DBU Catalysed Enantioselective Degradative Rearrangement: a Way to Tetrasubstituted 2-Aryl-2-Amino Esters

Article abstract of DOI:10.1002/adsc.202100493

Herein we report a catalytic, easily scalable protocol for the enantioselective synthesis of Tetrasubstituted α-aryl-α-amino acid derivatives, using a biphasic system composed by catalytic DBU in DME and aqueous solutions of Na₂CO₃. Under very mild reaction conditions, without using metal or chiral additives, this heterogeneous system promotes the degradative rearrangement of functionalized N-aryl sulphonyl α-amino esters into the corresponding tetrasubstituted 2-aryl-2-amino esters, with high enantiomeric ratios (up to 97.5:2.5) and good yields (up to 95%). (Figure presented.).

Full text of DOI:10.1002/adsc.202100493

RESEARCH ARTICLE
doi.org/10.1002/adsc.202100493
DBU Catalysed Enantioselective Degradative Rearrangement:
a Way to Tetrasubstituted 2-Aryl-2-Amino Esters
Camilla Loro,a Roberto Sala,a Michele Penso,b and Francesca Foschia,*
a
Dipartimento di Scienza e Alta Tecnologia, Università degli Studi dell’Insubria, Via Valleggio 9, IT-20100 Como, Italy
phone: (+39)-3468854369
E-mail: Francesca.foschi@uninsubria.it
CNR-Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” (SCITEC), Via Golgi 19, IT-20133 Milano, Italy
b
Manuscript received: April 22, 2021; Revised manuscript received: June 7, 2021;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202100493
Abstract: Herein we report a catalytic, easily scalable protocol for the enantioselective synthesis of
Tetrasubstituted α-aryl-α-amino acid derivatives, using a biphasic system composed by catalytic DBU in DME
and aqueous solutions of Na2CO3. Under very mild reaction conditions, without using metal or chiral additives,
this heterogeneous system promotes the degradative rearrangement of functionalized N-aryl sulphonyl α-amino
esters into the corresponding tetrasubstituted 2-aryl-2-amino esters, with high enantiomeric ratios (up to
97.5:2.5) and good yields (up to 95%).
Keywords: Asymmetric enolate arylation; memory of chirality; unnatural amino acids; DBU-catalysed
rearrangement
Introduction
presence of an organometallic base and involving the
functionalization of an amino acid through ‘self-
During the last two decades, there has been increasing regeneration of chirality’,[5] via Sommelet-Hauser
interest in the synthesis of constrained non-coded rearrangement,[6] or adopting the Kawabata’s principles
amino acids, extensively used to change conforma- of “memory of chirality” (MOC).[7]
tional freedom of non-natural amino acid peptides,
providing access to new bioactive poly-functionalized thesis of “chimera” amino acids,[8] we reported a one-
molecules.[1]
pot process for the synthesis of α-aryl α-amino esters
During our previous studies concerning the syn-
In this wide spreading research field, α-tetrasubsti- starting from the corresponding N-arylsulfonyl-2-
tuted α-amino acids and related compounds play a amino esters 1a (Figure 1, path a).[9] Using a strong
critical role in the design of peptidase-resistant anti- inorganic base, such as NaH, the formation of the
biotics and in the control of secondary structure of target product 3a proceeds with a good enantioselec-
peptidomimetics, because the introduction of a fourth tivity through N-allylation of 1a, followed by degrada-
substituent into the Cα of an amino acid backbone tive rearrangement of the 4-nitrosulfonyl group (4-
changes its structural and functional properties.[2] nosyl, Nsp), with loss of SO2 and migration of the aryl
Therefore, the demand of new, cleaner, sustainable, group, in a one-pot process. In contrast, the rearrange-
and easily scalable processes for the synthesis of these ment reaction conducted on the preformed N-allylated
building blocks is rapidly growing.
intermediate 2a,[10] gave the product 3a with very low
Many elegant methods have been established for ee (path b). Finally, 1a did not react as such and was
the stereoselective synthesis of α-substituted deriva- recovered unchanged (path c). Thus, crucial to the
tives starting from amino acids templates.[3] Further- enantioselectivity of the process is the co-presence of
more, the synthetic methods for tetrasubstituted α-aryl enolate 2a’ and aza-anion 1a’, which stabilizes the
amino acids mainly require the use of specialized metal conformational geometry of the reactive species 2a’
catalysts (usually palladium, iron, rhodium, chromium, that is forced to evolve mainly toward the retention
and copper based)[4] for enol-aryl coupling reactions. enantiomer 3a.
Other intriguing processes are conducted in the
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Table 1. Promoted DBU intramolecular arylation of 2a: opti-
mization of the reaction conditions.[a]
DBU
(mmol)
additive/
system
t
3a
(%)
ee
(%)
(h)
1
2
3
4
5
6
7
8
9
4[b]
1
0.1
0.1
0.1
–
0.1
–
0.1
0.1
–
–
–
6
88
44
8[c]
85
59
–
95
95
–
71
94
–
94
–
94
–
24
48
16
24
48
48
48
48
48
DMSO/H[d]
TEA/H[d]
TEA/H[d]
Na2CO3an/SL[e]
Na2CO3an/SL[e]
Na2CO3aq/LL[f]
NaHCO3aq/LL[f]
67
–
Figure 1. Synthesis of α-aryl α-amino esters, comparison
between previous[9] and present results.
75
10
<5[c]
[a]
°
2a (1 mmol), DME (1 mL), 25 C.
[b] Runs carried out using 2a/DME solutions 1, 0.5, and
0.25 molLÀ 1.
Herein we report that this synthetic approach can be
greatly improved by using catalytic amounts of DBU
and an additive unable to generate and/or stabilize the
enolate species 2a’. This catalytic system, through a
[c] ee not detected.
[d] 1 mmol. H=homogeneous system.
synergic effect between the components, is able to [e] Solid, anhydrous; 2 mmol. SL=solid-liquid heterogeneous
system.
increase the rigidity of the enolate 2a’, forcing the
aryl-intramolecular attack from a specific side. This
device resulted in many benefits in terms of stereo-
selectivity, applicability, scalability, and sustainability.
[f] Aqueous solution (1 mL, 2 mollÀ 1). LL=liquid-liquid heter-
ogeneous system.
2a increased, but the process was less enantioselective
(entry 4). Operating with catalytic DBU and a stoichio-
Results and Discussion
Encouraged by the results achieved in the synthesis of metric amount of either triethylamine (TEA) (entry 5)
substituted [d]benzosultams through organo-superbases or solid-anhydrous Na2CO3 (entry 7), under solid-
promoted intramolecular SNAr of (polyfluoro) liquid (SL) heterogeneous conditions, results analo-
arylsulphonamides,[11] the rearrangement reaction of 2a gous to those obtained using excess DBU were
to 3a was tested using a series of organic bases and reached. The run conducted with Na2CO3 as sole base
solvents. Preliminary runs indicated that the best yields (entry 8) confirmed the crucial role in the enol-2a
and ee’s of 3a could be reached by using 1,5- formation played by DBU, since in its absence the
diazabiciclo(5.4.0)undec-7-ene (DBU) as the base rearrangement does not proceed. Remarkably, analo-
(4 mol equiv. with respect 2a) in dimethoxyethane gous good results were achieved also by using aqueous
(DME) (Table 1, entry 1).
Na2CO3 as an additive under liquid-liquid (LL)
With the aim of increasing the green aspect of the heterogeneous conditions (entry 9). Finally, the use of
process, in subsequent runs we tested the efficiency of NaHCO3 instead of Na2CO3 under LL conditions
the DBU/DME system, by varying the concentration (entry 10) was detrimental to the reaction progress,
and the amount of DBU. While the reaction concen- probably due to the relative acidity of the hydro-
tration did not affect the reaction course (Table 1, note gencarbonate ion. The liquid-liquid DBUcat/DME/
b), the use of an equimolar amount of base resulted in Na2CO3aq system was chosen for further applications
a lower yield of 3a, without ee erosion (entry 2). The and to the scale-up of this rearrangement, because it is
reaction conducted with 0.1 mol equiv. of DBU safety and operationally simple, requiring neither
(entry 3) afforded 3a in a very low yield. Stimulat- temperature control nor anhydrous/inert environments.
ingly, the addition of stoichiometric amounts of an
It is worth noting that in the reaction carried out in
additive (entries 4–10) activated a DBU catalytic cycle. the homogeneous DBU/DME system (entry 1), we
In particular, in the experiment conducted in DME in observed the formation of a new liquid-liquid biphasic
the presence of 1 mol equiv. of DMSO, under mixture. The characterization of the lower liquid phase
“specifically solvation” conditions,[12] the reactivity of was consistent with the formation of a DBU-onium
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ionic-liquid [3aSO2]À [DBUH]+ (Scheme 1), in agree- were coupled with a very low substrate reactivity.
ments with the literature data regarding the ionic- Conversely, the alanine derivative 2d quickly reacts
liquids formation by DBU trapping of SO2.[13] On the with poor enantioselectivity.
basis of these evidences and of the ions-pairs reactivity
These data indicate a strong reactivity dependence
under specific solvation conditions,[14] we could as- on the increasing size of the side chain: the smaller the
sume that at first 2a forms the DBU-stabilized enol- steric hindrance around the reacting centre, the greater
2a, which rapidly rearranges to the stable ionic-liquid the reactivity. Thus, we synthesized the N-allyl
[3aSO2]À [DBUH]+ that, in turn, exchanges its cation sulphonamido methyl ester 4a to test the influence of
with Na2CO3. Finally, the unstable sodium intermediate decreasing the steric hindrance on the ester functional
forms the product 3a by loss of SO2 and protonation. group.[15] As expected, 4a reacts faster than its tert-
In the reaction using DMSO as additive (Table 1, butyl analog 2a, providing the target product 5a in
entry 4), this aprotic dipolar solvent transforms the high yield and ee (Scheme 3). The crucial effect of the
tight ion-pair [3aSO2]À [DBUH]+ into a unstable ester moiety has been confirmed on several representa-
solvent-separated ion-pair that evolves to the rear- tive N-allyl p-nosylamido methyl esters 4b–j.
ranged 3a. As a secondary effect, DMSO, most
probably, solvated also enol-2a decreasing its racemi- tivity of the corresponding rearranged products 5a–g
zation half-life and the ee of 3a. was reached. Furthermore, while the iso-leucine com-
In addition to very high yields, good enantioselec-
The efficiency of the catalytic LL-system DBU- pound 5c was isolated as single diastereoisomer,
DME/Na2CO3aq was tested on representative N-allyl moderate ee’s of the methionine derivative 5e was
sulphonamido tert-butyl esters 2b–d (Scheme 2). The obtained. It is worth noting that the LL-catalytic
results indicated that, on the whole, the high enantio- system promoted the degradative rearrangement proc-
meric excesses of the rearranged products derived ess also on substrates bearing a free amine or hydroxy
from the hindered branched-chain compounds 2b,c group (tryptophan and tyrosine derivatives, 5f and 5g
respectively). On the other hand, the α-arylated
compound 5h deriving from threonine was not
isolated, due to its tendency to dehydrate, leading to
the optically pure α-vinyl-α-4-nitrophenyl-α-allylamino
Scheme 1. Proposed DBU catalytic cycle.
