Oxazoline-Promoted Rh-Catalyzed C-H Amidation of Benzene Derivatives with Sulfonamides and Trifluoroacetamide. A Comparative Study

Article abstract of DOI:10.1021/acs.joc.6b02481

A Rh-catalyzed ortho-amidation of 2-aryloxazolines offers an efficient and direct route to a range of sulfonamides. The scope of the reaction is very broad with respect to sulfonamide substrate, but the position and electronic nature of the substituents on the aryl moiety of the oxazoline lead to a surprising modulation of reactivity. The reactivity of sulfonamides in comparison to trifluoroacetamide is compared, the latter undergoing Rh-catalyzed amidation more rapidly.

Full text of DOI:10.1021/acs.joc.6b02481

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Featured Article
Oxazoline Promoted Rh-Catalyzed C-H Amidation of Benzene Derivatives
with Sulfonamides and Trifluoroacetamide. A Comparative Study
Tracy M.M. Maiden, Stephen Swanson, Panayiotis A. Procopiou, and Joseph P.A. Harrity
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02481 • Publication Date (Web): 03 Nov 2016
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Oxazoline Promoted Rh-Catalyzed C-H Amidation of Benzene Derivatives with
Sulfonamides and Trifluoroacetamide. A Comparative Study
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Tracy M. M. Maiden,a Stephen Swanson,b Panayiotis A. Procopioub and Joseph P. A.
Harritya,*
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aDepartment of Chemistry, University of Sheffield, Brook Hill, S3 7HF, UK
bGlaxoSmithKline, Stevenage, Hertfordshire, SG1 2NY, UK
j.harrity@sheffield.ac.uk
Abstract
A Rhꢀcatalyzed orthoꢀamidation of 2ꢀaryloxazolines offers an efficient and direct route to a
range of sulfonamides. The scope of the reaction is very broad with respect to sulfonamide
substrate, but the position and electronic nature of the substituents on the aryl moiety of the
oxazoline lead to a surprising modulation of reactivity. The reactivity of sulfonamides in
comparison to trifluoroacetamide is compared, the latter undergoing Rhꢀcatalyzed amidation
more rapidly.
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Introduction
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Sulfonamides represent an important functional group within organic chemistry as evidenced
by their prevalence within natural and nonꢀnatural compounds.1 Typical synthetic approaches
rely on the functionalization of anilines or amines with reactive sulfonyl chlorides (scheme
1a).2 BuchwaldꢀHartwig crossꢀcoupling represents a powerful and complementary CꢀN bond
forming alternative (scheme 1b). However, the methodology requires the use of a preꢀ
functionalized coupling partner in the form of a halide/pseudo halide.3 An alternative means
of introducing of the sulfonamide group is by CꢀH activation (scheme 1c). CꢀH activation has
emerged as a very successful approach towards the synthesis of complex molecular
scaffolds.4 In particular, CꢀH amidation protocols represent a powerful strategy for the
formation of C(sp2)ꢀN bonds, in which sulfonamides have been demonstrated to be successful
coupling partners.5
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Scheme 1: N-Arylsulfonamide synthetic methods
We recently disclosed an efficient and regioselective rhodiumꢀcatalyzed C-H
amidation/cyclization sequence to afford functionalized quinazoline and quinazolinone
derivatives.6 We also recently described the successful applicability of our methodology on
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2ꢀsubstituted pyridines.7 Within our rhodiumꢀcatalyzed C-H amidation step, we chose the
trifluoroacetamide as the amino source because of the ease of hydrolysis of this functionality.
However, we recognized the potential of this strategy to directly deliver a range of Nꢀaryl
sulfonamides and report herein the scope of this process. Moreover, we highlight some
surprising reactivity differences with regard to the substrate amine donors and aryl acceptors.
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Our investigations were inspired by Su and coꢀworkers who demonstrated the successful Rhꢀ
catalyzed reaction of 2ꢀphenyl pyridines with an array of functionalized sulfonamides.8 In
addition, a small selection of aryl oxazolines were disclosed (4 examples) that were employed
in conjunction with paraꢀtoluenesulfonamide. Given the potential for oxazolines to be used
as surrogates for carboxylic acid derivatives,9 we decided to fully investigate the scope of the
oxazoline directed rhodiumꢀcatalyzed C-H amidation of aromatic compounds with aryl
sulfonamides.
Results and Discussion
Our previous work had highlighted that oxazolines promote an unusually mild amidation
reaction when trifluoroacetamide is employed; the product yields are similar when the
reactions are conducted at 100 °C or 40 °C.6 Furthermore, the reaction was found to proceed
quite efficiently at room temperature. We decided to carry out a similar investigation using
paraꢀtoluenesulfonamide, in order to identify an optimal reaction temperature and to compare
the reactivity of this amine source with trifluoroacetamide. As depicted in scheme 2, the
reaction was found to proceed well at 100 °C affording the C-H amidated product in an
excellent yield of 92%. In contrast to trifluoroacetamide however, lowering the temperature
to 40 °C led to a significant drop in yield. Moreover, conducting the reaction at 25 °C
resulted in a poor isolated yield of 22% – highlighting the sluggish nature of this substrate at
ambient temperature. Overall, we were interested to note that the reaction conditions required
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to afford efficient Cꢀ(sp2)N bond formation were harsher in the case of the sulfonamide
versus trifluoroacetamide, implicating a key role of the amine donor’s role in dictating
reactivity.
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Scheme 2: Comparative study of reaction temperature on the reactivity of
trifluoroacetamide and para-toluenesulfonamide
We next decided to investigate the nature of sulfonamides which could be used in
conjunction with aryl oxazolines in the rhodiumꢀpromoted system (scheme 3). Pleasingly, a
range of aromatic sulfonamides could be used alongside the gemꢀdimethyl oxazoline
directing group at the optimum reaction temperature of 100 °C and only monoꢀaminated
products were observed in all cases. Under the standard reaction conditions both electron
withdrawing and electron donating functionalities were well tolerated by the sulfonamide
group. Additionally, orthoꢀ, metaꢀ and paraꢀmethyl functionalized sulfonamides afforded the
C-H amidated products in good to excellent yield. Finally, alkyl sulfonamides were found to
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be viable substrates in combination with both the unsubstituted and gemꢀdimethyl oxazoline
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directing group.
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Scheme 3: Sulfonamide scope
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H2NR2 (1.0 eq.)
[Cp*RhCl2]2 (2.5 mol %)
R1
R1
O
R1
R1
O
AgSbF6 (10 mol %)
N
N
PhI(OAc)2 (1.5 eq.)
CH2Cl2, 16 h
NHR2
R1 = H, Me
100 °C, sealed tube
O
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Me
Me
N
N
N
N
NH
NH
S
NH
S
NH
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CF3
OMe
Br
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O
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Me
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Me
Me
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O
7; 71%
8; 83%
9; 86%
10; 64%
We then turned our attention to the functionalities on the aryl oxazoline (scheme 4).
Pleasingly under the optimum reaction conditions, we found a small selection of
electronically distinct aryl oxazolines were well tolerated. Both electron poor and electron
rich aryl systems were successful, as demonstrated by the methoxyꢀ and trifluoromethylꢀ
substituted examples (12 and 13).
Scheme 4: Oxazoline scope
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In an effort to demonstrate utility of this particular transformation we targeted the synthesis
of sulfonamide 16, a known potassium ion channel inhibitor.10 We envisaged that the
employment of our optimal C-H amidation conditions for sulfonamides would readily deliver
16 from 3ꢀmethoxy substituted aryl oxazoline 15 and 3ꢀ(trifluoromethyl)benzenesulfonamide
(scheme 5). In the event, we were surprised to find that this reaction failed to proceed, even
after heating over an extended time period. In order to rule out the sulfonamide as the source
of low reactivity, 3ꢀ(trifluoromethyl)benzenesulfonamide was reacted with 2ꢀphenyl
oxazoline 17. This reaction proceeded smoothly to afford the corresponding product 18 in an
excellent yield of 83%. We next decided to further examine the reactivity of 3ꢀmethoxy
substituted aryl oxazoline 15 by subjecting it to our standard reaction conditions with
trifluoroacetamide. Interestingly, in this case we observed only a poor yield of 20% of
product 19. Finally, 4ꢀmethoxyphenyl oxazoline 20 was found to show good reactivity
towards 3ꢀ(trifluoromethyl)benzenesulfonamide, affording compound 21 in 62% yield. Taken
together, these results indicated that the C-H amidation reaction could be retarded by the
presence of an electron donating substituent situated meta to the oxazoline directing group.
Scheme 5: Initial investigations into the effect of electron donating groups on oxazoline
reactivity
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In order to explore the generality of this observation, an array of paraꢀ and metaꢀsubstituted
aryl oxazolines bearing both electron donating and electron withdrawing functionalities were
prepared. For the purpose of comparison, each substrate was subjected to the optimum
reaction conditions with paraꢀtoluenesulfonamide at 100 °C and trifluoroacetamide at 40 °C.
