Hg/Pt-catalyzed conversion of bromo alkynamines/alkynols to saturated and unsaturated γ-butyrolactams/lactones via intramolecular electrophilic cyclization

Article abstract of DOI:10.1039/c5ob02125a

Convenient and general Hg(ii)/Pt(iv) catalyzed syntheses of γ-butyrolactams and α,β-unsaturated γ-butyrolactones/lactams are described via intramolecular electrophilic cyclizations of bromoalkynes with tosylamino and hydroxyl tethers. The reaction features the use of wet solvents, the exclusion of any base and additive, mild conditions and practical yields. We also synthesised few chiral lactams through this pathway. Additionally, it is shown that the NHTs group distanced further from the homopropargylic position assists regioselective bromoalkyne hydration to yield useful α-bromoketones. Furthermore, Boc protected bromo homo propargyl amines undergo 6-endo-dig cyclization through Boc oxygen to give bromomethylene substituted oxazinones.

Full text of DOI:10.1039/c5ob02125a

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Hg/Pt-Catalyzed Conversion of Bromo Alkynamines/Alkynols to
Saturated and Unsaturated γ-butyrolactams/lactones via
Intramolecular Electrophilic Cyclization
Received 00th January 20xx,
Accepted 00th January 20xx
Yalla Kiran Kumar,a† Gadi Ranjith Kumara,b† and Maddi Sridhar Reddya,b*
DOI: 10.1039/x0xx00000x
A convenient and general Hg(II)/Pt(IV) catalyzed syntheses of γ-butyrolactams and α,β- unsaturated γ-
butyrolactones/lactams are described via an intramolecular electrophilic cyclizations of bromoalkynes with
tosylamino and hydroxyl tethers. The reaction features the use of wet solvents, the exclusion of any base and
additive, mild conditions and practical yields. We also synthesised few chiral lactams through this pathway.
Additionally, it is shown that NHTs group distanced farther from homopropargylic position assists for
regioselective bromoalkyne hydration to yield useful α-bromoketones. Further, Boc protected bromo homo
propargyl amines undergo 6-endo-dig cyclization through Boc oxygen to give bromomethylene substituted
oxazinones.
www.rsc.org/
and subsequent intramolecular nucleophilic attack has led to the
construction of numerous heterocycles with wide substitution
patterns.6 As part of our on-going program of unveiling the new
Introduction
Five-membered lactams1 and lactones2 (both saturated and
unsaturated) are prevalent sub structures frequently found in
biologically as well as pharmaceutically interesting molecules. For
instance, the molecules shown in Figure 13 are representative of
biologically relevant compounds bearing the related skeletons.
Further, they are often used as building blocks in the construction
of larger molecules. Consequently, the development of synthetic
approaches toward these scaffolds has been of broad interest for
organic chemists from long ago.4-5 On the other hand, since the last
decade, an explosion of alkyne chemistry via electrophilic activation
reactions of functionalized alkynes, we also reported various such
cyclic scaffolds in this way.7 In an earlier attempt, we showed that
the bromo alkynes with hydroxyl tether at proper distance would
undergo an intramolecular nucleophilic attack by using an
appropriate activating soft catalyst.7i We here in reveal some
interesting results of study of activation/cyclization of bromo
alkynes tethered with amino/hydroxyl group with and without
propargylic hydroxyl function.
Results and Discussion
Initially, we synthesized tosyl amino tethered bromo alkyne 3a from
readily available aziridine 1a via ring opening by TMS acetylide (to
get 2a) followed by Bromide-TMS group exchange. Activation (by a
soft catalyst) of alkyne would lead to intramolecular
hydroamination (4) with a regioselection of amine attack on
bromide attached alkyne terminus (5-endo-dig cyclization). The
intermediate would subsequently undergo hydrolysis to deliver the
lactam 5a. To test this, we treated 3a with 10 mol% AuCl3 in wet
toluene (adding 3 equivalents of water to toluene) at room
temperature (entry 1). As expected, the lactam 5a was cleanly
obtained in 70% yield. The other low valent Au-catalysts like AuCl
and PPh3AuCl were not very effective for the same conversion
(entries 2-3). The change of solvent to CH3CN proved to be negative
for the reaction (entry 4). Next, we screened the reaction with wet-
toluene/THF/DCE using Hg(OTf)2 as catalyst but to obtain the
product in unacceptable yields (entries 5-7).Pleasingly, the change
of solvent to wet-CH3CN furnished the product neatly in 95% yield
Figure 1. Some representative biologically active lactams/lactones
a.Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, BS-
10/1, Sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India.
b.Academy of Scientific and Innovative Research, New Delhi 110001, India.
† Contributed equally.
Electronic Supplementary Information (ESI) available: See
DOI: 10.1039/x0xx00000x
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outcome of the reaction (only 6-12% reduction in yield). Notably,
electronic factors were also not influencing the reaction as the
electron deficient chloro- and nitro-phenyl substituted lactams (5i-j)
were obtained in as good yields like their electron rich counterparts
(5c-h). Next, we synthesized various 5-alkyl substituted adducts this
way. Thus benzyl lactam 5k was obtained in 85% yield.
(entry 8). Increase of water equivalents (above 3 equiv) gradually
decreased the yields and water as only solvent completely halted
the reaction (entries 9-11). The yield was dropped to 50% when
HgCl2 was used instead of Hg(OTf)2 (entry 12). Cu(OTf)2 could not
catalyse the reaction (entry 13).
Table 1. Optimization studies
Pleasingly, the same reaction when conducted on optically active
3k(S) (obtained from L-phenyl alanine), the product 5k(R) was
obtained with excellent ee (>99.9, see Supporting Information for
HPLC data). Similarly, several chiral pure bromo propargyl amides
were synthesized from various amino acids and converted to the
corresponding enantiomerically enriched lactam adducts (5l-o) in
excellent yields (88-95%). Finally, the reaction could also be
extended to the synthesis of 5,5-disubstituted γ-lactam 5p in
practical yield of 82%. To facilitate the liberation of free amide by
easier deprotection,
a nosyl protected lactam 5q was also
synthesized in the standard conditions.
Table 2. Synthesis of butyrolactams 5 via electrophilic cyclization of 3.
aReaction conditions: 3a (1.0 mmol), catalyst (10 mol %), H2O (3 equiv), solvent
(0.25 M), RT, 18 h, open air. bIsolated yield. cSM was recovered. d0.5 equivalents
of 2,6-lutidine was used as base.
Interestingly, when we performed the reaction with Hg(OTf)2 in the
absence of water, starting material was recovered as such (entry
14). It suggests that the initial cyclization is reversible. It gets
converted to product only in presence water. Surprisingly, use of
2,6-lutidine as base totally halted the reaction (entry 15). To verify
whether TfOH (which may be released from Hg(OTf)2) was
responsible for the reaction via hydrolysis of the alkyne moiety, we
conducted an experiment with 10 mol% TfOH (entry 16). No
reaction occurred, demonstrating that the Hg-or Au-catalyst was
necessary for activating alkyne for cyclization.