Scheme 2. Reactivity of N-allyl tert-butyl sulphonamido esters
2b–d.[a]
Scheme 3. Scope of the LL-catalytic process: Synthesis of α-4-
nitrophenyl-α-allylamino methyl esters 5a–g, 6h.[a]
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ester 6h. As reported in the literature,[16] enantiomeric
A different behaviour was observed when substrates
enriched α-vinylated α-amino acids are difficult to bearing different arylsulphonamides groups were em-
synthesize and are susceptible to further important ployed (Scheme 5). In particular, compared to 2a,
transformations and functionalizations, such as ring- compounds bearing a para-nitro group and a substitu-
closing metathesis giving access to cyclic amino acids. ent in the meta- or ortho-position (9a,b) gave minor
The effect of the N-substituents on the reactivity yields. The same behaviour was detected for the ortho-
was then investigated. Thus, p-nosylamido methyl nitro substituted derivative 9c. On the other hand,
ester 1b was N-alkylated under SL-PTC conditions arylsulphonamides having in the para-position a
with representative alkyl halides to the corresponding poorer electron-withdrawing group (EWG) than the
compounds 7a–c that, in turn, were subjected to the nitro group, furnished the correspondent α-arylated
classical DBU-LL system (Scheme 4) and the α- product (10d–f) in lower both yields and ee’s. To
tetrasubstituted esters 8a–c were isolated in good conclude, arylsulphonamides containing either a meta-
yields and ee’s.
nitro group or a methyl were unreactive. Self –
disproportionation of enantiomers (SDE) effects were
also explored,[17] considering that amino acids deriva-
tives could exhibit SDE magnitude.[18] In additions, we
have just exploited this intriguing phenomena for the
enantioselective crystallization of partially resolved
benzo[d]sultams derived from phenyl glicine.[19] In
agreement with the SDE chromatography procedure,
three experiments were done on compound 3a (ee
°
71%; 1 experiment: column chromatographic –
°
Acetone/DCM (1:6); 2 experiment: column chromato-
°
graphic - AcOEt/hexane (1:4); 3 experiment: column
filtration - MeOH/DCM (5:95)]. The [α]D20 value of all
individual fractions were consistent with the sample
value. In the view of these data, we could assume that
SDE effects during the purification step influenced the
detected ee’s in a range of +/À 5%. These data, on the
whole, indicated the ability of the catalytic system to
promote the aryl migration reaction on substrates
bearing on the aromatic ring an EWG able to stabilize
an intermediate pseudo-Meisenheimer complex.
On these experimental bases, a plausible reaction
mechanism is shown in Scheme 6 taking the phenyl-
alanine derivative 4a as the model and assuming it in
its two conformers A and B which bear the arylsulpho-
namides moiety on opposite side along the C=N bond.
Most probably, treatment of 4a with the coordinating
solvent DME shifts the equilibrium toward the less
crowded conformation A. As the consequence, DBU
favours the enol formation through an intermolecular
H-bond from the less crowded side of A forming C.
This latter, through the Re-face attack, evolves into a
chiral spiro-Meisenheimer intermediate D that, in turn,
undergoes the stereoselective S-Cα migration of the
aryl group, with an overall configuration retention.
Scheme 4. Scope of the LL-catalytic process: effect of the N-
substituent.[a]
Conclusion
In summary, we have found that the LL-catalytic
system DBU-DME/Na2CO3aq., can be conveniently
employed for asymmetric α-arylation of amino ester
enols, avoiding the use of heavy metals, high value
metals or strongly basic systems. These mild reaction
conditions, which do not require anhydrous, inert
environments and high or low reaction temperature,
Scheme 5. Reactivity of substituted arylsulphonamido esters
9a–f.[a]
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General Procedure for the Synthesis of N-Alkyl
Arylsulphonamido Esters
In a screw cap vial, a heterogeneous mixture of N-H
sulphonamido ester (1.0 mmol), TEBA (23 mg, 0.1 mmol),
anhydrous potassium carbonate (221 mg, 1.6 mmol), and
alkylating agent (1.5 mmol) solution in anhydrous acetonitrile
°
(3 mL) was vigorously stirred at 25 C until completion (TLC
analysis). The crude was then diluted with AcOEt (5 mL) and
filtered through a celite pad. After evaporation of the solvent
under reduced pressure (RV), the crude was purified by FCC to
afford the desired N-alkyl sulphonamide. The known com-
pounds completely matched with the reported data.[21] Starting
material, product, yield, chromatographic eluant, physical and
analytical data of new products 4a–h, 7a–c, 9a–f are as
follows.
(S)-Methyl 2-(N-Allyl-4-Nitrophenylsulfonamido)-
3-Phenylpropanoate (4a)
methyl [(4-nitrophenyl)sulfonyl]-L-phenylalaninate (364 mg);
allyl bromide (181.5 mg); FCC-AcOEt/hexane (1:5). 4a
(388 mg, 96%, 5 h); yellow wax, [α]D20 =À 20.3 (c 1, CHCl3).
1H NMR (300 MHz, CDCl3) δ 8.10 (d, 2H, J=8.7 Hz), 7.51 (d,
2H, J=8.7 Hz), 7.18–7.16 (m, 3H), 6.88–6.84 (m, 2H), 5.96–
5.83 (m, 1H), 5.24 (dd, 1H, J=17.4, 1.2 Hz), 5.14 (dd, 1H, J=
9.9, 1.2 Hz), 4.87–4.85 (m, 1H), 4.04–3.86 (m, 2H), 3.75 (s,
3H), 3.35 (dd, 1H, J=14.4, 6.3), 3.11 (dd, 1H, J=14.4,
9.0 Hz). 13C NMR (75 MHz, CDCl3) δ 170.2, 149.6, 145.7,
136.3, 133.4, 129.0 (2CHAr), 128.6 (2CHAr), 128.5, 126.8
Scheme 6. Hypothesized reaction model.
(2CHAr), 123.7 (2CHAr), 118.8, 61.3, 52.0, 48.4, 36.6. IR ν
max
3299, 3030, 1731, 1530, 1349, 1164, 930 cmÀ 1. MS Calcd. for
C19H20N2O6S: 404.1; found [M+H+]: 405.1. Anal. Calcd. For
C19H20N2O6S: C, 56.43; H, 4.98; N, 6.93. Found: C, 56.60; H,
5.10; N, 6.82.
together with the use of readily available starting
materials, allow to prepare various amino acid com-
pounds functionalized with electron-deficient aryls.
The catalytic system DBU/DME-Na2CO3aq. works on
large scale with good efficiency, showing that the
process is a viable strategy to access enantioenriched (S)-Methyl 2-(N-Allyl-4-Nitrophenylsulfonamido)-
products susceptible to undergo further functionaliza- 4-Methylpentanoate (4b)
tion.
(S)-Methyl
4-methyl-2-(4-nitrophenylsulfonamido)pentanoate
(330 mg); allyl bromide (130 μL); FCC-AcOEt/hexane (1:2).
Sulphonamide 4b (367 mg, 99%, 1.5 h); pale yellow wax,
[α]D20 =À 66.9 (c=1.1, CHCl3). 1H-NMR (300 MHz, CDCl3)
δ 8.29 (d, 2H, J=8.8 Hz), 7.98 (d, 2H, J=8.8 Hz), 5.86–5.73
(m, 1H), 5.19–5.08 (m, 2H), 4.65–4.61 (m, 1H), 3.93 (dd, 1H,
J=16.5, 11.1 Hz), 3.77 (dd, 1H, J=16.5, 7.4 Hz), 3.47 (s, 3H),
1.71–1.61 (m, 3H), 0.94 (d, 3H, J=6.0 Hz), 0.88 (d, 3H, J=
6.1 Hz). 13C-NMR (75 MHz, CDCl3) δ 171.2, 149.9, 145.6,
134.6, 128.7 (2CHAr), 123.9 (2CHAr), 117.9, 58.4, 51.9, 48.4,
Experimental Section
General Procedure for the Synthesis of N-H Aryl-
sulphonamido Esters
To a suspension of the α-amino ester hydrochloride (5.0 mmol)
in dry dichloromethane (20 mL), DIPEA (1.42 g, 11 mmol) was
added dropwise (10 min) at 25 C. The reaction mixture was
°
°
stirred for further 10 min, then cooled to 0 C, and the sulphonyl
38.7, 24.1, 22.5, 21.0. IR ν
3285, 3032, 2941, 1725, 1530,
max
chloride (5.1 mmol) was added dropwise (10 min). The result-
ing solution was stirred until completion (TLC control), then
was diluted with dichloromethane (10 mL), washed with
saturated NH4Cl solution (2×10 mL), saturated NaHCO3 sol-
ution (2×10 mL) and brine (10 mL), dried over MgSO4, and
filtered. After evaporation of the solvent under vacuum (RV),
the crude was purified by flash column chromatography (FCC)
to afford the correspondent sulphonamide. Spectroscopic data
for all known compounds were identical to those reported in
literature.[20] For all other N-H arylsulphonamido esters see the
Supporting Information.