As shown in scheme 6 and in a similar manner to above, the incorporation of an electron
donating methoxy group paraꢀ to the oxazoline was highly successful with both amino
sources delivering the corresponding products in high yield. In contrast, when the methoxy
group was meta- to the directing group the reaction was significantly retarded. These data
clearly show that the positioning of the functional group can have a profound effect on
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reactivity. Next, the reactivity of methyl substituted oxazolines was investigated. We
observed better overall reactivity in these cases, however, the combination of a metaꢀmethyl
group and the less reactive sulfonamide resulted in product 29 being generated in rather
modest yield. Switching to an electron withdrawing ester substituent, we were interested to
note that both paraꢀ and metaꢀfunctionalized examples afforded similar reaction outcomes.
Both substrates were reactive and the desired compounds were isolated in good yields.
Finally, we wanted to explore the effect of a fluorine group on the C-H amidation reaction. In
this series, the paraꢀfunctionalized example produced the C-H amidated products with both
amino sources in good to excellent yield. However, in the case of the metaꢀfunctionalized
example, we observed insertion at the more hindered position between the oxazoline and the
fluoride. This regioselectivity was surprising as we had not observed the analogous
regiochemical C-H insertion in any of our other metaꢀsubstituted examples. The outcome was
independent of amine source and both paraꢀtoluenesulfonamide and trifluoroacetamide
inserted into the 2ꢀposition of the aryl ring with high selectivity and yield. The structure of
the C-H amination product arising from the reaction between 3ꢀfluro substituted oxazoline
and paraꢀtoluenesulfonamide was unambiguously confirmed by Xꢀray crystallography.11
Notably, selective insertion into the 2ꢀposition of similar metaꢀfluoro scaffolds by C-H
activation methodologies has received only scant precedent. Reports by Sanford and others
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demonstrated insertion into the 6ꢀposition under palladiumꢀcatalyzed C-H activation.12
A
single report by Yu described a mixture of insertion products (1:1.5 C2:C6) when Nꢀ(2ꢀ(4,5ꢀ
dihydrooxazolꢀ2ꢀyl)phenyl)ꢀ2ꢀfluorobenzamide is subjected to C-H amidation conditions
with stoichiometric Cu(OAc)2 and paraꢀtoluenesulfonamide.13
Scheme 6: Comparative study of meta-substituted versus para-substituted substrates
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H2NR2(1.0 eq.)
4
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[Cp*RhCl2]2 (2.5 mol %)
O
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AgSbF6 (10 mol %)
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N
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R1
R1
PhI(OAc)2 (1.5 eq.)
CH2Cl2, 16 h
NHR2
R2 = Ts or COCF3
100 °C (sealed tube) or 40 °C
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O
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R1
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NHR2
NHR2
22; R1=Me2N; R2=Ts 0%
23; R1=Me2N; R2=COCF3 24%
24; R1=Me2N; R2=Ts 0%
25; R1=Me2N; R2=COCF3 12%
12; R1=MeO; R2=Ts 72%
26; R1=MeO; R2=COCF3 100%
27; R1=MeO; R2=Ts 0%
19; R1=MeO; R2=COCF3 20%
11; R1=Me; R2=Ts 78%
28; R1=Me; R2=COCF3 84%
29; R1=Me; R2=Ts 47%
30; R1=Me; R2=COCF3 72%
31; R1=MeO2C; R2=Ts 73%
32; R1=MeO2C; R2=COCF3 92% 34; R1=MeO2C; R2=COCF3 77%
33; R1=MeO2C; R2=Ts 57%
NHR2O
O
F
N
N
F
NHR2
35; R2 = Ts 72%
36; R2 = COCF3 97%
37; R2 = Ts 61%
38; R2 = COCF3 60%
We were interested to note that in all of the cases examined the trifluoroacetamide is superior
to that of the sulfonamide, both in terms of milder conditions and higher yield. The reactivity
and selectivity trends observed in the C-H amidation of various aromatic oxazolines with
trifluoroacetamide and sulfonamides is intriguing, and our observations highlight some
unexpected trends. In particular, we felt that the low reactivity observed in the cases of
dimethylaminoꢀfunctionalized aromatics, and the metaꢀmethoxy aromatic substrates, together
with the unusual regioselectivity observed with the meta-fluoro substrate were particularly
intriguing and warranted further investigation. Accordingly, we decided to conduct deuterium
labelling experiments and these are shown in Scheme 7.8,14 We conducted the reaction
between 3ꢀmethoxy aryloxazoline 15 and paraꢀtoluenesulfonamide in the presence of
deuterated methanol, and observed 74% mass recovery. The mixture did not contain
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amidation product, but we observed almost quantitative deuterium incorporation affording a
mixture of monoꢀ and diꢀdeuterated materials 39 and 40. This result confirms that rhodacycle
formation proceeds under the reaction conditions, but suggests that the problematic step in
the catalytic cycle is related to the formation of Rh(V)ꢀnitrenoid species B. Although the
origin of this effect await further study, it may be that the presence of an electron donating
metaꢀsubstituent (with respect to the directing group) results in a strengthening the carbonꢀ
rhodium bond in rhodacycle A retarding nitrene insertion, or that strong electron donation
reduces the propensity for formation of Rhꢀnitrenoid intermediates. In addition, running the
same reaction of 3ꢀdimethylamino aryl oxazoline 41 resulted in <5% deuterium incorporation
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(as judged by 400 MHz H NMR spectroscopy) and only recovery of the starting material,
suggesting that slow cyclometallation is occurring in this case. Finally, carrying out the
deuterium labelling experiment with the metaꢀfluoro aryloxazoline we were able to observe a
mixture which contained C-H amidation product 37 and a 1:1 mixture of recovered starting
material and mono C2 deuterated starting material. The observation of C2ꢀselective mono
deuteration indicated that it is likely that selective rhodacycle formation gives rise to the
observed product, rather than product determining nitrene insertion. We believe the selective
rhodacycle formation is a result of the enhanced acidity of the proton ortho to the fluoro
substituent.
Scheme 7: Deuterium incorporation studies and abbreviated mechanism
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Finally, in order to show the potential of this method for synthesis of functionalized scaffolds
we targeted the C-H amidation of 2ꢀchloropyridine 44 (scheme 8). This substrate underwent
smooth amidation and in high regiocontrol to generate 45.7 Subsequent hydrolysis of the
acetamide followed by the oxazoline delivered azaꢀanthranilic ester 46 in acceptable overall
yield.
Scheme 8: Synthesis of multi-functionalized heterocycles
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In conclusion, we have described the extension of our rhodiumꢀpromoted C-H amidation
conditions to sulfonamide amino sources. We found a reaction temperature of 100 °C was
key to affording efficient amidation with a range of aryl and alkyl sulfonamides, and that a
range of functionalized oxazoline scaffolds were well tolerated. Through investigation and
comparative study, we found aryl oxazolines with electron donating metaꢀsubstituents were
incompatible with the reaction system whilst their paraꢀsubstituted counterparts were highly
successful. Mechanistic studies suggested this could be due to the inhibition of the formation
of key Rh(V)ꢀnitrenoid species, or a slow nitrene insertion step. Additionally, we observed
the opposite regioselectivity of amide insertion with 3ꢀfluoro aryloxazoline and determined
this observation to be the result of regioselective rhodacycle formation.
Experimental Section
The following substrates were prepared according to a previously reported procedures 2ꢀ(pꢀ
tolyl)ꢀ4,5ꢀdihydrooxazole6,
trifluoromethylphenyl)ꢀ4,5ꢀdihydrooxazole6, 2ꢀ(4ꢀbromophenyl)ꢀ4,5ꢀdihydrooxazole6, 2ꢀ(mꢀ
tolyl)ꢀ4,5ꢀdihydrooxazole6, 2ꢀ(4ꢀfluorophenyl)ꢀ4,5ꢀdihydrooxazole6,
dihydrooxazolꢀ2ꢀyl)benzoate6 and 2ꢀ(2ꢀchloropyridinꢀ4ꢀyl)ꢀ4,5ꢀdihydrooxazole (44).7
2ꢀ(4ꢀmethoxyphenyl)ꢀ4,5ꢀdihydrooxazole
(20)6,
2ꢀ(4ꢀ
methyl
3ꢀ(4,5ꢀ
General procedure A: Amide Synthesis. To a dried round bottomed flask was added ester (1.0
eq.) and heated to 55 °C with stirring. Upon reaching the desired temperature ethanolamine
(1.5 eq.) was added slowly via syringe and the reaction was stirred for 3 h before cooling to
room temperature, and stirring for a further 18 hours. The crude reaction mixture was then
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purified by recrystallisation or flash column chromatography on silica gel eluting with
dichloromethane and methanol (1% MeOH to 20% MeOH) or ethyl acetate (100%) to afford
the amide products.
