8.41 (dd, J
=
11.1, 3.1 Hz, 1H), 8.08 – 7.93 (m, 2H), 7.86 (d, J = 5.9 Hz, 1H), 7.64 – 7.45 (m, 1H), 7.42
(
ddd, J = 8.2, 6.8, 1.4 Hz, 2H), 7.16 – 7.05 (m, 2H), 7.02 (d, J = 5.9 Hz, 1H), 3.40 (s, 3H);
1
3
1
C{ H} NMR (126 MHz, CDCl ) δ 165.5 (d, J = 264.6 Hz), 157.6, 140.9, 137.4, 136.2 (d, J
3
=
3.0 Hz), 130.5 (d, J = 9.4 Hz), 130.1, 126.2, 126.1, 125.9, 123.7, 116.70 (d, J = 22.7 Hz),
+
114.2, 45.2; HRMS (ESIꢀTOF) calc. for C16
H
13FN
2
OS [M + H] 301.0811; found 301.0803.
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀmethyl(4ꢀnitrophenyl)sulfoximine (3ag): TLC (Hexane/EtOAc,
o
1
6:4) R
f
= 0.40; Yield 70% (46 mg); Yellow solid; m.p.: 106ꢀ108 C; H NMR (400 MHz,
CDCl ) δ 8.48 (d, J = 8.2 Hz, 1H), 8.39 – 8..32 (m, 2H), 8.25 – 8.23(m, 2H), 7.85 – 7.84 (m,
3
13
1
1
H), 7.71 – 7.66ꢀ7.53 (m, 3H), 7.12 (t, J = 6.9 Hz, 1H), 3.50 (s, 3H); C{ H} NMR (126
MHz, CDCl ) δ 156.96 (s), 150.44 (s), 146.63 (s), 140.70 (s), 137.50 (s), 130.30 (s), 129.24
s), 126.29 (d, J = 9.8 Hz), 125.79 (s), 124.58 (s), 123.47 (s), 114.73 (s), 45.02 (s); HRMS
3
(
+
(ESIꢀTOF) calc. for C16
14 3 3
H N O S [M + H] 328.0756; found 328.0749.
Nꢀ[1ꢀIsoquinolinyl]ꢀS,SꢀDiphenylsulfoximine (3ah): TLC (Hexane/EtOAc, 7:3) R = 0.60;
f
o
1
Yield 68% (46 mg); White solid; m.p.: 138ꢀ142 C; H NMR (400 MHz, CDCl ) δ 8.72 (d, J
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= 8.1 Hz, 1H), 8.13 (dd, J = 8.0, 1.3 Hz, 4H), 7.87 (d, J = 5.8 Hz, 1H), 7.66 (dt, J = 6.7, 4.4
1
3
1
Hz, 2H), 7.60 – 7.56 (m, 1H), 7.53 – 7.45 (m, 6H), 7.08 (d, J = 5.8 Hz, 1H); C{ H} NMR
(126 MHz, CDCl
3
) δ 157.3, 141.2, 141.2, 137.4, 132.5, 130.0, 129.3, 128.1, 126.2, 126.1,
+
1
25.9, 124.1, 114.1; HRMS (ESIꢀTOF) calc. for C H N OS [M + H] 345.1062; found
2
1
16
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
345.1058.
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀtetramethelenesulfoximine (3ai): TLC (Hexane/EtOAc, 7:3) R
f
=
o
1
0
.18; Yield 62% (30 mg); White solid; m.p.: 178ꢀ180 C; H NMR (500 MHz, CDCl
d, J = 8.3 Hz, 1H), 8.06 (d, J = 5.9 Hz, 1H), 7.67 (d, J = 8.1 Hz, 1H), 7.63 – 7.58 (m, 1H),
.48 (t, J = 7.2 Hz, 1H), 7.14 (d, J = 5.9 Hz, 1H), 3.81 – 3.74 (m, 2H), 3.42 (m, 2H), 2.42 –
3
) δ 8.41
(
7
13
1
2.33 (m, 2H), 2.29 – 2.22 (m, 2H); C{ H} NMR (126 MHz, CDCl ) δ 158.5, 140.9, 137.4,
3
14 2
130.1, 126.0, 126.0, 125.9, 123.4, 113.8, 53.0, 23.8; HRMS (ESIꢀTOF) calc. for C13H N OS
+
[
M + H] 247.0905; found 247.0898.
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀdimethylsulfoximine (3aj): TLC (Hexane/EtOAc, 1:1) R
f
= 0.30;
o
1
Yield 70% (30 mg); White solid; m.p.: 119ꢀ123 C; H NMR (500 MHz, CDCl ) δ 8.39 (d, J
3
=
8.3 Hz, 1H), 8.05 (d, J = 5.9 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.63 – 7.58 (m, 1H), 7.47
13
1
(
dd, J = 11.5, 4.5 Hz, 1H), 7.14 (d, J = 5.8 Hz, 1H), 3.46 (s, 6H); C{ H} NMR (126 MHz,
CDCl
3
) δ 158.1, 140.8, 137.4, 130.1, 126.0, 126.0, 125.9, 123.5, 113.8, 42.3; HRMS (ESIꢀ
+
TOF) calc. for C11
H
12
N
2
OS [M + H] 221.0749; found 221.0725.