1341, 1166, 938 cmÀ 1. MS Calcd. for C16H22N2O6S: 370.1.
Found [M+Na+]: 393.1. Anal. Calcd. For C16H22N2O6S: C,
51.88; H, 5.99; N, 7.56. Found: C, 51.76; H, 5.87; N, 7.68.
(2S,3S)-Methyl 2-(N-Allyl-
4-Nitrophenylsulfonamido)-3-Methylpentanoate
(4c)
(2S,3S)-Methyl-3-methyl-2-(4-nitrophenylsulfonamido)
pentanoate (330 mg); allyl bromide (130 μL); FCC-AcOEt/
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hexane (1:2). Sulphonamide 4c (322 mg, 87%, 1.5 h); pale
yellow wax, [α]D20 =À 105.0 (c=1.1, CHCl3). 1H-NMR
(300 MHz, CDCl3) δ 8.28 (d, 2H, J=8.9 Hz), 7.96 (d, 2H, J=
8.9 Hz), 5.81–5.67 (m, 1H), 5.19–5.0 (m, 2H), 4.19 (d, 1H, J=
10.8 Hz), 4.03 (dd, 1H, J=16.5, 7.5 Hz), 3.89 (dd, 1H, J=
16.5, 5.1 Hz), 3.40 (s, 3H), 1.91–1.81 (m, 1H), 1.72–1.59 (m,
1H), 1.14–1.01 (m, 1H), 0.87–0.81 (m, 6H).13C-NMR (75 MHz,
CDCl3) δ 170.5, 149.9, 145.5, 134.4, 128.7 (2CHAr), 123.7
(tt, J=10.1, 6.5 Hz, 1H), 5.16 (d, J=17.2 Hz, 1H), 5.06 (d, 1H,
J=10.1 Hz), 4.86 (dd, 1H, J=9.2, 5.8 Hz), 4.01 (dd, 1H, J=
16.2, 6.6 Hz), 3.89 (dd, 1H, J=16.2, 6.1 Hz), 3.57 (s, 3H), 3.41
(dd, 1H, J=15.1, 5.6 Hz), 3.09 (dd, 1H, J=15.1, 9.5 Hz). 13C-
NMR (75 MHz, CDCl3) δ 170.9, 149.4, 145.7, 136.1, 134.0,
128.2 (2CHAr), 123.4 (2CHAr), 123.2, 122.5, 119.9, 118.8,
118.4, 111.4, 110.3, 60.1, 52.4, 48.3, 26.2. IR ν
3333, 3264,
max
3008, 1745, 1519, 1143, 954. cmÀ 1. MS Calcd. for
C21H21N3O6S: 443.1. Found [M+H+]: 444.1. Anal. Calcd. For
C21H21N3O6S: C, 56.88; H, 4.77; N, 9.48. Found: C, 56.72; H,
4.63; N, 9.62.
(2CHAr), 118.1, 64.5, 51.4, 47.9, 34.2, 25.0, 15.2, 10.3. IR ν
max
3299, 3030, 2948, 1465, 1731, 1530, 1349, 1164, 930 cmÀ 1. MS
Calcd. for C16H22N2O6S: 370.1. Found [M+Na+]: 393.1. Anal.
Calcd. For C16H22N2O6S: C, 51.88; H, 5.99; N, 7.56. Found: C,
52.02; H, 6.13; N, 7.46.
(S)-Methyl 2-(N-Allyl-4-Nitrophenylsulfonamido)-
3-(4-Hydroxyphenyl)Propanoate (4g)
(S)-Methyl 2-(N-Allyl-4-Nitrophenylsulfonamido)-
(S)-Methyl3-(4-hydroxyphenyl)-2-(4-nitrophenylsulfonamido)
propanoate (420 mg); allyl bromide (130 μL); FCC-AcOEt/
hexane (1:1). Sulfonamide 4g (370 mg, 88%, 24 h); yellow
wax, [α]D20 =À 47.3 (c=1.1, CHCl3). 1H-NMR (300 MHz,
CDCl3) δ 8.22 (d, 2H, J=8.8 Hz), 7.78 (d, 2H, J=8.8 Hz),
7.04 (d, 2H, J=8.3 Hz), 6.74 (d, 2H, J=8.3 Hz), 6.07 (bs, 1H),
5.78–5.60 (m, 1H), 5.27–5.14 (m, 2H), 4.85 (dd, 1H, J=8.8,
6.4 Hz), 4.03–3.86 (m, 2H), 3.63 (s, 3H), 3.30 (dd, 1H, J=
14.4, 6.2 Hz), 2.95 (dd, 1H, J=14.4, 9.0 Hz). 13C-NMR
(75 MHz, CDCl3): δ 170.7, 155.0, 149.7, 145.7, 133.4, 130.2
(2CHAr), 128.6 (2CHAr), 128.0, 123.8 (2CHAr), 119.0, 115.5
2-(Cyclohexa-1,4-Dien-1-Yl)Acetate (4d)
(S)-Methyl 2-(cyclohexa-1,4-dien-1-yl)-2-(4-nitrophenylsulfona-
mido)acetate (352 mg); allyl bromide (130 μL); FCC-AcOEt/
hexane (1:4). Sulphonamide 4d (330 mg, 84%, 4 h); yellow
wax, [α]D20 =À 18.2 (c=1.1, CHCl3). 1H-NMR (300 MHz,
CDCl3) δ 8.35 (d, 2H, J=8.7 Hz), 7.99 (d, 2H, J=8.7 Hz),
5.87–5.69 (m, 3H), 5.69 (s, 1H), 5.58 (s, 1H), 5.16–5.08 (m,
2H), 5.02 (s, 1H), 4.05–3.93 (m, 2H), 3.59 (s, 3H), 2.80–2.66
(m, 4H). 13C-NMR (75 MHz, CDCl3) δ 169.8, 150.0, 145.5,
134.5, 128.8 (2CHAr), 128.5, 126.7, 124.1 (2CHAr), 123.4,
123.0, 118.1, 64.4, 52.1, 48.3, 28.0, 26.8. IR ν
3200, 3017,
(2CHAr), 61.7, 52.3, 48.5, 35.2. IR ν
3554, 3319, 3021,
max
max
1724, 1578, 1530, 1289, 1134, 989 cmÀ 1. MS Calcd. for
C18H20N2O6S: 392.1. Found [M+H+]: 393.1. Anal. Calcd. For
C18H20N2O6S: C, 55.09; H, 5.14; N, 7.14. Found: C, 55.41; H,
5.43; N, 6.95.
1731, 1537, 1179, 923 cmÀ 1. MS Calcd. for C19H20N2O7S:
420.1. Found [M+H+]: 421.2. Anal. Calcd. For C19H20N2O7S:
C, 54.28; H, 4.80; N, 6.66. Found: C, 54.63; H, 5.06; N, 6.49.
(2S)-Methyl 2-(N-Allyl-4-Nitrophenylsulfonamido)-
3-Hydroxybutanoate (4h)
(S)-Methyl 2-(N-Allyl-4-Nitrophenylsulfonamido)-
4-(Methylthio)Butanoate (4e)
(2S)-Methyl-3-hydroxy-2-(4-nitrophenylsulfonamido)butanoate
(318 mg); allyl bromide (130 μL); FCC-AcOEt/hexane (1:1).
Sulfonamide 4h (315 mg, 88%, 24 h); clare wax, [α]D20 =À 65.6
(S)-Methyl
4-(methylthio)-2-(4-nitrophenylsulfonamido)
butanoate (348 mg); allyl bromide (130 μL); FCC-AcOEt/
hexane (1:3). Sulfonamide 4e (330 mg, 85%, 10 h); clare wax,
[α]D20 =À 21.9 (c 1.1, CHCl3). 1H-NMR (300 MHz, CDCl3)
δ 8.37 (d, 2H, J=8.4 Hz), 8.06 (d, 2H, J=8.4 Hz), 5.89–5.75
(m, 1H), 5.28–5.17 (m, 2H), 4.84–4.79 (m, 1H), 4.02 (dd, 1H,
J=16.2, 5.4 Hz), 3.81 (dd, 1H, J=16.2, 7.2 Hz), 3.58 (s, 3H),
2.67–2.53 (m, 2H), 2.33–1.98 (m, 5H). 13C-NMR (75 MHz,
CDCl3): δ 170.6, 150.0, 145.7, 133.9, 128.8 (2CHAr), 124.0
(2CHAr), 118.9, 59.0, 52.4, 49.0, 30.5, 29.4, 15.4. IR ν max 3279,
1709, 1541, 1350, 1323, 1256, 1172, 1139, 1075, 931,
754 cmÀ 1. MS Calcd. for C15H20N2O6S2: 388.1. Found [M+Na+
]: 411.1. Anal. Calcd. For C15H20N2O6S2: C, 46.38; H, 5.19; N,
7.21. Found: C, 46.73; H, 5.48; N, 7.05.
1
(c=1, CHCl3). H-NMR (300 MHz, CDCl3) δ 8.36 (d, 2H, J=
8.7 Hz), 8.05 (d, 2H, J=8.7 Hz), 5.96–5.83 (m, 1H), 5.28–5.17
(m, 2H), 4.52–4.46 (m, 2H), 4.11 (dd, 1H, J=16.2, 10.5 Hz),
4.00 (dd, 1H, J=16.2, 7.2 Hz), 3.59 (s, 3H), 2.11 (bs, 1H), 1.34
(d, 3H, J=6.3 Hz). 13C-NMR (75 MHz, CDCl3) δ 169.7, 150.0,
145.5, 134.3, 128.9 (2CHAr), 123.9 (2CHAr), 118.9, 66.8, 65.1,
52.3, 49.9, 20.0. IR ν
3499, 3203, 3021, 1745, 1579, 1171,
max
986 cmÀ 1. MS Calcd. for C14H18N2O7S: 358.0. Found [M+H+]:
359.1. Anal. Calcd. For C14H18N2O7S: C, 46.92; H, 5.06; N,
7.82. Found: C, 47.21; H, 5.35; N, 7.59.
(S)-Methyl 2-[4-Nitro-N-(Prop-2-Ynyl)
Phenylsulfonamido]-3-Phenylpropanoate (7a)
(S)-Methyl N-Allyl-N-[(4-Nitrophenyl)Sulfonyl]-L-
Tryptophanate (4f)
Methyl [(4-nitrophenyl)sulfonyl]-L-phenylalaninate (364 mg);
propargyl bromide (114 μL); FCC-AcOEt/hexane (1:3). Sulpho-
namide 7a (382 mg, 95%, 5 h); yellow wax, [α]D20 =À 29.1 (c=
Methyl
3-(1H-indol-3-yl)-2
(4-nitrophenylsulfonamido)
1
propanoate (403 mg); allyl bromide (130 μL) for 8 h. FCC-
AcOEt/hexane (1:4). Sulfonamide 4f (302 mg, 68%); yellow
wax, [α]D20 =À 27.4 (c 0.9 CHCl3). 1H-NMR (300 MHz, CDCl3)
δ 7.95 (s, 1H), 7.90 (d, 2H, J=8.6 Hz), 7.54 (d, 2H, J=
8.6 Hz), 7.45 (d, 1H, J=7.7 Hz), 7.20 (t, 1H, J=7.1 Hz), 7.11
(t, 1H, J=7.4 Hz), 7.04 (t, J=7.3 Hz, 1H), 6.90 (s, 1H), 5.70
1.2, CHCl3). H-NMR (300 MHz, CDCl3) δ 8.18 (d, 2H, J=
8.7 Hz), 7.82 (d, 2H, J=8.7 Hz), 7.24 (s, 5H), 4.89–4.85 (m,
1H), 4.43–4.21 (m, 2H), 3.65 (s, 3H), 3.43–3.36 (m, 1H), 3.05
(dd, 1H, J=14.1, 8.7 Hz), 2.23 (s, 1H). 13C-NMR (75 MHz,
CDCl3) δ 170.1, 149.9, 145.5, 136.2, 129.2 (2CHAr), 128.8
(2CHAr), 128.6 (2CHAr), 127.1, 123.7 (2CHAr), 73.8, 61.8, 52.5,
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36.1, 34.4. IR ν
3299, 3030, 1731, 1530, 1164, 930 cmÀ 1.
For C20H19F3N2O6S: C, 50.85; H, 4.05; N, 5.93. Found: C,
51.06; H, 4.24; N, 5.77.
max
MS Calcd. for C19H18N2O6S: 402.1. Found [M+Na+]: 425.1.
Anal. Calcd. For C19H18N2O6S: C, 56.71; H, 4.51; N, 6.96.
Found: C, 56.96; H, 4.73; N, 6.78.
(S)-Methyl 2-(N-Allyl-2-Methoxy-
4-Nitrophenylsulfonamido)-3-Phenylpropanoate
(9b)
(S)-Methyl 2- [N-Benzyl-
4-Nitrophenylsulfonamido]-3-Phenylpropanoate
(7b)
(S)-Methyl 2-(2-methoxy-4-nitrophenylsulfonamido)-3-phenyl-
propanoate D (394 mg); allyl bromide (130 μL); FCC-AcOEt/
hexane (1:3). Sulfonamide 9b (343 mg, 79%, 4 h); yellow wax,
[α]D20 =À 20.3 (c=1.1, CHCl3). 1H-NMR (300 MHz, CDCl3)
δ 8.04 (d, 1H, J=8.4 Hz), 7.83 (d, 1H, J=8.4 Hz), 7.72 (s,
1H), 7.28–7.12 (m, 5H), 5.88–5.75 (m, 1H), 5.26–5.09 (m, 2H),
4.83 (t, 1H, J=7.5 Hz), 4.16 (d, 2H, J=5.7 Hz), 3.92 (s, 3H),
3.54 (s, 3H), 3.31 (dd, 1H, J=13.8, 7.5 Hz), 3.03 (dd, 1H, J=
13.8, 7.8 Hz). 13C-NMR (75 MHz, CDCl3): δ 170.8, 157.0,
151.2, 136.4, 135.1, 134.4, 132.1, 129. 1 (2CHAr), 128.4
(2CHAr), 126.9, 118.0, 114.9, 107.1, 61.0, 56.5, 52.0, 49.2, 36.9.
Methyl [(4-nitrophenyl)sulfonyl]-L-phenylalaninate (364 mg);
benzyl bromide (114 μL); FCC-AcOEt/hexane (1:5). Sulphona-
mide 7b (418 mg, 92%, 5 h); yellow wax, [α]D20 =À 19.6 (c=
1
1.2, CHCl3). H-NMR (300 MHz, CDCl3): δ 8.20 (d, 2H, J=
8.8 Hz), 7.77 (d, 2H, J=8.8 Hz), 7.44–7.32 (m, 2H), 7.27–7.10
(m, 8H), 4.90 (t, 1H, J=7.5 Hz), 4.64–4.59 (m, 1H), 4.42 (d,
1H, J=15.4 Hz), 3.50 (s, 3H), 3.28 (dd, 1H, J=14.1, 7.5 Hz),
2.97 (dd, 1H, J=14.1, 7.5 Hz). 13C-NMR (75 MHz, CDCl3)
δ 170.2, 149.7, 146.0, 136.5, 135.3, 129.2 (2CHAr), 128.9
(2CHAr), 128.8 (2CHAr), 128.6 (2CHAr), 128.5 (2CHAr), 128.1,
IR ν
3430, 1736, 1354, 1313, 1295, 1272, 1250, 1148,
max
127.1, 123.8 (2CHAr), 61.7, 52.2, 50.0, 36.9. IR ν
3308,
916 cmÀ 1. MS Calcd. for C20H22N2O7S: 434.1. Found [M+Na+
]: 457.1. Anal. Calcd. For C20H22N2O7S: C, 55.29; H, 5.10; N,
6.45. Found: C, 55.52; H, 5.32; N, 6.28.
max
2999, 1749, 1578, 1189, 990 cmÀ 1. MS Calcd. for C23H22N2O6S:
454.1. Found [M+H+]: 455.1. Anal. Calcd. For C23H22N2O6S:
C, 60.78; H, 4.88; N, 6.16. Found: C, 61.02; H, 5.09; N, 5.99.
(S)-Methyl 2-(N-Allyl-2-Nitrophenylsulfonamido)-
3-Phenylpropanoate (9c)
(S)-Methyl 2-(N-Butyl-4-Nitrophenylsulfonamido)-
3-Phenylpropanoate (7c)
(S)-Methyl
2-(2-nitrophenylsulfonamido)3-phenylpropanoate
Methyl [(4-nitrophenyl)sulfonyl]-L-phenylalaninate (364 mg);
n-butyl bromide (162 μL); FCC-AcOEt/hexane (1:4). Sulphona-
mide 7c (387 mg, 92%, 5 h); yellow wax, [α]D20 =À 17.6 (c=
(364 mg); allyl bromide (130 μL) for 2 h; FCC-AcOEt/hexane
20
(1:4). Sulfonamide 9c (287 mg, 71%); yellow wax, [α]D
=
1
À 24.9 (c=1.1, CHCl3). H-NMR (300 MHz, CDCl3) δ 7.87 (d,
1H, J=7.8 Hz), 7.70–7.56 (m, 3H), 7.32–7.23 (m, 6H), 5.89–
5.75 (m, 1H), 5.28–5.12 (m, 2H), 4.93 (t, 1H, J=7.6 Hz), 4.15
(dd, 1H, J=16.5, 6.3 Hz), 4.04 (dd, 1H, J=16.5, 6.6 Hz), 3.58
(s, 3H), 3.39 (dd, 1H, J=14.1, 7.8 Hz), 3.07 (dd, 1H, J=14.1,
7.5 Hz). 13C-NMR (75 MHz, CDCl3) δ 170.5, 148.0, 136.5,
134.4, 133.9, 132.9, 131.8, 130.9, 129.3 (2CHAr), 128.6
1
1.2, CHCl3). H-NMR (300 MHz, CDCl3) δ 8.23 (d, 2H, J=
8.7 Hz), 7.82 (d, 2H, J=8.7 Hz), 7.38–7.21 (m, 5H), 4.86 (t,
1H J=9.0 Hz, ), 3.58 (s, 3H), 3.42–3.20 (m, 3H), 3.15–3.03
(m, 1H), 1.65–1.54 (m, 2H), 1.34–1.25 (m, 2H), 0.92 (t, 3H, J=
6.0 Hz).13C-NMR (75 MHz, CDCl3) δ 170.6, 149.8, 145.9,
136.5, 129.1 (2CHAr), 128.7 (2CHAr), 128.5 (2CHAr), 127.1,
123.9 (2CHAr), 61.6, 52.3, 46.1, 36.6, 32.0, 20.2, 13.6. IR ν
(2CHAr), 127.0, 124.0, 118.5, 61.3, 52.2, 48.9, 36.4. IR ν
max
max
3276, 1719, 1529, 1354, 1308, 1263, 1172, 1151, 1089, 1066,
931, 856, 835, 742 cmÀ 1. MS Calcd. for C20H24N2O6S: 420.1.
Found [M+H+]: 421.1. Anal. Calcd. For C20H24N2O6S: C,
57.13; H, 5.75; N, 6.66. Found: C, 57.32; H, 5.95; N, 6.51.
3276, 1719, 1529, 1354, 1308, 1263, 1172, 1151, 1089, 1066,
931, 856, 835, 742 cmÀ 1. MS Calcd. for C19H20N2O6S: 404.1.
Found [M+H+]: 405.1. Anal. Calcd. For C19H20N2O6S: C,
56.43; H, 4.98; N, 6.93. Found: C, 56.75; H, 5.26; N, 6.76.