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Synthesis of N-(2-hydroxyethyl)-3-methoxybenzamide15. Following general procedure A,
using ethyl 3ꢀmethoxybenzoate (3.09 g, 17.2 mmol) and ethanolamine (1.57 g, 25.8 mmol)
the amide product was afforded as a yellow oil (3.18 g, 95%). 1H NMR (400 MHz, CDCl3): δ
7.35 (1H, s), 7.29 (2H, dd, J = 4.0, 2.5 Hz), 7.05 – 6.93 (2H, m), 3.82 – 3.77 (5H, m), 3.58
(2H, app dd, J = 10.0, 5.0 Hz); 13C{1H} NMR (100.6 MHz, CDCl3): δ 168.7, 159.9, 135.7,
129.7, 119.0, 117.9, 112.5, 62.2, 55.5, 43.0.
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Synthesis of 3-fluoro-N-(2-hydroxyethyl)benzamide16. Following general procedure A, using
ethyl 3ꢀfluorobenzoate (2.29 g, 13.6 mmol) and ethanolamine (1.25 g, 20.4 mmol) the amide
1
product was afforded as a yellow oil (1.62 g, 65%). H NMR (400 MHz, DMSOꢀd6): δ 8.53
(1H, s), 7.74 – 7.68 (1H, m), 7.65 (1H, ddd, J = 10.0, 2.5, 1.5 Hz), 7.51 (1H, td, J = 8.0, 6.0
13
Hz), 7.42 – 7.32 (1H, m), 3.51 (2H, q, J = 6.0 Hz), 3.33 (2H, q, J = 6.0 Hz); C{1H} NMR
(100.6 MHz, DMSOꢀd6): δ 164.9 (d, J = 2.0 Hz), 161.9 (d, J = 244.0 Hz), 136.9 (d, J = 6.5
Hz), 130.4 (d, J = 8.0 Hz), 123.3 (d, J = 2.5 Hz), 117.9 (d, J = 21.0 Hz), 114.0 (d, J = 22.5
Hz), 59.6, 42.3; 19F NMR (376.5 MHz, DMSOꢀd6); δ – 113.0.
General procedure B: Amide Synthesis. To a stirred solution of benzoic acid (1.0 eq.) in dry
dichloromethane (0.2 M) at 0 °C was added oxalyl chloride (3.0 eq.) and DMF (few drops).
The reaction was allowed to warm to room temperature and stirred for a period of 3 hours
before removing the solvent in vacuo. The crude residue was then dissolved in dry
dichloromethane (0.2 M) and cooled to 0 °C using an ice bath. Triethylamine (3.0 eq.) was
then added, followed by ethanolamine (3.0 eq.) via syringe. The reaction was allowed to
warm to room temperature and stir overnight. The reaction mixture was then dry loaded onto
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silica gel and purified by flash column chromatography on silica gel eluting with
dichloromethane and methanol (0 to 10% MeOH) to afford the amide products.
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Synthesis of 4-(dimethylamino)-N-(2-hydroxyethyl)benzamide. Following general procedure
B, using 4ꢀdimethylaminobenzoic acid (1.00 g, 6.05 mmol), oxalyl chloride (2.31 g, 18.2
mmol) and DMF (few drops) in dichloromethane (30 mL), then ethanolamine (1.11 g, 18.2
mmol), triethylamine (1.84 g, 18.2 mmol) and dichloromethane (30 mL) the amide product
was afforded as a colorless amorphous solid (763 mg, 61%). FTIR: vmax/ cmꢀ1 (neat) 3362
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(m), 2943 (w), 2871 (w), 1609 (m), 1521 (m), 1205 (m), 1056 (m); H NMR (400 MHz,
MeODꢀd4): δ 7.89 – 7.50 (2H, m), 6.93 – 6.52 (2H, m), 3.69 (2H, t, J = 6.0 Hz), 3.48 (2H, t, J
= 6.0 Hz), 3.00 (6H, s); 13C{1H} NMR (100.6 MHz, MeODꢀd4): δ 170.7, 154.3, 129.7, 121.9,
112.1, 61.9, 43.4, 40.2; HRMS: m/z [MH]+ C11H17N2O2 calcd. 209.1285, found 209.1288.
Synthesis of 3-(dimethylamino)-N-(2-hydroxyethyl)benzamide. Following general procedure
B, using 3ꢀdimethylaminobenzoic acid (1.00 g, 6.05 mmol), oxalyl chloride (2.31 g, 18.2
mmol) and DMF (few drops) in dichloromethane (30 mL), then ethanolamine (1.11 g, 18.2
mmol), triethylamine (1.84 g, 18.2 mmol) and dichloromethane (30 mL) the amide product
was afforded as a yellow oil (626 mg, 50%). FTIR: vmax/ cmꢀ1 (neat) 2807 (w), 1636 (m),
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1598 (m), 1350 (m), 1055 (s), 994 (s); H NMR (400 MHz, CDCl3): δ 7.29 – 7.22 (2H, m),
7.02 (1H, d, J = 8.0 Hz), 6.87 (1H, d, J = 8.0, 2.5 Hz), 6.68 (1H, br s), 3.85 – 3.80 (2H, app
13
m), 3.62 (2H, app dd, J = 10.0, 5.5 Hz), 2.99 (6H, s); C{1H} NMR (100.6 MHz, CDCl3): δ
169.6, 150.6, 135.2, 129.4, 115.8, 114.7, 111.7, 62.8, 43.2, 40.9; HRMS: m/z [MH]+
C11H17N2O2 calcd. 209.1285, found 209.1286.
Synthesis of methyl 4-((2-hydroxyethyl)carbamoyl)benzoate. Following general procedure B,
using 4ꢀ(methoxycarbonyl)benzoic acid (1.00 g, 5.55 mmol), oxalyl chloride (2.11 g, 16.6
mmol) and DMF (few drops) in dichloromethane (28 mL), then ethanolamine (1.01 g, 16.7
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mmol), triethylamine (1.68 g, 16.7 mmol) and dichloromethane (28 mL) the amide product
was afforded as a colorless amorphous solid (820 mg, 66%). FTIR: vmax/ cmꢀ1 (neat) 3330
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(w), 3287 (w), 1714 (m), 1633 (m), 1550 (m), 1283 (s), 1111 (s), 1052 (s); H NMR (400
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MHz, MeODꢀd4): δ 8.11 – 8.07 (2H, m), 7.94 – 7.90 (2H, m), 3.93 (3H, s), 3.72 (2H, t, J =
6.0 Hz), 3.52 (2H, t, J = 6.0 Hz); 13C{1H} NMR (100.6 MHz, MeODꢀd4): δ 169.5, 167.7,
139.9, 133.9, 130.6, 128.5, 61.5, 52.9, 43.7; HRMS: m/z [MH]+ C11H14NO4 calcd. 224.0917,
found 224.0920.
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General procedure C: Oxazoline Synthesis. To a dried round bottomed flask was added
amide (1.0 eq.) and dry dichloromethane (0.6 M). With stirring NEt3 (1.9 eq.) was then
added, followed by DMAP (0.2 eq.) and pꢀTsCl (1.7 eq.). The reaction mixture was allowed
to stir at room temperature overnight, before being diluted with dichloromethane and water.
The mixture was then transferred to a separating funnel and the layers partitioned. The
aqueous layer was further extracted with dichloromethane. The combined organic layers were
dried over anhydrous MgSO4, filtered and the solvent was removed in vacuo. The crude
residue was dissolved in MeOH (0.5 M) and NaOH pellets (3.0 eq.) were added in one
portion. The reaction mixture was stirred at room temperature for 1 – 3 h before removing the
solvent in vacuo. The residue was dissolved in dichloromethane and water, and transferred to
a separating funnel. The layers were partitioned and the aqueous layer was further extracted
with dichloromethane and ethyl acetate. The combined organic layers were dried over
anhydrous MgSO4, filtered and the solvent was removed in vacuo. The residue was purified
by flash column chromatography on silica gel eluting with petroleum ether (40/60) and ethyl
acetate (0% ethyl acetate to 100% ethyl acetate) to afford the oxazoline products.
Synthesis of 4-(4,5-dihydrooxazol-2-yl)-N,N-dimethylaniline. Following general procedure C,
using 4ꢀ(dimethylamino)ꢀNꢀ(2ꢀhydroxyethyl)benzamide (690 mg, 3.31 mmol), pꢀTsCl (1.07
g, 5.63 mmol), NEt3 (636 mg, 6.29 mmol), DMAP (81 mg, 0.66 mmol) and dichloromethane
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(5.5 mL), then using NaOH pellets (400 mg, 9.93 mmol) and MeOH (6.6 mL), the oxazoline
product was afforded as a colorless amorphous solid (347 mg, 55%). FTIR: vmax/ cmꢀ1 (neat)
2970 (w), 1641 (m), 1603 (s), 1530 (m), 1354 (m), 1324 (m), 1187 (s), 1159 (s), 1066 (s); 1H
NMR (400 MHz, CDCl3): δ 7.79 – 7.73 (2H, m), 6.64 – 6.58 (2H, m), 4.30 (2H, t, J = 9.5
Hz), 3.94 (1H, t, J = 9.5 Hz), 2.94 (6H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 165.0,
152.1, 129.4, 114.8, 111.0, 67.1, 54.6, 40.0; HRMS: m/z [MH]+ C11H15N2O calcd. 191.1179,
found 191.1180.