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀdibutylsulfoximine (3ak): TLC (Hexane/EtOAc, 9:1) R = 0.70;
f
1
Yield 65% (40 mg); Gummy solid; H NMR (400 MHz, CDCl ) δ 8.48 (d, J = 8.3 Hz, 1H),
3
8
.05 (d, J = 5.9 Hz, 1H), 7.69– 7.60(m, 2H), 7.53 – 7.49 (m, 1H), 7.14 (d, J = 5.9 Hz, 1H),
.68 (ddd, J = 13.8, 10.9, 5.5 Hz, 2H), 3.55 (ddd, J = 13.8, 10.8, 5.5 Hz, 2H), 2.01 – 1.83 (m,
3
13
1
4H), 1.56 – 1.47 (m, 4H), 1.09 – 0.96 (m, 1H); C{ H} NMR (126 MHz, CDCl
3
) δ 158.1,
140.7, 137.4, 130.0, 127.0, 123.7, 113.5, 51.5, 24.3, 21.7, 13.6; HRMS (ESIꢀTOF) calc. for
+
C H N OS [M + H] 305.1688; found 305.1682.
17
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3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀethylphenylsulfoximine (3am):
o
1
TLC (Hexane/EtOAc, 1:1) R
NMR (500 MHz, CDCl ) δ 8.58 (d, J = 8.2 Hz, 1H), 8.05 – 8.01 (m, 2H), 7.92 (d, J = 5.9 Hz,
H), 7.67 (d, J = 8.0 Hz, 1H), 7.65 – 7.59 (m, 2H), 7.57 – 7.50 (m, 3H), 7.09 (d, J = 5.9 Hz,
f
= 0.55; Yield 72% (42 mg); White solid; m.p.: 107ꢀ110 C; H
3
1
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
1
H), 3.76 – 3.59 (m, 2H), 1.31 (t, J = 7.4 Hz, 3H); C{ H} NMR (126 MHz, CDCl ) δ 157.8,
3
141.1, 137.7, 137.4, 133.0, 130.0, 129.3, 128.6, 126.1, 126.0, 125.9, 123.8, 113.9, 51.1, 7.9;
+
HRMS (ESIꢀTOF) calc. for C17
H
17
N
2
OS [M + H] 297.1062; found 297.1031.
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀpropylphenylsulfoximine (3an):
TLC (Hexane/EtOAc, 7:3) Rf = 0.68; Yield 70% (43 mg); White solid; m.p.: 104ꢀ105 C; H
NMR (400 MHz, CDCl ) δ 8.56 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 7.5 Hz, 2H), 7.91 (d, J = 5.8
Hz, 1H), 7.66 – 7.56 (m, 3H), 7.51 (t, J = 7.5 Hz, 3H), 7.07 (d, J = 5.8 Hz, 1H), 3.64 – 3.57
o
1
3
13
1
(
m, 2H), 1.88 – 1.72 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H); C{ H} NMR (126 MHz, CDCl
3
) δ
1
5
57.8, 141.1, 138.4, 137.4, 132.9, 129.9, 129.3, 128.5, 126.1, 126.0, 125.9, 123.8, 113.8,
+
19 2
8.4, 16.8, 12.8; HRMS (ESIꢀTOF) calc. for C18H N OS [M + H] 311.1218; found
311.1191.
Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀbutylphenylsulfoximine (3ao):
TLC (Hexane/EtOAc, 8:2) R = 0.49; Yield 69% (44 mg); White solid; m.p.: 102ꢀ103 C; H
o
1
f
NMR (500 MHz, CDCl
H), 7.67 (d, J = 8.1 Hz, 1H), 7.64 – 7.58 (m, 2H), 7.54 (ddd, J = 12.0, 5.0, 3.1 Hz, 3H), 7.09
d, J = 5.8 Hz, 1H), 3.69 – 3.58 (m, 2H), 1.85 – 1.67 (m, 2H), 1.43 – 1.35 (m, 2H), 0.89 (t, J
3
) δ 8.57 (d, J = 8.3 Hz, 1H), 8.05 – 8.01 (m, 2H), 7.92 (d, J = 5.8 Hz,
1
(
13
1
= 7.3 Hz, 3H); C{ H} NMR (126 MHz, CDCl ) δ 157.8, 141.1, 138.4, 137.4, 132.9, 129.9,
3
129.3, 128.5, 126.1, 126.0, 125.9, 123.8, 113.8, 56.5, 24.9, 21.4, 13.5; HRMS (ESIꢀTOF)
+
calc. for C19
H
21
N
2
OS [M + H] 325.1375; found 325.1389.
26
Nꢀ[2ꢀPyridinyl]ꢀS,Sꢀmethylphenylsulfoximine (4aa): TLC (Hexane/EtOAc, 1:1) R
f
=
o
1
0
3
.10; Yield 37% (17 mg); Yellow solid; m.p.: 133ꢀ135 C; H NMR (400 MHz, CDCl ) δ
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8.10 – 8.07 (m, 1H), 8.05 – 8.01 (m, 2H), 7.58 (dt, J = 14.9, 7.2 Hz, 3H), 7.48 (td, J = 8.2, 1.9
1
3
1
Hz, 1H), 6.87 (d, J = 8.2 Hz, 1H), 6.73 (dd, J = 6.4, 5.3 Hz, 1H), 3.37 (s, 3H); C{ H} NMR
(126 MHz, CDCl
3
) δ 158.9, 147.8, 140.1, 137.7, 133.0, 129.4, 127.8, 116.6, 116.1, 45.5;
+
HRMS (ESIꢀTOF) calc. for C H N OS [M + H] 233.0749; found 233.0747.
