δ,ε-unsaturated α,β-diamino acids as building blocks for the asymmetric synthesis of diverse α,β-diamino acids

Article abstract of DOI:10.1021/jo5022162

A building block approach for the synthesis of ±,β-diamino acids is described, which involves the diastereodivergent preparation of two sets of orthogonally protected δ,ε-unsaturated ±,β-diamino acids as templates for the preparation of 12 new ±β-diamino acids of biological relevance using simple techniques.

Full text of DOI:10.1021/jo5022162

Note
pubs.acs.org/joc
δ,ε-Unsaturated α,β-Diamino Acids as Building Blocks for the
Asymmetric Synthesis of Diverse α,β-Diamino Acids
Nemai Saha, Bhaskar Chatterjee, and Shital K. Chattopadhyay*
Department of Chemistry, University of Kalyani, Kalyani-741235, West Bengal, India
S
* Supporting Information
ABSTRACT: A building block approach for the synthesis of α,β-diamino acids is described, which involves the
diastereodivergent preparation of two sets of orthogonally protected δ,ε-unsaturated α,β-diamino acids as templates for the
preparation of 12 new α,β-diamino acids of biological relevance using simple techniques.
α-Amino acids are Nature’s versatile building blocks that have
found widespread use in the area of molecular design.1,2 Thus, a
number of synthetic building blocks and templates for the
preparation of diverse natural and non-natural α-amino acids
have emerged over the last few decades.3 In this regard, the β,γ-
unsaturated amino acid vinylglycine,4 the γ,δ-unsaturated amino
acid allylglycine and its congeners,5 and the δ,ε-unsaturated
amino acid homoallylglycine6 (Hag) have proved to be of
distinct advantage as templates for many possible C−C and C−
hetero bond forming transformations. The biological relevance7
of α,β-diamino acids has similarly triggered synthetic activities,
and a number of elegant methodologies based on the use of the
aza-Mannich reaction,8 the aza-Henry reaction,9 chiral pool
materials,10 sigmatropic rearrangements,11 cycloaddition reac-
tions,12 asymmetric catalytic transformations,13 either in the
context of synthesis of many important nature-inspired
molecules or on their own merits, have been developed.
Substrate- or reagent-controlled diastereodivergent synthesis of
syn- and anti-α,β-diamino acid derivatives have also been
elegantly developed.14 However, the use of α,β-diamino acids as
building blocks for the synthesis of other α,β-diamino acids, in
particular, through C−C bond formation, is less documented.
Herein, we report two epimeric sets of orthogonally protected
α,β-diamino acids 7−8 and 11−12 (Scheme 1) as new building
blocks for the synthesis of diverse α,β-diamino acids.
dehydrative condensation between Garner’s aldehyde 117 and
4-methoxybenzyl amine. Thus, allylation of the imine 2 with
allylzinc bromide under optimized reaction conditions provided
the syn-homoallylic amine 3 as the major isomer (74%),
together with a small amount of the anti-isomer 4 (12%). On
the contrary, when allylation of 2 was carried out with allyl
magnesium bromide, the homoallylic amine 4 was formed as
the major isomer in a similar yield and diastereomeric excess.
The products 3 and 4 were then separately converted to the
desired building blocks over a three-step sequence involving
protection of the β-nitrogen with Cbz-Cl, one-pot depro-
tection−oxidation of the oxazolidine unit with Jones’ reagent,
and esterification of the resulting carboxylic acids 6 and 10.
The stereochemical assignment of the amines 3 and 4 was
based on Cram’s open chain and chelate models with further
support from the synthetic work described later (Scheme 5).
The protected pair of templates 7−8 and 11−12 exhibited
hindered rotation, and significant signal multiplication occurred
when the 1H and 13C NMR spectra were recorded in CDCl3 at
room temperature, questioning the diastereomeric purity of the
1
products. However, recording their H NMR spectra at higher
temperature clearly established their homogeneity as a single
set of signals was observed (Figure 1, Supporting Information).
This kind of hindered rotation of N-carbamates is well-
precedented.17c
The allylation of α-chiral imines has emerged as an efficient
method for the synthesis of enantio-enriched homoallylic
amines.15 On the basis of our continuing interest16 in strategic
stereodivergent allylation of α-chiral imines, we studied the
allylation reaction of the chiral imine 2, prepared by
Received: September 26, 2014
© XXXX American Chemical Society
A
DOI: 10.1021/jo5022162
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The Journal of Organic Chemistry
Note
Scheme 1. Diastereodivergent Synthesis of α,β-Diamino Acid Building Blocks 7, 8, 11, and 12
a
Scheme 2. Diastereodivergent Synthesis of DAP and 2,3-Diaminosuberic Acid Derivatives
a
Cat. 13 is benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro-(tricyclohexylphosphine)ruthenium.
Addition of organometallic reagents to imines derived from
Garner’s aldehyde has been studied earlier with varying
amounts of diastereoselectivity.18 However, the present
diastereodivergent allylation protocol is of significant advantage
in the sense that reagent-controlled switching of diastereose-
lectivity was reported to be problematic in earlier instances.
Having access to the stereochemically pure syn- and anti-
diamino acid building blocks with orthogonal protection, we
considered their conversion to other diamino acids. 2,6-
Diaminopimelic acid (DAP) has found widespread utility as
an important naturally occurring diamino acid.19 However,
exploration of other regio-isomeric pimelic acids (e.g., 2,3-
diaminopimelic acid) and homologues thereof remains
important. We opted for a cross-metathesis (CM) reaction of
the prepared building blocks 7, 8, 11, and 12 toward the
fulfillment of some of these objectives in view of several elegant
reports20 on CM-mediated transformations of α-amino acids
and peptides. Thus, the CM reaction of 7 with tert-butyl
acrylate proceeded better in the presence of Grubbs’ second-
generation catalyst 13 (G-II)21a under optimized conditions to
provide the unsaturated ester 14 in good yield (82%) (Scheme
2). One-pot hydrogenolytic removal of the double protections
on the β-nitrogen as well as saturation of the double bond in 14
delivered the diaminopimelic acid derivative 15. The attempted
CM reaction of 7 with the terminal and nonconjugated olefin
(Type-1 according to Grubbs’ classification21b) benzyl
butenoate proved to be a little sluggish, but efficacious. The
CM product 16 was obtained in good yield but as an E/Z
B
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The Journal of Organic Chemistry
Note
mixture (84:16). One-pot hydrogenolytic removal of the N-
Cbz, N-PMB, and O-Bn protection groups, as well as saturation
of the double bond, proceeded well to produce the hitherto
unknown 2,3-diaminosuberic acid derivative 17. The building
block 11 was similarly converted into the epimeric
diaminopimelic acid derivative 19 and the diaminosuberic
acid derivative 21 through the CM products 18 and 20 in
It was pleasing to note that the epimeric piperidinyl glycine
derivative 26 could be obtained from 25 with similar efficiency.
As an extension, we considered the CM reaction of the
prepared templates with styrene derivatives to obtain
compounds reminiscent of DOPA and tyrosine. The CM
reaction of 7 with 1,2-dimethoxy-4-styrylbenzene proceeded
somewhat sluggishly, and the product 27 (Scheme 4) was
obtained (E:Z = 89:11) in a modest yield of 65%. In an
analogous event, the CM reaction of 7 with 1-methoxy-4-
styrylbenzene proceeded in a similar fashion to provide 28 (E:Z
= 81:19). These CM products were then separately subjected
to the one-pot, three-step deprotection−saturation cascade to
obtain the desired DOPA and tyrosine analogues 29 and 30,
respectively.The corresponding epimeric set of compounds, 33
and 34, were similarly prepared from 11 (Scheme 4). It is
interesting to note that significant homodimerization of the
styrene unit was observed, while dimerization products from
either of the diamino acid building blocks 7 and 11 were almost
undetected.
1
comparable overall yields. A variable-temperature H NMR
study on 18 revealed its E-geometry as a doublet of 16 Hz
could be located at δ 5.45 in the 1H NMR spectrum (Figure 2,
Supporting Information).
α,β-Diamino acids, wherein the β-nitrogen is part of a
heterocyclic ring, have proven to be of importance in the design
of modified peptides.22 We realized that a cyclization involving
the β-nitrogen and the remote carboxy function in 15 or 19
would constitute a short synthesis of piperidinyl glycines.