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Synthesis of 3-(4,5-dihydrooxazol-2-yl)-N,N-dimethylaniline (41). Following general
procedure C, using 3ꢀ(dimethylamino)ꢀNꢀ(2ꢀhydroxyethyl)benzamide (577 mg, 2.77 mmol),
pꢀTsCl (898 mg, 4.71 mmol), NEt3 (532 mg, 5.26 mmol), DMAP (68 mg, 0.55 mmol) and
dichloromethane (5.0 mL), then using NaOH pellets (332 mg, 8.31 mmol) and MeOH (6.0
mL), the oxazoline product 41 was afforded as a colorless amorphous solid (272 mg, 52%).
FTIR: vmax/ cmꢀ1 (neat) 2977 (w), 1646 (m), 1591 (s), 1496 (s), 1433 (s), 1367 (s), 1350 (s),
1253 (s), 1238 (s), 1066 (s); 1H NMR (400 MHz, CDCl3): δ 7.36 – 7.33 (1H, m), 7.32 – 7.27
(2H, m), 6.86 (1H, dt, J = 7.0, 2.5 Hz), 4.44 (2H, t, J = 9.5 Hz), 4.07 (2H, t, J = 9.5 Hz), 3.00
(6H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 165.5, 150.5, 129.1, 128.4, 116.5, 115.6,
112.0, 67.6, 54.9, 40.7; HRMS: m/z [MH]+ C11H15N2O calcd. 191.1179, found 191.1180.
Synthesis of 2-(3-methoxyphenyl)-4,5-dihydrooxazole (15)17. Following general procedure C,
using Nꢀ(2ꢀhydroxyethyl)ꢀ3ꢀmethoxybenzamide (1.00 g, 5.12 mmol), pꢀTsCl (1.66 g, 8.71
mmol), NEt3 (984 mg, 1.36 mmol), DMAP (125 mg, 1.02 mmol) and dichloromethane (8.5
mL), then using NaOH pellets (614 mg, 15.4 mmol) and MeOH (10.2 mL), the oxazoline
product 15 was afforded as a colorless solid (572 mg, 63%). M.p.: 60 – 61 °C (lit., 59 – 60
°C)4; 1H NMR (400 MHz, CDCl3): δ 7.49 – 7.45 (1H, m), 7.43 (1H, dd, J = 2.5, 1.5 Hz), 7.24
(1H, t, J = 8.0 Hz), 6.95 (1H, ddd, J = 8.0, 2.5, 1.0 Hz), 4.33 (2H, t, J = 9.5 Hz), 3.97 (2H, t, J
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= 9.5 Hz), 3.76 (3H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 164.5, 159.4, 129.3, 128.9,
120.5, 117.9, 112.5, 67.6, 55.3, 54.8.
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Synthesis of 2-(3-fluorophenyl)-4,5-dihydrooxazole (42). Following general procedure C,
using 3ꢀfluoroꢀNꢀ(2ꢀhydroxyethyl)benzamide (1.00 g, 5.46 mmol), pꢀTsCl (1.77 g, 9.28
mmol), NEt3 (1.05 g, 10.4 mmol), DMAP (133 mg, 1.09 mmol) and dichloromethane (9.1
mL), then using NaOH pellets (655 mg, 16.4 mmol) and MeOH (11 mL), the oxazoline
product 42 was afforded as a yellow oil (688 mg, 76%). FTIR: vmax/ cmꢀ1 (neat) 2991 (w),
2912 (w), 1649 (m), 1585 (s), 1270 (s), 1185 (s), 1055 (s), 949 (s), 842 (s), 715 (s); 1H NMR
(400 MHz, CDCl3): δ 7.71 (1H, d, J = 8.0 Hz), 7.65 – 7.58 (1H, m), 7.35 (1H, td, J = 8.0, 5.5
Hz), 7.14 (1H, td, J = 8.5, 2.5 Hz), 4.41 (2H, t, J = 9.5 Hz), 4.04 (2H, t, J = 9.5 Hz); 13C{1H}
NMR (100.6 MHz, CDCl3): δ 163.7 (d, J = 3.0 Hz), 162.6 (d, J = 246.0 Hz), 130.0 (d, J = 8.0
Hz), 124.0 (d, J = 3.0 Hz), 118.3 (d, J = 21.0 Hz), 115.3 (d, J = 23.5 Hz), 67.9, 55.0; 19F
NMR (376.5 MHz, CDCl3); δ – 112.7; HRMS: m/z [MH]+ C9H9FNO calcd. 166.0663, found
166.0664.
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Synthesis of methyl 4-(4,5-dihydrooxazol-2-yl)benzoate18. Following general procedure C,
using methyl 4ꢀ((2ꢀhydroxyethyl)carbamoyl)benzoate (650 mg, 2.91 mmol), pꢀTsCl (945 mg,
4.95 mmol), NEt3 (559 mg, 5.53 mmol), DMAP (71 mg, 0.58 mmol) and dichloromethane (5
mL), then using NaOH pellets (116 mg, 6.42 mmol) and MeOH (6 mL), the oxazoline
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product was afforded as a colorless amorphous solid (409 mg, 68%). H NMR (400 MHz,
CDCl3): δ 8.07 – 8.01 (2H, m), 8.00 – 7.93 (2H, m), 4.42 (2H, t, J = 9.5 Hz), 4.05 (2H, t, J =
9.5 Hz), 3.89 (3H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 166.5, 163.9, 132.5, 131.8,
129.6, 128.2, 67.9, 55.2, 52.4.
General procedure D: C-H Amidation. To a dried Schlenk tube was added oxazoline (2.0
eq.), [Cp*RhCl2]2 (2.5 mol %), AgSbF6 (10 mol %), PhI(OAc)2 (1.5 eq.) and sulfonamide
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(1.0 eq.). The tube was fitted with a rubber septum, and placed under an atmosphere of
nitrogen, followed by the addition of dry dichloromethane via syringe (0.1 M). The septum
was replaced by a Teflon screwcap under nitrogen flow. The reaction mixture was stirred at
40 – 45 °C for 18 h. After cooling to room temperature the solvent was removed in vacuo and
the residue was purified by flash column chromatography on silica gel eluting with petroleum
ether (40/60) followed by dichloromethane or petroleum ether (40/60) and ethyl acetate (0%
ethyl acetate to 40% ethyl acteate) to afford the aminated products.
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Synthesis of 2,2,2-trifluoro-N-[2-(4,5-dihydro-2-oxazolyl)phenyl]-acetamide (1)6. Following
general procedure D, using trifluoroacetamide (23 mg, 0.20 mmol) and 2ꢀphenylꢀ2ꢀoxazoline
(59 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7 mg, 0.02 mmol) and
PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2 mL) at 40 °C for 16 h, product 1 was
isolated as a colorless solid (48 mg, 92%). M.p.: 74 – 75 °C (pentane); FTIR: vmax/ cmꢀ1
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(neat) 3054 (w), 2915 (w), 1734 (s), 1260 (s); H NMR (400 MHz, CDCl3): δ 13.69 (1H, s),
8.68 (1H, dd, J = 8.5 and 1.0 Hz), 7.90 (1H, dd, J = 8.5 and 1.0 Hz), 7.52 (1H, t, J = 8.5 Hz),
7.21 (1H, t, J = 8.5 Hz), 4.43 (2H, t, J = 9.5 Hz), 4.16 (2H, t, J = 9.5 Hz); 13C{1H} NMR
(100.6 MHz, CDCl3): δ 164.7, 155.7 (q, J = 37.5 Hz), 137.7, 132.9, 129.4, 124.5, 120.3,
116.1 (q, J = 288.5 Hz), 114.5, 66.8, 54.5; 19F NMR (376.5 MHz, CDCl3); δ – 76.0; HRMS:
m/z [MH]+ C11H10N2O2F3 calcd. 259.0694, found 259.0704.
Synthesis of N-[2-(4,5-dihydro-2-oxazolyl)phenyl]-4-methyl-benzenesulfonamide (2)8.
Following general procedure D, using pꢀtoluenesulfonamide (34 mg, 0.20 mmol) and 2ꢀ
phenylꢀ2ꢀoxazoline (59 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7
mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2 mL) at 100 °C for
16 h, product 2 was isolated as a colorless solid (58 mg, 92%). M.p.: 191 – 193 °C (lit.,19 195
– 199 °C); 1H NMR (400 MHz, CDCl3): δ 12.36 (1H, s), 7.78 – 7.70 (3H, m), 7.64 (1H, dd, J
= 8.0 and 1.0 Hz), 7.37 – 7.29 (1H, m), 7.20 (2H, d, J = 8.0 Hz), 6.99 (1H, td, J = 8.0 and 1.0
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Hz), 4.39 – 4.31 (2H, m), 4.16 – 4.08 (2H, m), 2.34 (3H, s); 13C{1H} NMR (100.6 MHz,
CDCl3): δ 164.5, 143.5, 139.1, 136.9, 132.4, 129.5, 129.4, 127.2, 122.3, 117.8, 113.5, 66.5,
54.5, 21.5.