12
12
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
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30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ[4ꢀPyridinyl]ꢀS,Sꢀmethylphenylsulfoximine (4aa'): TLC (Hexane/EtOAc, 1:1) R = 0.25;
f
o
1
Yield 37% (17 mg); White solid; m.p.: 105ꢀ106 C; H NMR (400 MHz, CDCl
3
) δ 8.08 (s,
1H), 7.97 (t, J = 6.5 Hz, 3H), 7.66 – 7.61 (m, 1H), 7.56 (t, J = 7.5 Hz, 2H), 7.41 (d, J = 7.9
13
1
Hz, 1H), 7.28 (t, J = 7.7 Hz, 1H), 3.40 (s, 3H); C{ H} NMR (126 MHz, CDCl
3
) δ 172.9,
138.6, 137.3, 134.1, 134.0, 132.1, 129.8, 129.5, 129.4, 127.5, 127.1, 44.4; HRMS (ESIꢀTOF)
+
calc. for C H N OS [M + H] 233.0749; found 233.0743.
12
12
2
Nꢀ[2ꢀ(3ꢀMethyl)ꢀpyridinyl]ꢀS,Sꢀmethylphenylsulfoximine (4ad): TLC (Hexane/EtOAc,
o
1
7
:3) R
CDCl
7.53 (m, 2H), 7.35 – 7.33(m, 1H), 6.67 (dd, J = 7.2, 5.0 Hz, 1H), 3.41 (s, 3H), 2.31 (s, 3H);
f
= 0.30; Yield 35% (17 mg); Yellow solid; m.p.: 98ꢀ102 C; H NMR (400 MHz,
3
) δ 8.06 – 8.04 (m, 2H), 7.93 (dd, J = 3.1, 1.8 Hz, 1H), 7.62 – 7.59 (m, 1H), 7.56 –
1
3
1
C{ H} NMR (126 MHz, CDCl ) δ 158.0, 145.0, 140.8, 137.7, 132.8, 129.3, 127.7, 125.3,
3
+
1
16.2, 45.0, 18.0; HRMS (ESIꢀTOF) calc. for C13
47.0904.
H
15
N
2
OS [M + H] 247.0905; found
2
Nꢀ[2ꢀ(3ꢀMethyl)ꢀpyridinyl]ꢀS,Sꢀmethyl(4ꢀnitrophenyl)sulfoximine
(4ae):
TLC
1
(Hexane/EtOAc, 7:3) R = 0.30; Yield 30% (18 mg); Gummy solid; H NMR (400 MHz,
f
CDCl ) δ 8.38 (d, J = 8.8 Hz, 2H), 8.22 (d, J = 8.7 Hz, 2H), 7.86 (d, J = 4.5 Hz, 1H), 7.38 (d,
3
13
1
J = 8.9 Hz, 1H), 6.70 (t, J = 15.5 Hz, 1H), 3.41 (s, 3H), 2.31 (s, 3H); C{ H} NMR (126
MHz, CDCl
3
) δ 156.4, 150.2, 146.8, 144.2, 138.1, 129.2, 125.6, 124.2, 116.7, 44.9, 17.7;
+
HRMS (ESIꢀTOF) calc. for C13
H
14
N
3
O
3
S [M + H] 292.0756; found 292.0757.
Nꢀ[2ꢀ(3ꢀBromo)ꢀpyridinyl]ꢀS,Sꢀmethylphenylsulfoximine (4af): TLC (Hexane/EtOAc, 7:3)
o
1
R = 0.35; Yield 28% (17 mg); White solid; m.p.: 121ꢀ122 C; H NMR (400 MHz, CDCl ) δ
f
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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5
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6
8.12 – 8.08 (m, 2H), 8.03 – 7.99 (m, 1H), 7.76 (dd, J = 7.7, 1.6 Hz, 1H), 7.66 – 7.61 (m, 1H),
13
1
7
.57 (dd, J = 11.5, 4.1 Hz, 2H), 6.63 (dd, J = 7.7, 4.9 Hz, 1H), 3.43 (s, 3H); C{ H} NMR
(126 MHz, CDCl
3
) δ 156.7, 146.4, 140.9, 139.9, 133.2, 129.4, 127.8, 117.0, 113.0, 77.3,
+
7
7.0, 76.8, 44.8; HRMS (ESIꢀTOF) calc. for C H BrN OS [M + H] 310.9854 and
12
11
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
312.9833; found 310.9854 and 312.9834.
Nꢀ[2ꢀ(5ꢀBromo)ꢀpyridinyl]ꢀS,Sꢀmethylphenylsulfoximine (4af'): TLC (Hexane/EtOAc,
o
1
7
:3) R
CDCl ) δ 8.09 (d, J = 2.4 Hz, 1H), 8.00 (d, J = 7.6 Hz, 2H), 7.63 (t, J = 7.3 Hz, 1H), 7.58 –
.54 (m, 3H), 6.77 (d, J = 8.7 Hz, 1H), 3.35 (s, 3H); C{ H} NMR (126 MHz, CDCl ) δ
f
= 0.30; Yield 14% (8 mg); White solid; m.p.: 131ꢀ134 C; H NMR (400 MHz,
3
13
1
7
3
157.6, 148.4, 140.2, 139.6, 133.2, 129.5, 127.8, 118.2, 111.7, 77.3, 77.0, 76.8, 45.5; HRMS
81
+
(ESIꢀTOF) calc. for C12
2
H11 BrN OS [M + H] 312.9833; found 312.9834.