Further, the synthetic brevity will not be compromised if the
cyclization event could be conducted concurrently during the
hydrogenolysis step. Thus, the CM product 22 (Scheme 3),
α-Amino acid derivatives having a lipophilic side chain are
receiving current attention in peptide engineering and tuning of
biological activity.23 Therefore, the preparation of the
corresponding diamino acids remains important. We utilized
the second set of templates 8 and 12 in this regard. Thus, the
CM reaction of 8 with the unactivated olefin 1-decene
proceeded in good yield, leading to 35 (Scheme 5). The one-
Scheme 3. Synthesis of Two Diastereomeric Piperidinyl
Glycine Derivatives
Scheme 5. Diastereodivergent Synthesis of Lipophilic α,β-
Diamino Acids and β-Lactams
obtained from a reaction of 7 with methyl acrylate, on
treatment with hydrogen in the presence of Pd-C in methanol
underwent smooth conversion into the piperidone derivative
24 in a yield of 74% over a one-pot four-step sequence, the
exact order of the chemical steps in this sequence being
uncertain. Similarly, exhaustive hydrogenation of the benzyl
acrylate derivative 23 under identical conditions led to the
cyclized product 24 (70%), perhaps indicating that, at least in
this instance, hydrogenolysis of an N-Cbz group is taking place
faster than deprotection of the benzyl ester function as
otherwise the cyclization event would be difficult to interpret.
pot hydrogenolytic removal of the benzyl ester moiety, as well
as saturation of the double bond, provided the free β-amino
acid 36. Compound 39 was similarly prepared from 12. We
opted to demonstrate the utility of these β-amino acid
Scheme 4. Diastereodivergent Synthesis of DOPA and Tyrosine Analogue
C
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The Journal of Organic Chemistry
Note
(R)-tert-Butyl-4-((S)-1-(4-methoxybenzylamino)but-3-enyl)-
2,2-dimethyloxazolidine-3-carboxylate (3). A stirred solution of
the Garner’s aldehyde 1 (2.00 g, 8.73 mmol) in dry THF (30 mL) was
cooled to 5 °C, and anhydrous MgSO4 (4.20 g, 34.9 mmol) was added
under an argon atmosphere. After stirring for 10 min, a solution of 4-
methoxybenzyl amine (1.32 g, 9.60 mmol) in THF (6 mL) was added
dropwise over 10 min. The reaction mixture was then allowed to come
to rt and was stirred for 20 h. It was filtered, and the filtrate was
concentrated in vacuo, and diluted with dry THF (25 mL). The
solution was cooled to −5 °C, and then a solution of allylzinc bromide
[prepared in situ by treating allyl bromide (1.3 mL) with Zn dust (1.1
g) in dry THF (20 mL) at rt for 20 min] was added dropwise over 30
min. The mixture was stirred at this temperature for 6 h and then
quenched by the slow addition of aq. NH4Cl solution (5 mL) before
being extracted with EtOAc (2 × 50 mL). The combined organic
extract was washed with water (50 mL) and brine solution (50 mL)
and dried (MgSO4). It was then filtered, and the filtrate was
concentrated in vacuo to leave a crude product, which was purified by
flash chromatography over silica gel using EtOAc/hexane (1:19) to
derivatives through their conversion to the corresponding β-
lactams in view of known importance of amino-substituted β-
lactams.24 The building blocks 8 and 12 proved to be better
since their reactive functionalities for lactam ring formation
could be unraveled in a single hydrogenation step. The β-amino
acids 36 and 39 thus obtained were cyclized in the presence of
Mukaiyama’s reagent to the desired targets 37 and 40,
1
respectively (Scheme 5). In the H NMR spectrum of 37, Ha
appeared as a double doublet (dd, Ja,b = 4.8 Hz, Ja,NH = 8 Hz),
1
whereas, in the H NMR spectrum of 40, Ha appeared as a
doublet (Ja,NH = 7.2 Hz) indicating little coupling with Hb.
These data were diagonistic of their stereochemistry,25 and
hence of the newly created stereocenters in 3 and 4.
Interestingly, compound 37 formed gels with hydrocarbon
solvents, including petroleum ether. From the SEM micrograph
displayed in Figure 1, it is evident that this gel is microporous
with pores measuring 0.5−8 μm in diameter. Structurally
similar organogels have found applications in oil-spill
recovery.26
give 3 (2.5 g, 74%), followed by 4 (0.4 g, 12%), both as oils. 3: [α]D25
−
17.0 (c 2.2, CHCl3). IR (CHCl3): 3350, 2977, 2934, 1698, 1612, 1512,
1388 cm−1. 1H NMR (DMSO-d6, 400 MHz): δ 7.20 (d, J = 8.4 Hz, 2
H), 6.84 (d, J = 8.4 Hz, 2H), 5.79−5.70 (m, 1H), 5.10−5.07 (m, 2H),
4.02−3.98 (m, 2H), 3.90 (dd, J = 6.8, 9.2 Hz, 1H), 3.72 (s, 3H), 3.67−
3.62 (m, 2H), 3.35−3.33 (br m, 1H), 2.97−2.93 (m, 1H), 2.31−2.27
(m, 1H), 1.95−1.92 (m, 1H), 1.42−1.23 (m, 15H). 13C NMR
(DMSO-d6, 75 MHz, 70 °C): δ 158.2, 152.1, 136.5, 133.1, 128.8,
116.5, 113.6, 93.5, 79.2, 63.4, 58.5, 57.2, 55.0, 50.8, 34.0, 28.0, 26.1.
HRMS (QTOF ES+) found m/z 391.2594 (M + H)+; C22H35N2O4
requires 391.2597.
(R)-tert-Butyl 4-((R)-1-(4-Methoxybenzylamino)but-3-enyl)-
2,2-dimethyloxazolidine-3-carboxylate (4). The imine 2 was
prepared as described above from the aldehyde 1 (1.0 g, 4.37 mmol),
dry THF (20 mL), 4-methoxybenzyl amine (0.66 g, 4.80 mmol), and
anhydrous MgSO4 (2.1 g, 17.5 mmol). It was filtered under an inert
atmosphere, and the filtrate was concentrated in vacuo, which was used
as such in the next step.
Figure 1. SEM micrograph of freeze-dried 37, demonstrating that the
To a stirred solution of allylmagnesium bromide (1 M, 9.0 mL, 8.75
mmol) in dry Et2O/THF (1:1) (15 mL) at −30 °C was added a
solution of the imine 2 (1.5 g, 4.37 mmol) in dry Et2O (5 mL)
dropwise over 10 min under argon. After 8 h, the mixture was
quenched with aq. NH4Cl solution (5 mL) and then extracted with
EtOAc (2 × 50 mL). The combined organic extract was washed with
water (50 mL) and brine solution (50 mL) and dried (MgSO4). It was
then filtered, and the filtrate was concentrated in vacuo. The crude
product was purified by flash chromatography over silica gel using
EtOAc/hexane (1:19) to give 3 (0.17 g, 10%), followed by 4 (1.28 g,
75%), both as oils. 4: [α]D25 − 41.4 (c 1.2, CHCl3). IR (CHCl3): 3345,
2977, 2933, 1697, 1612, 1512, 1388, 1366, 1248. 1H NMR (DMSO-d6,
400 MHz): δ 7.18 (d, J = 8.4 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 5.82−
5.77 (m, 1H), 5.04 (m, 2H), 4.03 (br m, 1H), 3.88−3.76 (m, 2H),
3.71 (s, 3H), 3.67−3.62 (m, 1H), 3.58 (d, J = 13.2 Hz, 1H), 3.34 (br
m, 1H), 2.94−2.91 (m, 1H), 2.30−2.17 (m, 1H), 2.01−1.95 (m, 1H),
1.51−1.23 (m, 15H). 13C NMR (DMSO-d6, 75 MHz, 70 °C): δ 158.0,
151.4, 136.0, 132.8, 128.7, 116.0, 113.4, 93.1, 78.8, 63.3, 59.4, 57.3,
54.7, 50.7, 36.1, 27.7, 26.2. HRMS (QTOF ES+) found m/z 391.2594
(M + H)+. C22H35N2O4 requires 391.2597.
gel is composed of a network of interconnected pores.
In brief, we have developed efficient synthetic protocols to
prepare a set of four orthogonally protected δ,ε-unsaturated
α,β-diamino acids as new building blocks and demonstrated
their utility for the preparation of 12 new α,β-diamino acids of
potential biological relevance having (i) a polar (CO2H)
headgroup, (ii) a terminal aromatic residue, (iii) an appended
piperidone ring, and (iv) a lipophilic side chain utilizing the
cross-metathesis reaction as the key step. The versatile
reactivity of the double bond should allow this building block
approach suitable for the synthesis of other α,β-diamino acids
and derivatives thereof for peptide engineering. The method-
ology developed may thus find several applications.
EXPERIMENTAL SECTION
■
General. Column chromatography was performed on silica gel,
Merck grade 230−400 mesh. TLC plates were visualized with UV, in
an iodine chamber, or with vaniline solution, unless noted otherwise.
IR spectra were recorded using KBr disks, chloroform solution, or as
(R)-tert-Butyl 4-((S)-1-((Benzyloxycarbonyl)(4-methoxy-
benzyl)amino)but-3-enyl)-2,2-dimethyloxazolidine-3-carbox-
ylate (5). To a stirred solution of the amine 3 (2.5 g, 6.4 mmol) in
EtOAc (15 mL) and water (2 mL) was added NaHCO3 (1.10 g, 12.8
mmol), followed by benzyl chloroformate (1.10 mL, 7.7 mmol) slowly
over 10 min at rt. The resulting mixture was stirred for 3 h before
being diluted with water (10 mL) and extracted with EtOAc (2 × 25
mL). The combined organic layer was washed with brine solution (25
mL) and dried over (MgSO4). It was then filtered, and the filtrate was
concentrated in vacuo to give a pale yellow crude product, which was
purified by flash column chromatography using EtOAc/hexane (1:19)
to give 5 (3.30 g, 98%) as a colorless oil. [α]2D5 + 12.5 (c 1.1, CHCl3).
1
neat samples. H NMR and 13C NMR spectra were recorded at 400
and 100 MHz, respectively. Several compounds reported herein
exhibited extensive rotamerism complicating analysis of NMR spectra.
However, recording such spectra at higher temperature (70−80 °C)
resolved the problem in the majority of cases.
Dichloromethane was distilled over calcium hydride under an inert
atmosphere. THF, benzene, and ether were freshly distilled under
argon from a purple solution of sodium benzophenone ketyl. Unless
stated otherwise, all reagents were purchased from commercial sources
and used without additional purification.
