Synthesis of Five-, Six-, and Seven-Membered 1,3- and 1,4-Heterocyclic Compounds via Intramolecular Hydroalkoxylation/Hydrothioalkoxylation of Alkenols/Thioalkenols

Article abstract of DOI:10.1021/acs.joc.5b00049

Intramolecular hydroalkoxylation/hydrothioalkoxylation of nitrogen-tethered alkenes and alcohols/thiols mediated by boron trifluoride etherate leads to five-membered thiazolidine, six-membered 1,4-oxazines (morpholines) and tetrahydro-2H-1,4-thiazines (th

Full text of DOI:10.1021/acs.joc.5b00049

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Article
Synthesis of 5,6- and 7-membered 1,3- and 1,4-heterocyclic
compounds via intramolecular hydroalkoxylation/
hydrothio-alkoxylation of alkenols/ thioalkenols
Manash Jyoti Deka, Kiran Indukuri, Sabera Sultana, Madhurjya Borah, and Anil Kumar Saikia
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00049 • Publication Date (Web): 10 Apr 2015
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Synthesis of 5,6- and 7-membered 1,3- and 1,4-heterocyclic
compounds via intramolecular hydroalkoxylation/hydrothio-
alkoxylation of alkenols/ thioalkenols
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Manash J. Deka, Kiran Indukuri, Sabera Sultana, Madhurjya Borah and Anil K. Saikia*
Department of Chemistry
Indian Institute of Technology Guwahati, Guwahati - 781039, India.
Fax: +91-361-2690762.
E-mail: asaikia@iitg.ernet.in
RECEIVED DATE (will be automatically inserted after manuscript is accepted).
ABSTRACT: Intramolecular hydroalkoxylation/hydrothioalkoxylation of nitrogen tethered
alkenes and alcohols/thiols mediated by boron trifluoride etherate leads to 5-membered
thiazolidine, 6-membered 1,4-oxazines (morpholines) and
(thiomorpholines) and 7-membered 1,4-oxazepanes in good yields.
tetrahydro-2H-1,4-thiazine
INTRODUCTION
Substituted 1,4-oxazines, tetrahydro-2H-1,4-thiazines and 1,4-oxazepanes are widely
distributed in many naturally occurring and biologically active molecules.1 For example,
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reboxetine (1), a morpholine containing compound shows antidepressant properties.2
Similarly, the compounds 2 and 3 possess anti-inflammatory and GABAB receptor-antagonist
properties.3 1,4-Oxazepane unit is found in naturally occurring alkaloid batrachotoxin (4),
which acts as ligand for CC chemokine receptors, such as CCRl (Figure 1).1d-e,4 These
heterocyclic scaffolds are versatile synthetic units in organic synthesis particularly for the
construction of agrochemicals, fungicides and bactericides.5 1,4-Oxazines are also used as
chiral auxiliary.6 On the other hand, thiazolines are known as flavouring agent and are found
in fruits and vegetables.7 They are also known to possess biological activities such as anti-
cancer,8 antimicrobial,9 anti-hypertensive10 activity and are used as building blocks in peptide
synthesis.11
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Figure 1. Biologically important morpholine and 1,4-oxazepane derivatives
Numerous synthetic approaches have been developed for the preparation of 1,4-oxazines and
1,4-oxazepanes such as ring closure of amino diols,12 amino alcohols and bromosulphonium
salts,13 double allylic substitution by amino alcohols,14 cyclization of N-tethered
haloalcohols,15 reductive amination of diketones,16 reductive etherification of N-tethered
ketoalcohols,17 cyclization of O-protected amino alcohols,18 oxirane ring opening by
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tosylamide and subsequent cyclization19 and ring opening of aziridines.20 Recently, Chemler
and co-workers have reported the synthesis of 1,4-oxazines via intramolecular cyclization of
N-tethered alkene-alkanol mediated by copper.21 The thiazolidines are synthesized by
Asinger method, a multicomponent reaction between an α-mercaptoketone, an aldehyde and
ammonia.22 Another method is condensation of cysteine and aldehydes.23 These methods
have their own merits and demerits but some of them suffer from serious problems such as
lack of selectivity,23a,c low yields15c,16,19 and harsh reaction conditions.21 Moreover,
intramolecular hydroalkoxylation/ hydrothio-alkoxylation reactions are currently of great
interest for the synthesis of five and six membered cyclic ethers and thioethers using γ-and δ-
hydroxy/ thio olefins in the presence of transition metal and lanthanide catalysts such as
[PtCl2(H2C=CH2)]2, AgOTf, Ph3PAuOTf, Au nanocluster (Au:PVP), CeCl3·7H2O−NaI,
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.
Ln(OTf)3, In(OTf)3 and Yb(OTf)3.24 Similarly, BF3 OEt2 has been used for the synthesis of
tetrahydrocannabinols, cannabinoid derivatives and in total synthesis of quinone and
hydroquinone sesquiterpenes via intermolecular addition of phenol to alkene.25 But, the use
.
of BF3 OEt2 in intramolecular hydroalkoxylation/ hydrothio-alkoxylation reaction for the
synthesis of 5,6- and 7-membered 1,3- and 1,4-heterocyclic compounds has not been reported
so far. We now present a general and transition metal free methodology for the synthesis of
1,4-oxazines, 1,4-oxazepanes and thiazolidines using intramolecular hydroalkoxylation/
hydrothioalkoxylation of alkenols/ thioalkenols mediated by boron trifluoride etherate at
ambient temperature in moderate to good yields.
RESULTS AND DISCUSSION
In continuation of our interest in oxygen and nitrogen heterocycles,26 we were in search of
synthesizing heterocyclic frameworks having two heteroatoms. To start with alkenol 5d was
treated with 1.2 equivalents of boron trifluoride etherate in dichloromethane at room
temperature for 5 h and 2-methyl-2-phenyl-4-tosylmorpholine 6d was obtained in 90% yield.
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The reaction was also performed in different Lewis and Brønsted acidic conditions and the
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results are shown in Table 1. The reaction with 0.5 equivalents of BF3 OEt2 furnished only
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38% yield over 12 h. Metal triflates such as zinc, copper, indium and silver triflates were also
screened for the reaction. Out of these, only zinc and indium triflates gave 5% and 30%
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Table 1. Optimization of the reaction conditiona
yields, respectively. Similarly, metal salts InCl3, CeCl3·7H2O and FeCl3 failed to give the
desired product, but starting material was recovered in 98% yield. Brønsted acids such as
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toluene sulfonic acid (TsOH), camphorsulfonic acid (CSA) and triflic acid (TfOH) gave 19%,
26% and 52% yields, respectively, whereas HF did not work. The reaction was also screened
in other solvents such as toluene (entry 14), acetonitrile (entry 15) and THF (entry 16), and
gave 72%, 26% and 53% yields, respectively. Therefore, BF3·Et2O in CH2Cl2 at room
temperature was found to be the best conditions for this reaction.
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Having obtained the optimized conditions, we further examined the scope of the reaction with
a variety of substrates, which were synthesized according to the literature methods either by
allylation of N-tosyl amino alcohols/ thiols or substitution reaction between phenyl acetyl
bromide and allyl/homoallyl tosylamide followed by the reduction of ketone (Scheme 1).27
Scheme 1. Synthesis of starting materials
It was observed from the Table 2 that, primary and secondary alkenols, having alkyl and aryl
substituted olefinic groups, 5a-5l (entries 1-12) gave the desired 1,4-oxazines in good yields.
In case of secondary alkenols, the substrates having electron-withdrawing aromatic
substituents (entries 7-11) gave good yields, whereas electron-donating aromatic substituted
alkenol 5l decomposed under these reaction conditions (entry 12). The chiral substrates 5e
and 5f (entries 5 and 6) gave single diastereomers with 2-alkyl and 5-phenyl groups cis to
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Table 2. Synthesis of 1,4- oxazines and 1,4-oxazepanes
Ts
N
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R1
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BF3 OEt2 (1.2 equiv)
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R2
OH
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n = 1, 2
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Table 2. continued
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each other. Similarly, the secondary alkenols 5g, 5i and 5j also produced exclusively single
diastereomers having a cis relationship between the phenyl groups at 2,6-positions. The cis
stereochemistry was confirmed by X-ray crystallographic structures of 6f,g (Figure 2).28
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This method also worked well for the phenolic compound 5m (entry 13) and gave 2-methyl-
2-phenyl-4-tosyl-3,4-dihydro-2H-benzo[b]-[1,4]-oxazine 6m in 68% yield. Similarly,
alkenols 5n-5q (entries 14-17) gave the corresponding 1,4-oxazepanes 6n-q in good yields.
The isomeric alkenols 5n and 5o gave same product 6n. On the other hand, substrate having
terminal alkene 5r (entry 18) was unreactive under the same reaction conditions and starting
material was recovered in 98%.
6f
6g
Figure 2. ORTEP Diagram of compounds 6f and 6g
After successful study of this methodology to the synthesis of 1,4-oxazines and oxazepanes,
its application to the synthesis of 1,4-thiaoxazines and thiazepanes was explored. The starting
material thioalkene 5s-t (Table 3, entries 1 and 2) when treated with boron trifluoride etherate
under the same reaction conditions gave 2-methyl-2-phenyl-4-tosylthiaoxazine 6s and 2-
(prop-1-en-2-yl)-4-tosylthiomorpholine 6t in 70% and 73% yields, respectively. On the other
hand, substrates 5u-x (Table 3, entries 3-6) having substitution at the α-position to N-tosyl
group gave thiazolidines 7u-x (Table 3) in 66%, 71%, 59% and 74% yields, respectively.