Nꢀ[2ꢀ(6ꢀPhenyl)ꢀpyridinyl]ꢀS,Sꢀmethylphenylsulfoximine (4ag): TLC (Hexane/EtOAc,
o
1
7:3) R
f
= 0.40; Yield 65% (40 mg); White solid; m.p.: 117ꢀ119 C; H NMR (500 MHz,
CDCl ) δ 7.99 (d, J = 7.4 Hz, 2H), 7.55 – 7.45 (m, 6H), 7.20 (t, J = 8.4 Hz, 3H), 7.13 (d, J =
3
1
3
1
7
1
4
.6 Hz, 1H), 6.74 (d, J = 8.0 Hz, 1H), 3.31 (s, 3H); C{ H} NMR (126 MHz, CDCl ) δ
3
58.4, 154.9, 140.7, 139.1, 138.5, 132.8, 129.5, 128.4, 128.2, 127.7, 126.6, 114.9, 112.5,
+
5.5; HRMS (ESIꢀTOF) calc. for C18
H
16
N
2
OS [M + H] 309.1062; found 309.1060.
f
Nꢀ[2ꢀ(6ꢀPhenyl)ꢀpyridinyl]ꢀS,Sꢀdibutylsulfoximine (4ah): TLC (Hexane/EtOAc, 9:1) R =
o
1
0.60; Yield 35% (23 mg); Yellow solid; m.p.: 115ꢀ118 C; H NMR (400 MHz, CDCl ) δ
3
7
1
1
.99 – 7.92 (m, 2H), 7.55 (t, J = 7.8 Hz, 1H), 7.44 (dt, J = 13.3, 4.9 Hz, 2H), 7.44 – 7.41 (m,
H), 7.27 – 7.18 (m, 1H), 6.76 (d, J = 8.0 Hz, 1H), 3.53 (m, J = 13.8, 9.7, 6.4 Hz, 4H), 1.87 –
13
1
.75 (m, 4H), 1.45 (dd, J = 14.9, 7.4 Hz, 4H), 0.96 – 0.86 (m, 6H); C{ H} NMR (126 MHz,
CDCl
3
) δ 159.1, 155.0, 139.6, 138.4, 128.5, 126.6, 115.2, 112.2, 51.8, 24.3, 21.7, 13.6;
+
HRMS (ESIꢀTOF) calc. for C H N OS [M + H] 331.1839; found 331.1836.
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Nꢀ[6ꢀ(2ꢀBromoꢀ4ꢀchloro)ꢀpyridinyl]ꢀS,Sꢀmethyl(4ꢀnotrophenyl)sulfoximine (4ai): TLC
o
1
(
Hexane/EtOAc, 7:3) R
f
= 0.30; Yield 25% (19 mg); Brownish solid; m.p.: 124ꢀ126 C; H
NMR (400 MHz, CDCl
3
) δ 8.42 (dd, J = 7.0, 1.8 Hz, 2H), 8..19 (m, 2H), 6.95 (d, J = 1.5 Hz,
1
3
1
1
H), 6.79 (d, J = 1.5 Hz, 1H), 3.42 (s, 3H); C{ H} NMR (126 MHz, CDCl ) δ 158.5, 150.5,
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
146.0, 145.5, 139.2, 129.2, 124.6, 120.2, 115.1, 44.7; HRMS (ESIꢀTOF) calc. for
81
+
12 3 3
C H10 BrClN O S [M + H] 391.9294; found 391.9273.
Nꢀ[6ꢀ(2ꢀBromoꢀ4ꢀchloro)ꢀpyridinyl]ꢀS,Sꢀdibutylsulfoximine (4aj): TLC (Hexane/EtOAc,
1
9:1) R
f
= 0.70; Yield 30% (22 mg); Colourless oil; H NMR (400 MHz, CDCl
3
) δ 6.94 (d, J =
1.5 Hz, 1H), 6.72 (d, J = 1.5 Hz, 1H), 3.49 – 3.38 (m, 4H), 1.87 – 1.73 (m, 4H), 1.52 – 1.42
1
3
1
(m, 4H), 0.96 (t, J = 7.4 Hz, 6H); C{ H} NMR (126 MHz, CDCl ) δ 159.7, 145.7, 139.0,
3
8
1
1
2
18.8, 115.0, 51.7, 29.7, 24.0, 21.6, 13.5; HRMS (ESIꢀTOF) calc. for C13H21 BrClN OS [M
+
+
H] 369.0226; found 369.0216.
Nꢀ[2ꢀ(4ꢀtertꢀButyl)ꢀpyridinyl]ꢀS,Sꢀmethylphenylsulfoximine (4ak): TLC (Hexane/EtOAc,
1
7:3) R = 0.25; Yield 75% (43 mg); Colourless oil; H NMR (400 MHz, CDCl ) δ 8.04 (d, J =
f
3
7.7 Hz, 2H), 7.99 (d, J = 5.5 Hz, 1H), 7.60 (t, J = 7.3 Hz, 1H), 7.55 (t, J = 7.6 Hz, 2H), 6.87
13
1
(
d, J = 0.7 Hz, 1H), 6.76 (dd, J = 5.5, 1.1 Hz, 1H), 3.38 (s, 3H), 1.25 (s, 9H); C{ H} NMR
(126 MHz, CDCl
3
) δ 161.8, 159.0, 147.4, 140.4, 132.9, 129.4, 127.8, 113.6, 45.4, 34.6, 30.5;
+
HRMS (ESIꢀTOF) calc. for C16
H
21
N
2
OS [M + H] 289.1375; found 289.1374.
Nꢀ[2ꢀ(4ꢀCyano)ꢀpyridinyl]ꢀS,Sꢀmethylphenylsulfoximine (4al): TLC (Hexane/EtOAc, 7:3)
o
1
R = 0.30; Yield 65% (34 mg); Pale yellow solid; m.p.: 105ꢀ108 C; H NMR (400 MHz,
f
CDCl
3
) δ 8.16 (dd, J = 5.2, 0.7 Hz, 1H), 7.99 (dd, J = 5.2, 3.3 Hz, 2H), 7.65 (ddd, J = 6.6,
3.8, 1.2 Hz, 1H), 7.59 – 7.53(m, 2H), 7.08 – 7.07 (m, 1H), 6.90 (dd, J = 5.2, 1.4 Hz, 1H),
1
3
1
3.37 (s, 3H). C{ H} NMR (126 MHz, CDCl
3
) δ 159.8, 148.9, 139.3, 133.4, 129.6, 127.6,
+
1
21.6, 119.1, 116.8, 45.5; HRMS (ESIꢀTOF) calc. for C H N OS [M + H] 258.0701; found
13
12
3
258.0687.