With the optimised conditions in hand, we turned to evaluate the
generality of the method. First, a range of 4-bromo homopropargyl
amides 3 were synthesized; few from benzaldehydes (3b-j) and
others from readily available amino acids (3k-o).8 As is evident from
Table 2, a variety of substituents like alkyl, aryl, halogen, methoxy,
and nitro groups were tolerated in the reaction to afford the
products in excellent yields. Thus, the alkyl (Me, Et and t-But)
tethered phenyl substituted lactam (5b-f) could be synthesized in
excellent yields (85-92%). Electron rich phenyl substituted products
(5g-h) were obtained with equal ease (76-88%). After the clean
syntheses of 5f and 5h, it appears that steric factors from ortho
substitution on phenyl rings showed negligible effect on the
Excited with the above results, we moved on to the substrates with
amine group distanced from bromo alkyne group by one carbon so
that the cyclization (6-endo-dig) on to bromo attached alkyne group
would lead to δ-lactams. Surprisingly, we observed the exclusive
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formation (88%) regioselectively hydrolysed product α- by Carretero et al.10 Since this finding has a considerable variation in
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DOI: 10.1039/C5OB02125A
bromoketone 10a (Scheme 1). This must have happened through 5- bringing bromomethylene substituted products staging a plat form
exo-dig cyclization followed by hydrolysis reaction. Tempted by the for further manipulation via various metal mediated couplings of
multifunctional nature of the products, and various literature uses vinyl bromide group, we pursued for its generality. Similar to 12a,
of α-bromoketones,9 we quickly checked this new reaction’s methyl, methoxy and chloro substituted phenyl adducts (12b-d)
generality. Thus, methyl-, ethyl- and dimethyl-substituted were obtained in excellent yields (72-82%).
substrates were tested and smoothly converted to the
corresponding α-bromoketones (10b-d). Next, the substrate 7e with
further parted amino group was subjected to the standard reaction
conditions. Again, the reaction led to the selective hydrolysis via
relatively less energetic 6-exo-dig pathway (compared to other
possible 7-endo-dig cyclization) to produce α-bromoketone 10e. We
next tested the reaction on substrate lacking the NHTs group 7f so
as to know its involvement/importance. As expected, 10f was
observed to be inert to the reaction suggesting that the assistance
of NHTs was necessary to initiate the hydrolysis. This is the
reminiscent of the work by Nishizawa et al where they showed the
hydroxyl assisted hydrolysis of the alkyne group.6c What we have
shown here is that not only NHTs group assists in such hydrolysis in
similar way, but the sensitive bromide group survives the hydrolysis
reaction and remains as a useful handle at alpha to the keto group
in the product.
Scheme 2. Synthesis of oxazinones 12 via electrophilic cyclization.
We next became interested in studying the reactivity pattern of
propargylic alcohol system which could lead to unsaturated cycles.
We first prepared various 1,2-dihydroxy-4-bromo-3-ynes 15a-k to
see whether it would undergo the expected cascade reaction
including electrophilic cyclization, hydrolysis followed by
elimination of benzylic hydroxyl group to deliver the α,β-
unsaturated γ-butyrolactone 16a-k. An optimization study led to
identify PtCl4 as the most suitable catalyst for the transformation.8
Thus, 15a was converted to 16a in 82% yield using 10 mol% PtCl4 in
wet THF with no assistance of any base or additive (Table 3). We
first aimed at 5-unsubstituted adducts (like 16a-f) as they are found
in various applications in the literature through functionalization of
both C5 acidic protons.11 Thus, methyl, chloro and fluoro
substituted phenyl adducts (16b-d) were synthesized in excellent
yields (80-90%). Methoxyphenyl substituted lactone 16e was
Scheme 1. NHTs assisted selective hydrolysis of bromoalkynes.
obtained in lower yield of 65%. Further, 4-alkyl adduct 16f was also
synthesized in similar (65%). Next, 4,5-trisubstituted adducts were
targeted. Thus, 4-phenyl-5,5-dimethyl product 16g was produced in
excellent yield of 89%. A variety of substitution (Me, OMe, Br) on
phenyl ring was well tolerated (16i-k in 82-90% yields). Finally, 5-
spiro substituted adduct 16h was obtained in equal ease (93%).
Next, similar cyclization for α,β-unsaturated γ-butyrolactam was
tested. The reaction was found to be slightly less efficient compared
to their lactone counterparts. Thus, 4-phenyl adduct 16l was
furnished in 50% yield. Electron rich phenyl substituted lactams like
In parallel, we also studied the reactivity of Boc-protected
substrates like 11 for the similar cyclizations (Scheme 2).
Unfortunately, neither any product nor starting material was
recovered. We attribute this to the Boc group sensitivity to the
acidic conditions exerted by the presence of water with triflate
(TfOH formation). Interestingly, when subjected the 11a to the
alternate reagent AuCl3 (Table 1, entry 1), we obtained oxazinone
12a via cyclization of Boc oxygen instead of NH group. This kind of
cyclization on terminal and ester substituted alkynes were reported
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16m and 16n were obtained in 35% and 36% yields respectively General Information:
where as halo- substitution on phenyl ring completely deterred the
General Information: All reagents and solvents were purchased
reaction. But, 5,5-disubstituted adducts 16o-p in contrast were
obtained in excellent yields (72-78%). The acidic protons in earlier
cases might have assisted for some unwanted aromatizations.
from commercial sources and used without purification. NMR
1
spectra were recorded with a 400 MHz spectrometer for H NMR,
100 MHz for 13C NMR spectroscopy. Chemical shifts are reported
relative to the residual signals of tetramethylsilane in CDCl3 or
deuterated solvent CDCl3/[D6]DMSO for 1H and 13C NMR
spectroscopy. Multiplicities are reported as follows: singlet (s),
doublet (d), broad singlet (bs), doublet of doublets (dd), triplet (t),
quartet (q), multiplet (m). HRMS were recorded by using QTof mass
spectrometer. Column chromatography was performed with silica
gel (100–200 mesh) as the stationary phase. All reactions were
monitored by using TLC. The purity and characterization of
compounds were further established by using HRMS.
Table 3. Synthesis of 16 via electrophilic cyclization.
2.1. General Procedure A, for the synthesis of 5 from 3:
To the substrate 3a (165 mg, 0.5 mmol) dissolved in acetonitrile (2
ml) were added H2O (27 mg, 3 equiv) and Hg(OTf)2 (25 mg, 0.1
mmol). The mixture was stirred at room temperature till the
completion of the reaction (TLC, 18 h). The reaction mixture was
then added water (4 ml) followed by brine solution (4 ml) and
extracted with ethyl acetate (3 x 6 ml). The combined extracts were
dried over Na2SO4, filtered and concentrated. The crude was
purified by column chromatography (silicagel, 10-20% EtOAc in
hexanes) to get the pure product 5a (123mg).
5-ethyl-1-tosylpyrrolidin-2-one (5a): 92% yield (123 mg); white
1
solid; mp 117-119 oC; Rf = 0.30 (SiO2, 30% EtOAc/Hexanes); H NMR
(400 MHz, CDCl3) δ: 7.94 (d, J = 8.2 Hz, 2H); 7.31 (d, J = 8.2 Hz, 2H);
4.37-4.31 (m, 1H); 2.55-2.46 (m, 1H); 2.42 (s, 3H); 2.36-2.29 (m, 1H);
2.21-2.11 (m, 1H); 2.05-1.95 (m, 1H); 1.88-1.81 (m, 1H); 1.75-1.64
(m, 1H); 0.91 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 173.6,
144.9, 136.1, 129.5, 128.3, 61.5, 30.8, 27.6, 23.0, 21.6, 9.3; IR (neat)
ν 3030, 1610, 1365, 1219; HRMS (ESI-TOF) calcd for C13H18NO3S [M
+ H]+ 268.1007, found 268.1002.