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Substrate 5v and 5x (entries 4 and 6) gave two inseparable diastereomers 7v and 7x in 71%
and 74% overall yield, respectively. The substrate 5w gave hydrolyzed product 7w under this
reaction conditions. On the other hand, 5x having hydroxyl and thiol groups gave thiazolidine
7x selectively, without formation of any morpholine products. The stereochemistry of the
Table 3. Synthesis of tetrahydro-2H-1,4-thiazine and thiazolidine
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thiazolidine was determined by H and nOe experiment of 7u (Figure 3). There is a strong
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nOe between protons at C-2 and C-4 of 7u, which confirms that they are cis to each other.
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nOe
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H
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H
MeO2C
4
S
Figure 3. nOe diagram of compound 7u
The exact mechanism of formation of 1,4-oxazines and 1,4-oxazepanes or their sulfur
analogues
via
intramolecular
hydroalkoxylation/hydrothioalkoxylation
of
alkenols/thioalkenols mediated by boron trifluoride etherate is not known. But mechanisms
for the hydroalkoxylation of alkenols promoted by transition metal or lanthanide reagents are
proposed by different groups, where metal forms a coordinated complex with alcohols and
olefinic groups.21 The same mechanism cannot be applied in this case as boron cannot form
such type of complex. An alternative mechanism is proposed which can be explained as
follows. The alkenol/thioalkenols 5 reacts with boron trifluoride etherate to form intermediate
A, an ion pair, of which the proton adds to the double bond to give more stable carbocation
B. The carbocation B is then attacked by alkoxide/ ion to form 1,4-oxazines, 1,4-oxazepanes
and thiazine (Scheme 2, I). This explains the incapability of formation of product by the
substrate 5r, where the carbocation B is not stable. On the other hand, the mechanism for the
formation of thiazolidine products 7u-x can be explained as follows. First thiol reacts with
boron trifluoride etherate to form intermediate C, an ion pair, of which the proton adds to the
double bond to give carbocation D, which is similar to intermediate B. This intermediate D
undergoes 1,2 hydride shift to give rearranged carbocation E, which is stabilized by ester or
hydroxyl groups present at position 2. Finally, the thiol group attacks the carbocation E to
give more stable five membered compounds 7u-x (Scheme 2, II).24k The presence of ester and
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hydroxyl groups at 2-position are crucial for the formation of five membered ring, which can
be exemplified by the fact that the compound 5t having methyl group at 2-position gave six
membered ring 6t.
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Scheme 2. Plausible mechanism of the reaction
CONCLUSIONS
In conclusion, we have developed a mild and efficient general method for the synthesis of
substituted 1,4-oxazines, 1,4-oxazepanes and thiazolidines via intramolecular cyclization
reaction of alkenols/thioalkenols in good yields and excellent diastereoselectivity. The
reaction is highly atom economic and compatible to a wide range of functional groups such
as ester, hydroxy, -CF3, bromo and alkyne. Furthermore, N-tethered alkenthiol having
substituents at the α-position to nitrogen provides an excellent access to a diverse array of
thiazolidine derivatives with 2,4-cis relationship.
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EXPERIMENTAL SECTION
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General Information: All the reagents were of reagent grade (AR grade) and were used
as purchased without further purification. Silica gel (60-120 mesh size) was used for column
chromatography. Reactions were monitored by TLC on silica gel GF254 (0.25 mm). Melting
points were recorded in an open capillary tube and are uncorrected. Fourier transform-infra
red (FT-IR) spectra were recorded as neat liquid or KBr pellets. NMR spectra were recorded
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in CDCl3 with tetramethylsilane as the internal standard for H (600 MHz, 400 MHz) or C
(150 MHz, 100 MHz) NMR. Chemical shifts (δ) are reported in ppm and spin-spin coupling
constants (J) are given in Hz. HRMS spectra were recorded using Q-TOF mass spectrometer.
Synthesis of starting materials
General procedure for the synthesis of starting materials 5a-f, 5h-o and 5q-x: Amino
alcohol or thiol (8a-f, 8h-o and 8q-x) (1.0 equiv) in anhydrous DMF was added to the stirred
solution of sodium hydride (1.2 equiv) in dry DMF under inert atmosphere at 0 °C. After
complete evolution of hydrogen gas, substituted allyl bromide (1.0 equiv) in DMF was added
drop wise for 10 min and the reaction was stirred at room temperature for 16 h. After
completion of the reaction, brine solution was added to the reaction mixture and extracted
with ethylacetate. The organic layer was further washed with brine solution for 2-3 times.
The combined organic layers were dried over Na2SO4 and concentrated in rotary evoparator.
The obtained crude was subjected to column chromatography over silica gel giving
corresponding products (5a-f, 5h-o and 5q-x).
General procedure for the synthesis of starting materials 5g,p: Tosyl amide 9g,p (1.0
equiv) in anhydrous DMF was added to the stirred solution of sodium hydride (1.2 equiv) in
dry DMF under inert atmosphere at 0 °C. After complete evolution of hydrogen gas,
bromoacetophenone (1.0 equiv) in DMF was added drop wise for 10 min and the reaction
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was stirred at room temperature for 10 h. After completion of the reaction, brine solution was
added to the reaction mixture and extracted with ethyl acetate. The organic layer was further
washed with brine solution (2x15 mL). The combined organic layers were dried over Na2SO4
and concentrated in rotary evaporator. The crude was subjected to column chromatography
over silica gel giving corresponding products 10g,p.
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10g,p (1.0 equiv) in dry THF was added to a stirred suspension of LAH (1.0 equiv) in THF
at 0 °C. The reaction mixture was stirred at room temperature for 5 h, after that the reaction
mixture was quenched with 2 N NaOH and passed through celite pad and washed with ethyl
acetate. The mixture was treated with brine, extracted with EtOAc and the combined organic
extracts were dried over anhydrous Na2SO4, filtered and concentrated invacuo. The crude
product was purified using column chromatography to give resulted compounds 5g,p.
N-(2-Hydroxyethyl)-4-methyl-N-(2-methylallyl)benzene-sulfonamide (5a):
o
White solid; mp 74-76 C; Rf (hexane/ EtOAc 7:3) 0.47; yield 393 mg, 73%; 1H NMR (400
MHz, CDCl3) δ 1.70 (s, 3 H), 2.40 (s, 3 H), 3.15 (t, J = 5.6 Hz, 2 H), 3.65 (t, J = 5.6 Hz, 2 H),
3.68 (s, 2 H), 4.84 (s, 1 H), 4.88 (s, 1 H), 7.28 (d, J = 7.6 Hz, 2 H), 7.68 (d, J = 8.8 Hz, 2 H);
13C NMR (100 MHz, CDCl3) δ 20.0, 21.7, 50.6, 56.4, 61.2, 115.0, 127.5, 129.9, 136.0, 141.0,
143.8; IR (KBr, neat) 3440, 2924, 1334, 1159, 1020, 708 cm-1; HRMS (ESI) calcd. for
C13H20NO3S (M + H)+ 270.1158, found 270.1157.
(R)-N-(2-Hydroxy-1-phenylethyl)-4-methyl-N-(2-methy-lallyl)benzenesulfonamide (5b):
25
Colourless gum; Rf (hexane/ EtOAc 7:3) 0.54; yield 566 mg, 82%; [α]D = - 81.0 (c = 0.15,
1
CH2Cl2). H NMR (400 MHz, CDCl3) δ 1.68 (s, 3 H), 2.45 (s, 3 H), 3.32 (d, J = 16.0 Hz, 1
H), 3.93 (d, J = 16.0 Hz, 1 H), 4.02 (dd, J = 11.2 and 6.0 Hz, 1 H), 4.16 (dd, J = 11.2 and 8.8
Hz, 1 H), 4.82 (s, 1 H), 4.87 (s, 1 H), 4.95 (dd, J = 8.8 and 6.4 Hz, 1 H), 6.83 (d, J = 7.6 Hz, 2
13
H), 7.16-7.27 (m, 3 H), 7.29 (d, J = 8.0 Hz, 2 H), 7.71 (d, J = 8.4 Hz, 2 H); C NMR (100
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MHz, CDCl3) δ 20.0, 21.7, 51.3, 62.8, 62.9, 114.0, 127.5, 128.5, 128.6, 128.8, 129.9, 135.2,
138.0, 142.6, 143.7; IR (KBr, neat) 3532, 2953, 2925, 1742, 1658, 1439, 1339, 1159, 1093,
816, 709 cm-1; HRMS (ESI) calcd. for C19H24NO3S (M + H)+ 346.1471, found 346.1477.
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(S)-Methyl 3-hydroxy-2-(4-methyl-N-(2-methylallyl)phenyl-sulfonamido)propanoate (5c):
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Pale yellow oil; Rf (hexane/ EtOAc 7:3) 0.46; yield 432 mg, 66%; [α]D = - 29.0 (c = 0.1,
CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 1.67 (s, 3 H), 2.43 (s, 3 H), 3.59 (s, 3 H), 3.75 (d, J =
16.2 Hz, 1 H), 3.82 (dd, J = 11.4 and 6.0 Hz, 1 H), 3.92 (d, J = 15.6 Hz, 1 H), 4.10-4.14 (m,
1 H), 4.41 (t, J = 6.6 Hz, 1 H), 4.94 (s, 1 H), 5.00 (s, 1 H), 7.30 (d, J = 7.8 Hz, 2 H), 7.73 (d, J
= 8.4 Hz, 2 H); 13C NMR (150 MHz, CDCl3) δ 20.0, 21.7, 52.3, 53.5, 61.0, 61.7, 114.9,
127.8, 129.7, 136.8, 141.6, 143.9, 170.4; IR (KBr, neat) 3528, 2924, 2855, 1598, 1496, 1330,
1159, 1020, 898, 701 cm-1; HRMS (ESI) calcd. for C15H22NO5S (M + H)+ 328.1213, found
328.1219.
