Efficient enantiospecific synthesis of ent-conduramine F-1

Article abstract of DOI:10.1016/j.tet.2018.09.058

An efficient enantiospecific total synthesis of ent-conduramine F-1 (aminocyclohexenetriol) was accomplished starting from the bis-Weinreb amide of tartaric acid. Key reactions in the synthesis include the desymmetrization of tartaric acid amide with viny

Full text of DOI:10.1016/j.tet.2018.09.058

Accepted Manuscript
Efficient enantiospecific synthesis of ent-conduramine F-1
Kavirayani R. Prasad, Vipin Ashok Rangari
PII:
S0040-4020(18)31172-4
10.1016/j.tet.2018.09.058
TET 29830
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 8 July 2018
Revised Date: 25 September 2018
Accepted Date: 30 September 2018
Please cite this article as: Prasad KR, Rangari VA, Efficient enantiospecific synthesis of
ent-conduramine F-1, Tetrahedron (2018), doi: https://doi.org/10.1016/j.tet.2018.09.058.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Efficient Enantiospecific Synthesis of ent-Conduramine F-1
Kavirayani R. Prasad* and Vipin Ashok Rangari
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, INDIA

ACCEPTED MANUSCRIPT
Efficient Enantiospecific Synthesis of ent-Conduramine F-1
Kavirayani R. Prasad* and Vipin Ashok Rangari
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, INDIA
E-mail: prasad@iisc.ac.in; FAX: +91-80-23600529
Abstract: An efficient enantiospecific total synthesis of ent-conduramine F-1
(aminocyclohexenetriol) was accomplished starting from the bis-Weinreb amide of tartaric acid.
Key reactions in the synthesis include the desymmetrization of tartaric acid amide with
vinylmagnesium bromide and installation of the required amine using Ellman sulfinimine. Ring
closing metathesis was used to synthesize the required alkene in the cyclohexene.
Keywords: amino cyclohexenetriols, ent-conduramine F-1, chiral pool, sulfinimines, total synthesis
Introduction
Aminocyclitols are important classes of compounds in medicinal chemistry. Aminocyclitol (1) is
also a key structural unit in bio-active natural products minosaminomycin (8) and hygromycin A
1
(
9). Conduramines (3-5), the dehydro analogues of amino cyclitols are synthetic derivatives of
naturally occurring conduritols in which one of the allylic hydroxy groups is replaced with an
amine. Conduramines not only exhibit interesting biological profiles, but also serve as precursors
for the synthesis of aminocyclitols and the Amaryllidaceae alkaloids such as lycoricidine (7)
2
(Fig.1).
Fig.1. Aminocyclitol containing natural products and conduramines
While a number of methods were reported in literature for the synthesis of conduramines,
2
formation of the double bond of the cyclohexene by Ring Closing Metathesis (RCM) reaction is the
most desirable. Of the RCM reaction used for the synthesis of conduramines, Yan’s group
disclosed the synthesis of tetraacetates of conduramine A and E from tartaric acid using RCM
3
reaction and 3,3-sigmatropic rearrangement of allylic azide as the key step. Rao et. al. disclosed
4
the synthesis of N-benzyl conduramine E and F from mannitol using RCM strategy. They failed to
produce the conduramines by deprotection of the benzyl group instead synthesized the
dihydroconduramines. Similar difficulties in the debenzylation and purification of N-benzyl
5
conduramines were encountered by Vogel’s group in their synthesis of conduramines. Partha and
6
Shaw disclosed a formal synthesis of both enantiomers of conduramine E using RCM, however
the precursor was synthesized in a multi-step sequence from the sugars galactose and mannose
using Petasis reaction as the key step. Ham et. al. synthesized conduramine F-1 employing RCM
1