5-phenyl-1-tosylpyrrolidin-2-one (5b): 90% yield (142 mg); white
aReaction conditions: 15a (1.0 mmol), PtCl4 (0.1 mmol), H2O (3 equiv), THF (4 mL),
RT, 18 h, open air. bIsolated yield.
1
solid; mp 146-148 oC; Rf = 0.40 (SiO2, 30% EtOAc/Hexanes); H NMR
(400 MHz, CDCl3) δ: 7.56 (d, J = 8.3 Hz, 2H); 7.31-7.26 (m, 3H); 7.17
(d, J = 8.3 Hz, 2H); 7.13-7.10 (m, 2H); 5.44 (dd, J = 8.5, 2.0 Hz, 1H);
2.74-2.46 (m, 3H); 2.39 (s, 3H); 2.01-1.93 (m, 1H); 13C NMR (100
MHz, CDCl3) δ: 173.6, 144.9, 140.7, 135.5, 129.2, 128.8, 128.5,
128.1, 126.1, 63.1, 30.7, 28.4, 21.7; IR (neat) ν 3120, 1650, 1384,
1215; HRMS (ESI-TOF) calcd for C17H18NO3S [M + H]+ 316.1007,
found 316.1009.
In summary, we have shown some interesting reactions of
bromoalkynes tethered with hydroxyl or amino group. How the
reaction pathway changes depending on the position of the tether
and substitution on amino group, and based on the presence or
absence of the propargyl hydroxyl group is well studied for the
formation
of
various
interesting
scaffolds
like
saturated/unsaturated lactams, unsaturated lactones, oxazinones
and α-bromoketones. Further, it is shown that the synthetic
approach described here are equally potential for the synthesis of
enantiopure adducts.
5-p-tolyl-1-tosylpyrrolidin-2-one (5c): 91% yield (150 mg); white
1
solid; mp 137-139 oC; Rf = 0.50 (SiO2, 30% EtOAc/Hexanes); H NMR
(400 MHz, CDCl3) δ: 7.59 (d, J = 8.3 Hz, 2H); 7.17 (d, J = 8.3 Hz, 2H);
7.09 (d, J = 7.9 Hz, 2H); 7.01 (d, J = 7.9 Hz, 2H); 5.41 (dd, J = 8.2, 1.6
Hz, 1H); 2.72-2.44 (m, 3H); 2.39 (s, 3H); 2.34 (s, 3H); 1.98-1.92 (m,
Experimental Section
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1H); 13C NMR (100 MHz, CDCl3) δ: 173.6, 144.8, 137.8, 137.7, 135.5, 5-(4-chlorophenyl)-1-tosylpyrrolidin-2-one (5i): 85% yield (149 mg);
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1
DOI: 10.1039/C5OB02125A
129.4, 129.1, 128.5, 126.0, 62.9, 30.6, 28.4, 21.6, 21.1; IR (neat) ν white solid; mp 148-150 C; Rf = 0.50 (SiO2, 30% EtOAc/Hexanes); H
3098, 1657, 1360, 1201; HRMS (ESI-TOF) calcd for C18H20NO3S [M + NMR (400 MHz, CDCl3) δ: 7.59 (d, J = 8.3 Hz, 2H); 7.27-7.22 (m, 2H);
H]+ 330.1164, found 330.1164.
7.19 (d, J = 8.3 Hz, 2H); 7.05 (d, J = 8.4 Hz, 2H); 5.38 (dd, J = 8.0, 1.8
Hz, 1H); 2.68-2.43 (m, 3H); 2.39 (s, 3H); 1.95-1.86 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ: 173.4, 145.2, 139.4, 135.5, 134.0, 129.4, 129.0,
128.5, 127.5, 62.4, 30.6, 28.3, 21.7; IR (neat) ν 3022, 1603, 1386,
1215; HRMS (ESI-TOF) calcd for C17H17ClNO3S [M + H]+ 350.0618,
found 350.0615.
5-(4-ethylphenyl)-1-tosylpyrrolidin-2-one (5d): 91% yield (156 mg);
white solid; mp 145-147 oC; Rf = 0.50 (SiO2, 30% EtOAc/Hexanes); 1H
NMR (400 MHz, CDCl3) δ: 7.55 (d, J = 8.3 Hz, 2H); 7.14 (d, J = 8.3 Hz,
2H); 7.10 (d, J = 8.1 Hz, 2H); 7.02 (d, J = 8.1 Hz, 2H); 5.41(dd, J = 8.4,
1.8 Hz, 1H); 2.70-2.48 (m, 5H); 2.38 (s, 3H); 2.00-1.94(m, 1H); 1.24
(t, J = 7.6 Hz, 3H);13C NMR (100 MHz, CDCl3) δ: 173.5, 144.7, 144.2, 5-(3-nitrophenyl)-1-tosylpyrrolidin-2-one (5j): 89% yield (160 mg);
137.8, 135.5, 129.0, 128.5, 128.2, 126.1, 62.9, 30.7, 28.5, 28.2, 21.6, white solid; mp 190-192 oC; Rf = 0.30 (SiO2, 30% EtOAc/Hexanes); 1H
15.6; IR (neat) ν 3120, 1632, 1399, 1253; HRMS (ESI-TOF) calcd for NMR (400 MHz, CDCl3) δ: 8.17-8.14 (m, 1H); 7.88 (t, J = 1.8 Hz, 1H);
C19H22NO3S [M + H]+ 344.1320, found 344.1320.
7.64 (d, J = 8.3 Hz, 2H); 7.58-7.50 (m, 2H); 7.21 (d, J = 8.3 Hz, 2H);
5.51 (dd, J = 8.0, 2.7 Hz, 1H); 2.72-2.50 (m, 3H); 2.40 (s, 3H); 2.01-
1.92 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 173.1, 148.4, 145.6,
143.0, 135.2, 132.2, 130.0, 129.4, 128.2, 123.0, 120.8, 62.1, 30.3,
28.2, 21.6; IR (neat) ν 3096, 1645, 1352, 1232; HRMS (ESI-TOF) calcd
for C17H17N2O5S [M + H]+ 361.0858, found 361.0855.
5-(4-tert-butylphenyl)-1-tosylpyrrolidin-2-one (5e): 92% yield (171
mg); white solid; mp 137-139 oC; Rf
= 0.50 (SiO2, 30%
1
EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 7.51 (d, J = 8.3 Hz,
2H); 7.28-7.26 (m, 2H); 7.11 (d, J = 8.3 Hz, 2H); 7.05-7.01 (m, 2H);
5.41 (dd, J = 8.6, 1.9 Hz, 1H); 2.27-2.48 (m, 3H); 2.34 (s, 3H); 2.02-
1.96 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 173.5, 151.1, 144.6, (R)-5-benzyl-1-tosylpyrrolidin-2-one (5k): 85% yield (140 mg);
137.4, 135.6, 129.0, 128.4, 125.9, 125.6, 62.8, 34.5, 31.3, 30.8, 28.0, white solid; mp 115-117 oC; Rf = 0.40 (SiO2, 30% EtOAc/Hexanes); 1H
21.6; IR (neat) ν 2099, 1663, 1365, 1200; HRMS (ESI-TOF) calcd for NMR (400 MHz, CDCl3) δ: 7.98 (d, J = 8.3 Hz, 2H); 7.35-7.17 (m, 7H);
C21H26NO3S [M + H]+ 372.1633, found 372.1625.