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Nꢀ[2ꢀ(4ꢀTrifluoromethyl)ꢀpyridinyl]ꢀS,Sꢀmethyl(4ꢀnitrophenyl)sulfoximine (4am): TLC
o
1
(Hexane/EtOAc, 7:3) R
f
= 0.35; Yield 75% (52 mg); Yellow solid; m.p.: 120ꢀ123 C; H
NMR (400 MHz, CDCl
3
) δ 8.38 – 8.33 (m, 2H), 8.19 – 8.17 (m, 2H), 8.09 (d, J = 5.2 Hz,
13
1
1
H), 7.07 (s, 1H), 6.92 (d, J = 5.1 Hz, 1H), 3.39 (s, 3H); C{ H} NMR (126 MHz, CDCl ) δ
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
159.0, 150.5, 148.7, 145.9, 140.1 (q, J = 33.5 Hz), 129.2, 124.7, 122.8(q, J = 273.4 Hz),
+
11 3 3 3
112.9(d, J = 3.8 Hz) 112.0, 45.1; HRMS (ESIꢀTOF) calc. for C13H F N O S [M + H]
346.0468; found 346.0463.
Nꢀ[2ꢀ(4ꢀNitro)ꢀpyridinyl]ꢀS,Sꢀmethylphenylsulfoximine (4an):
o
1
TLC (Hexane/EtOAc, 1:1) R = 0.50; Yield 15% (8 mg); Yellow solid; m.p.: 145ꢀ147 C; H
f
NMR (400 MHz, CDCl ) δ 8.26 (d, J = 5.6 Hz, 1H), 8.04 – 8.00 (m, 2H), 7.66 (t, J = 7.4 Hz,
3
13
1
1
H), 7.58 (dd, J = 13.1, 4.8 Hz, 3H), 7.41 (dd, J = 5.6, 2.0 Hz, 1H), 3.40 (s, 3H); C{ H}
NMR (101 MHz, CDCl
3
) δ 161.2, 155.4, 149.7, 139.2, 133.4, 129.6, 127.6, 109.8, 108.1,
+
45.5; HRMS (ESIꢀTOF) calc. for C12
H
11
N
3
O
3
S [M + H] 278.0599; found 278.0594.
Methyl((3ꢀmethylꢀ4ꢀnitropyridinꢀ2ꢀyl)imino)(phenyl)ꢀsulfanone
(4ao):
TLC
o
1
(
Hexane/EtOAc, 7:3) R = 0.20; Yield 35% (20mg); Yellow solid; m.p.: 105ꢀ108 C; H
f
3
NMR (400 MHz, CDCl ) δ 8.02– 7.98 (m, 3H), 7.68 – 7.62 (m, 1H), 7.62 – 7.56 (m, 2H),
1
3
7
3
.02 (d, J = 5.5 Hz, 1H), 3.41 (s, 3H), 2.45 (s, 3H). C NMR (126 MHz, CDCl ) δ 160.56 (s),
156.43 (s), 145.67 (s), 139.74 (s), 133.34 (s), 129.57 (s), 127.60 (s), 118.40 (s), 109.05 (s),
+
45.22 (s), 13.34 (s). HRMS (ESIꢀTOF) calc. for C H N O S [M + H] 292.0750; found
1
3
14
3
3
292.0750.
Nꢀ[2ꢀQuinolinyl]ꢀS,Sꢀmethylphenylsulfoximine (4ca): TLC (Hexane/EtOAc, 7:3) R
f
=
o
1
0
.15; Yield 80% (45 mg); White solid; m.p.: 162ꢀ165 C; H NMR (400 MHz, CDCl
3
) δ 8.10
(d, J = 7.2 Hz, 2H), 7.91 (d, J = 8.7 Hz, 1H), 7.68 – 7.47 (m, 6H), 7.29 (d, J = 7.1 Hz, 1H),
1
3
1
7
.05 (d, J = 8.7 Hz, 1H), 3.51 (s, 3H); C{ H} NMR (126 MHz, CDCl ) δ 158.1, 147.3,
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140.2, 137.6, 133.1, 129.4, 128.9, 127.8, 127.5, 127.1, 124.5, 123.6, 118.1, 77.3, 77.0, 76.8,
+
45.2; HRMS (ESIꢀTOF) calc. for C16
H
14
N
2
OS [M + H] 283.0905; found 283.0901.
Nꢀ[2ꢀQuinolinyl]ꢀS,Sꢀmethyl(4ꢀbromophenyl)sulfoximine (4cb):
o
1
TLC (Hexane/EtOAc, 7:3) R = 0.20; Yield 69% (49 mg); White solid; m.p.: 117ꢀ119 C; H
f
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NMR (400 MHz, CDCl ) δ 7.93 (dd, J = 12.3, 8.7 Hz, 3H), 7.70 – 7.61 (m, 4H), 7.53 – 7.47
3
13
1
(
m, 1H), 7.29 (d, J = 7.0 Hz, 1H), 7.03 (d, J = 8.7 Hz, 1H), 3.47 (s, 3H); C{ H} NMR (126
MHz, CDCl ) δ 157.8, 147.1, 139.4, 137.7, 132.6, 129.4, 129.0, 128.2, 127.4, 127.1, 124.5,
3
81
+
1
23.8, 118.0, 45.2; HRMS (ESIꢀTOF) calc. for C16
62.9985.