N-(2-Hydroxyethyl)-4-methyl-N-(2-phenylallyl)benzene-sulfonamide (5d):
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Colourless solid, mp 83-85 C; Rf (hexane/ EtOAc 7:3) 0.48; yield 596 mg, 90%; H NMR
(600 MHz, CDCl3) δ 2.44 (s, 3 H), 3.16 (t, J = 5.4 Hz, 2 H), 3.56 (t, J = 5.4 Hz, 2 H), 4.24 (s,
2 H), 5.23 (s, 1 H), 5.50 (s, 1 H), 7.26-7.36 (m, 5 H), 7.46 (d, J = 7.8 Hz, 2 H), 7.67 (d, J =
7.8 Hz, 2 H); 13C NMR (150 MHz, CDCl3) δ 21.7, 50.3, 53.9, 61.2, 117.0, 126.7, 127.7,
128.5, 128.8, 130.0, 135.4, 138.0, 143.2, 143.9; IR (KBr, neat) 3527, 2925, 1598, 1495, 1334,
1185, 1016, 916, 709 cm-1; HRMS (ESI) calcd. for C18H22NO3S (M + H)+ 332.1315, found
332.1318.
(S)-N-(1-Hydroxypropan-2-yl)-4-methyl-N-(2-phenylallyl)-benzenesulfonamide (5e):
Pale yellow gum; Rf (hexane/ EtOAc 7:3) 0.53; yield 449 mg, 65%; [α]D25 = + 26.0 (c = 0.14,
CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 0.86 (d, J = 6.6 Hz, 3 H), 2.43 (s, 3 H), 3.35 (dd, J =
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11.4 and 4.8 Hz,1 H), 3.48 (dd, J = 12.0 and 9.0 Hz, 1 H), 3.91-3.97 (m, 1 H), 4.04 (d, J =
15.6 Hz, 1 H), 4.62 (d, J = 16.2 Hz, 1 H), 5.39 (s, 1 H), 5.45 (s, 1 H), 7.25-7.40 (m, 5 H),
7.46 (t, J = 7.2 Hz, 2 H), 7.69 (d, J = 8.4 Hz, 2 H); 13C NMR (150 MHz, CDCl3) δ 13.6, 21.7,
48.3, 56.2, 65.0, 115.9, 126.9, 127.5, 128.5, 128.8, 130.0, 137.5, 138.6, 143.7, 145.5; IR
(KBr, neat) 3538, 2925, 1598, 1495, 1334, 1155, 1026, 912, 738 cm-1; HRMS (ESI) calcd.
for C19H24NO3S (M + H)+ 346.1471, found 346.1469.
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(S)-N-(1-Hydroxy-3-phenylpropan-2-yl)-4-methyl-N-(2-phenylallyl)benzenesulfonamide (5f):
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Pale yellow oil; Rf (hexane/ EtOAc 4:1) 0.55; yield 598 mg, 71%; [α]D = - 26.0 (c = 0.1,
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CH2Cl2). H NMR (600 MHz, CDCl3) δ 2.43 (s, 3 H), 2.54 (dd, J = 13.8 and 4.2 Hz, 1 H),
2.73 (dd, J = 13.2 and 10.8 Hz, 1 H), 3.44 (dd, J = 11.4 and 3.0 Hz, 1 H), 3.57 (dd, J = 12.0
and 9.0 Hz, 1 H), 3.88-3.94 (m, 1 H), 4.31 (d, J = 16.2 Hz, 1 H), 4.57 (d, J = 16.2 Hz, 1 H),
5.44 (s, 1 H), 5.49 (s, 1 H), 6.93 (d, J = 6.6 Hz, 2 H), 7.16-7.21 (m, 2 H), 7.29 (d, J = 7.8 Hz,
2 H), 7.32-7.36 (m, 4 H), 7.43 (d, J = 8.4 Hz, 2 H), 7.71 (d, J = 8.4 Hz, 2 H); 13C NMR (150
MHz, CDCl3) δ 21.7, 36.0, 49.5, 62.2, 62.4, 116.3, 126.8, 126.9, 127.8, 128.5, 128.8, 128.83,
129.2, 130.0, 137.5, 138.0, 138.6, 143.9, 145.4; IR (KBr, neat) 3479, 2926, 1494, 1331, 1157,
1041, 814, 701 cm-1; HRMS (ESI) calcd. for C25H28NO3S (M + H)+ 422.1784, found
422.1781.
N-(2-Hydroxy-2-phenylethyl)-4-methyl-N-(2-phenylallyl)-benzenesulfonamide (5g):
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Colourless gum; Rf (hexane/ EtOAc 4:1) 0.50; yield 459 mg, 56%; H NMR (400 MHz,
CDCl3) δ 2.41 (s, 3 H), 3.05 (dd, J = 15.2 and 2.4 Hz, 1 H), 3.25 (dd, J = 15.2 and 9.6 Hz, 1
H), 4.16 (d, J = 14.8 Hz, 1 H), 4.46 (d, J = 14.8 Hz, 1 H), 4.79 (dd, J = 10.0 and 2.4 Hz, 1
H), 5.23 (s, 1 H), 5.54 (s, 1 H), 7.22-7.37 (m, 10 H), 7.45-7.49 (m, 2 H), 7.65 (d, J = 8.4 Hz,
2 H); 13C NMR (150 MHz, CDCl3) δ 21.4, 53.8, 56.1, 72.1, 117.1, 125.7, 126.0, 126.4, 127.2,
127.4, 127.7, 128.3, 128.6, 129.6, 129.7, 137.8, 142.9, 143.7; IR (KBr, neat) 3538, 2925,
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1598, 1495, 1334, 1155, 1026, 912, 738 cm-1; HRMS (ESI) calcd. for C24H25NNaO3S (M +
Na)+ 430.1447, found 430.1456.
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N-(2-(3-Bromophenyl)-2-hydroxyethyl)-4-methyl-N-(2-methylallyl)benzenesulfonamide (5h):
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White solid, mp 89-91 C; Rf (hexane/ EtOAc 9:1) 0.39; yield 711 mg, 84%; H NMR (600
MHz, CDCl3) δ 1.70 (s, 3 H), 2.42 (s, 3 H), 3.04 (dd, J = 15.0 and 3.0 Hz, 1 H), 3.31 (dd, J =
15.0 and 9.6 Hz, 1 H), 3.43 (brs, 1 H), 3.58 (d, J = 14.4 Hz, 1 H), 3.92 (d, J = 15.0 Hz, 1 H),
4.86 (d, J = 9.0 Hz, 1 H), 4.89 (s, 1 H), 4.97 (s, 1 H), 7.18 (t, J = 7.8 Hz, 1 H), 7.23 (d, J = 7.8
Hz, 1 H), 7.30 (d, J = 7.8 Hz, 2 H), 7.38 (d, J = 7.8 Hz, 1 H), 7.47 (s, 1 H), 7.70 (d, J = 8.4
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Hz, 2 H); C NMR (100 MHz, CDCl3) δ 20.0, 21.7, 56.4, 56.9, 72.0, 115.7, 122.8, 124.8,
127.5, 129.2, 130.0, 130.2, 131.0, 135.9, 140.8, 144.0, 144.1; IR (KBr, neat) 3482, 2923,
1597, 1427, 1333, 1155, 1091, 922, 655 cm-1; HRMS (ESI) calcd. for C19H23BrNO3S (M +
H)+ 424.0577, found 424.0574.
N-(2-(3-Bromophenyl)-2-hydroxyethyl)-4-methyl-N-(2-phenylallyl)benzenesulfonamide (5i):
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Pale yellow gum, Rf (hexane/ EtOAc 4:1) 0.50; yield 757 mg, 78%; H NMR (600 MHz,
CDCl3) δ 2.42 (s, 3 H), 3.01-3.07 (m, 2 H), 3.21 (dd, J = 15.0 and 9.0 Hz, 1 H), 4.12 (d, J =
14.4 Hz, 1 H), 4.46 (d, J = 14.4 Hz, 1 H), 4.73 (d, J = 9.6 Hz, 1 H), 5.23 (s, 1 H), 5.56 (s, 1
H), 7.16 (t, J = 7.2 Hz, 2 H), 7.29 (d, J = 7.8 Hz, 2 H), 7.32-7.38 (m, 4 H), 7.40 (s 1 H), 7.48
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(d, J = 7.8 Hz, 2 H), 7.65 (d, J = 7.8 Hz, 2 H); C NMR (150 MHz, CDCl3) δ 21.7, 54.4,
56.3, 71.8, 117.6, 122.8, 124.7, 126.7, 127.7, 128.7, 128.9, 129.1, 130.1, 130.2, 131.0, 135.2,
137.8, 143.1, 143.9, 144.2; IR (KBr, neat) 3501, 2923, 1597, 1449, 1334, 1157, 1093, 911,
696 cm-1; HRMS (ESI) calcd. for C24H25BrNO3S (M + H)+ 486.0733, found 486.0730.