4.64-4.57 (m,. 1H); 3.31 (dd, J = 13.4, 3.3 Hz, 1H); 2.85 (dd, J = 13.4,
8.8 Hz, 1H); 2.42 (s, 3H); 2.18-1.92 (m, 3H); 1.88-1.81 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 173.6, 145.3, 136.5, 136.2, 129.7, 128.9,
128.6, 127.2, 61.1, 40.8, 30.6, 23.0, 21.8; IR (neat) ν 3023, 1610,
1361, 1216; HRMS (ESI-TOF) calcd for C18H20NO3S [M + H]+
330.1164, found 330.1157.
5-o-tolyl-1-tosylpyrrolidin-2-one (5f): 85% yield (140 mg); white
solid; mp 136-138 oC; Rf = 0.50 (SiO2, 20% EtOAc/Hexanes); H NMR
(400 MHz, CDCl3) δ: 7.66 (d, J = 8.3 Hz, 2H); 7.22-7.15 (m, 4H); 7.01-
6.97 (m, 1H); 6.80 (d, J = 7.7, 1H); 5.69 (dd, J = 8.1, 1.6 Hz, 1H); 2.69-
2.44 (m, 3H); 2.41 (s, 6H); 1.88-1.83 (m, 1H); 13C NMR (100 MHz,
1
CDCl3) δ: 173.8, 144.9, 138.5, 135.4, 134.4, 131.0, 129.1, 128.7, (S)-5-methyl-1-tosylpyrrolidin-2-one (5l): 95% yield (120 mg); white
1
127.7, 126.1, 124.5, 59.4, 30.3, 27.3, 21.6, 19.1; IR (neat) ν 3100, solid; mp 140-142 oC; Rf = 0.30 (SiO2, 30% EtOAc/Hexanes); H NMR
1632, 1320, 1253; HRMS (ESI-TOF) calcd for C18H20NO3S [M + H]+ (400 MHz, CDCl3) δ: 7.94 (d, J = 8.3 Hz, 2H); 7.32 (d, J = 8.3 Hz, 2H);
330.1164, found 330.1164.
4.56-4.47 (m, 1H); 2.60-2.49 (m, 1H); 2.42 (s, 3H); 2.38-2.22 (m, 2H);
1.74-1.67 (m, 1H); 1.46 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ: 173.3, 145.0, 136.2, 129.5, 128.3, 56.4, 30.6, 26.7, 21.7,
21.5; IR (neat) ν 3030, 1610, 1365, 1219; HRMS (ESI-TOF) calcd for
C12H16NO3S [M + H]+ 254.0851, found 254.0851.
5-(4-methoxyphenyl)-1-tosylpyrrolidin-2-one (5g): 88% yield (152
mg); white solid; mp 102-104 oC; Rf
= 0.4 (SiO2, 30%
1
EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 7.55 (d, J = 8.3 Hz,
2H); 7.16 (d, J = 8.3 Hz, 2H); 7.04 (d, J = 8.7 Hz, 2H); 6.80 (d, J = 8.7
Hz, 2H); 5.40 (dd, J = 8.6, 2.2 Hz, 1H); 3.81 (s, 3H); 2.73-2.45 (m, 3H); (R)-5-isopropyl-1-tosylpyrrolidin-2-one (5m): 90% yield (127 mg);
2.38 (s, 3H); 1.98-1.92 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 173.6, white solid; mp 116-118 oC; Rf = 0.30 (SiO2, 30% EtOAc/Hexanes); 1H
159.5, 144.9, 135.7, 132.9, 129.2, 128.6, 127.5, 114.2, 62.7, 55.4, NMR (400 MHz, CDCl3) δ: 7.95 (d, J = 8.4 Hz, 2H); 7.31 (d, J = 8.4 Hz,
30.8, 28.4, 21.7; IR (neat) ν 3022, 1611, 1248, 1216; HRMS (ESI-TOF) 2H); 4.39-4.33 (m, 1H); 2.56-2.46 (m, 1H); 2.46-2.29 (m, 5H); 2.11-
calcd for C18H20NO4S [M + H]+ 346.1113, found 346.1116.
1.97 (m, 1H); 1.94-1.84 (m, 1H); 0.97 (d, J = 6.9 Hz, 3H); 0.71 (d, J =
6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 174.1, 144.9, 136.0, 129.5,
128.4, 65.0, 31.7, 31.4, 21.7, 18.9, 18.5, 14.9; IR (neat) ν 3022, 1603,
1386, 1215; HRMS (ESI-TOF) calcd for C14H20NO3S [M + H]+
282.1164, found 282.1154.
5-(2-methoxyphenyl)-1-tosylpyrrolidin-2-one (5h): 76% yield (131
mg); white solid; mp 128-130 oC; Rf
EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 7.51 (d, J = 8.3 Hz,
= 0.40 (SiO2, 20%
1
2H); 7.31-7.26 (m, 1H); 7.18-7.13 (m, 3H); 6.94-6.90 (m, 2H); 5.56
(dd, J = 8.1, 1.2 Hz, 1H); 3.46 (s, 3H); 2.76-2.49 (m, 3H); 2.39 (s, 3H); (R)-5-isobutyl-1-tosylpyrrolidin-2-one (5n): 88% yield (130 mg);
2.02-1.94 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 174.3, 156.5, 144.3, white solid; mp 102-104 oC; Rf = 0.30 (SiO2, 30% EtOAc/Hexanes); 1H
135.7, 129.4, 129.0, 128.9, 128.3, 127.9, 120.3, 110.7, 60.6, 54.7, NMR (400 MHz, CDCl3) δ: 7.94 (d, J = 8.3 Hz, 2H); 7.32 (d, J = 8.3 Hz,
31.4, 25.6, 21.5; IR (neat) ν 3054, 1653, 1324, 1231; HRMS (ESI-TOF) 2H); 4.45-4.38 (m, 1H); 2.59-2.48 (m, 1H); 2.43 (s, 3H); 2.36-2.27 (m,
calcd for C18H20NO4S [M + H]+ 346.1113, found 346.1116.
1H); 2.20-2.08 (m, 1H); 1.89-1.81 (m, 2H); 1.69-1.61 (m, 1H); 1.54-
1.45 (m, 1H); 1.01 (d, J = 6.5 Hz, 3H); 0.96 (d, J = 6.5 Hz, 3H); 13C
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DOI: 10.1039/C5OB02125A
NMR (100 MHz, CDCl3) δ: 173.4, 144.9, 136.3, 129.5, 128.4, 59.2, 1715, 1397, 675; HRMS (ESI-TOF) calcd for C14H21BrNaNO3S [M +
43.2, 30.5, 25.4, 23.9, 23.8, 21.7, 21.3; IR (neat) ν 3020, 1610, 1385, Na]+ 384.0245, found 384.0239.
1220; HRMS (ESI-TOF) calcd for C15H22NO3S [M + H]+ 296.1320,
(S)-N-(6-bromo-5-oxohexan-2-yl)-4-methylbenzenesulfonamide
(10c): 90% yield (156 mg); white solid; mp 88-90 oC; Rf = 0.40 (SiO2,
found 296.1321.