1
IR (KBr): 2978, 2935, 1695, 1613, 1513, 1366, 1248 cm−1. H NMR
D
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(DMSO-d6, 300 MHz, 75 °C): δ 7.33 (br m, 5H), 7.21 (d, J = 8.7 Hz,
2H), 6.83 (d, J = 8.7 Hz, 2H), 5.42−5.29 (m, 1H), 5.16−5.04 (m,
2H), 4.98−4.52 (m, 2H), 4.57−4.52 (m, 1H), 4.29−4.23 (m, 1H),
4.14 (t, J = 5.7 Hz, 1H), 4.06−4.03 (m, 1H), 3.98−3.92 (m, 1H), 3.76
(m, 4H), 2.31−2.19 (m, 2H), 1.56 (s, 3H), 1.44 (s, 9H), 1.40 (s, 3H).
13C NMR (DMSO-d6, 75 MHz, 75 °C): δ 158.1, 151.8, 136.4, 135.3,
130.4, 128.5 (2 rotamers), 127.8 (2 rotamers), 127.3, 115.8, 113.4,
92.9, 79.3, 66.1, 63.8, 59.1, 58.7, 54.8, 49.2, 31.6, 27.7, 26.5, 23.2.
HRMS (QTOF ES+) found m/z 547.2781 (M + Na)+. C30H40N2NaO6
requires 547.2784.
(m, 4H), 4.90−4.85 (m, 2H), 4.54−4.64 (m, 2H), 3.93−3.90 (m, 1H),
3.76 (s, 3H), 2.54−2.51 (m, 1H), 2.19−2.16 (m, 1H), 1.42 (s, 9H).
13C NMR (CDCl3, 100 MHz): δ 171.2, 159.1, 156.8, 155.8, 136.2,
135.4, 133.6, 129.5, 129.4, 128.7, 128.6, 128.5, 128.4, 128.2, 127.9,
118.3, 113.8, 79.6, 67.6, 67.2, 60.0, 56.7, 55.2, 52.2, 33.8, 28.4. HRMS
(QTOF ES+) found m/z 611.2738 (M + Na)+, C34H40N2NaO7
requires 611.2733.
(R)-tert-Butyl 4-((R)-1-((Benzyloxycarbonyl)(4-methoxy-
benzyl)amino)but-3-enyl)-2,2-dimethyloxazolidine-3-carbox-
ylate (9). Compound 9 was prepared following the procedure
described for compound 5. Yield = 1.29 g from 1.01 g of 4, 96%. [α]D25
− 20.2 (c 2.4, CHCl3); IR (CHCl3): 2978, 2935, 1698, 1612, 1513,
(2R,3S)-3-((Benzyloxycarbonyl)(4-methoxybenzyl)amino)-2-
(tert-butoxycarbonylamino)hex-5-enoic Acid (6). Jones’ reagent
(3.0 mL) was added dropwise to a stirred solution of the acetonide 5
(1.00 g, 1.91 mmol) in acetone (12 mL) at 10 °C. The resulting
mixture was stirred for 3 h at rt and then quenched with isopropanol
(1.0 mL). The volatiles were evaporated in vacuo, and the residue was
extracted with EtOAc (2 × 20 mL). The combined organic extract was
washed with water (2 × 10 mL) and the brine solution (10 mL) and
dried (MgSO4). It was then filtered, and the filtrate was concentrated
under reduced pressure to leave a crude viscous liquid, which was
purified by flash chromatography over silica gel using EtOAc/hexane
(2:3) to provide 6 (0.85 g, 81%) as a colorless gum. [α]2D5 + 13.5 (c
1.0, CHCl3). IR (CHCl3): 3361, 2977, 1745, 1700, 1612, 1513, 1367,
1
1376, 1248 cm−1; H NMR (DMSO-d6, 300 MHz, 90 °C): δ 7.23 (s,
5H), 7.15 (d, J = 5.1 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 5.63−5.55 (m,
1H), 5.16 (s, 2H), 4.98−4.87 (m, 2H), 4.57−4.52 (m, 1H), 4.34−4.09
(m, 3H), 3.73 (s, 4H), 3.60−3.55 (m, 1H), 2.53−2.21 (m, 2H), 1.55−
1.49 (m, 15H). 13C NMR (DMSO-d6, 75 MHz, 70 °C): δ 159.0,
156.8, 152.4, 137.2, 135.9, 131.1, 129.1, 128.8, 128.6, 128.0, 117.1,
114.3, 94.0, 80.0, 67.0, 65.7, 65.4, 59.7, 58.8, 55.5, 33.8, 28.4, 27.8,
23.9. HRMS (QTOF ES+) found m/z 547.2782 (M + Na)+.
C30H40N2NaO6 requires 547.2784.
(2R,3R)-3-((Benzyloxycarbonyl)(4-methoxybenzyl)amino)-2-
(tert-butoxycarbonylamino)hex-5-enoic Acid (10). Compound
10 was prepared following the procedure described for compound 6.
Yield = 0.75 g from 1.0 g of 9, 79%. [α]2D5 − 17.8 (c 0.9, CHCl3). IR
(CHCl3): 3366, 2975, 1745, 1702, 1611, 1513, 1367, 1247, 1164 cm−1.
1H NMR (DMSO-d6, 300 MHz, 70 °C): δ 7.32−7.30 (br m, 5H), 7.18
(m, 2H), 6.91−6.82 (m, 2H), 5.35−5.30 (m, 1H), 5.11 (s, 2H), 4.76−
4.72 (m, 2H), 4.50−4.45 (m, 2H), 4.34−4.21 (m, 2H), 3.71 (s, 3H),
2.48−2.32 (m, 2H), 1.38 (s, 9H); 13C NMR (DMSO-d6, 75 MHz, 70
°C): δ 172.7, 158.9, 156.4, 155.6, 137.2, 135.5, 131.0, 129.9, 128.6,
128.2, 127.8, 117.0, 114.0, 78.9, 66.9, 58.7, 56.5, 55.5, 49.7, 33.7, 28.7.
HRMS (QTOF ES+) found m/z 521.2266 (M + Na)+, C27H34N2NaO7
requires 521.2264.
1
1248, 1162 cm−1. H NMR (400 MHz, CDCl3): δ 8.72 (brm, 1H),
7.4−7.30 (m, 5H), 7.17 (d, J = 7.6 Hz, 2H), 6.79 (d, J = 8.4 Hz, 2H),
5.42−5.32 (m, 1H), 5.24−5.11 (m, 2H), 4.91 (d, J = 11.2 Hz, 2H),
4.72 (d, J = 15.2 Hz, 1H), 4.51 (t, J = 5.1 Hz, 1H), 4.07 (d, J = 15.2
Hz, 1H), 3.95−3.83 (m, 1H), 3.78 (s, 3H), 2.61−2.57 (m, 1H), 2.22−
2.17 (m, 1H), 1.44 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 175.0,
159.1, 157.1, 156.3, 16.1, 133.6, 129.8, 129.3, 128.5, 128.1 127.9, 118.4,
113.9, 80.0, 67.7, 59.7, 56.4, 55.2, 52.5, 33.8, 28.4. HRMS (QTOF
ES+) found m/z 521.2266 (M + Na)+, C27H34N2NaO7 requires
521.2264.
(2R,3S)-Methyl 3-((Benzyloxycarbonyl)(4-methoxybenzyl)-
amino)-2-(tert-butoxycarbonylamino)hex-5-enoate (7). To a
stirred solution of the carboxylic acid 6 (500 mg, 1.00 mmol) in dry
DMF (6 mL) was added Cs2CO3 (652 mg, 2.00 mmol), followed by
methyl iodide (125 μL, 2.00 mmol) dropwise at 0 °C. The resulting
solution was stirred for 1 h at rt before being diluted with water (10
mL) and extracted with Et2O (2 × 25 mL). The combined organic
extract was washed with water (25 mL) and brine solution (25 mL)
and dried (MgSO4). It was then filtered, and the filtrate was
concentrated in vacuo to give the crude product, which was purified by
flash chromatography using EtOAc/hexane (1:9) to give 7 (0.5 g,
97%) as a colorless oil. [α]D25 + 4.5 (c 1.6, CHCl3). IR (CHCl3): 3370,
2976, 2932, 1746, 1713, 1699, 1612, 1513, 1366, 1248, 1173 cm−1. 1H
NMR (CDCl3, 400 MHz): δ 7.33−7.25 (m, 5H), 7.12 (d, J = 7.6 Hz,
2H), 6.80 (d, J = 7.2 Hz, 2H), 6.43 (brm, 1H), 5.49−5.41 (m, 1H),
5.19−5.14 (m, 2H), 4.93 (d, J = 10.8 Hz, 2H), 4.61 (d, J = 15.2 Hz,
1H), 4.50−4.47 (m, 1H), 4.04−4.96 (m, 2H), 3.79 (s, 3H), 3.66 (s,
3H), 2.54−2.29 (m, 2H), 1.42 (s, 9H); 13C NMR (CDCl3, 100 MHz):
δ 171.5, 158.9, 156.6, 155.5, 136.0, 133.4, 129.3, 128.3, 127.9, 127.7,
118.1, 113.7, 79.4, 67.3, 59.7, 56.2, 55.0, 52.0, 51.7, 33.5, 28.1. HRMS
(QTOF ES+) found m/z 535.2422 (M + Na)+, C28H36N2NaO7
requires 535.2420.