N-(2-Hydroxy-2-(3-(phenylethynyl)phenyl)ethyl)-4-methyl-N-(2-phenylallyl)-
benzenesulfonamide (5j):
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Plae yellow gum; Rf (hexane/ EtOAc 4:1) 0.40; yield 720 mg, 71%; H NMR (600 MHz,
CDCl3) δ 2.41 (s, 3 H), 3.02-3.08 (m, 2 H), 3.26 (dd, J = 15.0 and 9.6 Hz, 1 H), 4.15 (d, J =
14.4 Hz, 1 H), 4.47 (d, J = 14.4 Hz, 1 H), 4.79 (d, J = 9.0 Hz, 1 H), 5.25 (s, 1 H), 5.56 (s, 1
H), 7.23 (d, J = 7.8 Hz, 1 H), 7.26-7.36 (m, 9 H), 7.43 (d, J = 7.8 Hz, 2 H), 7.50 (d, J = 7.8
Hz, 2 H), 7.53 (d, J = 7.8 Hz, 2 H), 7.66 (d, J = 8.4 Hz, 2 H); 13C NMR (150 MHz, CDCl3) δ
21.7, 54.3, 56.3, 72.0, 89.4, 89.8, 117.5, 123.4, 123.6, 126.0, 126.7, 127.7, 128.5, 128.57,
128.6, 128.7, 128.9, 129.2, 130.0, 131.1, 131.8, 135.4, 138.0, 141.9, 143.1, 144.1; IR (KBr,
neat) 3497, 2923, 1599, 1493, 1444, 1334, 1157, 1093, 912, 812, 696 cm-1; HRMS (ESI)
calcd. for C32H30NO3S (M + H)+ 508.1941, found 508.1939.
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N-(2-Hydroxy-2-(4-(trifluoromethyl)phenyl)ethyl)-4-methyl-N-(2-methylallyl)benzene-
sulfonamide (5k):
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Colorless gum; Rf (hexane/ EtOAc 9:1) 0.50; yield 653 mg, 79%; H NMR (400 MHz,
CDCl3) δ 1.72 (s, 3 H), 2.42 (s, 3 H), 3.05 (d, J = 15.2, 1 H), 3.31 (dd, J = 15.2 and 9.6 Hz, 1
H), 3.58 (d, J = 15.2 Hz, 2 H), 3.95 (d, J = 14.4 Hz, 1 H), 4.90 (s, 1 H), 4.95-4.99 (m, 2 H),
7.31 (d, J = 8.0 Hz, 2 H), 7.46 (d, J = 8.0 Hz, 2 H), 7.58 (d, J = 8.0 Hz, 2 H), 7.70 (d, J = 8.0
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Hz, 2 H); C NMR (150 MHz, CDCl3) δ 20.0, 21.7, 56.5, 57.0, 72.3, 115.8, 124.3 (q, J =
270.0 Hz), 125.6, 126.5, 127.5, 130.1, 130.2 (q, J = 31.5 Hz), 135.9, 140.9, 144.1, 145.8; 19F
NMR (376 MHz, C6F6/CDCl3): 99.22; IR (KBr, neat) 3502, 2925, 1598, 1417, 1326, 1158,
1123, 1067, 921, 815, 777 cm-1; HRMS (ESI) calcd. for C20H23F3NO3S (M + H)+ 414.1345,
found 414.1359.
N-(2-Hydroxy-2-(4-methoxyphenyl)ethyl)-4-methyl-N-(2-methylallyl)benzenesulfonamide
(5l):
1
Pale yellow gum; Rf (hexane/ EtOAc 4:1) 0.48; yield 503 mg, 67%; H NMR (600 MHz,
CDCl3) δ 1.71 (s, 3 H), 2.41 (s, 3 H), 3.03 (dd, J = 15.6 and 3.0 Hz, 1 H), 3.16 (brs, 1 H),
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3.35 (dd, J = 15.6 and 9.6 Hz, 1 H), 3.61 (d, J = 14.4 Hz, 1 H), 3.79 (s, 3 H), 3.90 (d, J = 15.0
Hz, 1 H), 4.85 (d, J = 9.0 Hz, 1 H), 4.88 (s, 1 H), 4.96 (s, 1 H), 6.86 (d, J = 9.0 Hz, 2 H),
7.24 (d, J = 9.0 Hz, 2 H), 7.29 (d, J = 7.8 Hz, 2 H), 7.71 (d, J = 8.4 Hz, 2 H); 13C NMR (150
MHz, CDCl3) δ 20.1, 21.7, 55.5, 56.6, 56.7, 72.2, 114.1, 115.5, 127.3, 127.5, 130.0, 133.9,
136.3, 141.0, 143.9, 159.5; IR (KBr, neat) 3508, 2924, 1612, 1514, 1444, 1334, 1156, 1033,
919, 656 cm-1; Anal. calcd. for C20H26NO4S: C 63.97, H 6.71, N 3.73, found C 64.05, H 6.76,
N 3.64.
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N-(2-Hydroxyphenyl)-4-methyl-N-(2-phenylallyl)-benzenesulfonamide (5m):
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Pale yellow gum; Rf (hexane/ EtOAc 7:3) 0.57; yield 570 mg, 75%; H NMR (400 MHz,
CDCl3) δ 2.45 (s, 3 H), 4.94 (s, 1 H), 5.26 (s, 1 H), 5.68 (s, 1 H), 6.32 (d, J = 8.4 Hz, 1 H),
6.50 (t, J = 8.6 Hz, 1 H), 6.87 (d, J = 8.4 Hz, 1 H), 7.13 (t, J = 7.6 Hz, 1 H), 7.26-7.45 (m, 8
H), 7.52 (d, J = 8.4 Hz, 2 H); 13C NMR (150 MHz, CDCl3) δ 21.9, 55.6, 117.4, 117.8, 120.1,
124.9, 126.8, 127.5, 128.5, 128.6, 128.9, 129.8, 130.1, 133.7, 137.7, 142.2, 144.6, 155.3; IR
(KBr, neat) 3508, 2852, 1597, 1493, 1344, 1161, 1091, 814, 704 cm-1; HRMS (ESI) calcd.
for C22H22NO3S (M + H)+ 380.1315, found 380.1323.
N-(2-Hydroxyethyl)-4-methyl-N-(3-methylbut-3-en-1-yl)-benzenesulfonamide (5n):
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Colourless oil; Rf (hexane/ EtOAc 7:3) 0.40; yield 490 mg, 90%; H NMR (600 MHz,
CDCl3) δ 1.70 (s, 3 H), 2.24 (t, J = 7.8 Hz, 2 H), 2.41 (s, 3 H), 2.57 (brs, 1 H), 3.23 (t, J = 5.4
Hz, 2 H ), 3.26 (t, J = 7.8 Hz, 2 H ), 3.74 (t, J = 4.8 Hz, 2 H ), 4.67 (s, 1 H), 4.76 (s, 1 H),
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7.30 (d, J = 7.8 Hz, 2 H), 7.69 (d, J = 7.8 Hz, 2 H); C NMR (100 MHz, CDCl3) δ 21.6,
22.6, 37.0, 48.6, 51.0, 61.4, 112.4, 127.4, 129.9, 136.1, 142.3, 143.7; IR (KBr, neat) 3517,
2931, 1598, 1454, 1378, 1158, 1088, 815, 734 cm-1; HRMS (ESI) calcd. for C14H21NNaO3S
(M + Na)+ 306.1134, found 306.1133.
N-(2-Hydroxyethyl)-4-methyl-N-(3-methylbut-2-en-1-yl)-benzenesulfonamide (5o):
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Pale yellow oil; Rf (hexane/ EtOAc 7:3) 0.40; yield 496 mg, 81%; H NMR (400 MHz,
CDCl3) δ 1.62 (s, 3 H), 1.67 (s, 3 H), 2.43 (s, 3 H), 3.20 (t, J = 5.6 Hz, 2 H), 3.72 (t, J = 4.8
Hz, 2 H ), 3.84 (d, J = 7.2 Hz, 2 H ), 5.02 (dt, J = 6.8 and 1.6 Hz, 1 H), 7.31 (d, J = 8.4 Hz, 2
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H), 7.70 (d, J = 7.6 Hz, 2 H); C NMR (100 MHz, CDCl3) δ 18.0, 21.7, 25.9, 47.1, 49.9,
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61.4, 119.0, 127.5, 129.9, 136.6, 137.7, 143.6; IR (KBr, neat) 3524, 2926, 1598, 1448, 1336,
1158, 1090, 816, 702 cm-1; HRMS (ESI) calcd. for C14H21NaNO3S (M + Na)+ 306.1134,
found 306.1136.
N-(2-Hydroxy-2-phenylethyl)-4-methyl-N-(3-methylbut-3-en-1-yl)benzenesulfonamide (5p):
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Pale yellow gum; Rf (hexane/ EtOAc 7:3) 0.60; yield 470 mg, 66%; H NMR (600 MHz,
CDCl3) δ 1.71 (s, 3 H), 2.14 (t, J = 7.2 Hz, 2 H), 2.41 (s, 3 H), 3.05 (dd, J = 13.2 and 6.6 Hz,
2 H), 3.26-3.35 (m, 2 H), 4.68 (s, 1 H), 4.78 (s, 1 H), 4.95 (dd, J = 9.0 and 3.6 Hz, 1 H), 7.28-
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7.39 (m, 7 H), 7.71 (d, J = 8.4 Hz, 2 H); C NMR (150 MHz, CDCl3) δ 21.7, 22.7, 37.4,
49.1, 57.1, 73.0, 112.5, 126.1, 127.3, 127.5, 128.8, 129.9, 130.0, 141.6, 142.4, 143.8; IR
(KBr, neat) 3504, 2924, 1494, 1454, 1329, 1157, 1092, 814, 700 cm-1; HRMS (ESI) calcd.
for C20H26NO3S (M + H)+ 360.1628, found 360.1635.