(R)-5-sec-butyl-1-tosylpyrrolidin-2-one (5o): 90% yield (133 mg); 30% EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ 7.73-7.69 (m,
white solid; mp 132-134 oC; Rf = 0.30 (SiO2, 30% EtOAc/Hexanes); 1H 2H); 7.31-7.28 (m, 2H); 4.38 (d, J = 8.9 Hz, 1H); 3.94-3.87 (m, 2H);
NMR (400 MHz, CDCl3) δ: 7.95 (d, J = 8.3 Hz, 2H); 7.32 (d, J = 8.3 Hz, 3.34-3.23 (m, 1H); 2.84-2.75 (m, 1H); 2.72-2.64 (m, 1H); 2.42 (s, 3H);
2H); 4.48-4.44 (m, 1H); 2.47-2.32 (m, 5H); 2.31-2.23 (m, 1H); 2.10- 1.84-1.76 (m, 1H); 1.59-1.51 (m, 1H); 0.94 (d, J = 6.6 Hz, 3H); 13C
1.99 (m, 1H); 1.90-1.82 (m, 1H); 1.43-1.32 (m, 1H); 1.29-1.17 (m, NMR (100 MHz, CDCl3) δ: 202.1, 143.6, 137.9, 129.9, 127.1, 49.5,
1H); 0.99 (t, J = 7.3 Hz, 3H); 0.69 (d, J = 6.9 Hz, 3H); 13C NMR (100 36.1, 34.8, 31.3, 22.1, 21.7; IR (neat) ν 3369, 1715, 1397, 675; HRMS
MHz, CDCl3) δ: 174.2, 144.9, 136.1, 129.5, 128.5, 63.8, 38.3, 31.8, (ESI-TOF) calcd for C13H19BrNO3S [M
26.4, 21.7, 18.6, 12.4, 12.0; IR (neat) ν 3021, 1620, 1388, 1216; 348.0255.
HRMS (ESI-TOF) calcd for C15H22NO3S [M + H]+ 296.1320, found
+
H]+ 348.0269, found
N-(6-bromo-2-methyl-5-oxohexan-2-yl)-4-
methylbenzenesulfonamide (10d): 92% yield (166 mg); white solid;
296.1321.
o
1
5,5-dimethyl-1-tosylpyrrolidin-2-one (5p): 82% yield (110 mg); mp 116-118 C; Rf = 0.40 (SiO2, 30% EtOAc/Hexanes); H NMR (400
white solid; mp 112-114 oC; Rf = 0.30 (SiO2, 30% EtOAc/Hexanes); 1H MHz, CDCl3) δ: 7.76 (d, J = 8.2 Hz, 2H); 7.28 (d, J = 8.2 Hz, 2H); 4.78
NMR (400 MHz, CDCl3) δ: 7.94 (d, J = 8.3 Hz, 2H); 7.31 (d, J = 8.3 Hz, (s, 1H); 3.86 (s, 2H); 2.69 (t, J = 7.4 Hz, 2H); 2.42 (s, 3H); 1.84 (t, J =
2H); 2.42-2.37 (m, 5H); 1.92 (t, J = 8.2 Hz, 2H); 1.68 (s, 6H); 13C NMR 7.4 Hz, 2H); 1.15 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 201.8, 143.2,
(100 MHz, CDCl3) δ: 174.0, 144.7, 136.8, 129.8, 128.7, 67.1, 35.8, 140.3, 129.7, 127.0, 56.4, 36.0, 34.9, 34.4, 27.9, 21.6; IR (neat) ν
30.0, 28.3, 21.7; IR (neat) ν 3021, 1620, 1388, 1216; HRMS (ESI-TOF) 3399, 1723, 1403, 682; HRMS (ESI-TOF) calcd for C14H20BrNaNO3S
calcd for C13H18NO3S [M + H]+ 268.1007, found 268.1016.
[M + Na]+ 384.0245, found 384.0239.
5,5-dimethyl-1-((4-nitrophenyl)sulfonyl)pyrrolidin-2-one (5q): 75% N-(6-bromo-5-oxohexyl)-4-methylbenzenesulfonamide (10e): 75%
yield (112 mg); white solid; mp 168-170 oC; Rf = 0.20 (SiO2, 30% yield (130 mg); white solid; mp 96-98 oC; Rf = 0.30 (SiO2, 30%
1
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ: 8.36-8.33 (m, 2H); EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 7.73 (d, J = 8.3 Hz,
8.26-8.23 (m, 2H); 2.43 (t, J = 8.1 Hz, 2H); 1.97 (t, J = 8.1 Hz, 2H); 2H); 7.30 (d, J = 8.3 Hz, 2H); 4.81 (t, J = 6.2 Hz, 1H); 3.84 (s, 2H); 2.91
1.70 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 174.2, 150.7, 144.9, (q, J = 6.4 Hz, 2H); 2.61 (t, J = 7.0 Hz, 2H); 2.41 (s, 3H); 1.64-1.56 (m,
130.2, 124.0, 67.8, 35.8, 29.9, 28.4; IR (neat) ν 3068, 1636, 1394, 2H); 1.51-1.44 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 201.9, 143.6,
1210; HRMS (ESI-TOF) calcd for C12H15N2O5S [M + H]+ 299.0702, 136.9, 129.8, 127.2, 42.8, 39.0, 34.3, 28.8, 21.6, 20.6; IR (neat) ν
found 299.0692.
3396, 1710, 1403, 680; HRMS (ESI-TOF) calcd for C13H19BrNO3S [M +
H]+ 348.0269, found 348.0255.
(R)-N-(6-bromo-5-oxo-1-phenylhexan-2-yl)-4-
methylbenzenesulfonamide (10a): 88% yield (186 mg); white solid; tert-butyl (4-bromo-1-phenylbut-3-yn-1-yl)carbamate (11a): 80%
mp 108-110 C; Rf = 0.40 (SiO2, 30% EtOAc/Hexanes); H NMR (400 yield (259 mg); white solid; mp 122-124 oC;Rf = 0.7 (SiO2, 20%
MHz, CDCl3) δ: 7.65 (d, J = 8.2 Hz, 2H); 7.27 (d, J = 7.3 Hz, 2H); 7.23- EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ: 7.38-7.25 (m, 5H);
7.19 (m, 3H); 6.97-6.94 (m, 2H); 4.36 (d, J = 8.8 Hz, 1H); 3.93-3.86 5.06 (s, 1H); 4.87 (s, 1H); 2.81-2.62 (m, 2H); 1.43 (s, 9H); 13C NMR
(m, 2H); 3.54-3.46 (m, 1H); 2.85-2.77 (m, 1H); 2.71-2.53 (m, 3H); (100 MHz, CDCl3) δ: 155.2, 128.7, 127.8, 126.4, 80.1, 76.2, 52.8,
2.44 (s, 3H); 1.94-1.86 (m, 1H); 1.61-1.52 (m, 1H); 13C NMR (100 41.3, 28.5, 27.9; IR (neat) ν 3460, 2198, 1721, 685; HRMS (ESI-TOF)
MHz, CDCl3) δ: 202.0, 143.5, 137.7, 136.6, 129.8, 129.4, 128.7, calcd for C15H19BrNO2 [M + H]+ 326.0574, found 326.0564.