ACCEPTED MANUSCRIPT
7
using their trademark chiral oxazine as the starting point. We have been involved in the use of
tartaric acid in the total synthesis of natural products for a decade. We have established that the
γ-oxo-amides derived from tartaric acid amides serve as excellent building blocks for the synthesis
of diverse oxygenated natural products. The strategy involves the desymmetrization of the
Weinreb amide/ dimethyl amide derived from tartaric acid with various Grignard reagents and
8
further transformations. In continuation of our efforts, herein, we report the total synthesis of
9
ent-conduramine F-1 (5) starting from L-tartaric acid. We reasoned that ent-conduramine F-1 (5)
can be accessed from the protected aminol 10. Addition of vinylmagnesium bromide to the
Weinreb amide 14 will lead to the mono keto amide, the subsequent reduction of which should
form the required allylic alcohol 13. Addition of vinyl Grignard reagent to the sulfinimine 12
obtained from the elaboration of 13 should install the amine part with requisite stereochemistry
thus leading to the RCM precursor 11. The introduction of sulfinimine not only controls the
diastereoselective formation of the amine but also can easily be deprotected (Scheme-1), a
problem that was encountered with the benzyl protection can be circumvented.
Scheme-1: Retrosynthesis for ent-conduramine F-1 (5)
Results and Discussion
Thus, the synthetic sequence commenced with the addition of vinylmagnesium bromide to the
1
0
11
bis-Weinreb amide 14 derived from tartaric acid to afford the mono ketoamide 15 in 74% yield.
Stereoselective reduction of the ketone in 15 under Luche conditions furnished the alcohol 13 in
8
1
2
8% yield. Protection of the hydroxy group in 13 as the tert-butyldimethylsilyl ether 16 was
accomplished in 89% yield. Treatment of 16 with DIBAL-H transformed the Weinreb amide to the
1
3
corresponding aldehyde, which on condensation with the (S)-tert-butylsulfinamide afforded the
sulfinimine 12 in 79% yield for two steps. Addition of vinylmagnesium bromide to the sulfinimine
1
4
1
2 yielded the sulfinamide 17 in 89% yield. Interestingly, the sense of induction is not controlled
by the chirality of the sulfinimine but is more influenced by the inherent tartrate moiety.
Deprotection of the TBS ether in 17 furnished the diene containing amino alcohol 11 in 94% yield.
1
5
Treatment of the diene 11 with Grubbs’ second-generation catalyst cleanly afforded the masked
aminotrihydroxycyclohexene 10 in 86% yield. Deprotection of the acetonide as well as the sulfinyl
group in 10 with HCl in MeOH and further neutralization with NaHCO produced ent-conduramine
3
F-1 (5) in 60% yield (Scheme-2). Physical and spectral characteristics of the synthesized sample is
9
b
in complete agreement with that reported in the literature.
Conclusion
In conclusion, an efficient enantiospecific total synthesis of ent-conduramine F-1 (amino
trihydroxycyclohexene) was accomplished from the bis-Weinreb amide of tartaric acid in 9 steps
and in 19.8% overall yield. Key features of the synthesis include the formation of the cyclohexene
2

ACCEPTED MANUSCRIPT
core by RCM reaction and stereoselective reduction of a vinyl ketone and addition of vinyl
Grignard reagent to the sulfinimine derived from tartaric acid to install the required alcohol and
amine stereogenic centers respectively.
Scheme-2: Total synthesis of ent-conduramine F1
Experimental: General Information: Column chromatography was performed on silica gel, Acme
grade 100−200 mesh. TLC plates were visualized either with UV in an iodine chamber or with
phosphomolybdic acid spray unless noted otherwise. All reagents were purchased from
commercial sources and used without additional purification. THF was freshly distilled over Na-
benzophenone ketyl. Melting points were recorded using melting point apparatus in capillary
1
13
tubes and are uncorrected. Unless stated otherwise, H (400 MHz) and C (100 MHz) spectra were
recorded on 400 MHz spectrophotometers in CDCl as solvent with TMS as reference. High-
3
resolution mass spectra (HRMS) were recorded on a Q-TOF micromass spectrometer using
electron spray ionization mode.
Preparation of (4R,5R)-5-acryloyl-N-methoxy-N,2,2-trimethyl-1,3-dioxolane-4-carboxamide (15):
To a stirred solution of the diamide 14 (1.0 g, 3.62 mmol) in THF (20 mL) at −78 °C, under argon
atmosphere was added vinylmagnesium bromide solution (14 mL of 0.35 M in THF, 4.9 mmol)
dropwise for 5 min. The reaction mixture was allowed to stir for 45 min at the same temperature.
After completion of the reaction (TLC), the reaction mixture was poured into a cold (0°C) solution
of 1N HCl and diethyl ether (30 mL,1:1). The aqueous layer was extracted with EtOAc (2×20 mL).
The combined organic layer was washed with brine (20 mL), dried over sodium sulphate and
concentrated under vacuum. Purification of the residue thus obtained on silica gel column
chromatography using EtOAc:Hexane (3:7) as eluent yielded the compound 15 (0.65g, 74% ) as
2
4
colourless oil. Rf (1:1, EtOAc:Hexane) 0.6; [α] +2.40 (c 1.5, CHCl ); IR (Neat) 2987, 1671, 1607,
D
3
−1 1
1
379 cm ; H NMR (400 MHz, CDCl ) δ 6.74 (dd, J = 17.6 Hz, 10.8 Hz, 1H), 6.47 (dd, J = 17.6 Hz, 1.2
3
Hz, 1 H), 5.92 (dd, J = 10.8 Hz, 1.2 Hz,1 H), 5.16 (d, J = 4.4 Hz, 1H), 5.04 (d, J = 4.8 Hz, 1H), 3.71 (s, 3
1
3
H), 3.24 (bs, 3H), 1.53 (s, 3H), 1.43 (s, 3H); C NMR (100 MHz, CDCl ) δ 196.5, 169.9, 132.2, 130.9,
3
3