(2R,3R)-Methyl 3-((Benzyloxycarbonyl)(4-methoxybenzyl)-
amino)-2-(tert-butoxycarbonylamino)hex-5-enoate (11). Com-
pound 11 was prepared following the procedure described for
compound 7. Yield = 483 mg from 500 mg of 10, 94%. [α]D25
−
13.3 (c 0.6, CHCl3). 1H NMR (300 MHz, DMSO-d6, 70 °C): δ 7.32−
7.26 (m, 5H), 7.14 (d, J = 11.2 Hz, 2H), 6.81 (d, J = 8.4 Hz, 2H),
5.40−5.29 (m, 1H), 5.10 (d, J = 3.6 Hz, 2H), 4.82−4.75 (m, 2H),
4.45−4.35 (m, 2H), 4.19−4.09 (m, 2H), 3.72 (s, 3H), 3.47 (s, 3H),
2.38−2.31 (m, 2H), 1.35 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ
171.3, 158.8, 156.8 (156.2), 155.2, 136.4, 134.4, 130.1, 129.4, 129.1,
128.4, 128.0, 117.7, 113.7, 80.0, (67.7) 67.2, 59.9, 55.5, 55.2, 52.3, 50.2,
33.3, 28.3. HRMS (QTOF ES+) found m/z 535.2418 (M + Na)+,
C28H36N2NaO7 requires 535.2420.
(5R,6R)-Benzyl 5-Allyl-4-(4-methoxybenzyl)-10,10-dimethyl-
3,8-dioxo-1-phenyl-2,9-dioxa-4,7-diazaundecane-6-carbox-
ylate (12). Compound 12 was prepared following the procedure
described for compound 8. Yield = 566 mg from 500 mg of 10, 96%.
[α]2D5 − 7.3 (c 1.3, CHCl3). 1H NMR (DMSO-d6, 400 MHz, 70 °C): δ
7.33−7.31 (m, 10H), 7.14 (d, J = 7.2 Hz, 3H), 6.81 (d, J = 8.4 Hz,
2H), 5.36−5.33 (m, 1H), 5.12−5.07 (m, 2H), 5.03−4.95 (m, 2H),
4.82−4.76 (m, 2H), 4.55−4.52 (m, 1H), 4.38 (d, J = 15.6 Hz, 1H),
4.16−4.12 (m, 2H), 3.73 (s, 3H), 2.44−2.31 (m, 2H), 1.37 (s, 9H).
13C NMR (CDCl3, 100 MHz): δ (171.2) 170.8, 158.9, (156.7) 156.3,
155.3, 136.4, 135.3 (134.9), 134.4, 133.7, 130.1, 129.5, 129.1, 128.6
(overlap two signals), 128.4, 128.0, 117.8 (117.6), (113.9) 113.7,
(80.2) 80.0, (67.7) 67.4, 67.3 (67.1), 59.9, 55.8, 55.2, 50.2, 33.4, 28.3.
HRMS (QTOF ES+) found m/z 611.2738 (M + Na)+, C34H40N2NaO7
requires 611.2733.
(5S,6R,E)-1-tert-Butyl 7-Methyl 5-((benzyloxycarbonyl)(4-
methoxybenzyl)amino)-6-(tert-butoxycarbonylamino)hept-2-
enedioate (14). General Procedure for Cross-Metatheses. Grubbs’
second generation catalyst 13 (25 mg, 3 mol %) was added to a stirred
solution of the olefin 7 (500 mg, 0.98 mmol) and tert-butyl acrylate
(265 μL, 1.96 mmol) in anhydrous and degassed CH2Cl2 (6 mL) at rt,
and the reaction mixture was heated to reflux under argon for 3 h. It
was then concentrated in vacuo, and the residue was purified by flash
(5S,6R)-Benzyl 5-Allyl-4-(4-methoxybenzyl)-10,10-dimethyl-
3,8-dioxo-1-phenyl-2,9-dioxa-4,7-diazaundecane-6-carbox-
ylate (8). To a stirred solution of the carboxylic acid 6 (0.5 g, 1.0
mmol) in dry DMF (6 mL) was added Cs2CO3 (490 mg, 1.5 mmol),
followed by benzyl bromide (180 μL, 1.5 mmol) dropwise at 0 °C, and
the resulting solution was stirred for 1 h at rt before being diluted with
water (10 mL) and extracted with Et2O (2 × 25 mL). The combined
organic layer was washed with water (25 mL) and brine solution (25
mL) and dried (MgSO4). It was then filtered, and the filtrate was
concentrated in vacuo to give the crude product, which was purified by
flash chromatography using EtOAc/hexane (1:9) to give 8 (560 mg,
95%) as a colorless oil. [α]D25 + 16.6 (c 0.4, CHCl3). IR (CHCl3): 2977,
1
2931, 1712, 1514, 1250, 1164, 1029 cm−1. H NMR (CDCl3, 400
MHz): δ 7.34−7.30 (m, 10H), 7.01 (d, J = 7.6 Hz, 2H), 6.76 (d, J =
8.0 Hz, 2H), 6.02 (d, J = 8.0 Hz, 1H), 5.40−5.33 (m, 1H), 5.20−5.09
E
DOI: 10.1021/jo5022162
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
chromatography over silica gel using EtOAc/hexane (1:9) to afford the
α,β-unsaturated ester 14 as a colorless oil (490 mg, 82%). [α]2D5 −8.5
(c 0.8, CHCl3). IR (KBr): 3409, 2978, 2931, 1714, 1657, 1613, 1514,
1220, 1162 cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.34−7.28 (m, 5H),
7.11 (d, J = 7.6 Hz, 2H), 6.80 (d, J = 7.6 Hz, 2H), 6.48−6.41 (m, 2H),
5.59 (d, J = 15.2 Hz, 1H), 5.19−5.21 (m, 2H), 4.62 (d, J = 15.2 Hz,
1H), 4.53−4.51 (m, 1H), 4.11−4.05 (m, 2H), 3.78 (s, 3H), 3.66 (s,
3H), 2.66−2.63 (m, 1H), 2.42−2.40 (m, 1H), 1.45 (s, 9H), 1.42 (s,
9H). 13C NMR (CDCl3, 100 MHz): δ 171.4, 165.2, 159.2, 156.7,
155.6, 142.0, 136.1, 129.4, 129.0, 128.6, 128.2, 127.9, 126.1, 114.0
(113.9), 80.2, 79.8, 67.7, 59.1, 56.4, 55.2, 52.3, 52.0, 32.1, 28.3, 28.1.
HRMS (QTOF ES+) found m/z 635.2941 (M + Na)+, C33H44N2NaO9
requires 635.2945.
(2R,3S)-7-tert-Butyl 1-Methyl 3-Amino-2-(tert-butoxy-
carbonylamino)heptanedioate (15). Pd-C (10%) (15 mg) was
added to a stirred solution of the α,β-unsaturated ester 14 (200 mg,
mmol) in MeOH (4 mL), and the heterogeneous mixture was
vigorously stirred under a hydrogen atmosphere for 8 h. It was then
filtered through Celite, the filter cake was washed with MeOH (10
mL), and the filtrate was concentrated in vacuo to leave a crude
product, which, on purification by column chromatography over
neutral alumina using EtOAc/hexane (1:1), gave compound 15 (78
mg, 66%) as a colorless foam. [α]2D5 −26.1 (c 0.8, CHCl3). IR (KBr):
3390, 2978, 2932, 1722, 1715, 1646, 1495, 1367, 1164 cm−1. 1H NMR
(CDCl3, 400 MHz): δ 6.04 (s, 1H), 5.34 (d, J = 9.2 Hz, 1H), 4.38 (d, J
= 8.4 Hz, 1H), 3.84−3.80 (m, 1H), 3.78 (s, 3H), 3.74−3.72 (m, 1H),
2.41−2.39 (m, 1H), 2.31−2.25 (m, 1H), 1.94−1.92 (m, 2H), 1.72−
1.61 (m, 2H), 1.46 (s, 18H). 13C NMR (CDCl3, 100 MHz): δ 172.6,
172.3, 156.0, 80.2, 79.8, 57.1, 52.4, 35.0, 33.1, 28.3, 28.2, 21.5. HRMS
(QTOF ES+) found m/z 361.2335 (M + H)+, C17H33N2O6 requires
361.2339.
(6S, 7R)-1-Benzyl 8-Methyl 6-((Benzyloxycarbonyl)(4-
methoxybenzyl)amino)-7-(tert-butoxycarbonylamino)oct-3-
enedioate (16). Compound 16 was prepared following the procedure
described for compound 14 but employing a reaction time of 12 h.
Yield = 286 mg from 300 mg of 7, 74%. [α]2D5 + 4.5 (c 2.4, CHCl3); IR
(CHCl3): 3409, 2953, 2929, 1713, 1612, 1513, 1455, 1249, 1162 cm−1.
1H NMR (CDCl3, 400 MHz): δ 7.40−7.20 (m, 10H), 7.08 (d, J = 7.6
Hz, 2H), 6.76 (d, J = 7.6 Hz, 2H), 6.58−6.56 (m, 1H), 5.57−5.50 (m,
1H), 5.46−5.42 (m, 1H), 5.21−5.11 (m, 2H), 5.06−5.02 (m, 2H),
4.64 (d, J = 14.8 Hz, 1H), 4.53−4.49 (m, 1H), 3.91 (d, J = 14.2 Hz,
2H), 3.73 (s, 3H), 3.63 (s, 3H), 2.85−2.84 (m, 2H), 2.41−2.28 (m,
2H), 1.36 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ 171.6, 171.3,
159.1, 156.7, 155.8, 136.3, 135.9, 129.8, 129.6, 129.4, 128.6, 128.3,
128.0, 125.3, 114.0, 113.8, 79.5, 67.5, 66.3, 59.8, 56.6, 55.1, 52.2, 37.9,
32.3, 28.3. HRMS (QTOF ES+) found m/z 683.2943 (M + Na)+,
C37H44N2NaO9 requires 683.2945.