127.0, 126.8, 54.3, 41.9, 35.9, 34.8, 28.5, 21.6; IR (neat) ν 3415,
o
1
tert-butyl (4-bromo-1-(p-tolyl)but-3-yn-1-yl)carbamate (11b): 80%
yield (270 mg); white solid; mp 115-117 oC; Rf = 0.70 (SiO2, 20%
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ: 7.21-7.13 (m, 4H);
5.03 (s, 1H); 4.82 (s, 1H); 2.79-2.62 (m, 2H); 2.33 (s, 3H); 1.43 (s,
1725, 1396, 668; HRMS (ESI-TOF) calcd for C19H23BrNO3S [M + H]+
424.0582, found 424.0580.
N-(7-bromo-6-oxoheptan-3-yl)-4-methylbenzenesulfonamide
(10b): 90% yield (163 mg); colorless liquid; Rf = 0.40 (SiO2, 30% 9H); 13C NMR (100 MHz, CDCl3) δ: 155.1, 138.0, 137.4, 129.4, 126.3,
1
EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 7.71 (d, J = 8.2 Hz, 79.9, 76.4, 52.6, 41.1, 28.5, 27.9, 21.2; IR (neat) ν 3423, 2252, 1706,
2H); 7.28 (d, J = 8.2 Hz, 2H); 4.63 (d, J = 8.8 Hz, 1H); 3.93-3.86 (m, 650; HRMS (ESI-TOF) calcd for C16H21BrNO2 [M + H]+ 340.0735,
2H); 3.18-3.09 (m, 1H); 2.82-2.73 (m, 1H); 2.69-2.61 (m, 1H); 2.41 (s, found 340.0729.
3H); 1.89-1.81 (m, 1H); 1.56-1.47 (m, 1H); 1.37-1.24 (m, 2H); 0.66 (t,
J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 202.1, 143.5, 138.2,
129.8, 127.1, 54.7, 35.9, 34.8, 28.7, 28.6, 21.6, 9.8; IR (neat) ν 3369,
tert-butyl (4-bromo-1-(4-methoxyphenyl)but-3-yn-1-yl)carbamate
(11c): 75% yield (265 mg); white solid; mp 137-139 oC; Rf = 0.60
6 | J. Name., 2012, 00, 1-3
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(SiO2, 20% EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ: 7.23 (d, J = 3612, 3096, 1751, 682; HRMS (ESI-TOF) calcd for C12H13BrNO3 [M +
View Article Online
8.6 Hz, 2H); 6.87 (d, J = 8.6 Hz, 2H) 5.01 (s, 1H); 4.80 (s, 1H); 3.79 (s, H]+ 300.0058, found 300.0047.
3H); 2.76-2.63 (m, 2H); 1.43 (s, 9H); 13C NMR (100 MHz, CDCl3) δ:
DOI: 10.1039/C5OB02125A
(Z)-6-(bromomethylene)-4-(4-chlorophenyl)-1,3-oxazinan-2-one
(12d): 72% yield (108 mg); white solid; mp 171-173 oC; Rf = 0.30
(SiO2, 30% EtOAc/Hexanes); 1H NMR (400 MHz, DMSO-d6) δ: 8.42 (s,
1H); 7.45 (d, J = 8.4 Hz, 2H); 7.30 (d, J = 8.4 Hz, 2H); 5.60 (s, 1H);
159.2, 155.2, 133.2, 127.6, 114.1, 79.9, 76.4, 55.4, 52.4, 41.1, 28.5,
27.8; IR (neat) ν 3490, 2310, 1725, 680; HRMS (ESI-TOF) calcd for
C16H21BrNO3 [M + H]+ 356.0684, found 356.0673.
tert-butyl
(4-bromo-1-(4-chlorophenyl)but-3-yn-1-yl)carbamate 4.68-4.64 (m, 1H); 2.92 (dd, J = 14.5, 5.1 Hz, 1H); 2.65 (dd, J = 14.5,
(11d): 78% yield (279 mg); white solid; mp 128-130 oC; Rf = 0.70 5.8 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 149.5, 148.6, 140.2,
1
(SiO2, 20% EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 7. 32 (d, J 132.8, 128.9, 128.5, 84.1, 51.4, 33.4; IR (neat) ν 3419, 3021, 1741,
= 8.5 Hz, 2H); 7.24 (d, J = 8.5 Hz, 2H); 5.05 (s, 1H); 4.83 (s, 1H); 2.77- 669; HRMS (ESI-TOF) calcd for C11H10BrClNNaO2 [M + Na]+ 323.9397,
2.62 (m, 2H); 1.43 (s, 9H); 13C NMR (100 MHz, CDCl3) δ: 155.1, found 323.9390.
139.7, 133.5, 128.8, 127.8, 80.2, 75.8, 52.3 41.8, 28.5, 27.7; IR
2.3 General Procedure C for the synthesis of 16 from 15:
(neat)
ν 3432, 2260, 1706, 669; HRMS (ESI-TOF) calcd for
C15H18BrClNO2 [M + H]+ 360.0189, found 360.0195.
To the substrate 15a (120 g, 0.5 mmol) dissolved in THF (2 ml) were
added H2O (27 mg, 3 equiv) and PtCl4 (17 mg, 0.1 mmol). The
mixture was stirred at room temperature till the completion of the
2.2 General Procedure B, for the synthesis of 12 from 11:
To the substrate 11a (160 mg, 0.5 mmol) dissolved in toluene (2 ml) reaction (TLC, 18 h). The reaction mixture was then added water (4
was added AuCl3 (16 mg, 0.1 mmol). The mixture was stirred at ml) followed by brine solution (4 ml) and extracted with ethyl
room temperature till the completion of the reaction (TLC, 16 h). acetate (3 x 6 ml). The combined extracts were dried over Na2SO4,
The reaction mixture was then added water (4 ml) followed by filtered and concentrated. The crude was purified by column
brine solution (4 ml) and extracted with ethyl acetate (3 x 6 ml). The chromatography (silicagel, 10-15% EtOAc in hexanes) to get the
combined extracts were dried over Na2SO4, filtered and pure product 16a (66 mg).
concentrated. The crude was purified by column chromatography
(silicagel, 20-30% EtOAc in hexanes) to get the pure product 12a
(101 mg).
4-phenylfuran-2(5H)-one (16a): 82% yield (66 mg); white solid; mp
122-124 oC; Rf = 0.40 (SiO2, 20% EtOAc/Hexanes); 1H NMR (400
MHz, CDCl3) δ: 7.53-7.45 (m, 5H); 6.38 (t, J = 1.8 Hz, 1H); 5.23 (d, J =
(Z)-6-(bromomethylene)-4-phenyl-1,3-oxazinan-2-one (12a): 76% 1.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 173.9, 164.0, 131.9, 129.8,
yield (101 mg); white solid; mp 148-150 oC;Rf = 0.30 (SiO2, 30% 129.4, 126.6, 113.2, 71.1; IR (neat) ν 3019, 1740, 1643, 1215; HRMS
EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ: 7.34-7.26 (m, 3H); (ESI-TOF) calcd for C10H9O2 [M + H]+ 161.0603, found 161.0601.