(S)-Methyl 2-[N-Allyl-4-Nitro-3-(Trifluoromethyl)
Phenylsulfonamido]-3-Phenylpropanoate (9a)
(S)-Methyl 2-(4-Acetyl-N-Allylphenylsulfonamido)-
3-Phenylpropanoate (9d)
(S)-Methyl 2-(4-nitro-3-(trifluoromethyl)phenylsulfonamido)-3-
phenylpropanoate C (432 mg); allyl bromide (130 μL); FCC-
AcOEt/hexane (1:4). Sulphonamide 9a (425 mg, 90%, 4 h);
yellow wax, [α]D20 =À 19.8 (c=1.0, CHCl3).1H-NMR
(300 MHz, CDCl3) δ 8.17 (s, 1H), 7.86–7.78 (m, 2H), 7.28–
7.19 (m, 5H), 5.73–5.60 (m, 1H), 5.31–5.21 (m, 2H), 4.92–4.86
(m, 1H), 3.98 (dd, 1H, J=16.2, 6.3 Hz), 3.91 (dd, 1H, J=16.2,
9.9 Hz), 3.66 (s, 3H), 3.41 (dd, 1H, J=14.4, 6.3 Hz), 3.04 (dd,
1H, J=14.3, 9.0 Hz). 13C-NMR (75 MHz, CDCl3) δ 170.3,
144.7, 136.18, 133.0, 132.3, 132.1, 129.1 (2CHAr), 128.7
(2CHAr), 127.4, 127.2, 125.4, 125.3–125.1, 121.2 (d, 1CH, J=
(S)-Methyl 2-(4-acetylphenylsulfonamido)-3-phenylpropanoate
F (361 mg); allyl bromide (130 μL) for 3 h; FCC-AcOEt/hexane
20
(1:2). Sulphonamide 9d (309 mg, 77%); clare wax, [α]D
=
1
À 28.7(c=1.1, CHCl3). H-NMR (300 MHz, CDCl3) δ 7.98 (d,
2H, J=8.4 Hz), 7.77 (d, 2H, J=8.4 Hz), 7.32–7.22 (m, 5H),
5.79–5.66 (m, 1H), 5.26–5.13 (m, 2H), 4.90 (t, 1H, J=7.5 Hz),
3.97 (dd, 1H, J=13.8, 6.6 Hz), 3.89 (dd, 1H, J=13.8, 6.3 Hz),
3.58 (s, 3H), 3.37 (dd, 1H, J=14.1, 6.9 Hz), 3.04 (dd, 1H, J=
14.1, 8.1 Hz), 2.67 (s, 3H). 13C-NMR (75 MHz, CDCl3) δ 170.6,
164.4, 144.0, 139.8, 136.6, 134.0, 129.2 (2CHAr), 128.6
(2CHAr), 128.5 (2CHAr), 127.8 (2CHAr), 127.0, 118.6, 61.2,
272.0), 119.4, 61.8, 52.47, 48.8, 36.3. IR ν
3430, 1736,
52.1, 48.5, 36.5, 26.8. IR ν
3154, 1843, 1765, 1544, 1432,
max
max
1354, 1313, 1295, 1272, 1250, 1148, 916 cmÀ 1. MS Calcd. for
1312, 1271, 946 cmÀ 1. MS Calcd. for C21H23N2O5S: 401.1.
Found [M+Na+]: 424.1. Anal. Calcd. For C21H23N2O5S: C,
62.83; H, 5.77; N, 3.49. Found: C, 63.14; H, 6.07; N, 3.27.
C20H19F3N2O6S: 472.1. Found [M+H+]: 473.2. Anal. Calcd.
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95%, 24 h); yellow wax, [α]D20 = +16.6 (c 1.1, CHCl3), ee 95%
[CHIRALCEL OJÀ H, hexane/iPrOH (9:1), flow rate 1 mL/min,
P 32 bar, t1major 18.952, t2minor 23.470]. 1H NMR (300 MHz,
CDCl3) δ 8.11 (d, 2H, J=8.9 Hz), 7.52 (d, 2H, J=8.9 Hz), 7.17
(d, 2H, J=6.8 Hz), 6.86 (d, 2H, J=9.2 Hz), 5.96–5.84 (m, 1H),
5.25 (dd, 1H, J=13.7, 1.3 Hz), 5.11(dd, 1H, J=11.5, 1.3 Hz),
3.75 (s, 3H), 3.38 (d, 1H, J=13.6 Hz), 3.33 (d, 1H, J=
13.6 Hz), 3.16 (dd, 1H, J=13.9, 5.6 Hz), 3.06 (dd, 1H, J=
13.9, 5.6 Hz), 1.90 (bs, 1H) NH proton not visible. 13C NMR
(75 MHz, CDCl3) δ 173.3, 147.1, 135.7, 134.9, 134.8, 130.2 (2
CH2Ar), 128.2 (2 CH2Ar), 128.1 (2 CH2Ar), 127.0, 123.1 (2
CH2Ar), 116.1, 69.7, 52.4, 45.9, 43.4. IR ν max 3348, 3084, 3065,
3031, 1725, 1496, 1249, 842, 749 cmÀ 1. MS Calcd. for
C19H20N2O4: 340.1. Found [M+Na+]:363.1. Anal. Calcd. For.
C19H20N2O4: C, 67.05; H, 5.92; N, 8.23. Found: C, 67.17; H,
6.02; N, 8.14.
(S)-Methyl 2-(N-Allyl-4-Cyanophenylsulfonamido)-
3-Phenylpropanoate (9e)
(S)-Methyl 2-(2-methoxy-4-nitrophenylsulfonamido)-3-phenyl-
propanoate E (334 mg); allyl bromide (130 μL) for 4 h; FCC-
AcOEt/hexane (1:1). Sulfonamide 9e (315 mg, 82%); white
wax, [α]D20 =À 18.9 (c=1.2, CHCl3).1H-NMR (300 MHz,
CDCl3): δ 7.71–7.65 (m, 4H), 7.31–7.19 (m, 5H), 5.74–5.60 (m,
1H), 5.25–5.12 (m, 2H), 4.89 (t, 1H, J=7.8 Hz), 3.98 (dd, 1H,
J=16.3, 6.5 Hz), 3.85 (dd, 1H, J=16.3, 6.2 Hz), 3.61 (s, 3H),
3.39 (dd, 1H, J=14.4, 6.6 Hz), 3.02 (dd, 1H, J=14.4, 9.0 Hz).
13C-NMR (75 MHz, CDCl3): δ 170.5, 144.5, 136.5, 133.5, 132.5
(2CHAr), 129.2 (2CHAr), 128.7 (2CHAr), 128.1 (2CHAr), 127.1,
119.0, 117.3, 116.1, 61.4, 52.3, 48.6, 36.3. IR ν
3421, 2226,
max
1742, 1459, 1350, 1308, 1159, 636 cmÀ 1. MS Calcd. for
C20H20N2O4S: 384.1. Found [M+H+]: 385.1. Anal. Calcd. For
C20H20N2O4S: C, 62.48; H, 5.24; N, 7.29. Found: C, 62.30; H,
5.11; N, 7.48.
(R)-Methyl 2-(Allylamino)-4-Methyl-
2-(4-Nitrophenyl)Pentanoate (5b)
(S)-Methyl 2-[N-Allyl-4-(Methylsulfonyl)
Phenylsulfonamido]-3-Phenylpropanoate (9f)
(S)-Methyl
2-(N-allyl-4-nitrophenylsulfonamido)-4-meth-
ylpentanoate 4b (370 mg); FCC-AcOEt/hexane (1:4). 5b
(282 mg, 92%, 24 h); yellow wax, [α]D20 =À 25.3 (c 1, CHCl3),
ee 82% [CHIRALPAC AD, hexane/iPrOH (8:2), flow rate
1 mL/min, P 23 bar, t1major 7.304, t2minor 8.366]. 1H NMR
(300 MHz, CDCl3) δ 8.17 (d, 2H, J=8.7 Hz), 7.68 (d, 2H, J=
8.7 Hz), 5.96–5.83 (m, 1H), 5.243 (dd, 1H, J=17.1, 1.2 Hz),
5.09 (dd, 1H, J=10.2, 1.2 Hz), 3.69 (s, 3H), 3.01–2.89 (m,
2H), 2.14–1.96 (m, 2H), 1.63–1.51 (m, 1H), 0.85 (d, 3H, J=
6.6 Hz), 0.73 (d, 3H, J=6.6 Hz) NH proton not visible. 13C
NMR (75 MHz, CDCl3) δ 170.3,149.3, 147.2, 136.1, 127.8 (2
CH2Ar), 123.3 (2 CH2Ar), 115.8, 68.0, 52.3, 45.9, 44.6, 24.3,
(S)-Methyl 2-(4-(methylsulfonyl)phenylsulfonamido)-3-phenyl-
propanoate G (397 mg); allyl bromide (130 μL) for 3 h; FCC-
AcOEt/hexane (1:3). Sulfonamide 9f (394 mg, 90%); clare
wax, [α]D20 =À 46.5 (c=0.8, CHCl3). 1H-NMR (300 MHz,
CDCl3) δ 7.96 (d, 2H, J=8.4 Hz), 7.79 (d, 2H, J=8.4 Hz),
7.31–7.21 (m, 5H), 5.76–5.63 (m, 1H), 5.27–5.15 (m, 2H),
4.94–4.89 (m, 1H), 4.00 (dd, 1H, J=16.3, 6.5 Hz), 3.88 (dd,
1H, J=16.3, 6.1 Hz), 3.62 (s, 3H), 3.40 (dd, 1H, J=14.1,
6.3 Hz), 3.09 (s, 3H), 3.03 (dd, 1H, J=14.1, 8.7 Hz).13C-NMR
(75 MHz, CDCl3) δ 170.5, 145.3, 143.9, 136.5, 133.6, 129.2
(2CHAr), 128.7 (2CHAr), 128.4 (2CHAr), 127.9 (2CHAr), 127.2,
23.7, 23.6. IR ν
3341, 3087, 3031, 2930, 1725, 1604, 843,
max
735 cmÀ 1. MS Calcd. for. C16H22N2O4: 306.1; found [M+H+]:
307.2. Anal. Calcd. For C16H22N2O4: C, 62.73; H, 7.24; N, 9.14.
Found: C, 62.98; H, 7.37; N, 9.03.
119.0, 61.45, 52.3, 48.6, 44.3, 36.3. IR ν
3350, 1750, 1736,
max
1400, 1321, 1120, 680 cmÀ 1. MS Calcd. for C20H23NO6S2:
437.1. Found [M+H+]: 438.2. Anal. Calcd. For C20H23NO6S2:
C, 54.90; H, 5.30; N, 3.20. Found: C, 55.09; H, 5.44; N, 3.11.