2
H13 BrN OS [M + H] 362.9990; found
3
Nꢀ[2ꢀQuinolinyl]ꢀS,Sꢀmethyl(4ꢀchlorophenyl)sulfoximine (4cc):
TLC (Hexane/EtOAc, 7:3) R = 0.15; Yield 65% (41 mg); White solid; m.p.: 101ꢀ103 C; H
NMR (500 MHz, CDCl ) δ 8.03 (dd, J = 8.4, 3.6 Hz, 2H), 7.93 (dd, J = 8.7, 3.5 Hz, 1H), 7.63
dd, J = 8.0, 4.3 Hz, 2H), 7.53 – 7.48 (m, 3H), 7.29 (dd, J = 13.3, 5.6 Hz, 1H), 7.04 (dd, J =
o
1
f
3
(
1
3
1
8.7, 4.0 Hz, 1H), 3.48 (s, 3H); C{ H} NMR (126 MHz, CDCl ) δ 157.8, 147.1, 139.7,
3
138.7, 137.7, 129.7, 129.3, 129.0, 127.4, 127.2, 124.5, 123.8, 118.0, 45.2; HRMS (ESIꢀTOF)
+
calc. for C16
H13ClN
2
OS [M + H] 317.0515; found 317.0511.
Nꢀ[2ꢀQuinolinyl]ꢀS,Sꢀdimethylsulfoximine (4cd): TLC (Hexane/EtOAc, 1:1) R
f
= 0.10;
) δ 7.87 (d, J
= 7.8 Hz, 1H), 7.72 (d, J = 7.0 Hz, 1H), 7.59 (d, J = 7.0 Hz, 1H), 7.50 (s, 1H), 7.25 (s, 1H),
o
1
Yield 53% (24 mg); White solid; m.p.: 104ꢀ106 C; H NMR (500 MHz, CDCl
3
1
3
1
6
.90 (d, J = 7.9 Hz, 1H), 3.40 (s, 6H); C{ H} NMR (126 MHz, CDCl ) δ 158.5, 147.1,
3
137.8, 129.1, 127.3, 127.0, 124.3, 123.6, 118.4, 77.33, 77.0, 76.8, 42.4; HRMS (ESIꢀTOF)
+
calc. for C11
H
12
N
2
OS [M + H] 221.0749; found 221.0738.
Nꢀ[2ꢀ(4ꢀMethyl)ꢀquinolinyl]ꢀS,Sꢀmethylphenylsulfoximine (4ce): TLC (Hexane/EtOAc,
o
1
7
:3) R = 0.15; Yield 72% (42 mg); White solid; m.p.: 121ꢀ122 C; H NMR (400 MHz,
f
CDCl ) δ 8.12 – 8.07 (m, 2H), 7.79 (d, J = 8.1 Hz, 1H), 7.67 (d, J = 8.3 Hz, 1H), 7.61 – 7.47
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4
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6
1
3
1
(m, 4H), 7.30 (t, J = 7.5 Hz, 1H), 6.92 (s, 1H), 3.49 (s, 3H), 2.56 (s, 3H); C{ H} NMR (101
MHz, CDCl
3
) δ 157.8, 147.2, 145.4, 140.4, 133.0, 129.3, 128.7, 128.0, 127.7, 124.8, 123.4,
+
1
23.3, 118.3, 45.3, 18.6; HRMS (ESIꢀTOF) calc. for C17
97.1058.
H
16
N
2
OS [M + H] 297.1062; found
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Nꢀ[2ꢀ(4ꢀMethyl)ꢀquinolinyl]ꢀS,Sꢀmethyl(4ꢀchlorophenyl)sulfoximine (4cf): TLC
o
1
(
Hexane/EtOAc, 7:3) R
500 MHz, CDCl
H), 7.50 (t, J = 8.2 Hz, 3H), 7.31 (t, J = 7.5 Hz, 1H), 6.91 (s, 1H), 3.46 (s, 3H), 2.58 (s, 3H);
f
= 0.20; Yield 60% (39 mg); White solid; m.p.: 112ꢀ114 C; H NMR
(
3
) δ 8.02 (d, J = 8.5 Hz, 2H), 7.80 (d, J = 8.1 Hz, 1H), 7.65 (d, J = 8.3 Hz,
1
1
3
1
C{ H} NMR (126 MHz, CDCl ) δ 157.5, 147.1, 145.7, 139.6, 138.9, 129.6, 129.3, 128.8,
3
127.9, 124.8, 123.5, 123.3, 118.1, 45.3, 18.7; HRMS (ESIꢀTOF) calc. for C H ClN OS [M
1
7
15
2
+
+
H] 331.0672; found 331.0667.
Nꢀ[2ꢀ(4ꢀMethyl)ꢀquinolinyl]ꢀS,Sꢀdimethylsulfoximine (4cg): TLC (Hexane/EtOAc, 1:1) R
f
o
1
=
0.15; Yield 65% (30 mg); White solid; m.p.: 102ꢀ104 C; H NMR (500 MHz, CDCl
3
) δ
7.83 (dd, J = 8.2, 0.9 Hz, 1H), 7.79 (d, J = 8.3 Hz, 1H), 7.58 – 7.54 (m, 1H), 7.37 – 7.32 (m,
1
3
1
1
H), 6.84 (s, 1H), 3.46 (s, 6H), 2.59 (s, 3H); C{ H} NMR (126 MHz, CDCl ) δ 158.2,
3
1
47.0, 145.7, 128.9, 127.5, 124.6, 123.5, 123.4, 118.5, 42.5, 18.7; HRMS (ESIꢀTOF) calc. for
+
C
12
H
14
N
2
OS [M + H] 235.0905; found 235.0903.