7.22-7.19 (m, 2H); 6.01 (s, 1H); 5.28-5.27 (m, 1H); 4.55-4.51 (m, 1H);
4-(p-tolyl)furan-2(5H)-one (16b): 80% yield (70 mg); white solid; mp
112-114 oC; Rf = 0.40 (SiO2, 20% EtOAc/Hexanes); 1H NMR (400
MHz, CDCl3) δ: 7.42 (d, J = 8.2 Hz, 2H); 7.29 (d, J = 8.2 Hz, 2H); 6.33
(t, J = 1.7 Hz, 1H); 5.22 (d, J = 1.7 Hz, 2H); 2.43 (s, 3H); 13C NMR (100
MHz, CDCl3) δ: 174.2, 164.1, 142.6, 130.1, 126.9, 126.5, 112.0, 71.1,
2.82-2.77 (m, 1H); 2.51-2.46 (m, 1H); 13C NMR (100 MHz, CDCl3) δ:
150.3, 147.5, 139.1, 129.3, 129.0, 126.1, 85.6, 53.8, 34.8; IR (neat) ν
3461, 3110, 1725, 623; HRMS (ESI-TOF) calcd for C11H11BrNO2 [M +
H]+ 267.9973, found 267.9979.
(Z)-6-(bromomethylene)-4-(p-tolyl)-1,3-oxazinan-2-one (12b): 78% 21.7; IR (neat) ν 3021, 1745, 1622, 1216; HRMS (ESI-TOF) calcd for
yield (110 mg); white solid; mp 157-159 oC; Rf = 0.30 (SiO2, 30% C11H11O2 [M + H]+ 175.0759, found 175.0748.
1
EtOAc/Hexanes); H NMR (400 MHz, DMSO-d6) δ: 8.37 (s, 1H); 7.18
4-(4-fluorophenyl)furan-2(5H)-one (16c): 85% yield (76 mg); white
(d, J = 7.9 Hz, 2H); 7.15 (d, J = 7.9 Hz, 2H); 5.58 (s, 1H); 4.61-4.56 (m,
1H); 2.90 (dd, J = 14.5, 5.1 Hz, 1H); 2.62 (dd, J = 14.5, 5.8 Hz, 1H);
2.29 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 149.6, 148.9, 138.2,
137.4, 129.5, 126.4, 83.8, 51.8, 33.6, 21.1; IR (neat) ν 3465, 3012,
1723, 652; HRMS (ESI-TOF) calcd for C12H13BrNO2 [M + H]+
282.0130, found 282.0125.
1
solid; mp 120-122 oC; Rf = 0.40 (SiO2, 20% EtOAc/Hexanes); H NMR
(400 MHz, CDCl3) δ: 7.54-7.49 (m, 2H); 7.19-7.14 (m, 2H); 6.33 (t, J =
1.7 Hz, 1H); 5.20 (d, J = 1.7 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ:
173.8, 164.8 (d, J = 252 Hz), 162.7, 128.7 (d, J = 9 Hz), 126.2, 116.8
(d, J = 22 Hz), 113.0, 71.0; IR (neat) ν 3021, 1749, 1626, 1216; HRMS
(ESI-TOF) calcd for C10H8FO2 [M + H]+ 179.0508, found 179.0505.
(Z)-6-(bromomethylene)-4-(4-methoxyphenyl)-1,3-oxazinan-2-one
(12c): 82% yield (122 mg); white solid; mp 148-150 oC; Rf = 0.20
(SiO2, 30% EtOAc/Hexanes); 1H NMR (400 MHz, CDCl3) δ: 7.19 (d, J =
8.6 Hz, 2H); 6.91 (d, J = 8.6 Hz, 2H); 5.89 (s, 1H); 5.35 (s, 1H); 4.54
(dd, J = 8.6, 4.1 Hz, 1H); 3.81 (s, 3H); 2.82 (dd, J = 14.3, 4.1 Hz, 1H);
2.53 (dd, J = 14.3, 8.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 160.0,
150.3, 147.6, 131.0, 127.4, 114.6, 85.4, 55.5, 53.3, 34.9; IR (neat) ν
4-(4-chlorophenyl)furan-2(5H)-one (16d): 90% yield (88 mg); white
solid; mp 158-160 oC; Rf = 0.40 (SiO2, 20% EtOAc/Hexanes); 1H NMR
(400 MHz, CDCl3) δ: 7.47-7.42 (m, 4H); 6.37 (t, J = 1.8 Hz, 1H); 5.19
(d, J = 1.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 173.6, 162.6, 138.1,
129.8, 128.3, 127.8, 113.7, 70.9; IR (neat) ν 3019, 1749, 1623, 1215;
HRMS (ESI-TOF) calcd for C10H8ClO2 [M + H]+ 195.0213, found
195.0208.
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DOI: 10.1039/C5OB02125A
4-(4-methoxyphenyl)furan-2(5H)-one (16e): 65% yield (62 mg); IR (neat) ν 3026, 1725, 1635, 1216; HRMS (ESI-TOF) calcd for
o
white solid; mp 129-131 C; Rf = 0.30 (SiO2, 20% EtOAc/Hexanes); C12H12BrO2 [M + H]+ 267.0021, found 267.0015.
1H NMR (400 MHz, CDCl3) δ: 7.45 (d, J = 8.0 Hz, 2H); 6.96 (d, J = 8.0
4-phenyl-1-tosyl-1H-pyrrol-2(5H)-one (16l): 50% yield (78 mg);
white solid; mp 168-170 oC; Rf = 0.50 (SiO2, 30% EtOAc/Hexanes); 1H
NMR (400 MHz, CDCl3) δ: 7.99 (d, J = 8.2 Hz, 2H); 7.51-7.42 (m, 5H);
7.33 (d, J = 8.2 Hz, 2H); 6.30 (t, J = 1.4 Hz, 1H); 4.83 (d, J = 1.4 Hz,
2H); 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 168.7, 157.8, 145.3,
Hz, 2H); 6.23 (t, J = 4.0 Hz, 1H); 5.18 (d, J = 4.0 Hz, 2H); 3.87 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 174.4, 163.7, 162.5, 128.3, 122.4,
114.8, 110.7, 71.1, 55.6; IR (neat) ν 3025, 1749, 1625, 1220; HRMS
(ESI-TOF) calcd for C11H11O3 [M + H]+ 191.0708, found 191.0710.
4-hexylfuran-2(5H)-one (16f): 65% yield (55 mg); red liquid; Rf = 135.6, 131.7, 130.6, 129.9, 129.4, 128.1, 126.3, 118.8, 51.9, 21.8; IR
1
0.30 (SiO2, 20% EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 5.82 (neat) ν 3030, 1636, 1402, 1217; HRMS (ESI-TOF) calcd for
(p, J = 1.7 Hz, 1H); 4.72 (d, J = 1.7 Hz, 2H); 2.42-2.36 (m, 2H); 1.61- C17H16NO3S [M + H]+ 314.0851, found 314.0841.