N-(2-Hydroxyethyl)-4-methyl-N-(3-phenylbut-3-en-1-yl)benzenesulfonamide (5q):
1
Pale yellow gum; Rf (hexane/ EtOAc 7:3) 0.45; yield 492 mg, 67%; H NMR (600 MHz,
CDCl3) δ 2.41 (s, 3 H), 2.82 (t, J = 7.2 Hz, 2 H), 3.23-3.27 (m, 4 H), 3.73 (t, J = 5.4 Hz, 2 H),
5.01 (s, 1 H), 5.36 (s, 1 H), 7.28 (d, J = 8.4 Hz, 2 H), 7.33 (t, J = 7.2 Hz, 3 H), 7.38 (d, J = 7.8
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Hz, 2 H), 7.68 (d, J = 8.4 Hz, 2 H); C NMR (150 MHz, CDCl3) δ 21.7, 35.4, 49.5, 51.6,
61.5, 114.6, 126.1, 127.5, 128.0, 128.7, 130.0, 136.3, 140.1, 143.7, 145.0; IR (KBr, neat)
3427, 2923, 2853, 1494, 1463, 1261, 1154, 1089, 1020, 801, 705 cm-1; HRMS (ESI) calcd.
for C19H23NNaO3S (M + Na)+ 368.1291, found 368.1300.
N-(2-Mercaptoethyl)-4-methyl-N-(2-phenylallyl)benzene-sulfonamide (5s):
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Pale yellow gum; Rf (hexane/ EtOAc 7.3) 0.60; yield 638 mg, 92%; H NMR (600 MHz,
CDCl3) δ 2.43 (s, 3 H), 2.49 (dd, J = 8.8 and 5.6 Hz, 2 H), 3.21 (dd, J = 10.8 and 8.0 Hz, 2
H), 4.18 (s, 2 H), 5.18 (s, 1 H), 5.46 (s, 1 H), 7.26-7.33 (m, 5 H), 7.41-7.46 (m, 2 H), 7.66 (d,
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J = 8.0 Hz, 2 H); C NMR (150 MHz, CDCl3) δ 21.7, 35.9, 47.4, 53.2, 117.3, 126.6, 127.5,
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128.4, 128.7, 130.0, 135.7, 137.8, 142.7, 143.8; IR (KBr, neat) 3058, 2924, 1597, 1445, 1339,
1159, 1090, 914, 818, 658 cm-1; HRMS (ESI) calcd. for C18H22NO2S2 (M + H)+ 348.1086,
found 348.1078.
N-(1-Mercaptopropan-2-yl)-4-methyl-N-(2-phenylallyl)benzenesulfonamide (5t):
Pale yellow gum; Rf (hexane/ EtOAc 19:1) 0.30; yield 267 mg, 74%; [α]D25 = + 8.0 (c = 0.1,
CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 1.07 (d, J = 6.6 Hz, 3 H), 2.36-2.41 (m, 1 H), 2.43 (s,
3 H), 2.54-2.59 (m, 1 H), 3.81-3.87 (m, 1 H), 4.07 (d, J = 16.2 Hz, 1 H), 4.49 (d, J = 16.2 Hz,
1 H), 5.36 (s, 1 H), 5.46 (s, 1 H), 7.28-7.32 (m, 3 H), 7.34 (t, J = 7.8 Hz, 2 H), 7.42 (d, J = 7.2
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Hz, 2 H), 7.69 (d, J = 7.8 Hz, 2 H); C NMR (150 MHz, CDCl3) δ 16.3, 21.7, 30.0, 48.5,
57.8, 116.3, 126.8, 127.5, 128.3, 128.7, 129.9, 137.6, 138.7, 143.6, 145.1; IR (KBr, neat)
3464, 2925, 2855, 1598, 1495, 1448, 1334, 1154, 1090, 998, 701 cm-1; HRMS (ESI) calcd.
for C19H24NO2S2 (M + H)+ 362.1243, found 362.1245.
(S)-Methyl 3-mercapto-2-(4-methyl-N-(2-methylallyl)phenyl-sulfonamido)propanoate (5u):
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Pale yellow gum; Rf (hexane/ EtOAc 7:3) 0.58; yield 453 mg, 66%; [α]D = +33.0 (c = 0.1,
CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 1.76 (s, 3 H), 2.42 (s, 3 H), 2.78 (d, J = 5.4 Hz, 2 H),
3.05 (d, J = 10.2 Hz, 2 H), 3.57 (s, 3 H), 4.10-4.14 (m, 1 H), 4.81 (s, 1 H), 4.86 (s, 1 H), 5.40
(d, J = 8.4 Hz, 1 H), 7.29 (d, J = 8.4 Hz, 2 H), 7.73 (d, J = 7.8 Hz, 2 H); 13C NMR (150 MHz,
CDCl3) δ 20.6, 21.7, 33.9, 39.9, 52.8, 55.5, 114.7, 127.4, 129.8, 136.9, 140.6, 143.9, 170.8;
IR (KBr, neat) 3277, 2923, 2854, 1744, 1598, 1436, 1341, 1160, 1090, 815, 662 cm-1; HRMS
(ESI) calcd. for C15H22NO4S2 (M + H)+ 344.0985, found 344.0989.
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Pale yellow gum; Rf (hexane/ EtOAc 7:3) 0.60; yield 494 mg, 61%; [α]D25 = +10.0 (c =0.05,
CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 2.41 (s, 3 H), 2.83 (d, J = 5.4 Hz, 2 H), 3.53 (s, 3 H),
3.57 (s, 2 H), 4.11-4.16 (m, 1 H), 5.21 (s, 1 H), 5.46 (s, 1 H), 7.26-7.30 (m, 3 H), 7.34 (t, J =
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7.2 Hz, 2 H), 7.41 (d, J = 7.2 Hz, 2 H), 7.72 (d, J = 8.4 Hz, 2 H); C NMR (150 MHz,
CDCl3) δ 21.7, 34.3, 37.1, 52.9, 55.6, 116.2, 126.5, 127.4, 128.1, 128.6, 129.9, 136.9, 139.0,
143.1, 144.0, 170.7; IR (KBr, neat) 3447, 2924, 1742, 1626, 1494, 1444, 1341, 1161, 1092,
908, 779 cm-1; HRMS (ESI) calcd. for C20H24NO4S2 (M + H)+ 406.1141, found 406.1141.
(S)-3-Mercapto-2-(4-methyl-N-(2-methylallyl)phenyl-sulfonamido)propyl acetate (5w):
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Pale yellow oil; Rf (hexane/ EtOAc 7:3) 0.42; yield 607 mg, 85%; [α]D = +15.0 (c = 0.1,
CH2Cl2). 1H NMR (400 MHz, CDCl3) δ 1.75 (s, 3 H), 1.94 (s, 3 H), 2.43 (s, 3 H), 2.54 (d, J =
10.8 Hz, 1 H), 2.56 (d, J = 9.2 Hz, 1 H), 2.93 (d, J = 7.2 Hz, 2 H), 3.58 (dt, J = 12.8 and 5.6
Hz, 1 H), 3.99 (dd, J = 12.0 and 4.4 Hz, 1 H), 4.18 (dd, J = 11.2 and 5.6 Hz, 1 H), 4.73 (s, 1
H), 4.82 (s, 1 H), 5.01 (d, J = 7.6 Hz, 1 H), 7.31 (d, J = 8.4 Hz, 2 H), 7.77 (d, J = 8.4 Hz, 2
H); 13C NMR (100 MHz, CDCl3) δ 20.6, 20.8, 21.7, 33.0, 39.8, 51.9, 64.7, 114.5, 127.3,
129.9, 137.7, 140.7, 143.8, 170.9; IR (KBr, neat) 3450, 2932, 1728, 1616, 1503, 1449, 1350,
1149, 1093, 909, 777 cm-1; HRMS (ESI) calcd. for C16H24NO4S2 (M + H)+ 358.1141, found
358.1140.
N-(1-Hydroxy-3-mercaptopropan-2-yl)-4-methyl-N-(2-phenylallyl)benzenesulfonamide (5x):
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Pale yellow oil; Rf (hexane/ EtOAc 3:2) 0.49; yield 566 mg, 75%; [α]D = - 9.0 (c = 0.4,
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CH2Cl2). H NMR (600 MHz, CDCl3) δ 2.41 (s, 3 H), 2.55 (dd, J = 6.6 and 2.4 Hz, 2 H),
3.29-3.34 (m, 2 H), 3.40 (d, J = 13.8 Hz, 1 H), 3.60 (s, 2 H), 5.07 (s, 1 H), 5.32 (brs, 1 H),
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5.37 (s, 1 H), 7.26-7.37 (m, 7 H), 7.75(d, J = 8.4 Hz, 2 H); C NMR (150 MHz, CDCl3) δ
21.7, 33.0, 36.8, 54.1, 63.6, 115.8, 126.4, 127.4, 128.2, 128.6, 130.0, 137.2, 139.0, 143.2,
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143.9; IR (KBr, neat) 3504, 3279, 2924, 1598, 1494, 1444, 1327, 1157, 1092, 1036, 814, 702
cm-1; HRMS (ESI) calcd. for C19H24NO3S2 (M + H)+ 378.1192, found 378.1193.