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Synthesis
of
N-[2-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-4-methoxy-
benzenesulfonamide (3). Following general procedure D, using 4ꢀmethoxybenzene
sulfonamide (37 mg, 0.20 mmol) and 4,4ꢀdimethylꢀ2ꢀphenylꢀ2ꢀoxazoline (70 mg, 0.40 mmol)
with [Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg,
0.30 mmol) in dichloromethane (2 mL) at 100 °C for 16 h, product 3 was isolated as a
colorless solid (46 mg, 64%). M.p.: 106 – 108 °C (dichloromethane/petroleum ether
(40/60)); FTIR: vmax/ cmꢀ1 (neat) 2974 (w), 2849 (w), 1336 (s), 1157 (s); H NMR (400 MHz,
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CDCl3): δ 12.22 (1H, s), 7.79 – 7.68 (4H, m), 7.39 – 7.31 (1H, m), 7.04 – 6.97 (1H, m), 6.87
– 6.80 (2H, m), 4.02 (2H, s), 3.79 (3H, s), 1.40 (6H, s); 13C{1H} NMR (100.6 MHz, CDCl3):
δ 162.1, 161.6, 139.1, 132.4, 131.7, 129.4, 129.3, 122.7, 118.8, 114.3, 114.1, 78.1, 68.1, 55.6,
28.6; HRMS: m/z [MH]+ C18H21N2O4S calcd. 361.1222, found 361.1237.
Synthesis
of
N-[2-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-4-bromo-
benzenesulfonamide (4). Following general procedure D, using 4ꢀbromobenzene sulfonamide
(47 mg, 0.20 mmol) and 4,4ꢀdimethylꢀ2ꢀphenylꢀ2ꢀoxazoline (70 mg, 0.40 mmol) with
[Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30
mmol) in dichloromethane (2 mL) at 100 °C for 16 h, product 4 was isolated as a colorless
solid (59 mg, 72%). M.p.: 111 – 114 °C (dichloromethane/petroleum ether (40/60)); FTIR:
vmax/ cmꢀ1 (neat) 3099 (w), 2961 (w), 2890 (w), 1336 (s), 1160 (s), 1064 (s); H NMR (400
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MHz, CDCl3): δ 12.37 (1H, s), 7.76 – 7.65 (4H, m), 7.55 – 7.49 (2H, m), 7.41 – 7.34 (1H, m),
7.08 – 7.01 (1H, m), 4.03 (2H, s), 1.39 (6H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 161.9,
139.0, 138.8, 132.5, 132.2, 129.5, 128.8, 127.7, 123.2, 118.8, 114.5, 78.2, 68.1, 28.6; HRMS:
m/z [MH]+ C17H18N2O3S79Br calcd. 409.0222, found 409.0216.
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Synthesis
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N-(2-(4,4-dimethyl-1,5-dihydrooxazol-2-yl)phenyl)-4-
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(trifluoromethyl)benzenesulfonamide (5). Following general procedure D, using 4ꢀ
trifluoromethylbenzene sulfonamide (45 mg, 0.20 mmol) and 4,4ꢀdimethylꢀ2ꢀphenylꢀ2ꢀ
oxazoline (70 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7 mg, 0.02
mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2 mL) at 100 °C for 16 h,
product 5 was isolated as a colorless solid (46 mg, 76%). M.p.: 80 – 81 °C
(dichloromethane/petroleum ether (40/60)); FTIR: vmax/ cmꢀ1 (neat) 2980 (w), 1628 (m), 1506
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(m), 1340 (m), 1321 (s), 1161 (s), 1129 (s), 1059 (s); H NMR (400 MHz, CDCl3): δ 12.50
(1H, s), 7.94 (2H, d, J = 8.0 Hz), 7.77 – 7.72 (2H, m), 7.65 (2H, d, J = 8.0 Hz), 7.39 (1H,
ddd, J = 8.5, 7.5, 1.5 Hz), 7.06 (1H, td, J = 8.0, 1.0 Hz), 4.03 (2H, s), 1.39 (6H, s); 13C{1H}
NMR (100.6 MHz, CDCl3): δ 162.0, 143.6, 138.6, 134.5 (q, J = 33.0 Hz), 132.6, 129.5,
127.7, 126.1 (q, J = 3.5 Hz), 123.4, 123.3 (q, J = 273.0 Hz), 118.9, 114.5, 78.2, 68.1, 28.6;
19F NMR (376.5 MHz; CDCl3): δ – 63.1; HRMS: m/z [MH]+ C18H18N2O3F3S calcd.
399.0990, found 399.0986.
Synthesis
of
N-[2-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-4-methyl-
benzenesulfonamide (6)8. Following general procedure D, using pꢀtoluenesulfonamide (34
mg, 0.20 mmol) and 4,4ꢀdimethylꢀ2ꢀphenylꢀ2ꢀoxazoline (70 mg, 0.40 mmol) with
[Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30
mmol) in dichloromethane (2 mL) at 100 °C for 16 h, product 6 was isolated as a colorless
solid (43 mg, 62%). M.p.: 104 – 106 °C (dichloromethane/petroleum ether (40/60)); 1H NMR
(400 MHz, CDCl3): δ 12.29 (1H, s), 7.71 (4H, m), 7.42 – 7.31 (1H, m), 7.17 (2H, d, J = 8.5
Hz), 7.07 – 6.96 (1H, m), 4.02 (2H, s), 2.33 (3H, s), 1.42 (6H, s); 13C{1H} NMR (100.6 MHz,
CDCl3): δ 161.9, 143.6, 139.3, 137.1, 132.4, 129.5, 129.3, 127.3, 122.7, 118.8, 114.3, 78.1,
68.1, 28.6, 21.6.
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Synthesis of N-(2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)phenyl)-3-methylbenzenesulfonamide
(7). Following general procedure D, using 3ꢀmethylbenzene sulfonamide (39 mg, 0.20 mmol)
and 4,4ꢀdimethylꢀ2ꢀphenylꢀ2ꢀoxazoline (70 mg, 0.20 mmol) with [Cp*RhCl2]2 (3 mg, 0.005
mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2
mL) at 100 °C for 16 h, product 7 was isolated as a colorless solid (49 mg, 71%). M.p.: 98 –
99 °C (dichloromethane/petroleum ether (40/60)); FTIR: vmax/ cmꢀ1 (neat) 2971 (w), 1631
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(m), 1500 (m), 1340 (s), 1280 (m), 1161 (s), 1062 (s); H NMR (400 MHz, CDCl3): δ 12.30
(1H, s), 7.76 – 7.69 (2H, m), 7.65 – 7.63 (1H, m), 7.62 – 7.59 (1H, m), 7.36 (1H, ddd, J = 8.5,
7.5, 1.5 Hz), 7.29 – 7.23 (2H, m), 7.01 (1H, ddd, J = 8.5, 7.5, 1.0 Hz), 4.02 (2H, s), 2.32 (3H,
s), 1.39 (6H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 161.9, 139.9, 139.2, 139.0, 133.6,
132.4, 129.3, 128.7, 127.5, 124.4, 122.8, 118.8, 114.4, 78.1, 68.1, 28.6, 21.4; HRMS: m/z
[MH]+ C18H21N2O3S calcd. 345.1273, found 345.1288.
Synthesis of N-(2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)phenyl)-2-methylbenzenesulfonamide
(8). Following general procedure D, using 2ꢀmethylbenzene sulfonamide (34 mg, 0.20 mmol)
and 4,4ꢀdimethylꢀ2ꢀphenylꢀ2ꢀoxazoline (70 mg, 0.20 mmol) with [Cp*RhCl2]2 (3 mg, 0.005
mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2
mL) at 100 °C for 16 h, product 8 was isolated as a colorless solid (57 mg, 83%). M.p.: 96 –
97 °C (dichloromethane/petroleum ether (40/60)); FTIR: vmax/ cmꢀ1 (neat) 2967 (w), 1631
(m), 1500 (m), 1337 (s), 1270 (s), 1158 (s), 1136 (s), 1056 (s), 1043 (s); 1H NMR (400 MHz,
CDCl3): δ 12.64 (1H, s), 8.12 (1H, dd, J = 8.0, 1.5 Hz), 7.74 (1H, dd, J = 8.0, 1.5 Hz), 7.56
(1H, dd, J = 8.5, 1.0 Hz), 7.39 (1H, td, J = 7.5, 1.5 Hz), 7.33 – 7.24 (2H, m), 7.21 (1H, d, J =
7.5 Hz), 6.95 (1H, ddd, J = 8.5, 7.5, 1.0 Hz), 4.06 (2H, s), 2.66 (3H, s), 1.41 (6H, s); 13C{1H}
NMR (100.6 MHz, CDCl3): δ 162.0, 139.1, 137.8, 137.6, 133.0, 132.7, 132.5, 130.3, 129.4,
126.0, 121.8, 116.3, 112.8, 78.1, 68.1, 28.6, 20.2; HRMS: m/z [MH]+ C18H21N2O3S calcd.