1.53 (m, 2H); 1.39-1.26 (m, 6H); 0.88 (t, J = 7.0 Hz, 3H); 13C NMR
4-(4-ethylphenyl)-1-tosyl-1H-pyrrol-2(5H)-one (16m): 35% yield (60
(100 MHz, CDCl3) δ: 174.3, 170.8, 115.5, 73.2, 31.5, 29.0, 28.7, 27.3,
22.6, 14.1; IR (neat) ν 1748, 1638, 1216; HRMS (ESI-TOF) calcd for
C10H17O2 [M + H]+ 169.1229, found 169.1127.
mg); white solid; mp 150-152 oC; Rf
= 0.50 (SiO2, 30%
1
EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 7.98 (d, J = 8.3 Hz,
2H); 7.41 (d, J = 8.3 Hz, 2H); 7.33 (d, J = 8.1 Hz, 2H); 7.26 (d, J = 8.1
5,5-dimethyl-4-phenylfuran-2(5H)-one (16g): 89% yield (84 mg); Hz, 2H); 6.25 (t, J = 1.4 Hz, 1H); 4.81 (d, J = 1.4 Hz, 2H); 2.68 (q, J =
o
1
white solid; mp 95-97 C; Rf = 0.40 (SiO2, 20% EtOAc/Hexanes); H 7.5 Hz, 2H); 2.42 (s, 3H); 1.24 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz,
NMR (400 MHz, CDCl3) δ: 7.54-7.51 (m, 2H); 7.48-7.45 (m, 3H); 6.21 CDCl3) δ: 168.7, 157.8, 148.6, 145.0, 135.5, 129.7, 128.8, 127.9,
(s, 1H); 1.70 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 172.2, 171.5, 126.2, 117.6, 51.7, 28.8, 21.6, 15.2; IR (neat) ν 3019, 1701, 1167;
130.9, 130.4, 129.2, 127.6, 114.8, 87.4, 26.4; IR (neat) ν 3019, 1736, HRMS (ESI-TOF) calcd for C19H20NO3S [M + H]+ 342.1164, found
1643, 1215; HRMS (ESI-TOF) calcd for C12H13O2 [M + H]+ 189.0916, 342.1161.
found 189.0910
4-(4-methoxyphenyl)-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (16n):
o
4-phenyl-1-oxaspiro[4.5]dec-3-en-2-one (16h): 93% yield (106 mg); 36% yield (63 mg); white solid; mp 142-144 C; Rf = 0.30 (SiO2, 30%
1
1
colorless liquid; Rf = 0.40 (SiO2, 20% EtOAc/Hexanes); H NMR (400 EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 7.98 (d, J = 7.7 Hz,
MHz, CDCl3) δ: 7.51-7.41 (m, 5H); 6.13 (s, 1H); 2.03-1.92 (m, 2H); 2H); 7.44 (d, J = 8.4 Hz, 2H); 7.33(d, J = 7.7 Hz, 2H); 6.93 (d, J = 8.4
1.87-1.68 (m, 6H); 1.29-1.21 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: Hz, 2H); 6.17 (s, 1H); 4.79 (s, 2H); 3.85 (s, 3H); 2.42 (s, 3H); 13C NMR
172.9, 171.8, 131.1, 130.4, 129.0, 127.6, 115.8, 89.5, 34.6, 24.6, (100 MHz, CDCl3) δ: 168.9, 162.3, 157.4, 144.9, 135.6, 129.7, 127.9,
22.3; IR (neat) ν 3019, 1741, 1642, 1220; HRMS (ESI-TOF) calcd for 127.9, 123.1, 116.3, 114.7, 55.5, 51.7, 21.6; IR (neat) ν 3022, 1660,
C15H17O2 [M + H]+ 229.1229, found 229.1217.
1217; HRMS (ESI-TOF) calcd for C18H18NO4S [M + H]+ 344.0957,
found 344.0951.
5,5-dimethyl-4-(p-tolyl)furan-2(5H)-one (16i): 88% yield (89 mg);
colorless liquid; Rf = 0.40 (SiO2, 20% EtOAc/Hexanes); H NMR (500 5,5-dimethyl-1-tosyl-1H-pyrrol-2(5H)-one (16o): 78% yield (104
MHz, CDCl3) δ: 7.34 (d, J = 8.2 Hz, 2H); 7.16 (d, J = 8.2 Hz, 2H); 6.08 mg); white solid; mp 133-135 oC; Rf
(s, 1H); 2.30(s, 3H); 1.59 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 171.9, EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 7.97 (d, J = 8.3 Hz,
171.6, 141.4, 129.8, 127.6, 127.2, 113.5, 87.2, 26.4, 21.4; IR (neat) ν 2H); 7.30 (d, J = 8.3 Hz, 2H); 7.02 (d, J = 6.0 Hz, 1H); 5.86 (d, J = 6.0
3019, 1740, 1640, 1225; HRMS (ESI-TOF) calcd for C13H15O2 [M + H]+ Hz, 1H); 2.41 (s, 3H); 1.72 (s, 6H); 13C NMR (100 MHz, CDCl3) δ:
1
= 0.50 (SiO2, 30%
1
203.1072, found 203.1070.
168.4, 159.1, 144.8, 136.9, 129.4, 128.5, 122.5, 69.6, 25.0, 21.7; IR
(neat) ν 3019, 1715, 1167; HRMS (ESI-TOF) calcd for C13H16NO3S [M
+ H]+ 266.0851, found 266.0840.
4-(4-methoxyphenyl)-5,5-dimethylfuran-2(5H)-one (16j): 82% yield
(90 mg); colorless liquid; Rf = 0.30 (SiO2, 20% EtOAc/Hexanes); 1H
NMR (400 MHz, CDCl3) δ: 7.52-7.49 (m, 2H); 6.97-6.94 (m, 2H); 6.12 1-tosyl-1-azaspiro[4.5]dec-3-en-2-one (16p): 72% yield (110 mg);
(s, 1H); 3.84 (s, 3H); 1.68 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 171.8, white solid; mp 145-147 oC; Rf = 0.40 (SiO2, 30% EtOAc/Hexanes); 1H
171.4, 161.7, 129.4, 122.3, 114.6, 112.0, 87.0, 55.5, 26.5; IR (neat) ν NMR (400 MHz, CDCl3) δ: 7.96 (d, J = 8.3 Hz, 2H); 7.64 (d, J = 6.2 Hz,
3020, 1744, 1613, 1216; HRMS (ESI-TOF) calcd for C13H15O3 [M + H]+ 1H); 7.29 (d, J = 8.3 Hz, 2H); 5.94 (d, J = 6.2 Hz, 1H); 2.89-2.81 (m,
219.1021, found 219.1015.
2H); 2.41 (s, 3H); 1.93-1.79 (m, 3H); 1.69-1.66 (m, 2H); 1.55-1.37 (m,
3H); 13C NMR (100 MHz, CDCl3) δ: 168.3, 155.2, 144.6, 136.9, 129.2,
128.4, 123.4, 74.1, 34.1, 24.7, 24.2, 21.6; IR (neat) ν 2934, 1682,
1296, 1219; HRMS (ESI-TOF) calcd for C16H20NO3S [M + H]+
306.1164, found 306.1163.
4-(4-bromophenyl)-5,5-dimethylfuran-2(5H)-one (16k): 90% yield
(120 mg); white solid; mp 134-136 oC; Rf = 0.40 (SiO2, 20%
1
EtOAc/Hexanes); H NMR (400 MHz, CDCl3) δ: 7.60 (d, J = 8.6 Hz,
2H); 7.39 (d, J = 8.6 Hz, 2H); 6.20 (s, 1H); 1.67 (s, 6H); 13C NMR (100
MHz, CDCl3) δ: 171.0, 170.8, 132.5, 129.2, 129.0, 125.4, 87.2, 26.2;
Acknowledgements
8 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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Journal Name
ARTICLE
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CSIR-CDRI for the analytical support. We gratefully acknowledge the
financial support by CSIR (THUNDER, BSC 0102) and DST (SB/FT/CS-
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