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General Procedure for the Synthesis of 6a-t & 7u-x: To a stirred solution of compound 5a-
x (1 mmol.) in dichloromethane (5 mL), 1.2 equivalents of borontrifluoride etherate under
nitrogen atmosphere was added at room temperature. Then it was continuously stirred for 5 h.
After completion of the reaction, the reaction mixture was quenched by addition of saturated
sodium bicarbonate solution (5 mL). The aqueous layer was extracted with dichloromethane
(3 X 10 mL) and the organic layer was dried over anhydrous Na2SO4. After concentration
under vacuum, the crude product was purified using column chromatography on silica gel
with ethylacetate and hexane as eluents.
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2,2-Dimethyl-4-tosylmorpholine (6a):
White solid, mp 92-94 oC; Rf (hexane/ EtOAc 4:1) 0.47; yield 223 mg, 83%; 1H NMR (600
MHz, CDCl3) δ 1.26 (s, 6 H), 2.44 (s, 3 H), 2.72 (s, 2 H), 2.91 (t, J = 4.8 Hz, 2 H), 3.77 (t, J
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= 4.8 Hz, 2 H), 7.33 (d, J = 7.8 Hz, 2 H), 7.61 (t, J = 8.4 Hz, 2 H); C NMR (150 MHz,
CDCl3) 21.7 (2C), 24.6, 45.9, 54.9, 60.4, 71.2, 128.0, 129.9, 132.6, 144.0; IR (KBr, neat)
2978, 2877, 1598, 1351, 1166, 1099, 759 cm-1; HRMS (ESI) calcd. for C13H20NO3S (M + H)+
270.1158 found 270.1157.
(R)-2,2-Dimethyl-5-phenyl-4-tosylmorpholine (6b):
Pale yellow solid, mp 77-79 oC; Rf (hexane/ EtOAc 4:1) 0.47; yield 245 mg, 71%; [α]D25 = -
68.5 (c = 0.33, CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 1.24 (s, 3 H), 1.25 (s, 3 H), 2.37 (s, 3
H), 3.11 (d, J = 13.2 Hz, 1 H), 3.23 (d, J = 12.6 Hz, 1 H), 3.99 (dd, J = 12.0 and 2.4 Hz, 1
H), 4.10 (dd, J = 12.0 and 4.2 Hz, 1 H), 4.71 (t, J = 3.0 Hz, 1 H), 7.16 (d, J = 8.4 Hz, 2 H),
7.21-7.23 (m, 3 H), 7.36-7.38 (m, 2 H), 7.47 (d, J = 8.4 Hz, 2 H); 13C NMR (150 MHz,
CDCl3) 21.6, 22.4, 26.7, 50.6, 55.8, 64.7, 71.4, 127.5, 127.9, 128.4, 128.7, 129.5, 137.1,
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137.8, 143.3; IR (KBr, neat) 2975, 2872, 1599, 1495, 1340, 1164, 1026, 705 cm-1; HRMS
(ESI) calcd. for C19H24NO3S (M + H)+ 346.1471 found 346.1471.
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(S)-Methyl 6,6-dimethyl-4-tosylmorpholine-3-carboxylate (6c):
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Pale yellow gum; Rf (hexane/ EtOAc 4:1) 0.50; yield 281 mg, 86%; [α]D25 = - 70.0 (c = 0.1,
CH2Cl2). 1H NMR (400 MHz, CDCl3) δ 1.14 (s, 3 H), 1.26 (s, 3 H), 2.40 (s, 3 H), 3.12 (d, J =
12.4 Hz, 1 H), 3.32 (d, J = 12. 8 Hz, 1 H), 3.52 (s, 3 H), 4.00-4.10 (m, 2 H), 4.44 (d, J = 3.6
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Hz, 1 H), 7.26 (d, J = 8.0 Hz, 2 H), 7.62 (d, J = 8.4 Hz, 2 H); C NMR (100 MHz, CDCl3)
20.8, 21.7, 27.5, 50.6, 52.5, 54.5, 62.5, 71.2, 127.5, 129.6, 136.6, 143.6, 169.7; IR (KBr, neat)
2981, 1339, 1154, 1091, 1049, 905, 815, 741 cm-1; HRMS (ESI) calcd. for C15H22NO5S (M +
H)+ 328.1213 found 328.1225.
2-Methyl-2-phenyl-4-tosylmorpholine (6d):
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Pale yellow solid, mp 126-128 C; Rf (hexane/ EtOAc 4:1) 0.50; yield 298 mg, 90%; H
NMR (600 MHz, CDCl3) δ 1.44 (s, 3 H), 2.45 (s, 3 H), 2.71-2.78 (m, 2 H), 3.13 (d, J = 11.4
Hz, 1 H), 3.62-3.68 (m, 1 H), 3.72-3.79 (m, 2 H), 7.28 (d, J = 7.8 Hz, 1 H), 7.34-7.39 (m, 4
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H), 7.47 (d, J = 7.8 Hz, 2 H), 7.65 (d, J = 7.8 Hz, 2 H); C NMR (100 MHz, CDCl3) 21.6,
28.1, 45.7, 52.7, 60.7, 75.1, 126.1, 127.3, 127.9, 128.6, 129.9, 132.1, 142.7, 144.0; IR (KBr,
neat) 2977, 2853, 1599, 1458, 1351, 1168, 1093, 802, 701 cm-1; HRMS (ESI) calcd. for
C18H22NO3S (M + H)+ 332.1315 found 332.1318.
(2S,5S)-2,5-Dimethyl-2-phenyl-4-tosylmorpholine (6e):
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Pale yellow oil; Rf (hexane/ EtOAc 4:1) 0.60; yield 255 mg, 74%; [α]D = + 48.0 (c = 0.1,
CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 1.02 (d, J = 6.6 Hz, 3 H), 1.58 (s, 3 H), 2.41 (s, 3 H),
3.26 (d, J = 12.6 Hz, 1 H), 3.52 (d, J = 11.4 and 2.4 Hz, 2 H), 3.84-3.88 (m, 1 H), 4.07-4.10
(m, 1 H), 7.26-7.30 (m, 3 H), 7.37 (t, J = 7.2 Hz, 2 H), 7.47 (d, J = 7.2 Hz, 2 H), 7.68 (d, J =
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7.8 Hz, 2 H); C NMR (100 MHz, CDCl3) 13.5, 21.7, 22.6, 49.0, 49.5, 65.9, 74.7, 124.9,
127.3, 127.5, 128.6, 129.9, 137.1, 143.6, 144.9; IR (KBr, neat) 2978, 2874, 1590, 1447, 1338,
1152, 1021, 800, 701 cm-1; HRMS (ESI) calcd. for C19H24NO3S (M + H)+ 346.1471 found
346.1471.
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(2S,5S)-5-Benzyl-2-methyl-2-phenyl-4-tosylmorpholine (6f):
Pale yellow solid, mp 95-97 oC; Rf (hexane/ EtOAc 4:1) 0.65; yield 265 mg, 63%; [α]D25 = +
26.0 (c = 0.1, CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 1.60 (s, 3 H), 2.41 (s, 3 H), 2.44 (dd, J
= 13.2 and 3.0 Hz, 1 H), 3.03 (dd, J = 13.2 and 10.8 Hz, 1 H), 3.19 (d, J = 12.6 Hz, 1 H),
3.64 (d, J = 12.0 Hz, 1 H), 3.77 (d, J = 12.6 Hz, 1 H), 3.93-3.99 (m, 2 H), 7.14 (d, J = 7.2
Hz, 2 H), 7.21 (t, J = 7.2 Hz, 1 H), 7.27-7.33 (m, 5 H), 7.40 (t, J = 7.8 Hz, 2 H), 7.53 (d, J =
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7.8 Hz, 2 H), 7.71 (d, J = 8.4 Hz, 2 H); C NMR (150 MHz, CDCl3) 21.5, 21.7, 32.3, 49.7,
54.4, 61.1, 74.2, 124.7, 126.8, 127.2, 127.6, 128.7, 128.9, 129.7, 130.1, 137.8, 138.0, 143.7,
145.4; IR (KBr, neat) 2924, 2872, 1599, 1448, 1339, 1165, 1052, 814, 702 cm-1; HRMS
(ESI) calcd. for C25H28NO3S (M + H)+ 422.1784 found 422.1782.
(2S*,6R*)-2-Methyl-2,6-diphenyl-4-tosylmorpholine (6g):
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Pale yellow solid, mp 191-193 C; Rf (hexane/ EtOAc 4:1) 0.70; yield 180 mg, 79%; H
NMR (400 MHz, CDCl3) δ 1.83 (s, 3 H), 2.14 (t, J = 10.8 Hz, 1 H), 2.29 (d, J = 11.4 Hz, 1
H), 2.37 (s, 3 H), 3.87 (dd, J = 10.8 and 2.4 Hz, 1 H), 5.18 (dd, J = 10.2 and 3.0 Hz, 1 H),
7.24 (d, J = 7.2 Hz, 2 H), 7.27-7.45 (m, 8 H), 7.52 (d, J = 7.8 Hz, 1 H), 7.55 (d, J = 7.8 Hz, 2
H); 13C NMR (100 MHz, CDCl3) δ 21.7, 22.3, 52.5, 54.8, 71.4, 75.4, 124.7, 126.5, 127.6,
127.9, 128.4, 128.6, 128.8, 130.0, 132.6, 139.5, 144.1, 145.3; IR (KBr, neat) 2928, 1558,
1447, 1351, 1168, 1091, 999, 699 cm-1; HRMS (ESI) calcd. for C24H26NO3S (M + H)+
408.1628 found 408.1644.