Nꢀ[2ꢀ(5ꢀBromo)ꢀquinolinyl]ꢀS,Sꢀmethylphenylsulfoximine (4ch): TLC (Hexane/EtOAc,
o
7:3) R = 0.20; Yield 63% (45 mg); White solid; m.p.: 119ꢀ120 C; 1H NMR (400 MHz,
f
CDCl ) δ 8.27 (d, J = 9.0 Hz, 1H), 8.08 (d, J = 7.4 Hz, 2H), 7.63 – 7.52 (m, 5H), 7.32 (t, J =
3
13
1
8
.0 Hz, 1H), 7.12 (d, J = 9.0 Hz, 1H), 3.50 (s, 3H); C{ H} NMR (126 MHz, CDCl
3
) δ
1
58.8, 148.1, 139.9, 136.9, 133.2, 129.4, 129.2, 127.7, 127.3, 127.3, 123.8, 121.6, 119.3,
81
77.3, 77.0, 76.84, 45.2; HRMS (ESIꢀTOF) calc. for C16
found 363.0014
2
H13 BrN OS [M + H]+ 362.9998;
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Nꢀ[2ꢀ(8ꢀMethoxy)ꢀquinolinyl]ꢀS,Sꢀmethylphenylsulfoximine (4ci): TLC (Hexane/EtOAc,
o
1
7
:3) R
f
= 0.12; Yield 70% (43 mg); White solid; m.p.: 160ꢀ164 C; H NMR (400 MHz,
) δ 8.16 (d, J = 7.2 Hz, 2H), 7.87 (d, J = 8.7 Hz, 1H), 7.63 – 7.52 (m, 3H), 7.24 – 7.17
m, 2H), 7.05 (d, J = 8.7 Hz, 1H), 6.92 (dd, J = 6.6, 2.2 Hz, 1H), 3.94 (s, 3H), 3.61 (s, 3H);
CDCl
3
(
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
3
1
C{ H} NMR (126 MHz, CDCl ) δ 157.1, 154.3, 140.1, 138.9, 137.6, 133.0, 129.2, 127.9,
3
1
25.4, 123.5, 119.3, 118.1, 108.6, 56.0, 44.9; HRMS (ESIꢀTOF) calc. for C17
H]+ 313.1011; found 313.1005.
Nꢀ[2ꢀ(6ꢀBromo)ꢀquinolinyl]ꢀS,Sꢀmethylphenylsulfoximine (4cj): TLC (Hexane/EtOAc,
16 2 2
H N O S [M +
o
1
7
:3) R = 0.35; Yield 70% (51 mg); Yellow solid; m.p.: 105ꢀ107 C; H NMR (400 MHz,
f
CDCl ) δ 8.26 – 8.24(d, 1H), 8.10 – 8.01 (m, 2H), 7.54 (m, 5H), 7.29 (dd, J = 14.6, 7.0 Hz,
3
13
1
1
H), 7.11 (dd, J = 8.9, 5.6 Hz, 1H), 3.47 (d, J = 5.5 Hz, 3H); C{ H} NMR (126 MHz,
CDCl ) δ 158.8, 148.1, 139.9, 136.8, 133.2, 129.3, 127.5, 123.8, 121.6, 119.4, 45.2; HRMS
ESIꢀTOF) calc. for C16
3
81
+
(
2
H14 BrN OS [M + H] 362.9984; found 363.0014.
Nꢀ[2ꢀ(6ꢀBromo)ꢀquinolinyl]ꢀS,Sꢀdibutylsulfoximine (4ck): TLC (Hexane/EtOAc, 9:1) R =
f
1
0
1
7
4
.70; Yield 60% (45 mg); Colourless oil; H NMR (400 MHz, CDCl ) δ 8.25 (d, J = 9.0 Hz,
3
H), 7.68 (dd, J = 8.4, 0.6 Hz, 1H), 7.54 (dd, J = 7.5, 1.0 Hz, 1H), 7.36 (t, J = 8.0 Hz, 1H),
.05 (d, J = 9.0 Hz, 1H),3.66ꢀ3.55 (m, 4H), 1.90 – 1.76 (m, 4H), 1.45 (dd, J = 14.9, 7.4 Hz,
1
3
1
3
H), 0.92 (t, J = 7.4 Hz, 6H); C{ H} NMR (126 MHz, CDCl ) δ 159.2, 148.2, 136.6, 127.0,
81
126.9, 123.6, 121.8, 119.9, 23.9, 21.7, 13.5; HRMS (ESIꢀTOF) calc. for C H BrN OS [M
17
24
2
+
+
H] 385.0772; found 385.0766.
(S)-(-)-Nꢀ[1ꢀIsoquinolinyl]ꢀS,Sꢀmethylphenylsulfoximine
((S)ꢀ(ꢀ)ꢀ3aa):
= 0.30; Yield 85% (47 mg); White solid; m.p.: 200ꢀ202 C; [
) δ 8.53 (d, J = 8.3 Hz, 1H), 8.11 (d, J = 7.6
TLC
o
(Hexane/EtOAc, 7:3) R
f
D
α] ꢀ
1
3
6.66° (c 1, CHCl
3
); H NMR (400 MHz, CDCl
3
Hz, 2H), 7.96 (d, J = 5.8 Hz, 1H), 7.59 (m, 6H), 7.11 (d, J = 5.8 Hz, 1H), 3.52 (s, 3H);
1
3
1
3
C{ H} NMR (126 MHz, CDCl ) δ 157.8, 141.0, 140.2, 137.4, 133.1, 130.0, 129.4, 127.7,
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5
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5
5
5
5
5
5
6
+
14 2
126.1, 126.0, 126.0, 123.7, 114.0, 45.0; HRMS (ESIꢀTOF) calc. for C16H N OS [M + H]
2
83.0905; found 283.0904; Chiral HPLC (ChiraSelectꢀAM, 250 × 4.6 mm, nꢀhexane/iꢀPrOH
=
95:5, 1 mL/min, λ = 210 nm, 254 nm): t [(S)ꢀ(ꢀ)ꢀ3aa] = 23.82.