124.8, 113.9, 79.7, 79.1, 67.3, 66.9, 55.4, 55.3, 52.3, 31.9, 28.5, 28.1.
HRMS (QTOF ES+) found m/z 635.2946 (M + Na)+, C33H44N2NaO9
requires 635.2945.
(2R,3R)-7-tert-Butyl 1-Methyl 3-Amino-2-(tert-butoxy-
carbonylamino)heptanedioate (19). Compound 19 was prepared
following the procedure described for compound 15. Yield = 80 mg
from 200 mg of 18, 68%. [α]D25 − 15.6 (c 0.75, CHCl3). IR (KBr):
3394, 2978, 2933, 1722, 1715, 1644, 1495, 1366, 1166 cm−1.1H NMR
(CDCl3, 400 MHz): δ 5.37 (d, J = 8.0 Hz, 1H), 4.23 (q, J = 4.0 Hz,
1H), 3.71−3.66 (m, 4H), 2.97−2.95 (m, 1H), 2.16 (dt, J = 2.0, 7.6 Hz,
2H), 1.75−1.66 9m, 1H), 1.60−1.47 (m, 2H), 1.37 (s, 18H), 1.28−
1.17 (m, 2H). 13C NMR (CDCl3, 100 MHz): δ 172.7, 171.7, 155.7,
80.2, 80.0, 58.6, 53.6, 52.2, 35.2, 33.5, 28.3, 28.1, 21.9. HRMS (QTOF
ES+) found m/z 361.2331 (M + H)+, C17H33N2O6 requires 361.2339.
(6R,7R)-1-Benzyl 8-Methyl 6-((Benzyloxycarbonyl)(4-
methoxybenzyl)amino)-7-(tert-butoxycarbonylamino)oct-3-
enedioate (20). Compound 20 was prepared following the procedure
described for compound 14. Yield = 270 mg from 300 mg of 11, 70%.
[α]2D5 − 8.2 (c 0.5, CHCl3). IR (CHCl3): 3410, 2954, 2932, 1713,
1
1612, 1513, 1456, 1249, 1161 cm−1. H NMR (DMSO-d6, 400 MHz,
70 °C): δ 7.35 (br m, 10H), 7.16 (d, J = 6.8 Hz, 3H), 6.82 (d, J = 8.4
Hz, 2H), 5.32−5.30 (m, 1H), 5.14−5.02 (m, 5H), 4.53−4.42 (m, 2H),
4.12−4.03 (m, 2H), 3.76 (s, 3H), 3.51 (s, 3H), 2.85 (d, J = 6.4 Hz,
2H), 2.49−2.33 (m, 2H), 1.39 (s, 9H). 13C NMR (DMSO-d6, 100
MHz, 25 °C): δ 172.0, 171.3, 158.8, 156.7, 155.8, 137.2, 137.1, 136.5,
130.5, 128.9, 128.8, 128.7, 128.5, 128.4, 128.2, 128.0, 124.7, 113.8,
79.0, 67.2, 66.7, 66.0, 63.4, 55.4, 55.3, 52.2, 37.7, 31.7, 28.6. HRMS
(QTOF ES+) found m/z 683.2941 (M + Na)+, C37H44N2NaO9
requires 683.2945.
(6R,7R)-6-Amino-7-(tert-butoxycarbonylamino)-8-methoxy-
8-oxooctanoic Acid (21). Compound 21 was prepared following the
procedure described for compound 17, using Pd(OH)2-C as catalyst.
Yield = 31 mg from 100 mg of 20, 65%. [α]2D5 + 9.1 (c 1.15, MeOH).
IR (net): 3360, 2925, 2855, 1742, 1722, 1695, 1613, 1514, 1251, 1161
1
cm−1. H NMR (CDCl3, 400 MHz): δ 12.02 (br m, 1H), 8.22 (m,
1H), 4.41 (dd, J = 4.0, 8.8 Hz, 1H), 3.59 (s, 3H), 3.57−3.54 (m, 1H),
2.11−2.08 (m, 2H), 1.49−1.21 (m, 17H). 13C NMR (CDCl3, 100
MHz): δ 174.7, 170.3, 156.2, 79.5, 55.0, 53.0, 51.5, 33.85, 33.8, 28.5,
24.5, 24.4. HRMS (QTOF ES+) found m/z 319.1864 (M + H)+,
C14H27N2O6 requires 319.1869.
(5S,6R,E)-Dimethyl 5-((Benzyloxycarbonyl)(4-methoxy-
benzyl)amino)-6-(tert-butoxy shycarbonylamino)hept-2-ene-
dioate (22). Compound 22 was prepared following the procedure
described for compound 14. Yield = 370 mg from 400 mg of 7, 83%.
[α]2D5 + 4.6 (c 0.85, CHCl3). IR (CHCl3): 3361, 2952, 2917, 1745,
1
1715, 1701, 1611, 1513, 1248, 1162 cm−1. H NMR (CDCl3, 400
MHz): δ 7.35−7.23 (m, 5H), 7.10 (d, J = 7.6 Hz, 2H), 6.79 (d, J = 7.6
Hz, 2H), 6.47−6.43 (m, 1H), 6.35 (d, J = 7.6 Hz, 1H), 5.62 (d, J =
15.2 Hz, 1H), 5.24−5.19 (m, 2H), 4.65 (d, J = 15.2 Hz, 1H), 4.51 (t, J
= 7.2 Hz, 1H), 4.12−3.92 (m, 2H), 3.79 (s, 3H), 3.61 (s, 6H), 2.58−
2.54 (m, 2H), 1.47 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ 171.3,
166.2, 159.2, 156.6, 155.7, 143.6, 136.1, 129.6, 128.9, 128.6, 128.2,
127.9, 123.8, 114.0, 79.8, 67.7, 59.0, 56.6, 55.2, 52.4, 51.4, 32.1, 28.3.
HRMS (QTOF ES+) found m/z 593.2479 (M + Na)+, C30H38N2NaO9
requires 593.2475.
(6S,7R)-6-Amino-7-(tert-butoxycarbonylamino)-8-methoxy-
8-oxo-octanoic Acid (17). Compound 17 was prepared following
the procedure described for compound 15, using Pd(OH)2 as catalyst,
and the reaction time was 6 h. Yield = 65 mg from 200 mg of 16, 68%.
[α]2D5 + 13.5 (c 1.1, MeOH). IR (net): 3360, 2925, 2855, 1742, 1722,
1695, 1613, 1514, 1251, 1161 cm−1. 1H NMR (CD3OD, 400 MHz): δ
4.48 (s, 1H), 3.80 (s, 3H), 3.64 (s, 1H), 2.33 (t, J = 7.2 Hz, 2H), 1.71−
1.62 (m, 6H), 1.45 (s, 9H). 13C NMR (CD3OD, 100 MHz): δ 175.9,
169.9, 156.9, 80.3, 53.9, 52.2, 33.1, 29.1, 27.2, 24.4, 24.1. HRMS
(QTOF ES+) found m/z 319.1862 (M + H)+, C14H27N2O6 requires
319.1869.
(5S,6R,E)-1-Benzyl 7-Methyl 5-((Benzyloxycarbonyl)(4-
methoxybenzyl)amino)-6-(tert-butoxycarbonylamino)hept-2-
enedioate (23). Compound 23 was prepared following the procedure
described for compound 14. Yield = 393 mg from 400 mg of 7, 78%.
[α]2D5 − 4.5 (c 0.9, CHCl3). IR (CHCl3): 3362, 2976, 2954, 1722,
(5R,6R,E)-1-tert-Butyl 7-Methyl 5-((Benzyloxycarbonyl)(4-
methoxybenzyl)amino)-6-(tert-butoxycarbonylamino)hept-2-
enedioate (18). Compound 18 was prepared following the procedure
described for compound 14. Yield = 377 mg from 400 mg of 11, 79%.
[α]2D5 − 6.2 (c 0.8, CHCl3). IR (KBr): 3408, 2978, 2930, 1714, 1657,
1
1715, 1698, 1612, 1514, 1251, 1164 cm−1. H NMR (CDCl3, 400
MHz): δ 7.23−7.15 (m, 10H), 6.99 (d, J = 7.2 Hz, 2H), 6.67 (d, J =
7.2 Hz, 2H), 6.45−6.41 (m, 1H), 6.32−6.30 (m, 1H), 5.58 (d, J = 15.2
Hz, 1H), 5.10−5.05 (m, 2H), 5.02−4.98 (m, 2H), 4.55 (d, J = 14.8
Hz, 1H), 4.46−4.44 (m, 1H), 3.90−3.86 (m, 2H), 3.62 (s, 3H), 3.56
(s, 3H), 2.48−2.46 (m, 2H), 1.32 (s, 9H). 13C NMR (CDCl3, 100
MHz): δ 171.3, 165.6, 159.2, 156.6, 155.6, 144.1, 136.1, 136.0, 129.6,
128.9, 128.6, 128.5, 128.2, 128.1, 127.9, 123.9, 114.0, 79.8, 67.7, 66.0,
59.0, 56.6, 55.1, 52.4, 52.2, 32.2, 28.3. HRMS (QTOF ES+) found m/z
669.2786 (M + Na)+, C36H42N2NaO9 requires 669.2788.