(2R,3S)-Methyl 2-(Allylamino)-3-Methyl-
2-(4-Nitrophenyl)Pentanoate (5c)
General Procedure for the Catalytic Rearrange-
ment of N-Alkyl Arylsulphonamido Esters
(2S,3S)-Methyl 2-(N-allyl-4-nitrophenylsulfonamido)-3-meth-
ylpentanoate 4c (370 mg); FCC-AcOEt/hexane (1:4). 5c
(248 mg, 83%, 72 h); yellow wax, [α]D20 =À 14.4 (c 1, CHCl3),
de 99%. 1H NMR (300 MHz, CDCl3) δ 8.21 (d, 2H, J=8.7 Hz),
7.71 (d, 2H, J=8.7 Hz), 5.97–5.88 (m, 1H), 5.27 (dd, J=17.1,
1.2 Hz, 1H), 5.11 (dd, 1H, J=10.5, 1.2 Hz), 3.73 (s, 3H), 2.97
(t, J=8.5 Hz, 2H), 2.14 (dd, 1H, J=14.4, 6.6 Hz), 2.02 (dd,
1H, J=14.4, 5.4 Hz), 1.92–1.83 (m, 1H), 0.88 (t, 3H, J=
6.6 Hz), 0.83 (d, 3H, J=6.8 Hz) NH proton not visible. 13C
NMR (75 MHz, CDCl3) δ 174.3, 149.3, 147.2, 136.1, 127.8 (2
CH2Ar), 123.3, (2 CH2Ar), 115.8, 68.0, 52.3, 46.0, 44.6, 24.3,
To a solution of N-alkyl sulfonamide (1.0 mmol) and DBU
(15 mg, 0.1 mmol) in dry DME (1 mL), a water solution (2 mL)
of Na2CO3 (212 mg, 2 mmol) was added, and the liquid-liquid
°
heterogeneus mixture was stirred at 25 C until completion
(TLC control). The reaction was then diluted with AcOEt
(10 mL), quenched and washed with aqueous 5% citric acid (2×
10 mL), saturated NaHCO3 solution (2×10 mL), and brine
(10 mL). The organic phase was dried over MgSO4, filtered,
and concentrated under reduced pressure (RV), giving the
correspondent product. The known compounds completely
matched with the reported data.[22] Starting material, product,
yield, chromatographic eluant, physical and analytical data of
new products 5a–h, 8a–c, 10a–f are as follows.
23.7, 23.4. IR ν
3341, 2974, 2934, 1723, 1644, 1520, 1349,
max
1244, 1160, 885 cmÀ 1. MS Calcd. for. C16H22N2O4: 306.1; found
[M+H+]: 307.2. Anal. Calcd. For C16H22N2O4: C, 62.73; H,
7.24; N, 9.14. Found: C, 62.91; H, 7.39; N, 9.08.
(R)-Methyl 2-(Allylamino)-2-(4-Nitrophenyl)-
3-Phenylpropanoate (5a)
(S)-methyl 2-(N-allyl-4-nitrophenylsulphonamido)-3-phenylpro-
panoate 4a (404 mg); FCC-AcOEt/hexane (1:3). 5a (323 mg,
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(R)-Methyl 2-(Allylamino)-2-(Cyclohexa-1,4-Dien-
1-Yl)-2-(4-Nitrophenyl)Acetate (5d)
(R)-Methyl 2-(Allylamino)-3-(4-Hydroxyphenyl)-
2-(4-Nitrophenyl)Propanoate (5g)
(S)-Methyl 2-(N-allyl-4-nitrophenylsulfonamido)-2-(cyclohexa-
1,4-dien-1-yl)acetate 4d (392 mg); FCC-AcOEt/hexane (1:5).
5d (309 mg, 94%, 24 h); yellow wax, [α]D20 = +14.9 (c 1,
CHCl3), ee 86% [CHIRALCEL OJÀ H, hexane/iPrOH (9:1),
(S)-methyl 2-(N-allyl-4-nitrophenylsulfonamido)-3-(4-hydroxy-
phenyl)propanoate 4g (420 mg); FCC-AcOEt/hexane (1:2). 5g
(303 mg, 85%, 48 h); yellow wax, [α]D20 =À 20.3 (c 1, CHCl3),
ee 79% [CHIRALPACK AD, hexane/iPrOH (7:3), flow rate
1 mL/min, P 25 bar, t1major 6.167, t2minor 6.590]. 1H NMR
(300 MHz, CDCl3) δ 8.11 (d, 2H, J=8.9 Hz), 7.52 (d, 2H, J=
8.8 Hz), 6.72 (d, J=8.4 Hz, 2H), 6.62 (d, 2H, J=8.5 Hz),
5.95–5.82 (m, 1H), 5.23 (dd, 1H, J=17.1, 1.2 Hz), 5.09 (dd,
1H, J=10.2, 1.2 Hz), 3.75 (s, 3H), 3.28 (s, 2H), 3.13 (dd, 1H,
J=13.9, 5.6 Hz), 3.03 (dd, 1H, J=13.8, 5.5 Hz) NH and OH
protons not visible. 13C NMR (75 MHz, CDCl3) δ 173.5, 154.8,
147.2, 135.8, 134.4, 131.5 (2 CH2Ar), 128.4 (2 CH2Ar), 126.9,
123.1 (2 CH2Ar), 116.0, 115.1 (2 CH2Ar), 70.0, 52.3, 46.2, 42.8.
IR ν max 3528, 3269, 2958, 2946, 1719, 1620, 1543, 1350, 1239,
978 cmÀ 1. MS Calcd. for. C19H20N2O5: 356.1; found [M+Na+]:
379.1. Anal. Calcd. For C19H20N2O5: C, 64.04; H, 5.66; N, 7.86.
Found: C, 64.18; H, 5.76; N, 7.79.
1
flow rate 1 mL/min, P 32 bar, t1major 22.129, t2minor 27.009]. H
NMR (300 MHz, CDCl3) δ 8.19 (d, 2H, J=8.2 Hz), 7.86 (d,
2H, J=8.2 Hz), 6.01–5.95 (m, 2H), 5.67 (s, 2H), 5.28 (d, 1H,
J=13.7 Hz), 5.15 (d, 1H, J=11.0 Hz), 3.78 (s, 3H), 3.05–3.03
(m, 2H), 2.83–2.80 (m, 2H), 2.51–2.49 (m, 2H), 2.13 (bs, 1H).
13C NMR (75 MHz, CDCl3) δ 172.3, 147.1, 146.7, 136.1, 133.,
129.5 (2 CH2Ar), 123.8, 123.3, 123.0, 122.9 (2 CH2Ar), 115.9,
73.0, 52.6, 46.7, 26.8, 25.7. IR ν
3348, 3076, 3029, 2927,
max
1730, 1597, 851 cmÀ 1. MS Calcd. for. C18H20N2O4: 328.1; found
[M+Na+]: 351.1. Anal. Calcd. For C18H20N2O4: C, 65.84; H,
6.14; N, 8.53. Found: C, 66.15; H, 6.40; N, 8.37.
(R)-Methyl 2-(Allylamino)-4-(Methylthio)-
2-(4-Nitrophenyl)Butanoate (5e)
(R)-Methyl 2-(Allylamino)-2-(4-Nitrophenyl)But-
3-Enoate (6h)
(S)-methyl 2-(N-allyl-4-nitrophenylsulfonamido)-4-(methylthio)
butanoate 4e (330 mg); FCC-AcOEt/hexane (1:3). 5e (242 mg,
78%, 48 h); yellow wax, [α]D20 = +11.1 (c 1, CHCl3), ee 62%
[CHIRALPACK AD, hexane/iPrOH (95:5), flow rate 1 mL/
(2S)-Methyl 2-(N-allyl-4-nitrophenylsulfonamido)-3-hydroxybu-
tanoate 4h (359 mg); FCC-AcOEt/hexane (1:5). 6h (251 mg,
91%, 48 h); yellow wax, [α]D20 =À 20.3 (c 1, CHCl3), ee <99%
[CHIRALCEL OJÀ H, hexane/iPrOH (95:5), flow rate 1 mL/
1
min, P 17 bar, t1major 5.945, t2minor 7.171]. H NMR (300 MHz,
CDCl3) δ 8.23 (d, 2H, J=8.7 Hz), 7.69 (d, 2H, J=8.6 Hz),
6.01–5.88 (m, 1H), 5.28 (d, 1H, J=13.6 Hz), 5.16 (d, 1H, J=
10.9 Hz), 3.77 (s, 3H), 3.12–2.98 (m, 2H), 2.54–2.19 (m, 4H),
2.07 (s, 3H) NH proton not visible. 13C NMR (75 MHz, CDCl3)
δ 173.5, 147.4, 135.5, 127.8, 127.5 (2 CH2Ar), 123.6 (2 CH2Ar),
1
min, P 15 bar, t1 23.067]. H NMR (300 MHz, CDCl3) δ 8.20
(d, 2H, J=8.7 Hz), 7.64 (d, 2H, J=8.6 Hz), 6.30 (dd, 1H, J=
17.5, 10.5 Hz), 5.95–5.84 (m, 1H), 5.44–5.39 (m, 2H), 5.24 (dd,
1H, J=17.1, 1.2 Hz), 5.09 (dd, 1H, J=9.9, 1.2 Hz), 3.78 (s,
3H), 3.04–3.02 (m, 2H), 2.29 (bs, 1H). 13C NMR (75 MHz,
CDCl3) δ 172.8, 147.9, 147.2, 136.6, 136.0, 128.2 (2 CH2Ar),
116.5, 68.1, 52.7, 46.1, 35.6, 28.2, 15.6. IR ν
3099, 3087,
max
3026, 2967, 1764, 1485, 1233, 987 cmÀ 1. MS Calcd. for.
C15H20N2O4S: 324.1; found [M+H+]: 325.2. Anal. Calcd. For
C15H20N2O4S: C, 55.54; H, 6.21; N, 8.64. Found: C, 55.77; H,
6.39; N, 8.52.