R
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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6
7
8
9
0
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4
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6
7
8
9
0
Nꢀ[2ꢀ(1,10ꢀPhenanthrolinyl)]ꢀS,Sꢀmethylphenylsulfoximine (6aa): TLC (CHCl /MeOH,
3
o
1
9
:1) R
f
= 0.20; Yield 42% (28 mg); White solid; m.p.: 155ꢀ158 C; H NMR (500 MHz,
) δ 9.10 (dd, J = 4.3, 1.7 Hz, 1H), 8.33 – 8.29 (m, 2H), 8.18 (dd, J = 8.1, 1.7 Hz, 1H),
.02 (d, J = 8.5 Hz, 1H), 7.67 (d, J = 8.7 Hz, 1H), 7.64 – 7.60 (m, 1H), 7.57 (ddd, J = 12.5,
CDCl
3
8
7
1
1
13
1
3
.8, 2.2 Hz, 4H), 7.25 (d, J = 8.5 Hz, 1H), 3.85 (s, 3H); C{ H} NMR (126 MHz, CDCl ) δ
58.5, 149.4, 145.3, 145.0, 139.9, 137.6, 135.7, 133.1, 129.1, 128.8, 127.8, 126.2, 123.9,
+
23.0, 122.3, 118.7, 44.6; HRMS (ESIꢀTOF) calc. for C19
H
15
N
3
OS [M + H] 334.1014;
found 334.1012.
Nꢀ[2ꢀ(6ꢀBipyridyl)]ꢀS,Sꢀmethylphenylsulfoximine (6ab): TLC (CHCl
3
/MeOH, 9.5:0.5) R
0.20; Yield 35% (21 mg); Yellow solid; m.p.: 135ꢀ138 C; H NMR (500 MHz, CDCl ) δ
.56 (d, J = 4.0 Hz, 1H), 8.09 (dd, J = 8.1, 1.4 Hz, 2H), 7.87 (d, J = 7.3 Hz, 1H), 7.76 (d, J =
8.0 Hz, 1H), 7.65 – 7.56 (m, 5H), 7.18 (ddd, J = 7.4, 4.8, 1.1 Hz, 1H), 6.92 (d, J = 7.7 Hz,
f
o
1
=
3
8
13
1
1
3
H), 3.39 (s, 3H); C{ H} NMR (126 MHz, CDCl ) δ 157.8, 156.0, 153.6, 148.5, 140.3,
1
38.6, 136.2, 132.7, 129.3, 127.6, 123.0, 120.9, 116.5, 113.1, 45.4; HRMS (ESIꢀTOF) calc.
+
for C17
H
15
N
3
OS [M + H] 310.1014; found 310.1019.
Quinine analogue (8aa): TLC (CHCl /MeOH, 9:1) R = 0.5; Yield 40% (34 mg); White
3
f
solid; IR (CHCl
3
): vmax = 3584, 3063, 2925, 2855, 1600, 1504, 1454, 1407, 1380, 1349, 1234,
1
1
7
1
026; H NMR (400 MHz, CDCl
3
) δ 8.09 (t, J = 7.1 Hz, 2H), 7.68 (d, J = 9.1 Hz, 1H), 7.63 –
.48 (m, 3H), 7.34 (ddd, J = 21.6, 14.2, 7.7 Hz, 6H), 7.24 – 7.18 (m, 2H), 5.72 (ddd, J = 18.2,
3.9, 8.0 Hz, 1H), 5.01 – 4.89 (m, 2H), 4.55 – 4.32 (m, 2H), 3.86 (s, 3H), 3.51 (d, J = 5.7 Hz,
3H), 3.41 (bs, 1H), 3.17 – 3.01 (m, 2H), 2.62 (d, J = 10.7 Hz, 2H), 2.26 (bs, 1H), 1.88 (bs,
13
1
3
3
H), 1.71 (d, J = 16.1 Hz, 2H), 1.48 (s, 1H); C{ H} NMR (126 MHz, CDCl ) δ 156.0,
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143.7, 142.0, 140.3, 138.2, 138.1, 133.0, 129.9, 129.3, 128.3, 127.9, 127.8, 127.7, 127.6,
127.4, 123.2, 120.5, 114.2, 70.8, 59.9, 57.1, 55.7, 45.4, 43.3, 40.0, 29.6, 27.9, 27.7, 27.7;
+
HRMS (ESIꢀTOF) calc. for C34
H
38
N
3
O
3
S [M + H] 568.2634; found 568.2623.
10
11
12
13
14
15
16
17
18
19
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ASSOCIATED CONTENT:
Supporting Information Copies of NMRs, HRMS spectras are given. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION:
Corresponding Author
* Eꢀmail: ppsingh@iiim.ac.in.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGEMENTS:
We are grateful to the financial support of CSIR through research grants BSCꢀ0108 and
HCPꢀ0001. SKA and MK thank UGC for the award of fellowship. MY thanks CSIR for the
award of fellowship. Authors thank Mr. Rajneesh Anand, Mrs. Deepika Singh support in
recording NMR and Mass spectroscopy. IIIM communication number: IIIM/1778/2015.
REFERENCES:
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1) (a) Craig, D.; Grellepois, F.; White, A. J. P. J. Org. Chem. 2005, 70, 6827ꢀ6832. (b)
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