1
1612, 1514, 1221, 1164 cm−1. H NMR (DMSO-d6, 400 MHz, 70
°C): δ 7.35−7.31 (m, 5H), 7.15 (d, J = 8.0 Hz, 3H)), 6.81 (d, J = 8.8
Hz, 2H), 6.42−6.34 (m, 1H), 5.45 (d, J = 15.6 Hz, 1H), 5.15 (s, 2H),
4.54−4.50 (m, 1H), 4.43 (d, J = 15.6 Hz, 1H), 4.21 (br d, J = 14.0 Hz,
2H), 3.74 (s, 3H), 3.53 (s, 3H), 2.51−2.48 (m, 2H), 1.41 (s, 9H), 1.39
(s, 9H). 13C NMR (DMSO-d6, 100 MHz, 25 °C): δ 171.8, 165.0,
158.8, 156.7, 155.8, 144.6, 137.0, 129.3, 128.8, 128.2, 128.1, 128.0,
F
DOI: 10.1021/jo5022162
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(R)-Methyl 2-(tert-Butoxycarbonylamino)-2-((S)-6-oxo-
piperidin-2-yl)acetate (24). Pd-C (10%) (16 mg) was added to a
stirred solution of the α,β-unsaturated ester 22 (200 mg, 0.35 mmol)
or 23 (200 mg, 0.31 mmol) in MeOH (5 mL), and the heterogeneous
mixture was vigorously stirred under a hydrogen atmosphere for 6 h. It
was then filtered through Celite, the filter cake was washed with
MeOH (10 mL), and the filtrate was concentrated in vacuo to leave a
crude product, which, on purification by column chromatography over
neutral alumina using EtOAc/hexane (3:2), gave compound 24 (74
mg, 74%) as a colorless foam. [α]2D5 − 30.0 (c 1.95, CHCl3). IR
15.2 Hz, 1H), 4.48 (t, J = 7.2 Hz, 1H), 3.95−3.88 (m, 1H), 3.71 (s,
3H), 3.66 (s, 3H), 3.60−3.56 (m, 4H), 2.51−2.44 (m, 2H), 1.36 (s,
9H). 13C NMR (CDCl3, 100 MHz): δ 171.8, 159.0, 158.9, 156.9,
155.8, 138.2, 136.3, 132.4, 129.9 (129.8), 129.7 (129.4), 128.5, 128.1,
127.9, 127.3, 123.1, 113.9, 113.8, 79.7, 67.5, 60.2, 56.8, 55.3, 55.2, 52.3,
52.1, 32.9, 28.4. HRMS (QTOF ES+) found m/z 641.2836 (M + Na)+,
C35H42N2NaO8 requires 641.2839.
(2R,3S)-Methyl 3-Amino-2-(tert-butoxycarbonylamino)-6-
(3,4-dimethoxyphenyl)hexanoate (29). Compound 29 was
prepared following the procedure described for compound 15. Yield
= 49 mg from 100 mg of 27, 81%). [α]2D5 − 8.6 (c 0.9, CHCl3). IR
(CHCl3): 3387, 2972, 2932, 1709, 1516, 1393, 1367, 1260, 1159,
1029, 764 cm−1. 1H NMR (CDCl3, 400 MHz): δ 6.82−6.70 (m, 1H),
6.63 (d, J = 6.8 Hz, 2H), 5.36 (d, J = 8.8 Hz, 1H), 4.20 (d, J = 8.4 Hz,
1H), 3.80 (s, 3H), 3.78 (s, 3H), 3.66 (s, 3H), 3.20 (brm, 1H), 2.55−
2.45 (m, 2H), 1.65−1.59 (m, 2H), 1.51−1.43 (m, 4H), 1.38 (s,
9H).13C NMR (CDCl3, 100 MHz): δ 172.8, 156.0, 148.8, 147.1, 134.7,
120.1, 111.6, 111.1, 79.8, 57.5, 55.9, 55.8, 52.7, 52.4, 35.3, 34.0, 29.7,
28.3. HRMS (QTOF ES+) found m/z 397.2332 (M + H)+,
C20H33N2O6 requires 397.2339.
(2R,3S)-Methyl 3-Amino-2-(tert-butoxycarbonylamino)-6-(4-
methoxyphenyl)hexanoate (30). Compound 30 was prepared
following the procedure described for compound 15. Yield = (48 mg
from 100 mg of 28, 80%). [α]2D5 − 3.2 (c 1.1, CHCl3). IR (CHCl3):
3374, 2954, 1714, 1514, 1247, 1164, 1034, 758 cm−1. 1H NMR
(CDCl3, 400 MHz): δ 6.87 (d, J = 6.0 Hz, 2H), 6.56 (d, J = 6.0 Hz,
2H), 6.28 (d, J = 6.0 Hz, 1H), 4.52 (d, J = 7.2 Hz, 1H), 3.62−3.55 (m,
4H), 3.53 (s, 3H), 2.35 (brm, 2H), 1.5 (brm, 4H), 1.21 (s, 9H). 13C
NMR (CDCl3, 100 MHz): δ 170.2, 157.8, 155.9, 133.4, 129.3, 113.8,
80.4, 55.2 (two signals), 53.7, 34.4, 29.9, 28.3, 27.3. HRMS (QTOF
ES+) found m/z 367.2225 (M + H)+, C19H31N2O5 requires 367.2233.
(2R,3R)-Methyl 3-((Benzyloxycarbonyl)(4-methoxybenzyl)-
amino)-2-(tert-butoxycarbonylamino)-6-(3,4-dimethoxy-
phenyl)hex-5-enoate (31). Compound 31 was prepared following
the procedure described for compound 27. Yield = 169 mg from 200
mg of 11, 67%. [α]2D5 −10.9 (c 0.69, CHCl3). IR (CHCl3): 3384, 2971,
1709, 1516, 1393, 1367, 1261, 1160, 1029, 762 cm−1. 1H NMR
(CDCl3, 400 MHz, 70 °C): δ 7.18−7.00 (m, 7H), 6.82−6.50 (m, 5H),
5.91 (d, J = 15.2 Hz, 1H), 5.48 (br m, 1H), 5.01 (s, 2H), 4.44−4.31
(m, 2H), 4.07−3.91 (m, 2H), 3.62−3.61 (overlapped two singlet, 6H),
3.49 (s, 3H), 3.40−3.33 (m, 4H), 2.42−2.31 (m, 2H), 1.25 (s, 9H).
13C NMR (CDCl3, 100 MHz, 70 °C): δ 171.7, 159.0 (158.9), 156.8,
1
(CHCl3): 3357, 2955, 1744, 1716, 1663, 1524, 1366, 1166 cm−1. H
NMR (CDCl3, 400 MHz): δ 6.45 (s, 1H), 5.63 (d, J = 8.0 Hz, 1H),
4.39 (d, J = 7.6 Hz, 1H), 3.88 (brs, 1H),3.79 (s, 3H), 2.41−2.25 (m,
2H), 1.93−1.92 (m, 2H), 1.73−158 (m, 2H), 1.45 (s, 9H). 13C NMR
(CDCl3, 100 MHz): δ 173.2, 171.2, 155.9, 80.4, 56.7, 54.1, 52.8, 31.2,
28.2, 25.2, 19.4. HRMS (QTOF ES+) found m/z 309.1423 (M + Na)+,
C13H22N2NaO5 requires 309.1426.
(5R,6R,E)-Dimethyl 5-((Benzyloxycarbonyl)(4-methoxy-
benzyl)amino)-6-(tert-butoxycarbonylamino)hept-2-enedioate
(25). Compound 25 was prepared following the procedure described
for compound 14. Yield = 361 mg from 400 mg of 11, 81%. [α]D25
−15.3 (c 0.8, CHCl3). IR (CHCl3): 3363, 2954, 2917, 1744, 1716,
1
1701, 1611, 1512, 1248, 1166 cm−1. H NMR (DMSO-d6, 300 MHz,
70 °C): δ 7.32−7.25 (m, 5H), 7.11 (d, J = 8.1 Hz, 2H), 6.78 (d, J = 8.4
Hz, 2H), 6.40−6.34 (m, 1H), 5.49 (d, J = 15.6 Hz, 1H), 5.13 (s, 2H),
4.52−4.43 (m, 2H), 4.10−4.01 (m, 2H), 3.71 (s, 3H), 3.64−3.54 (m,
4H), 3.49 (s, 3H), 2.48−2.43 (m, 2H), 1.35 (s, 9H). 13C NMR
(DMSO-d6, 75 MHz, 70 °C): δ 171.6, 166.0, 159.1, 156.6, 155.1,
145.5, 137.0, 130.3, 129.8, 128.7, 128.2, 128.0, 122.9, 114.1, 79.3, 67.1,
58.2, 55.5, 52.2, 51.3, 50.1, 32.0, 28.5. 13C NMR (CDCl3, 100 MHz, 25
°C): δ = 171.2, 166.3, 159.0, 156.5, 155.1, 144.8 (144.5), 136.4
(136.0), 130.0, 129.4, 128.5, 128.0, 123.0, (113.9) 113.8, 80.1, 67.8,
67.3, 59.5, 55.3, 55.1, 52.4, 51.2, 31.9, 28.2. HRMS (QTOF ES+)
found m/z 593.2476 (M + Na)+, C30H38N2NaO9 requires 593.2475.