345.1273, found 345.1270.
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Synthesis of N-[2-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-4-methanesulfonamide (9).
Following general procedure D, using methane sulfonamide (19 mg, 0.20 mmol) and 4,4ꢀ
dimethylꢀ2ꢀphenylꢀ2ꢀoxazoline (70 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005 mmol),
AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2 mL) at
100 °C for 16 h, product 9 was isolated as a colorless solid (46 mg, 86%). M.p.: 86 – 88 °C
(dichloromethane/petroleum ether (40/60)); FTIR: vmax/ cmꢀ1 (neat) 2971 (w), 2872 (w), 1322
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(m), 1142 (s), 1047 (s); H NMR (400 MHz, CDCl3): δ 12.01 (1H, s), 7.85 (1H, dd, J = 8.0
and 1.5 Hz), 7.72 (1H, dd, J = 8.5 and 1.0 Hz), 7.50 – 7.40 (1H, m), 7.16 – 7.06 (1H, m), 4.07
(2H, s), 3.01 (3H, s), 1.39 (6H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 161.9, 139.4, 132.7,
129.7, 122.8, 118.1, 114.1, 78.2, 68.1, 39.9, 28.6; HRMS: m/z [MH]+ C12H17N2O3S calcd.
269.0960, found 269.0959.
Synthesis of N-(2-(4,5-dihydrooxazol-2-yl)phenyl)methanesulfonamide (10). Following
general procedure D, using methane sulfonamide (19 mg, 0.20 mmol) and 2ꢀphenylꢀ2ꢀ
oxazoline (59 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7 mg, 0.02
mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2 mL) at 100 °C for 16 h,
product 10 was isolated as a colorless solid (31 mg, 64%). M.p.: 149 – 150 °C
(dichloromethane/petroleum ether (40/60)); FTIR: vmax/ cmꢀ1 (neat) 1634 (m), 1583 (m), 1494
(m), 1319 (s), 1251 (s), 1142 (s), 1055 (s); 1H NMR (400 MHz, CDCl3): δ 12.11 (1H, s), 7.89
(1H, dd, J = 8.0, 1.5 Hz), 7.75 (1H, dd, J = 8.5, 1.0 Hz), 7.52 – 7.43 (1H, app m), 7.13 (1H,
td, J = 8.0, 1.0 Hz), 4.42 (2H, t, J = 9.5 Hz), 4.15 (2H, t, J = 9.5 Hz), 3.05 (3H, s); 13C{1H}
NMR (100.6 MHz, CDCl3): δ 164.7, 139.5, 132.9, 129.9, 122.6, 117.4, 113.6, 66.7, 54.6,
40.0; HRMS: m/z [MH]+ C10H13N2O3S calcd. 241.0641, found 241.0647.
Synthesis of N-(2-(4,5-dihydrooxazol-2-yl)-5-methylphenyl)-4-methylbenzenesulfonamide
(11)8. Following general procedure D, using pꢀtoluenesulfonamide (34 mg, 0.20 mmol) and
2ꢀ(pꢀtolyl)ꢀ4,5ꢀdihydrooxazole (65 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005 mmol),
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AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2 mL) at
100 °C for 16 h, product 11 was isolated as a colorless solid (52 mg, 78%). M.p.: 117 –118
°C (dichloromethane/petroleum ether (40/60)); FTIR: vmax/ cmꢀ1 (neat) 2950 (w), 1641 (m),
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1591 (m), 1507 (m), 1360 (m), 1324 (s), 1263 (s), 1149 (s), 1058 (s); H NMR (400 MHz,
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CDCl3): δ 12.30 (1H, s), 7.74 (2H, d, J = 8.0 Hz), 7.60 (1H, d, J = 8.0 Hz), 7.47 (1H, s), 7.20
(2H, d, J = 8.0 Hz), 6.80 (1H, dd, J = 8.0, 1.0 Hz), 4.32 (2H, t, J = 9.5 Hz), 4.10 (2H, t, J =
9.5 Hz), 2.34 (3H, s), 2.30 (3H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 164.5, 143.6,
143.3, 139.1, 137.1, 129.6, 129.2, 127.3, 123.4, 118.5, 111.2, 66.5, 54.5, 22.0, 21.6; HRMS:
m/z [MH]+ C17H19N2O3S calcd. 331.1111, found 331.1117.
Synthesis of N-(2-(4,5-dihydrooxazol-2-yl)-5-methoxyphenyl)-4-methylbenzenesulfonamide
(12). Following general procedure D, using pꢀtoluenesulfonamide (34 mg, 0.20 mmol) and 2ꢀ
(4ꢀmethoxyphenyl)ꢀ4,5ꢀdihydrooxazole (71 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005
mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2
mL) at 100 °C for 16 h, product 12 was isolated as a colorless oil (50 mg, 72%). FTIR: vmax
/
cmꢀ1 (neat) 2970 (w), 1633 (s), 1606 (m), 1573 (s), 1512 (s), 1333 (s), 1142 (s), 1067 (s),
1036 (s); 1H NMR (400 MHz, CDCl3): δ 12.50 (1H, s), 7.76 (2H, d, J = 8.0 Hz), 7.63 (1H, d,
J = 9.0 Hz), 7.21 (1H, s), 7.20 – 7.17 (2H, app m), 6.50 (1H, dd, J = 9.0, 2.5 Hz), 4.31 (2H, t,
13
J = 9.5 Hz), 4.08 (2H, t, J = 9.5 Hz), 3.77 (3H, s), 2.34 (3H, s); C{1H} NMR (100.6 MHz,
CDCl3): δ 164.5, 162.7, 143.7, 141.0, 137.0, 130.8, 129.6, 127.4, 108.8, 106.5, 102.8, 66.4,
55.5, 54.4, 21.6; HRMS: m/z [MH]+ C17H19N2O4S calcd. 347.1060, found 347.1068.
Synthesis
of
N-(2-(4,5-dihydrooxazol-2-yl)-5-(trifluoromethyl)phenyl)-4-
methylbenzenesulfonamide (13). Following general procedure D, using pꢀtoluenesulfonamide
(34 mg, 0.20 mmol) and 2ꢀ(4ꢀtrifluoromethylphenyl)ꢀ4,5ꢀdihydrooxazole (86 mg, 0.40 mmol)
with [Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg,
0.30 mmol) in dichloromethane (2 mL) at 100 °C for 16 h, product 13 was isolated as a
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colorless solid (51 mg, 66%). M.p.: 160 – 161 °C (dichloromethane/petroleum ether (40/60));
FTIR: vmax/ cmꢀ1 (neat) 3089 (w), 2965 (w), 1646 (m), 1588 (m), 1522 (m), 1418 (s), 1321 (s),
1253 (s), 1159 (s), 1121 (s), 1083 (s), 1063 (s), 959 (s); 1H NMR (400 MHz, CDCl3): δ 12.43
(1H, s), 7.94 (1H, s), 7.85 (1H, d, J = 8.0 Hz), 7.77 (2H, d, J = 8.0 Hz), 7.25 – 7.20 (3H, m),
4.40 (2H, t, J = 9.5 Hz), 4.18 (2H, t, J = 9.5 Hz), 2.36 (3H, s); 13C{1H} NMR (100.6 MHz,
CDCl3): δ 163.7, 144.0, 139.4, 136.5, 133.85 (q, J = 33.0 Hz), 130.0, 129.7, 127.3, 123.3 (q,
J = 273.0 Hz), 118.6 (d, J = 3.5 Hz), 115.9, 114.4 (d, J = 4.0 Hz), 66.7, 54.6, 21.5; 19F NMR
(376.5 MHz; CDCl3): δ – 63.4; HRMS: m/z [MH]+ C17H16F3N2O3S calcd. 385.0828, found
385.0834.
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Synthesis of N-(5-bromo-2-(4,5-dihydrooxazol-2-yl)phenyl)-4-methylbenzenesulfonamide
(14). Following general procedure D, using pꢀtoluenesulfonamide (34 mg, 0.20 mmol) and 2ꢀ
(4ꢀbromophenyl)ꢀ4,5ꢀdihydrooxazole (90 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005
mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2
mL) at 100 °C for 16 h, product 14 was isolated as a colorless solid (64 mg, 80%). M.p.: 142
– 143 °C (dichloromethane/petroleum ether (40/60)); FTIR: vmax/ cmꢀ1 (neat) 3051 (w), 2980
(w), 1641 (s), 1593 (m), 1570 (m), 1489 (m), 1395 (m), 1357 (m), 1324 (s), 1256 (s), 1151
(s), 1086 (s), 1060 (s), 936 (s); 1H NMR (400 MHz, CDCl3): δ 12.40 (1H, s), 7.84 (1H, d, J =
2.0 Hz), 7.76 (2H, d, J = 8.0 Hz), 7.57 (1H, d, J = 8.5 Hz), 7.23 (2H, d, J = 8.0 Hz), 7.11 (1H,
13
dd, J = 8.5, 2.0 Hz), 4.35 (2H, t, J = 9.5 Hz), 4.11 (2H, t, J = 9.5 Hz), 2.36 (3H, s); C{1H}
NMR (100.6 MHz, CDCl3): δ 164.2, 144.0, 140.2, 136.7, 130.6, 129.8, 127.3, 126.9, 125.5,
120.6, 112.2, 66.7, 54.6, 21.7; HRMS: m/z [MH]+ C16H1679BrN2O3S calcd. 395.0060, found
395.0063.