123.5 (2 CH2Ar), 117.8, 116.0, 70.0, 52.9, 46.4. IR ν
3331,
max
2979, 2932, 1726, 1644, 1604, 1520, 1368, 1348, 1246, 1153,
852 cmÀ 1. MS Calcd. for. C14H16N2O4: 276.1; found [M+H+]:
277.1. Anal. Calcd. For C14H16N2O4: C, 60.86; H, 5.84; N,
10.14. Found: C, 60.70; H, 5.72; N, 10.29.
(R)-Methyl 2-(Allylamino)-3-(1H-Indol-3-Yl)-
2-(4-Nitrophenyl)Propanoate (5f)
(R)-Methyl 2-(4-Nitrophenyl)-3-Phenyl-2-(Prop-
(S)-Methyl N-allyl-N-[(4-nitrophenyl)sulfonyl]-L-tryptophanate
4f (420 mg); FCC-AcOEt/hexane (1:3). 5f (326 mg, 86%,
48 h); yellow wax, [α]D20 = +13.4 (c 1, CHCl3), ee 84%
[CHIRALCEL OJ, hexane/iPrOH (8:2), flow rate 1 mL/min, P
37 bar, t1major 30.885, t2minor 43.615]. 1H NMR (300 MHz,
CDCl3) δ 8.11 (m, 3H), 7.68 (d, J=8.3 Hz, 2H), 7.31–7.29 (m,
2H), 7.13 (t, J=7.3 Hz, 1H), 7.00 (t, J=7.2 Hz, 1H), 6.94 (s,
1H), 5.93–5.85 (m, 1H), 5.23 (d, J=17.1 Hz, 1H), 5.09 (d, J=
10.0 Hz, 1H), 3.68 (s, 3H), 3.60–3.52 (m, 2H), 3.15 (dd, J=
13.6, 4.4 Hz, 1H), 3.06 (dd, J=13.4, 4.4 Hz, 1H) NH proton
not visible. 13C NMR (75 MHz, CDCl3) δ 173.8, 147.2, 136.1,
135.6 (2 C), 128.4 (2 CH2Ar), 128.0, 123.7 (2 CH2Ar), 123.1,
122.0, 119.5, 118.5, 115.8, 111.0, 109.2, 69.7, 52.4, 46.4, 34.0.
IR ν max 3467, 3338, 1743, 1698, 1639, 1525, 1298, 1217, 1106,
988, 889 cmÀ 1. MS Calcd. for. C21H21N3O4: 379.2; found [M+
Na+]: 402.1. Anal. Calcd. For C21H21N3O4: C, 66.48; H, 5.58;
N, 11.08. Found: C, 66.35; H, 5.49; N, 11.16.
2-Ynylamino)Propanoate (8a)
(S)-methyl 2-(N-propargyl-4-nitrophenylsulphonamido)-3-phe-
nylpropanoate 7a (403 mg); FCC-AcOEt/hexane (1:4). 8a
(357 mg, 92%, 24 h); yellow wax, [α]D20 = +18.2 (c 1, CHCl3),
ee 91% [CHIRALCEL OJ, hexane/iPrOH (8:2), flow rate 1 mL/
1
min, P 21 bar, t1 8.585, t2 10.949]. H NMR (300 MHz, CDCl3)
δ 8.13 (d, 2H, J=8.8 Hz), 7.56 (d, 2H, J=8.8 Hz), 7.21–7.17
(m, 3H), 6.90 (d, J=7.3 Hz, 2H), 3.76 (s, 3H), 3.42–3.25 (m,
4H), 2.34 (bs, 1H), 2.22 (t, 1H, J=2.3 Hz). 13C NMR (75 MHz,
CDCl3) δ 173.0, 147.3, 147.0, 134.7, 130.3 (2 CH2Ar), 128.4 (2
CH2Ar), 128.2 (2 CH2Ar), 127.2, 123.2 (2 CH2Ar), 81.3, 71.7,
69.7, 52.4, 43.9, 33.4. IR ν
3342, 3296, 2130, 1723, 1604,
max
1523, 856, 735 cmÀ 1. MS Calcd. for. C19H18N2O4: 338.1; found
[M+H+]: 339.2. Anal. Calcd. For C19H18N2O4: C, 67.44; H,
5.36; N, 8.28. Found: C, 67.60; H, 5.43; N, 8.17.
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(R)-Methyl 2-(Benzylamino)-2-(4-Nitrophenyl)-
3-Phenylpropanoate (8b)
(R)-Methyl 2-(Allylamino)-2-(2-Methoxy-
4-Nitrophenyl)-3-Phenylpropanoate (10b)
(S)-methyl 2-(N-benzyl-4-nitrophenylsulphonamido)-3-phenyl-
propanoate 7b (454 mg); FCC-AcOEt/hexane (1:4). 8b
(328 mg, 84%, 24 h); yellow wax, [α]D20 = +8.5 (c 1, CHCl3),
ee 89% [CHIRALCEL OJ, hexane/iPrOH (9:1), flow rate 1 mL/
min, P 32 bar, t1 18.205, t2 21.975]. 1H NMR (300 MHz,
CDCl3) δ 8.13 (d, 2H, J=8.8 Hz), 7.60 (d, 2H, J=8.7 Hz),
7.35–7.16 (m, 8H), 6.92 (d, 2H, J=4.0 Hz), 3.78 (s, 3H), 3.75
(d, 1H, J=12.6 Hz), 3.61 (d, 1H, J=10.8 Hz), 3.45 (s, 2H),
2.21 (bs, 1H). 13C NMR (75 MHz, CDCl3) δ 173.1, 147.4,
147.3, 137.1, 134.8 (2 CH2Ar), 132.3 (2 CH2Ar), 130.3 (2 CH2Ar),
128.6 (2 CH2Ar), 128.5 (2 CH2Ar), 128.2, 128.1, 127.2, 123.2 (2
(S)-Methyl 2-(N-allyl-2-methoxy-4-nitrophenylsulfonamido)-3-
phenylpropanoate 9b (434 mg); FCC-AcOEt/hexane (1:3). 10b
(274 mg, 74%, 48 h); yellow wax, [α]D20 =À 15.2 (c 1, CHCl3),
ee 95% [CHIRALCEL OD, hexane/iPrOH (95:5), flow rate
1 mL/min, P 16 bar, t1major 5.430, t2
6.477]. 1H NMR
minor
(300 MHz, CDCl3) δ 7.68–7.63 (m, 2H), 7.29 (d, 1H, J=
8.5 Hz), 7.10–7.06 (m, 3H), 6.74 (d, 2H, J=8.7 Hz), 5.99–5.87
(m, 1H), 5.25 (dd, 1H, J=13.7, 1.5 Hz), 5.11 (dd, 1H, J=11.6,
1.5 Hz), 3.85 (s, 3H), 3.69 (s, 3H), 3.36–3.25 (m, 3H), 3.11 (dd,
1H, J=14.1, 5.7 Hz), 1.65 (bs, 1H). 13C NMR (75 MHz,
CDCl3) δ 173.0, 156.7, 156.6, 148.0, 135.8, 135.6, 130.3 (2
CH2Ar), 128.2, 127.4 (2 CH2Ar), 126.4, 115.9, 115.4, 105.57,
CH2Ar), 70.3, 52.5, 48.2, 43.5. IR ν
3343, 3030, 1725, 1604,
max
1369, 843, 734 cmÀ 1. MS Calcd. for. C23H22N2O4: 390.2; found
[M+Na+]: 413.2. Anal. Calcd. For C23H22N2O4: C, 70.75; H,
5.68; N, 7.17. Found: C, 70.94; H, 5.81; N, 7.02.
66.0, 55.9, 51.7, 45.8, 39.3. IR ν
3330, 3071, 3061, 3025,
max
1714, 1491, 1299, 1240, 800 cmÀ 1. MS Calcd. for. C20H22N2O5:
370.2; found [M+H+]: 371.2. Anal. Calcd. For C20H22N2O5: C,
64.85; H, 5.99; N, 7.56. Found: C, 65.02; H, 6.11; N, 7.44.
(R)-Methyl 2-(Butylamino)-2-(4-Nitrophenyl)-
3-Phenylpropanoate (8c)
(R)-Methyl 2-(Allylamino)-2-(2-Nitrophenyl)-
3-Phenylpropanoate (10c)
(S)-methyl 2-(N-butyl-4-nitrophenylsulphonamido)-3-phenylpro-
panoate 7c (420 mg); FCC-AcOEt/hexane (1:5). 8c (274 mg,
77%, 24 h); yellow wax, [α]D20 = +17.3 (c 1, CHCl3), ee 87%
[CHIRALPACK AD, hexane/iPrOH (8:2), flow rate 1 mL/min,
P 20 bar, t1major 5.414, t2minor 6.921]. 1H NMR (300 MHz, CDCl3)
δ 8.13 (d, 2H, J=8.7 Hz), 7.54 (d, 2H, J=8.3 Hz), 7.28–6.71
(m, 3H), 6.89–6.87 (m, 2H), 3.78 (s, 3H), 3.38 (s, 2H), 2.58–
2.40 (m, 2H), 1.81 (bs, 1H), 1.56–1.33 (m, 4H), 0.93 (t, 3H, J=
7.2 Hz). 13C NMR (75 MHz, CDCl3) δ 173.6, 148.2, 147.1,
135.2 (2 CH2Ar), 130.3 (2 CH2Ar), 128.3 (2 CH2Ar), 128.0, 126.9,
123.0 (2 CH2Ar), 70.1, 52.3, 43.4, 43.0, 32.5, 20.4, 13.9. IR ν max
3354, 2803, 1943, 1726, 1603, 1520, 1347, 1031, 800 cmÀ 1. MS
Calcd. for. C20H24N2O4: 356.2; found [M+H+]: 357.1. Anal.
Calcd. For C20H24N2O4: C, 67.40; H, 6.79; N, 7.86. Found: C,
67.66; H, 6.99; N, 7.69.