(R)-Methyl 2-(tert-Butoxycarbonylamino)-2-((R)-6-oxo-
piperidin-2-yl)acetate (26). Compound 26 was prepared following
the procedure described for compound 15. Yield = 66 mg from 200
mg of 25, 66%. [α]2D5 − 8.5 (c 2.3, CHCl3). IR (CHCl3): 3358, 2957,
1
1745, 1714, 1663, 1523, 1366, 1168 cm−1. H NMR (CDCl3, 400
MHz): δ 6.73 (s, 1 H), 5.71 (d, J = 8.0 Hz, 1H), 4.46 (dd, J = 4.4, 7.8
Hz, 1H), 3.79 (m, 4H), 2.41−2.27 (m, 2H), 1.94−1.92 (m, 1H),
1.80−1.77 (m, 2H), 1.45 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ
172.6, 170.2, 155.7, 80.6, 56.6, 55.2, 52.8, 31.0, 28.2, 23.9, 19.4. HRMS
(QTOF ES+) found m/z 309.1424 (M + Na)+, C13H22N2NaO5
requires 309.1426.
156.1, 149.6, 149.1, 137.2, 131.8, 131.0, 130.8, 129.9, 128.7, 128.2,
(128.1) 128.0, 125.1, 119.4 (119.3), (114.2) 114.1, 113.0, 110.6, 79.1,
67.1, 67.0, 59.3, 56.4, 56.2, 55.4, 52.3, 52.1, 32.9, 28.6. HRMS (QTOF
ES+) found m/z 671.2946 (M + Na)+, C36H44N2NaO9 requires
671.2945.
(2R,3S)-Methyl 3-((Benzyloxycarbonyl)(4-methoxybenzyl)-
amino)-2-(tert-butoxycarbonylamino)-6-(3,4-dimethoxy-
phenyl)hex-5-enoate (27). Compound 27 was prepared following
the procedure described for compound 14 but using 5 mol % of G-II
catalyst 13 with 3 equiv of styrene derivative, and the refluxing time
was 16 h. Yield = 164 mg from 200 mg of 7, 65%). [α]2D5 − 11.2 (c
0.76, CHCl3). IR (CHCl3): 3365, 2954, 2837, 1709, 1701, 1514, 1250,
1160, 1027, 755 cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.42−7.21 (m,
5H), 7.01 (d, J = 7.6 Hz, 2H), 6.68−6.58 (m, 5H), 6.41 (br d, 1H),
6.02 (d, J = 15.6 Hz, 1H), 5.53−5.46 (m, 1H), 5.15−5.07 (m, 2H),
4.57−4.46 (m, 2H), 3.92−3.84 (m, 2H), 3.78 (s, 3H), 3.76 (s, 3H),
3.64 (s, 3H), 3.58 (s, 3H), 2.47−2.43 (m, 2H), 1.34 (s, 9H). 13C NMR
(CDCl3, 100 MHz): δ 171.8, 159.0, 156.9, 155.8, 148.8, 148.5, 136.2,
132.7, 130.6, 129.6, 128.5, 128.1, 127.9, 123.4, 119.2, 113.9, 110.9,
108.7, 79.7, 67.5, 60.3, 56.7, 55.9, 55.8, 55.1, 52.3, 52.0, 32.9, 28.4.
HRMS (QTOF ES+) found m/z 671.2940 (M + Na)+, C36H44N2NaO9
requires 671.2945
(2R,3S,E)-Methyl 3-((Benzyloxycarbonyl)(4-methoxybenzyl)-
amino)-2-(tert-butoxycarbonylamino)-6-(4-methoxyphenyl)-
hex-5-enoate (28). Compound 28 was prepared following the
procedure described for compound 27. Yield = (166 mg from 200 mg
of 7, 69%). [α]2D5 − 15.5 (c 0.5, CHCl3). IR (CHCl3): 3374, 2954,
1711, 1513, 1249, 1174, 1033, 755 cm−1. 1H NMR (CDCl3, 400
MHz): δ 7.28−7.22 (m, 5H), 7.02 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 8.4
Hz, 2H), 6.74−6.61 (m, 4H), 6.41 (d, J = 8.0 Hz, 1H), 6.06 (d, J =
15.6 Hz, 1H), 5.49−5.45 (m, 2H), 5.17−5.06 (m, 2H), 4.57 (d, J =
(2R,3R,E)-Methyl 3-((Benzyloxycarbonyl)(4-methoxybenzyl)-
amino)-2-(tert-butoxycarbonylamino)-6-(4-methoxyphenyl)-
hex-5-enoate (32). Compound 32 was prepared following the
procedure described for compound 27. Yield = (149 mg from 200 mg
of 11, 62%). [α]2D5 − 17.2 (c 0.4, CHCl3). IR (CHCl3): 3374, 2956,
1711, 1513, 1249, 1174, 1034, 757 cm−1. 1H NMR (CDCl3, 400
MHz): δ 7.35−7.10 (m, 5H), 7.03−6.86 (m, 4H), 6.75−6.59 (m, 4H),
6.4 (m, 1H), 6.07−6.02 (m, 1H), 5.49−5.45 (m, 1H), 5.17−5.06 (m,
2H), 4.59−4.43 (m, 2H), 3.97−3.88 (m, 1H), 3.71 (s, 3H), 3.69−3.49
(m, 7H), 2.51−2.37 (m, 2H), 1.36 (s, 9H). 13C NMR (CDCl3, 100
MHz): δ 171.8 (171.4), 159.0, 158.9 (158.8), 156.9, 155.5, 136.3,
132.4, 130.0, 129.7, 129.3, 128.5, 128.4, 128.1 (128.0), 127.3, 127.27,
123.1, (113.9) 113.7, 80.1 (79.9), 67.5 (67.2), 60.1, 56.8, 55.7, 55.3,
55.2, 52.5 (52.3), 32.9, 28.3. HRMS (QTOF ES+) found m/z
641.2842 (M + Na)+, C35H42N2NaO8 requires 641.2839.
(2R,3R)-Methyl 3-Amino-2-(tert-butoxycarbonylamino)-6-
(3,4-dimethoxyphenyl)hexanoate (33). Compound 33 was
prepared following the procedure described for compound 15. Yield
= 48 mg, from 100 mg of 31, 78%). [α]2D5 − 6.5 (c 1.0, CHCl3). IR
(CHCl3): 3384, 2971, 1709, 1515, 1393, 1367, 1260, 1159, 1029, 766
1
cm−1. H NMR (DMSO-d6, 400 MHz, 25 °C): δ 6.77 (d, J = 8.0 Hz,
1H), 6.70 (s, 1H), 6.60 (d, J = 8.0 Hz, 1H), 4.32 (d, J = 8.4 Hz, 0.5H)
{4.26 (d, J = 8.0 Hz, 0.5H)}, 3.99 (dd, J = 7.2, 9.6 Hz, 1H), 3.92 (t, J =
G
DOI: 10.1021/jo5022162
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
8.4 Hz, 1H), 3.67 (s, 3H), 3.64 (s, 3H), 3.59−3.44 (m, 4H), 1.63−1.41
(m, 3H), 1.32−1.17 (m, 13H). NMR (DMSO-d6, 400 MHz, 70 °C): δ
= 6.84−6.68 (m, 3H), 4.36 (br m, 1H), 4.08−4.02 (m, 2H), 3.76−3.62
(m, 9H), 3.38 (m, 1H), 1.67−1.60 (m, 3H), 1.37 (br m, 13H). 13C
NMR (CDCl3, 100 MHz): δ 172.0, 152.8, 148.8, 147.2, 134.3, 120.2,
111.7, 111.2, 80.4, 63.6 (63.4), 61.6 (61.1), 55.9, 55.8, 51.9 (51.7),
35.3, 29.3, 28.8, 28.3. HRMS (QTOF ES+) found m/z 397.2344 (M +
H)+, C20H33N2O6 requires 397.2339.
(2R,3R)-Methyl 3-Amino-2-(tert-butoxycarbonylamino)-6-(4-
methoxyphenyl)hexanoate (34). Compound 34 was prepared
following the procedure described for compound 15. Yield = 43 mg
from 100 mg of 32, 72%). [α]2D5 − 4.2 (c 0.8, CHCl3). IR (CHCl3):
3374, 2956, 1714, 1513, 1247, 1164, 1032, 760 cm−1. 1H NMR
(CDCl3, 400 MHz, 70 °C): δ 8.41 (brm, 2H), 7.11 (d, J = 6.8 Hz,
2H), 6.84 (d, J = 8.0 Hz, 2H), 4.51−4.47 (m, 1H), 3.78 (s, 3H), 3.69
(s, 3H), 3.57−3.51 (m, 1H), 2.57−2.51 (m, 2H), 1.69−1.64 (m, 4H),
1.41 (s, 9H). 13C NMR (CDCl3, 100 MHz, 70 °C): δ 17.4, 158.1,
155.6, 133.9, 129.6, 114.3, 79.6, 55.6, 52.8, 52.0, 51.8, 34.3, 29.7, 28.6,
27.0. HRMS (QTOF ES+) found m/z 367.2229 (M + H)+,
C19H31N2O5 requires 367.2233.
(2R,3R)-Benzyl 3-((Benzyloxycarbonyl)(4-methoxybenzyl)-
amino)-2-(tert-butoxycarbonylamino)tetradec-5-enoate (38).