Synthesis of N-(2-(4,5-dihydrooxazol-2-yl)phenyl)-3-(trifluoromethyl)benzenesulfonamide
(18). Following general procedure D, using 3ꢀ(trifluoromethyl)benzenesulfonamide (45 mg,
0.20 mmol) and 2ꢀphenylꢀ2ꢀoxazoline (59 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005
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mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2
mL) at 100 °C for 16 h, product 18 was isolated as a colorless solid (61 mg, 83%). M.p.: 140
– 141 °C (dichloromethane/petroleum ether (40/60)); FTIR: vmax/ cmꢀ1 (neat) 3087 (w), 1639
(m), 1588 (w), 1502 (m), 1433 (w), 1329 (s), 1279 (s), 1253 (s), 1154 (s), 1124 (s), 1103 (s),
1068 (s); 1H NMR (400 MHz, CDCl3): δ 12.42 (1H, s), 8.13 (1H, s), 7.98 (1H, d, J = 8.0 Hz),
7.73 (2H, dd, J = 8.0, 1.5 Hz), 7.69 (1H, dd, J = 8.0, 1.0 Hz), 7.53 (1H, t, J = 8.0 Hz), 7.42 –
7.35 (1H, m), 7.06 (1H, td, J = 8.0, 1.0 Hz), 4.35 (2H, t, J = 9.0 Hz), 4.12 (2H, t, J = 9.0 Hz);
13C{1H} NMR (100.6 MHz, CDCl3): δ 164.7, 141.1, 138.5, 132.7, 131.6 (q, J = 33.5 Hz),
130.5, 129.7, 129.6, 129.5 (q, J = 3.5 Hz), 124.4 (q, J = 4.0 Hz), 123.5, 123.3 (q, J = 273.0
Hz), 119.0, 114.5, 66.7, 54.5; 19F NMR (376.5 MHz; CDCl3): δ – 62.9; HRMS: m/z [MH]+
C16H14F3N2O3S calcd. 371.0672, found 371.0676.
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Synthesis of N-(2-(4,5-dihydrooxazol-2-yl)-4-methoxyphenyl)-2,2,2-trifluoroacetamide (19).
Following general procedure D, using trifluoroacetamide (23 mg, 0.20 mmol) and 2ꢀ(3ꢀ
methoxyphenyl)ꢀ4,5ꢀdihydrooxazole (43 mg, 0.24 mmol) with [Cp*RhCl2]2 (3 mg, 0.005
mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2
mL) at 100 °C for 16 h, product 19 was isolated as a colorless solid (12 mg, 20%). M.p.: 125
– 126 °C (pentane); FTIR: vmax/ cmꢀ1 (neat) 2975 (w), 1712 (m), 1601 (m), 1558 (m), 1372
1
(m), 1276 (m), 1218 (m), 1131 (s), 1058 (s); H NMR (400 MHz, CDCl3): δ 13.40 (1H, s),
8.60 (1H, d, J = 9.0 Hz), 7.40 (1H, d, J = 3.0 Hz), 7.05 (1H, dd, J = 9.0, 3.0 Hz), 4.42 (2H, t,
J = 9.5 Hz), 4.15 (2H, t, J = 9.5 Hz), 3.82 (3H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ
164.5, 156.0, 155.2 (q, J = 37.5 Hz), 131.1, 121.8, 118.4, 116.2 (q, J = 288.5 Hz), 115.7,
114.1, 66.8, 55.7, 54.6; 19F NMR (376.5 MHz; CDCl3): δ – 75.9; HRMS: m/z [MH]+
C12H12F3N2O3 calcd. 289.0795, found 289.0794.
Synthesis
of
N-(2-(4,5-dihydrooxazol-2-yl)-5-methoxyphenyl)-3-
(trifluoromethyl)benzenesulfonamide (21). Following general procedure D, using 3ꢀ
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(trifluoromethyl)benzenesulfonamide (45 mg, 0.20 mmol) and 2ꢀ(3ꢀmethoxyphenyl)ꢀ4,5ꢀ
dihydrooxazole (71 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7 mg,
0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2 mL) at 100 °C for 16
h, product 21 was isolated as a colorless solid (50 mg, 62%). M.p.: 152 – 153 °C
(dichloromethane/petroleum ether (40/60)); FTIR: vmax/ cmꢀ1 (neat) 3081 (w), 2977 (w), 1644
(m), 1610 (m), 1577 (m), 1514 (m), 1370 (m), 1319 (s), 1260 (m), 1154 (s), 1109 (s), 1061
(s), 1035 (s); 1H NMR (400 MHz, CDCl3): δ 12.62 (1H, s), 8.16 (1H, s), 8.00 (1H, d, J = 8.0
Hz), 7.74 (1H, d, J = 8.0 Hz), 7.64 (1H, dd, J = 9.0 Hz), 7.55 (1H, t, J = 8.0 Hz), 7.22 (1H, d,
J = 2.5 Hz), 6.56 (1H, dd, J = 9.0, 2.5 Hz), 4.33 (2H, t, J = 9.5 Hz), 4.09 (2H, t, J = 9.5 Hz),
3.80 (3H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 164.6, 162.8, 141.1, 140.3, 131.6 (q, J =
33.5 Hz), 130.9, 130.5, 129.8, 129.5 (q, J = 3.5 Hz), 124.5 (q, J = 3.5 Hz), 123.3 (q, J = 273.0
Hz), 109.7, 107.2, 103.8, 66.6, 55.6, 54.2; 19F NMR (376.5 MHz; CDCl3): δ – 62.9; HRMS:
m/z [MH]+ C17H16F3N2O4S calcd. 401.0777, found 401.0784.
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Synthesis
of
N-(2-(4,5-dihydrooxazol-2-yl)-5-(dimethylamino)phenyl)-2,2,2-
trifluoroacetamide (23). Following general procedure D, using trifluoroacetamide (23 mg,
0.20 mmol) and 4ꢀ(4,5ꢀdihydrooxazolꢀ2ꢀyl)ꢀN,Nꢀdimethylaniline (46 mg, 0.24 mmol) with
[Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30
mmol) in dichloromethane (2 mL) at 40 °C for 16 h, product 26 was isolated as a colorless
solid (15 mg, 24%). M.p.: 132 – 133 °C (pentane); FTIR: vmax/ cmꢀ1 (neat) 2883 (w), 1710
(m), 1616 (m), 1580 (m), 1535 (m), 1370 (s), 1238 (m), 1149 (s), 1121 (s), 1063 (s); 1H NMR
(400 MHz, CDCl3): δ 13.84 (1H, s), 8.08 (1H, d, J = 2.5 Hz), 7.69 (1H, d, J = 9.0 Hz), 6.45
(1H, dd, J = 2.5, 9.0 Hz), 4.35 (2H, t, J = 9.5 Hz), 4.08 (2H, t, J = 9.5 Hz), 3.05 (6H, s);
13C{1H} NMR (100.6 MHz, CDCl3): δ 165.1, 155.8 (app d, J = 37.5 Hz), 153.0, 139.0, 130.3,
116.1 (app d, J = 288.5 Hz), 107.3, 103.0, 102.4, 66.4, 54.2, 40.2; 19F NMR (376.5 MHz,
CDCl3): δ – 76.0; HRMS: m/z [MH]+ C13H15F3N3O2 calcd. 302.1111, found 302.1111.
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Synthesis
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N-(2-(4,5-dihydrooxazol-2-yl)-4-(dimethylamino)phenyl)-2,2,2-
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trifluoroacetamide (25). Following general procedure D, using trifluoroacetamide (23 mg,
0.20 mmol) and 3ꢀ(4,5ꢀdihydrooxazolꢀ2ꢀyl)ꢀN,Nꢀdimethylaniline (46 mg, 0.24 mmol) with
[Cp*RhCl2]2 (3 mg, 0.005 mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30
mmol) in dichloromethane (2 mL) at 40 °C for 16 h, product 26 was isolated as an orange
solid (8 mg, 12%). M.p.: 119 – 120 °C (pentane); FTIR: vmax/ cmꢀ1 (neat) 3006 (w), 2982 (w),
1712 (m), 1597 (m), 1539 (m), 1264 (m), 1139 (s); 1H NMR (400 MHz, CDCl3): δ 13.32 (1H,
s), 8.56 (1H, d, J = 9.0 Hz), 7.23 (1H, d, J = 2.5 Hz), 6.89 (1H, dd, J = 9.0, 2.5 Hz), 4.42 (2H,
t, J = 9.5 Hz), 4.16 (2H, t, J = 9.5 Hz), 2.98 (6H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ
164.8, 154.6 (app d, J = 37.0 Hz), 147.0, 127.6, 121.5, 116.3, 116.2 (app d, J = 288.5 Hz),
115.3, 112.5, 66.6, 54.4, 40.7; 19F NMR (376.5 MHz, CDCl3): δ – 75.8; HRMS: m/z [MH]+
C13H14F3N3O2 calcd. 302.1111, found 302.1115.