(2S*,6R*)-6-(3-Bromophenyl)-2,2-dimethyl-4-tosylmorpholine (6h):
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White solid, mp 150-152 oC; Rf (hexane/ EtOAc 9:1) 0.65; yield 343 mg, 81%; 1H NMR (600
MHz, CDCl3) δ 1.27 (s, 3 H), 1.47 (s, 3 H), 1.99 (t, J = 10.8 Hz, 1 H), 2.14 (d, J = 11.4 Hz, 1
H), 2.42 (s, 3 H), 3.47 (dd, J = 10.8 and 1.2 Hz, 1 H), 3.73 (dd, J = 9.6 and 1.8 Hz, 1 H), 4.87
(dd, J = 10.8 and 3.0 Hz, 1 H), 7.19 (t, J = 7.8 Hz, 1 H), 7.22 (t, J = 7.2 Hz, 1 H), 7.31 (d, J =
7.8 Hz, 2 H), 7.40 (d, J = 7.8 Hz, 1 H), 7.48 (s, 1 H), 7.58 (d, J = 8.4 Hz, 2 H); 13C NMR
(150 MHz, CDCl3) δ 21.7, 21.8, 28.0, 52.0, 54.4, 70.8, 72.3, 122.8, 125.1, 127.9, 129.4,
130.0, 130.2, 131.4, 132.6, 141.7, 144.1; IR (KBr, neat) 2978, 1597, 1453, 1352, 1165, 1093,
998, 694 cm-1; HRMS (ESI) calcd. for C19H23BrNO3S (M + H)+ 424.0577, found 424.0576.
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(2S*,6R*)-6-(3-Bromophenyl)-2-methyl-2-phenyl-4-tosylmorpholine (6i):
White solid, mp 134-136 oC; Rf (hexane/ EtOAc 9:1) 0.48; yield 417 mg, 86%; 1H NMR (600
MHz, CDCl3) δ 1.82 (s, 3 H), 2.10 (t, J = 11.4 Hz, 1 H), 2.29 (d, J = 11.4 Hz, 1 H), 2.38 (s, 3
H), 3.85 (d, J = 11.4 Hz, 2 H), 5.14 (dd, J = 10.2 and 2.4 Hz, 1 H), 7.23-7.28 (m, 3 H), 7.30
(t, J = 7.8 Hz, 1 H), 7.34-7.40 (m, 4 H), 7.50 (d, J = 7.8 Hz, 2 H), 7.57 (d, J = 8.4 Hz, 2 H),
7.60 (s, 1 H); 13C NMR (150 MHz, CDCl3) δ 21.7, 22.3, 52.3, 54.7, 70.9, 75.7, 122.9, 124.6,
125.1, 127.7, 127.9, 128.7, 129.5, 130.1, 130.3, 131.6, 132.6, 141.8, 144.2, 145.0; IR (KBr,
neat) 2984, 1597, 1449, 1344, 1164, 1091, 999, 756, 694 cm-1; HRMS (ESI) calcd. for
C24H25BrNO3S (M + H)+ 486.0733, found 486.0731.
(2S*,6R*)-2-Methyl-2-phenyl-6-(3-(phenylethynyl)phenyl)-4-tosylmorpholine (6j):
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Colourless gum; Rf (hexane/ EtOAc 9:1) 0.38; yield 370 mg, 73%; H NMR (600 MHz,
CDCl3) δ 1.84 (s, 3 H), 2.14 (t, J = 11.4 Hz, 1 H), 2.31 (d, J = 11.4 Hz, 1 H), 2.38 (s, 3 H),
3.87 (d, J = 9.6 Hz, 2 H), 5.18 (dd, J = 10.8 and 3.0 Hz, 1 H), 7.31 (d, J = 7.2 Hz, 2 H), 7.35-
7.41 (m, 7 H), 7.50 (d, J = 7.8 Hz, 2 H), 7.52-7.55 (m, 4 H), 7.57 (d, J = 8.4 Hz, 2 H), 7.61 (s,
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1 H); C NMR (150 MHz, CDCl3) δ 21.7, 22.4, 52.4, 54.8, 71.2, 75.6, 89.2, 90.0, 123.3,
123.8, 124.7, 125.1, 126.4, 127.7, 127.9, 128.6, 128.63, 128.8, 129.6, 130.1, 131.6, 131.9,
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132.6, 139.8, 144.1, 145.2; IR (KBr, neat) 2924, 1600, 1493, 1450, 1348, 1165, 1094, 1002,
909, 697 cm-1; HRMS (ESI) calcd. for C32H30NO3S (M + H)+ 508.1941, found 508.1947.
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(2S*,6R*)-2,2-Dimethyl-4-tosyl-6-(4-(trifluoromethyl)phenyl)morpholine (6k):
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Colorless solid, mp 141-143 C; Rf (hexane/ EtOAc 9:1) 0.65; yield 380 mg, 92%; H NMR
(600 MHz, CDCl3) δ 1.29 (s, 3 H), 1.49 (s, 3 H), 2.00 (t, J = 10.8 Hz, 1 H), 2.16 (d, J = 11.4
Hz, 1 H), 2.43 (s, 3 H), 3.49 (dd, J = 11.4 and 1.2 Hz, 1 H), 3.78 (dt, J = 10.8 and 1.2 Hz, 1
H), 4.96 (dd, J = 10.8 and 3.0 Hz, 1 H), 7.31 (d, J = 8.4 Hz, 2 H), 7.44 (d, J = 8.4 Hz, 2 H),
7.57-7.60 (m, 4 H); 13C NMR (150 MHz, CDCl3) δ 21.7, 21.8, 28.0, 52.0, 54.5, 71.0, 72.4,
124.2 (q, J = 270.0 Hz), 125.6, 126.8, 127.9, 130.1, 130.5 (q, J = 33.0 Hz), 132.6, 143.4,
144.2; 19F NMR (376 MHz, C6F6/CDCl3): 99.12; IR (KBr, neat) 2926, 1599, 1454, 1325,
1165, 1093, 1029, 941, 667 cm-1; HRMS (ESI) calcd. for C20H23F3NO3S (M + H)+ 414.1345,
found 414.1343.
2-Methyl-2-phenyl-4-tosyl-3,4-dihydro-2H-benzo[b][1,4]-oxazine (6m):
Colourless solid, mp 119-121 oC; Rf (hexane/ EtOAc 4:1) 0.73; yield 258 mg, 68%; 1H NMR
(600 MHz, CDCl3) δ 1.67 (s, 3 H), 2.34 (s, 3 H), 3.97 (d, J = 12.6 Hz, 1 H), 4.14 (d, J = 12.6
Hz, 1 H), 6.77-6.80 (m, 1 H), 6.95-6.98 (m, 1 H), 7.02 (dd, J = 7.8 and 1.2 Hz, 1 H), 7.15 (d,
J = 7.8 Hz, 1 H), 7.32 (t, J = 7.2 Hz, 1 H), 7.36 (t, J = 7.2 Hz, 2 H), 7.44-7.50 (m, 6 H); 13C
NMR (150 MHz, CDCl3) δ 21.7, 26.0, 53.0, 77.5, 118.2, 119.0, 120.9, 124.5, 124.6, 125.3,
127.4, 127.9, 128.9, 129.9, 136.7, 142.6, 144.1, 144.7; IR (KBr, neat) 2927, 2869, 1598,
1493, 1352, 1165, 1090, 813, 700 cm-1; HRMS (ESI) calcd. for C22H22NO3S (M + H)+
380.1315 found 380.1316.
7,7-Dimethyl-4-tosyl-1,4-oxazepane (6n):
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Colourless solid, mp 62-64 C; Rf (hexane/ EtOAc 4:1) 0.50; yield 263 mg, 93%; H NMR
(600 MHz, CDCl3) δ 1.13 (s, 6 H), 1.91 (t, J = 4.8 Hz, 2 H), 2.42 (s, 3 H), 3.20-3.23 (m, 4 H),
3.70 (t, J = 4.2 Hz, 2 H), 7.31 (d, J = 7.8 Hz, 2 H), 7.64 (d, J = 8.4 Hz, 2 H); 13C NMR (100
MHz, CDCl3) δ 21.5, 27.7 (2C), 41.3, 43.8, 51.3, 62.6, 76.9, 127.3, 129.7, 134.8, 143.4; IR
(KBr, neat) 2973, 2870, 1598, 1452, 1385, 1163, 1034, 862, 718 cm-1; HRMS (ESI) calcd.
for C14H22NO3S (M + H)+ 284.1315 found 284.1316.