(S)-Methyl 2-(N-allyl-2-nitrophenylsulfonamido)-3-phenylpro-
panoate 9c (404 mg); FCC-AcOEt/hexane (1:4). 10c (265 mg,
78%, 24 h); yellow wax, [α]D20 =À 36.0 (c 1, CHCl3), ee 88%
[CHIRALCEL OJ, hexane/iPrOH (9:1), flow rate 1 mL/min, P
24 bar, t1major 19.644, t2
23.231]. 1H NMR (300 MHz,
minor
CDCl3) δ 7.88 (d, 1H, J=7.5 Hz), 7.50–7.32 (m, 3H), 7.18–
7.14 (m, 3H), 6.90 (d, 2H, J=6.0 Hz), 5.94–5.81 (m, 1H), 5.25
(d, 1H, J=13.7 Hz), 5.11 (d, 1H, J=11.0 Hz), 3.89 (bs, 1H),
3.81 (d, 1H, J=13.8 Hz), 3.73 (s, 3H), 3.54 (d, 1H, J=
13.8 Hz), 3.00 (d, 2H, J=4.7 Hz). 13C NMR (75 MHz, CDCl3)
δ 171.5, 149.9, 135.9, 135.8, 133.9, 131.7 (2 CH2Ar), 130.9,
130.4, 128.3 (2 CH2Ar), 127.6, 126.6, 124.8, 115.6, 67.8, 51.6,
46.0, 43.2. IR ν
3348, 3084, 3065, 3031, 1725, 1496, 1249,
max
842, 749 cmÀ 1. MS Calcd. for. C19H20N2O4: 340.1; found [M+
Na+]: 363.1. Anal. Calcd. For C19H20N2O4: C, 67.05; H, 5.92;
N, 8.23. Found C, 67.26; H, 6.11; N, 8.07.
(R)-Methyl 2-(Allylamino)-2-(4-Nitro-
3-(Trifluoromethyl)Phenyl)-3-Phenylpropanoate
(10a)
(R)-Methyl 2-(4-Acetylphenyl)-2-(Allylamino)-
3-Phenylpropanoate (10d)
(S)-Methyl
2-(N-allyl-4-nitro-3-(trifluoromethyl)
(S)-methyl 2-(4-acetyl-N-allylphenylsulfonamido)-3-phenylpro-
panoate 9d (401 mg); FCC-AcOEt/hexane (1:2). 10d (226 mg,
67%, 48 h); yellow wax, [α]D20 = +7.2 (c 1, CHCl3), ee 44%
[CHIRALPACK AD, hexane/iPrOH (8:2), flow rate 1 mL/min,
P 24 bar, t1major 5.894, t2minor 6.388]. 1H NMR (300 MHz, CDCl3)
δ 7.89 (d, 2H, J=8.0 Hz), 7.48–7.46 (m, 2H), 7.20–7.17 (m,
3H), 6.95–6.93 (m, 2H), 5.97–5.84 (m, 1H), 5.24 (d, 1H, J=
13.3 Hz), 5.15 (d, 1H, J=11.1 Hz), 3.73 (s, 3H), 3.46–3.41 (m,
2H), 3.16 (dd, 1H, J=13.7, 5.8 Hz), 3.06 (dd, 1H, J=13.6,
5.7 Hz), 2.59 (s, 3H), 1.85 (bs, 1H). 13C NMR (75 MHz,
CDCl3) δ 197.8, 173.9, 145.9, 136.3, 136.1, 135.6, 130.4 (2
CH2Ar), 128.2 (2 CH2Ar), 128.1 (2 CH2Ar), 127.1 (2 CH2Ar),
phenylsulfonamido)-3-phenylpropanoate 9a (472 mg); FCC-
AcOEt/hexane (1:3). 10a (322 mg, 79%, 24 h); yellow wax,
[α]D20 =À 11.3 (c 1, CHCl3), ee 93% [CHIRALPACK AD,
hexane/iPrOH (8:2), flow rate 1 mL/min, P 21 bar, t1major 4.636,
1
t2minor 5.502]. H NMR (300 MHz, CDCl3) δ 7.79–7.70 (m, 3H),
7.20–7.18 (m, 3H), 6.83 (d, 2H, J=7.5 Hz), 5.95–5.83 (m, 1H),
5.25 (d, 1H, J=13.7 Hz), 5.13 (d, 1H, J=10.1 Hz), 3.80 (s,
3H), 3.38 (d, 1H, J=13.4 Hz), 3.26 (d, 1H, J=13.4 Hz), 3.13
(dd, 1H, J=14.0, 5.7 Hz), 3.03 (dd, 1H, J=13.9, 5.4 Hz), 2.09
(bs, 1H). 13C NMR (75 MHz, CDCl3) δ 172.7, 147.0, 145.70,
135.2, 134.3, 132.3, 130.2 (2 CH2Ar), 128.3 (2 CH2Ar), 127.6,
127.5, 124.6, 123.1 (q, J=34.2 Hz), 121.9 (q, J=171.9), 116.5,
126.8, 115.9, 69.8, 52.2, 46.3, 42.7, 26.7. IR ν
3382, 3082,
69.9, 52.6, 46.5, 44.8. IR ν
3346, 2979, 2928, 1727, 1604,
max
max
3054, 3024, 1879, 1731, 1470, 1230, 851 cmÀ 1. MS Calcd. for.
C21H23NO3: 337.2; found [M+Na+]: 360.1. Anal. Calcd. For
C21H23NO3: C, 74.75; H, 6.87; N, 4.15. Found: C, 74.90; H,
7.16; N, 4.00.
1522, 1456, 1369, 1349, 1253, 1145, 1111, 855 cmÀ 1. MS
Calcd. for. C20H19F3N2O4: 408.1; found [M+Na+]: 431.1. Anal.
Calcd. For C20H19F3N2O4: C, 58.82; H, 4.69; N, 6.86. Found: C,
59.06; H, 4.87; N, 6.67.
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Webb, J. Am. Chem. Soc. 2016, 138, 688–695; i) R.
(R)-Methyl 2-(Allylamino)-2-(4-Cyanophenyl)-
Bucci, A. Contini, F. Clerici, S. Pellegrino, M. L. Gelmi,
Org. Chem. Front. 2019, 6, 972–982; j) F. Vaghi, R.
Bucci, F. Clerici, A. Contini, M. L. Gelmi, Org. Lett.
2020, 22, 6197–6202; k) R. Bucci, A. Bossi, E. Erba, F.
Vaghi, A. Saha, S. Yuran, D. Maggioni, M. L. Gelmi, M.
Reches, S. Pellegrino, Sci. Rep. 2020, 10, 19331.
3-Phenylpropanoate (10e)
(S)-Methyl 2-(N-allyl-4-cyanophenylsulfonamido)-3-phenylpro-
panoate 9e (384 mg); FCC-AcOEt/hexane (1:2). 10e (202 mg,
63%, 48 h); yellow wax, [α]D20 = +9.8 (c 1, CHCl3), ee 42%
[CHIRALCEL OJ, hexane/iPrOH (8:2), flow rate 0.8 mL/min,
1
P 32 bar, t1 17.937, t2 21.545]. H NMR (300 MHz, CDCl3)
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δ 7.60 (d, 2H, J=8.4 Hz), 7.55–7.43 (m, 2H), 7.28–7.13 (m,
5H), 5.97–5.88 (m, 1H), 5.27 (dd, 1H, J=17.1, 1.3 Hz), 5.14
(dd, 1H, J=9.8, 1.3 Hz), 3.78 (s, 3H), 3.37 (s, 2H), 3.18 (dd,
1H, J=13.8, 5.5 Hz), 3.07 (dd, 1H, J=13.8, 5.6 Hz) NH proton
not visible. 13C NMR (75 MHz, CDCl3) δ 170.3, 150.6, 135.8,
135.0, 131.9 (2 CH2Ar), 130.3 (2 CH2Ar), 128.3 (2 CH2Ar), 128.1
(2 CH2Ar), 127.1, 118.7, 116.0, 111.4, 69.9, 52.4, 46.4, 43.2. IR
ν
3325, 3067, 3059, 2267, 1721, 1466, 1230, 980 cmÀ 1. MS
max
Calcd. for. C20H20N2O2: 320.2; found [M+H+]: 321.2. Anal.
Calcd. For C20H20N2O2: C, 74.98; H, 6.29; N, 8.74. Found: C,
74.77; H, 6.15; N, 8.92.
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(R)-Methyl 2-(Allylamino)-2-(4-(Methylsulfonyl)
Phenyl)-3-Phenylpropanoate (10f)
(S)-Methyl 2-[N-allyl-4-(methylsulfonyl)phenylsulfonamido]-3-
phenylpropanoate 9f (437 mg); FCC-AcOEt/hexane (1:2). 10f
(273 mg, 73%, 48 h); yellow wax, [α]D20 = +13.1 (c 1, CHCl3),
ee 62% [CHIRALPACK AD, hexane/iPrOH (95:5), flow rate
1 mL/min, P 21 bar, t1major 11.324, t2minor 12.520]. 1H NMR
(300 MHz, CDCl3) δ 7.84 (d, 2H, J=8.5 Hz), 7.57 (d, 2H, J=
8.3 Hz), 7.18–7.16 (m, 3H), 6.88 (d, 2H J=3.5 Hz), 5.95–582
(m, 1H), 5.23 (d, 1H, J=13.3 Hz), 5.16 (d, 1H, J=10.9 Hz),
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3.74 (s, 3H), 3.36 (s, 2H), 3.17–3.03 (m, 5H), 2.18 (bs, 1H). 13
NMR (75 MHz, CDCl3) δ 173.38, 146.6, 139.7, 135.7, 135.0,
130.4 (2 CH2Ar), 128.4 (2 CH2Ar), 128.1, 128.0 (2 CH2Ar), 127.1
C
(2 CH2Ar), 116.2, 69.9, 52.3, 46.3, 44.5, 43.4. IR ν
3327,
max
3100, 3078, 3024, 1750, 1339, 1259, 902 cmÀ 1. MS Calcd. for.
C20H23NO4S: 373.1; found [M+H+]: 374.2. Anal. Calcd. For
C20H23NO4S: C, 64.32; H, 6.21; N, 3.75. Found: C, 64.58; H,
6.45; N, 3.56.
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DBU Catalysed Enantioselective Degradative Rearrange-
ment: a Way to Tetrasubstituted 2-Aryl-2-Amino Esters
Adv. Synth. Catal. 2021, 363, 1–13
C. Loro, R. Sala, M. Penso, F. Foschi*