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Synthesis of 2,2,2-trifluoro-N-[2ꢀ(4ꢀmethoxyphenyl)ꢀ4,5ꢀdihydroꢀoxazole]-acetamide (26)6.
Following general procedure D, using trifluoroacetamide (23 mg, 0.20 mmol) and 2ꢀ(4ꢀ
methoxyphenyl)ꢀ4,5ꢀdihydroꢀoxazole (71 mg, 0.400 mmol) with [Cp*RhCl2]2 (3 mg, 0.005
mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2
mL) at 40 °C for 16 h, product 26 was isolated as a colorless solid (57 mg, 100%). M.p.: 103
– 104 °C (pentane); FTIR: vmax/ cmꢀ1 (neat) 3117 (w), 2979 (w), 1714 (m), 1637 (m), 1181
1
(s), 1145 (s); H NMR (400 MHz, CDCl3): δ 13.84 (1H, s), 8.31 (1H, d, J = 2.5 Hz), 7.79
(1H, d, J = 8.5 Hz), 6.73 (1H, dd, J = 8.5, 2.5 Hz), 4.39 (2H, t, J = 9.5 Hz), 4.12 (2H, t, J =
9.5 Hz), 3.87 (3H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 164.7, 162.9, 155.8 (q, J = 37.5
Hz), 139.4, 130.6, 116.0 (q, J = 288.5 Hz), 111.0, 107.4, 105.3, 66.6, 55.7, 54.3; 19F NMR
(376.5 MHz, CDCl3): δ – 76.0; HRMS: m/z [MH]+ C12H12N2O3F3 calcd. 289.0800, found
289.0799.
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Synthesis of 2,2,2-trifluoro-N-[2ꢀ(4ꢀmethylphenyl)ꢀ4,5ꢀdihydroꢀoxazole]-acetamide (28)8.
Following general procedure D, using trifluoroacetamide (23 mg, 0.20 mmol) and 4,5ꢀ
dihydroꢀ2ꢀ(4ꢀmethylphenyl)ꢀoxazole (65 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005
mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2
mL) at 40 °C for 16 h, product 28 was isolated as a colorless solid (46 mg, 84%). M.p.: 120 –
121 °C (pentane); FTIR: vmax/ cmꢀ1 (neat) 3046 (w), 2958 (w), 1721 (s), 1637 (s), 1153 (s); 1H
NMR (400 MHz, CDCl3): δ 13.66 (1H, s), 8.52 (1H, s), 7.77 (1H, d, J = 8.0 Hz), 7.02 (1H, d,
J = 8.0 Hz), 4.41 (2H, t, J = 9.5 Hz), 4.14 (2H, t, J = 9.5 Hz), 2.42 (3H, s); 13C{1H} NMR
(100.6 MHz, CDCl3): 164.8, 155.6 (q, J = 37.5 Hz), 143.8, 137.5, 129.2, 125.3, 120.8, 116.1
(q, J = 289.0 Hz), 112.0, 66.7, 54.4, 22.1; 19F NMR (376.5 MHz, CDCl3): δ – 76.0; HRMS:
m/z [MH]+ C12H12N2O2F3 calcd. 273.0851, found 273.0861.
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Synthesis of N-(2-(4,5-dihydrooxazol-2-yl)-4-methylphenyl)-4-methylbenzenesulfonamide
(29). Following general procedure D, using pꢀtoluenesulfonamide (34 mg, 0.20 mmol) and 2ꢀ
(mꢀtolyl)ꢀ4,5ꢀdihydrooxazole (65 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005 mmol),
AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2 mL) at
100 °C for 16 h, product 29 was isolated as a colorless solid (31 mg, 47%). M.p.: 128 – 129
°C (pentane); FTIR: vmax/ cmꢀ1 (neat) 2985 (w), 2914 (w), 1633 (s), 1514 (m), 1334 (s), 1253
1
(s), 1152 (s), 1061 (s), 941 (m); H NMR (400 MHz, CDCl3): δ 12.10 (1H, s), 7.71 (2H, d, J
= 8.0 Hz), 7.55 (1H, d, J = 8.5 Hz), 7.53 (1H, d, J = 1.5 Hz), 7.18 (2H, d, J = 8.0 Hz), 7.15
(1H, dd, J = 8.5, 1.5 Hz), 4.33 (2H, t, J = 9.5 Hz), 4.11 (2H, t, J = 9.5 Hz), 2.34 (3H, s), 2.25
(3H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 164.6, 143.5, 137.1, 136.7, 133.2, 132.1,
129.7, 129.6, 127.3, 118.4, 113.8, 66.5, 54.6, 21.6, 20.7; HRMS: m/z [MH]+ C17H19N2O3S
calcd. 331.1111, found 331.1116.
Synthesis of 2,2,2-trifluoro-N-[2ꢀ(3ꢀmethylphenyl)ꢀ4,5ꢀdihydroꢀoxazole]-acetamide (30)6.
Following general procedure D, using trifluoroacetamide (65 mg, 0.20 mmol) and 2ꢀ(3ꢀ
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methylphenyl)ꢀ4,5ꢀdihydroꢀoxazole (104 mg, 0.400 mmol) with [Cp*RhCl2]2 (3 mg, 0.005
mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2
mL) at 40 °C for 16 h, product 30 was isolated as a colorless solid (39 mg, 72%). M.p.: 145 –
146 °C (pentane); FTIR: vmax/ cmꢀ1 (neat) 3096 (w), 2993 (w), 2887 (w), 1714 (m), 1615 (m),
1138 (s); 1H NMR (400 MHz, CDCl3): δ 13.56 (1H, s), 8.55 (1H, d, J = 8.5 Hz), 7.70 (1H, d,
J = 2.0 Hz), 7.32 (1H, dd, J = 8.5, 2.0 Hz), 4.42 (2H, t, J = 9.5 Hz), 4.15 (2H, t, J = 9.5 Hz),
2.36 (3H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ 164.7, 155.4 (q, J = 288.5 Hz), 135.3,
134.3, 133.4, 129.7, 120.3, 116.9 (q, J = 37.5 Hz), 114.4, 66.7, 54.5, 20.9; 19F NMR (376.5
MHz, CDCl3): δ – 76.0; HRMS: m/z [MH]+ C12H12N2O2F3 calcd. 273.0851, found 273.0859.
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Synthesis of methyl 4-(4,5-dihydrooxazol-2-yl)-3-(4-methylphenylsulfonamido)benzoate (31).
Following general procedure D, using pꢀtoluenesulfonamide (34 mg, 0.20 mmol) and methyl
4ꢀ(4,5ꢀdihydrooxazolꢀ2ꢀyl)benzoate (82 mg, 0.40 mmol) with [Cp*RhCl2]2 (3 mg, 0.005
mmol), AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2
mL) at 100 °C for 16 h, product 31 was isolated as a colorless solid (55 mg, 73%). M.p.: 136
– 137 °C (dichloromethane/petroleum ether (40/60)); FTIR: vmax/ cmꢀ1 (neat) 3016 (w), 2990
(w), 1720 (s), 1639 (s), 1578 (m), 1512 (m), 1327 (s), 1238 (s), 1157 (s), 1093 (s), 1063 (s),
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944 (s); H NMR (400 MHz, CDCl3): δ 12.30 (1H, s), 8.29 (1H, d, J = 1.5 Hz), 7.81 – 7.75
(3H, m), 7.63 (1H, dd, J = 8.0, 1.5 Hz), 7.22 (2H, d, J = 8.0 Hz), 4.38 (2H, t, J = 9.5 Hz),
4.16 (2H, t, J = 9.5 Hz), 3.91 (3H, s), 2.35 (3H, s); 13C{1H} NMR (100.6 MHz, CDCl3): δ
166.1, 164.1, 143.9, 139.3, 136.8, 133.5, 129.7, 129.6, 127.4, 123.1, 118.6, 116.9, 66.8, 54.7,
52.6, 21.6; HRMS: m/z [MH]+ C18H19N2O5S calcd. 375.1009, found 375.1014.
Synthesis of methyl 4-(4,5-dihydrooxazol-2-yl)-3-(2,2,2-trifluoroacetamido)benzoate (32).
Following general procedure D, using trifluoroacetamide (23 mg, 0.20 mmol) and methyl 4ꢀ
(4,5ꢀdihydrooxazolꢀ2ꢀyl)benzoate (49mg, 0.24 mmol) with [Cp*RhCl2]2 (3 mg, 0.005 mmol),
AgSbF6 (7 mg, 0.02 mmol) and PhI(OAc)2 (97 mg, 0.30 mmol) in dichloromethane (2 mL) at
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