Compound 38 was prepared following the procedure described for
compound 35. Yield = 362 mg from 400 mg of 12, 76%. [α]2D5 −5.7 (c
0.64, CHCl3). IR (CHCl3): 2956, 2929, 1715, 1514, 1501, 1251, 1176,
1029 cm−1. 1H NMR (CDCl3, 400 MHz): δ 7.28−7.09 (m, 11H), 6.95
(d, J = 8.0 Hz, 1H), 6.70−6.65 (m, 2H), 5.50 (d, J = 6.8 Hz, 1H),
5.19−4.79 (m, 6H), 4.59−4.52 (m, 1H), 4.25 (d, J = 16 Hz, 1H), 4.08
(d, J = 15.6 Hz, 1H), 3.67 (s, 3H), 2.46−2.18 (m, 2H), 1.70−1.64 (m,
2H), 1.34 (s, 9H), 1.27−1.04 (m, 12H), 0.79 (t, J = 6.8 Hz, 3H). 13C
NMR (DMSO-d6, 100 MHz): δ 171.0, 158.2, 156.3, 155.3, 136.6,
135.6, 132.4, 130.0, 128.2 (two signals), 127.9 (two signals), 127.7,
127.4, 113.6, 113.3, 78.5, 66.7, 66.5, 66.2, 66.1, 55.4, 54.9, 31.9, 31.3,
28.9, 28.8, 28.6, 28.5, 28.0, 27.7, 27.5, 22.1. HRMS (QTOF ES+)
found m/z 723.3981 (M + Na)+, C42H56N2NaO7 requires 723.3985.
(2R,3R)-3-Amino-2-(tert-butoxycarbonylamino)tetra-
decanoic Acid (39). Compound 39 was prepared following the
procedure described for compound 36. Yield = 81 mg from 200 mg of
38, 79%. [α]2D5 −7.8 (c 0.72, MeOH). IR (net): 3778, 3374, 2929,
1
2855, 1717, 1694, 1517, 1172, 1061 cm−1. H NMR (CD3OD, 400
MHz): δ 4.19 (brs, 1H), 3.60 (brm, 1H), 1.54 (m, 2H), 1.38−1.30 (m,
11H), 1.29−1.10 (m, 16H), 0.80 (t, J = 6.4 Hz, 3H). 13C NMR
(CD3OD, 100 MHz): δ 171.0, 157.0, 80.0, 54.9, 52.9, 31.7, 29.4 (two
signals), 29.3, 29.1, 29.0, 28.7, 27.3, 24.9, 22.4, 13.2. HRMS (QTOF
ES+) found m/z 381.2732(M + Na)+, C19H38N2NaO4 requires
381.2729.
tert-Butyl (3R,4R)-2-Oxo-4-undecylazetidin-3-ylcarbamate
(40). Compound 40 was prepared following the procedure described
for compound 37. Yield = 76 mg from 100 mg of 39, 80%. [α]2D5 + 9.0
(c 1.1, CHCl3). 1H NMR (CDCl3, 400 MHz): δ 6.45 (s, 1H), 5.33 (d,
J = 7.2 Hz, 1H), 4.26 (d, J = 7.2 Hz, 1H), 3.56 (t, J = 5.6 Hz, 1H),
1.65−1.51 (m, 2H), 1.38 (s, 9H), 1.19 (brs, 18H), 0.81 (t, J = 6.4 Hz,
3H). 13C NMR (CDCl3, 100 MHz): δ 167.9, 154.9, 80.3, 63.4, 58.6,
33.7, 31.9, 29.6, 29.5, 29.48, 29.4, 29.3, 28.3, 26.0, 22.7, 14.1. HRMS
(QTOF ES+) found m/z 363.2626 (M + Na)+, C19H36N2NaO3
requires 363.2624.
(2R,3S)-Benzyl 3-((Benzyloxycarbonyl)(4-methoxybenzyl)-
amino)-2-(tert-butoxycarbonylamino)tetradec-5-enoate (35).
Compound 35 was prepared following the procedure described for
compound 8 but using 3 equiv of 1-decene, 5 mol % of G-II catalyst
13, and a refluxing time of 12 h. Yield = 367 mg from 400 mg of 8,
77%. [α]2D5 + 19.0 (c 1.1, CHCl3). IR (CHCl3): 2956, 2927, 1716,
1
1514, 1499, 1250, 1175, 1029 cm−1. H NMR (CDCl3, 400 MHz): δ
7.35−7.24 (m, 10H), 7.01 (d, J = 7.6 Hz, 2H), 6.75 (m, 3H), 6.65 (d, J
= 4.0 Hz, 1H), 5.29−5.08 (m, 7H), 4.99−4.89 (m, 1H), 4.53−4.46 (m,
2H), 5.18−5.08 (m, 4H), 3.86−3.82 (m, 1H), 3.75 (br s, 4H), 2.44−
2.41 (m, 1H), 2.23−2.18 (m, 1H), 1.80−1.72 (m, 2H), 1.43 (s, 9H),
1.33−1.21 (m, 12H), 0.87 (t, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 100
MHz): δ 171.4, 159.0, 156.9, 155.8, 136.3, 135.4, 135.3, 134.6, 129.5,
128.7, 128.6, 128.5, 128.4, 128.1, 127.9, 124.7, 113.8, 79.5, 67.5, 67.1,
60.4, 56.9, 55.2, 52.3, 32.6, 31.9, 29.5, 29.3, 29.2, 28.4, 22.7, 14.2.
HRMS (QTOF ES+) found m/z 723.3982 (M + Na)+, C42H56N2NaO7
requires 723.3985.
ASSOCIATED CONTENT
(2R,3S)-3-Amino-2-(tert-butoxycarbonylamino)tetra-
decanoic Acid (36). Compound 36 was prepared following the
procedure described for compound 15 using Pd(OH)2-C as catalyst,
and the reaction time was 10 h. Yield = 84 mg from 200 mg of 35,
82%. [α]2D5 −17.3 (c 1.6, MeOH). IR (net): 3776, 3378, 2926, 2855,
1715, 1690, 1517, 1170, 1061 cm−1. 1H NMR (CD3OD, 400 MHz): δ
4.19 (brs, 1H), 3.44 (brm, 1H), 1.60 (m, 1H), 1.47−1.37 (m, 12H),
1.22−1.20 (m, 16H), 0.80 (t, J = 6.4 Hz, 3H). 13C NMR (CD3OD,
100 MHz): δ 172.5, 156.4, 79.7, 54.6, 52.4, 31.7, 29.4 (two signals),
29.3, 29.1, 29.0, 28.8, 27.3, 25.2, 22.4, 13.1. HRMS (QTOF ES+)
found m/z 381.2725 (M + Na)+, C19H38N2NaO4 requires 381.2729.
tert-Butyl (3R,4S)-2-Oxo-4-undecylazetidin-3-ylcarbamate
(37). To a stirred solution of 2-chloro-1-methylpyridinium iodide
(142 mg, 0.56 mmol) and DIEA (75 μL, 0.42 mmol) in dry CH3CN
(30 mL), a solution of the amino acid 36 (100 mg, 0.28 mmol) in dry
CH3CN (10 mL) was added slowly, and the resulting mixture was
heated up to 70 °C for 1 h, by which time the solution became clear.
The reaction mixture was allowed to come to rt, and stirring was
continued for 15 h. Then, the volatiles were evaporated off under
vacuum and the residue was extracted with EtOAc (2 × 30 mL). The
organic part was washed with water (2 × 25 mL) and brine solution
(30 mL) and then dried (MgSO4). It was then filtered, and the filtrate
was concentrated under reduced pressure to leave the crude product,
which was purified by flash chromatography using EtOAc/hexane
(15:85) to give the compound 37 (80 mg, 84%) as a colorless gel.
[α]2D5 −27.3 (c 0.9, CHCl3). IR (CHCl3): 3328, 2958, 2927, 2855,
■
S
* Supporting Information
1
Copies of H and 13C NMR spectra of all new compounds 3−
40, and HPLC chromatograms of compounds 3, 4, 7, 8, 11, 12,
14, 16, 18, 20, 22, 23, 25, 27, 28, 29, 30, 31, 32, 33, 34, 35, and
38 are included. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: skchatto@yahoo.com (S.K.C.).
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The work was supported by grants from D.S.T., Govt. of India
(SR/S1/OC/92/2012), and C.S.I.R. (02/0164/13/EMR-II),
Govt. of India. B.C. is also thankful to U.G.C., New Delhi, for a
D. S. Kothari postdoctoral fellowship.
REFERENCES
■
(1) Williams, R. M. In Synthesis of Optically Active a-Amino Acids;
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1
1763, 1697, 1525, 1367, 1251, 1169, 1050 cm−1. H NMR (CDCl3,
400 MHz): δ 6.04 (s, 1H), 5.12 (d, J = 8.0 Hz, 1H), 5.04 (dd, J = 4.8,
8.0 Hz, 1H), 3.75 (dt, J = 5.2, 7.6 Hz, 1H), 1.45 (s, 9H), 1.30−1.20
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two signals), 29.50, 29.3, 28.2, 25.9, 22.7, 14.1. HRMS (QTOF ES+)
found m/z 363.2620 (M + Na)+, C19H36N2NaO3 requires 363.2624.
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DOI: 10.1021/jo5022162
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The Journal of Organic Chemistry
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I
DOI: 10.1021/jo5022162
J. Org. Chem. XXXX, XXX, XXX−XXX