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7,7-Dimethyl-2-phenyl-4-tosyl-1,4-oxazepane (6p):
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Yellow solid, mp 137-139 C; Rf (hexane/ EtOAc 4:1) 0.68; yield 258 mg, 72%; H NMR
(600 MHz, CDCl3) δ 1.20 (s, 3 H), 1.21 (s, 3 H), 1.96 (dd, J = 15.6 and 7.2 Hz, 1 H), 2.13
(dd, J = 15.6 and 9.6 Hz,1 H), 2.42 (s, 3 H), 2.66 (dd, J = 12.6 and 9.6 Hz, 1 H), 2.83 (dd, J =
13.8 and 10.2 Hz, 1 H), 3.88 (dd, J = 13.2 and 7.8 Hz, 1 H), 3.98 (d, J = 12.6 Hz, 1 H), 4.84
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(d, J = 9.6 Hz, 1 H), 7.26-7.35 (m, 7 H), 7.63 (d, J = 8.4 Hz, 2 H); C NMR (150 MHz,
CDCl3) δ 21.7, 26.5, 29.5, 42.3, 44.0, 57.0, 73.9, 75.2, 126.1, 127.4, 127.7, 128.5, 129.9,
135.5, 141.0, 143.5; IR (KBr, neat) 2972, 2927, 1598, 1449, 1339, 1162, 1026, 890, 724 cm-
1; HRMS (ESI) calcd. for C20H26NO3S (M + H)+ 360.1628 found 360.1631.
7-Methyl-7-phenyl-4-tosyl-1,4-oxazepane (6q):
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Colourless gum; Rf (hexane/ EtOAc 7:3) 0.58; yield 275 mg, 75%; H NMR (600 MHz,
CDCl3) δ 1.44 (s, 3 H), 2.45 (s, 3 H), 2.72 (d, J = 12.0 Hz, 1 H), 2.76 (d, J = 8.4 Hz,1 H),
3.12 (d, J = 11.4 Hz, 1 H), 3.62-3.67 (m, 2 H), 3.73-3.79 (m, 3 H), 7.28 (t, J = 7.2 Hz, 1 H),
7.35 (d, J = 7.8 Hz, 2 H), 7.38 (t, J = 7.8 Hz, 2 H), 7.47 (d, J = 8.4 Hz, 2 H), 7.64 (d, J = 8.4
Hz, 2 H); 13C NMR (150 MHz, CDCl3) δ 21.8, 28.3, 29.9, 45.9, 52.8, 60.9, 75.3, 126.3,
127.5, 128.1, 128.9, 130.0, 132.4, 142.8, 144.1; IR (KBr, neat) 2923, 2853, 1530, 1453, 1349,
1165, 1092, 761, 660 cm-1; HRMS (ESI) calcd. for C19H23NNaO3S (M + Na)+ 368.1291
found 368.1288.
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2-Methyl-2-phenyl-4-tosylthiomorpholine (6s):
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Pale yellow solid, mp 121-123 C; Rf (hexane/ EtOAc 4:1) 0.70; yield 243 mg, 70%; H
NMR (400 MHz, CDCl3) δ 1.65 (s, 3 H), 2.44 (s, 3 H), 2.56-2.64 (m, 1 H), 2.75-2.82 (m, 1
H), 3.18-3.30 (m, 2 H), 3.32-3.39 (m, 1 H), 3.87 (d, J = 11.6 Hz, 1 H), 7.26 (t, J = 7.6 Hz, 1
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H), 7.31-7.38 (m, 4 H), 7.62 (d, J = 8.4 Hz, 2 H), 7.67 (d, J = 8.0 Hz, 2 H); C NMR (100
MHz, CDCl3) δ 21.7, 26.2, 46.5, 47.5 (2C), 57.6, 127.0, 127.4, 127.7, 128.7, 130.0, 133.8,
143.3, 144.0; IR (KBr, neat) 2922, 2853, 1597, 1494, 1454, 1338, 1285, 1164, 1089, 899, 762
cm-1; HRMS (ESI) calcd. for C18H22NO2S2 (M + H)+ 348.1086, found 348.1080.
2,5-Dimethyl-2-phenyl-4-tosylthiomorpholine (6t):
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Pale yellow gum; Rf (hexane/ EtOAc 19:1) 0.30; yield 311 mg, 86%; [α]D = +42.83 (c =
0.6, CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 1.12 (d, J = 6.6 Hz, 3 H), 1.85 (s, 3 H), 2.35 (d,
J = 13.2 Hz, 1 H), 2.42 (s, 3 H), 3.44-3.50 (m, 1 H), 3.85 (d, J = 13.2 Hz, 1 H), 4.48 (bs, 1 H),
7.27-7.31 (m, 3 H), 7.38 (t, J = 7.8 Hz, 2 H), 7.60 (d, J = 7.8 Hz, 2 H), 7.66 (d, J = 7.8 Hz, 2
H); 13C NMR (150 MHz, CDCl3) δ 13.5, 21.7, 24.0, 32.2, 45.4, 46.8, 51.2, 126.4, 127.1,
127.8, ,129.9, 137.9, 143.4, 143.7; IR (KBr, neat) 2924, 2855, 1598, 1495, 1446, 1337, 1167,
1029, 995, 697 cm-1; HRMS (ESI) calcd. for C19H24NO2S2 (M + H)+ 362.1243, found
362.1248.
(2S,4S)-Methyl 2-isopropyl-3-tosylthiazolidine-4-carboxylate (7u):
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Yellow gum; Rf (hexane/ EtOAc 4:1) 0.56; yield 226 mg, 66%; [α]D = - 2.0 (c = 0.06,
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CH2Cl2). H NMR (600 MHz, CDCl3) δ 0.98 (d, J = 6.6 Hz, 3 H), 1.11 (d, J = 6.6 Hz, 3
H),1.88-1.95 (m, 1 H), 2.44 (s, 3 H), 2.82 (dd, J = 11.4 and 7.8 Hz, 1 H), 3.23 (dd, J = 11.4
and 6.0 Hz, 1 H), 3.78 (s, 3 H), 4.61 (t, J = 6.6 Hz, 1 H), 4.71 (d, J = 8.4 Hz, 1 H), 7.33 (d, J
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= 8.4 Hz, 2 H), 7.74 (d, J = 8.4 Hz, 2 H); C NMR (100 MHz, CDCl3) δ 19.3, 20.5, 21.8,
33.9, 36.1, 53.1, 65.3, 74.9, 128.1, 130.1, 134.5, 144.6, 170.8; IR (KBr, neat) 2959, 2924,
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1742, 1438, 1350, 1164, 1090, 1009, 815, 661 cm-1; HRMS (ESI) calcd. for C15H22NO4S2 (M
+ H)+ 344.0985 found 344.0984.
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with a ratio of 7:3):
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Pale yellow gum; Rf (hexane/ EtOAc 4:1) 0.50; yield 288 mg, 71%; [α]D = - 5.0 (c = 0.08,
CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 1.43 (d, J = 7.2 Hz, 3 H, minor), 1.54 (d, J = 7.2 Hz,
3 H, major), 2.41 (s, 3 H, minor), 2.43 (s, 3 H, major), 2.72 (dd, J = 11.4 and 7.8 Hz, 1 H,
major), 2.92 (dd, J = 11.4 and 7.8 Hz, 1 H, minor), 3.00-3.06 (m, 2 H, major), 3.30 (dd, J =
11.4 and 6.6 Hz, 1 H, minor), 3.49 (dd, J = 11.4 and 6.0 Hz, 1 H, minor), 3.78 (s, 3 H,
minor), 3.80 (s, 3 H, major), 4.57-4.62 (m, 2 H, major, minor), 5.15 (d, J = 9.6 Hz, 1 H,
major), 5.18 (d, J = 6.6 Hz, 1 H, minor), 7.22-7.34 (m, 14 H, major, minor), 7.59 (d, J = 7.8
Hz, 2 H, minor), 7.77 (d, J = 8.4 Hz, 2 H, major); 13C NMR (150 MHz, CDCl3) δ 20.3, 21.7,
21.8, 22.9, 33.9, 34.0, 46.2, 48.0, 53.0, 53.1, 65.6, 66.2, 74.0, 74.1, 127.1, 127.2, 128.1,
128.2, 128.3, 128.5, 128.6, 130.0, 130.2, 134.1, 134.4, 142.8, 142.9, 144.6, 144.8, 170.5,
170.7; IR (KBr, neat) 2924, 2853, 1747, 1597, 1494, 1453, 1352, 1165, 1091, 815, 701 cm-1;
HRMS (ESI) calcd. for C20H24NO4S2 (M + H)+ 406.1141 found 406.1143.
((2S,4S)-2-Isopropyl-3-tosylthiazolidin-4-yl)methanol (7w):
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Yellow oil; Rf (hexane/ EtOAc 7:3) 0.30; yield 186 mg, 59%; [α]D = - 40.0 (c = 0.1,
CH2Cl2). 1H NMR (600 MHz, CDCl3) δ 1.01 (d, J = 6.6 Hz, 3 H), 1.13 (d, J = 6.6 Hz, 3 H),
1.93-1.99 (m, 1 H), 2.45 (s, 3 H), 2.66 (dd, J = 12.0 and 7.2 Hz, 1 H), 2.80 (dd, J = 12.0 and
6.0 Hz, 1 H), 3.74 (d, J = 6.0 Hz, 2 H), 4.01-4.06 (m, 1 H), 4.72 (d, J = 9.0 Hz, 1 H), 7.34 (d,
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J = 7.8 Hz, 2 H), 7.73 (d, J = 7.8 Hz, 2 H); C NMR (150 MHz, CDCl3) δ 19.6, 20.8, 21.8,
33.2, 36.1, 65.2, 66.3, 75.3, 128.3, 130.1, 134.3, 144.6; IR (KBr, neat) 3412, 2924, 2854,
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