ACCEPTED MANUSCRIPT
+
1
13.0, 81.1, 74.2, 61.6, 32.5, 26.6, 26.3. HRMS (ESI) [M+Na] found: 266.1005. C H NO Na
11 17 5
requires 266.1004.
Preparation
carboxamide (13): To a stirred solution of the amide 15 (0.63 g, 2.6 mmol) in MeOH (20 mL) at −78
C, was added a pre-mixed suspension of CeCl .7H O (3.67 g, 9.82 mmol) and NaBH (0.325 g, 8.85
of
(4R,5S)-5-((R)-1-hydroxyallyl)-N-methoxy-N,2,2-trimethyl-1,3-dioxolane-4-
°
3
2
4
mmol) in MeOH (10 mL) dropwise for 10 min. The reaction mixture was allowed to stir for 1.5 h at
the same temperature. After completion of the reaction (TLC), most of the solvent was evaporated
off. The residue thus obtained was dissolved in H O (20mL) and was extracted with EtOAc (2×20
2
mL). The combined organic layer was washed with brine (20 mL), dried over Na SO .and
2
4
concentrated. Purification of the residue obtained on silica gel column chromatography using
EtOAc:Hexane (1:1) as eluent yielded the compound 13 (0.56 g, 88%) as colourless oil with 99:1 dr.
2
4
−1 1
Rf (1:1, EtOAc:Hexane) 0.5; [α]D +2.36 (c 1.1, CHCl ); IR (Neat) 3446, 2987, 2934, 1600 cm ; H
3
NMR (400 MHz, CDCl ) δ 5.93 (ddd, J = 17.2 Hz, 10.8 Hz, 5.6 Hz, 1H), 5.48 (d, J = 17.2 Hz, 1 H), 5.26
3
(
d, J = 10.4 Hz, 1 H), 4.76 (bs, 1H), 4.50 (bs, 1H), 4.24 (bs, 1H), 3.75 (s, 3H), 3.24 (bs, 3H), 2.45 (bs,
1
3
1
7
H), 1.50 (s, 3H), 1.46 (s, 3H); C NMR (100 MHz, CDCl ) δ 170.2, 136.8, 116.8, 111.4, 80.5, 73.7,
3
+
1.8, 61.7, 32.4, 27.0, 26.1. HRMS (ESI) [M+Na] found 268.1159. C H NO Na requires 268.1161.
1
1
19
5
Preparation of (4R,5R)-5-((R)-1-((tert-butyldimethylsilyl)oxy)allyl)-N-methoxy-N,2,2-trimethyl-
,3-dioxolane-4-carboxamide (16): To a stirred solution of the alcohol 13 (0.26 g, 1.06 mmol) in
CH Cl (10 mL) at 0 °C was added TBSCl (0.47 g, 3.1 mmol), imidazole (0.37 g. 5.45 mmol), and
1
2
2
DMAP (0.013 g, 0.11 mmol) successively. The reaction mixture was heated to reflux for 5 h. After
completion of the reaction (TLC), the reaction mixture was diluted with EtOAc (20 mL) and was
poured into water (20 mL). The organic layer was separated, and the aqueous layer was extracted
with EtOAc (2×10 mL). The combined organic layer was washed with sat. solution of brine (10 mL)
and dried over sodium sulphate. Evaporation of the solvent gave crude residue which was purified
by silica gel column chromatography using EtOAc:Hexane (1:9) as eluent to yield the compound 16
2
4
(
0.34 g, 89%) as colourless oil. Rf (2:8, EtOAc:Hexane) 0.6; [α] +7.58 (c 1.3, CHCl ); IR (Neat)
D
3
−1 1
2
1
4
3
2
993, 1672, 1466, 1254 cm ; H NMR (400 MHz, CDCl ) δ 5.97 (ddd, J = 17.2 Hz, 10.8 Hz, 5.2 Hz,
H), 5.33 (dd, J = 17.2 Hz, 1.6 Hz, 1 H), 5.23 (dd, J = 10.8 Hz, 1.2 Hz, 1 H), 4.70 (s, 1H), 4.60 (s, 1H),
.41 (d, J = 4.8 Hz, 1H), 3.72 (s, 3H), 3.20 (bs, 3H), 1.44 (s, 6H), 0.87 (s, 9H), 0.05 (s, 3H), 0.04 (s,
3
1
3
H); C NMR (100 MHz, CDCl ).δ 170.3, 136.5, 116.4, 111.4, 80.3, 72.5, 72.2, 61.7, 32.2, 27.0, 26.3,
3
+
5.7 (3C), 18.2, −4.8, −5.1. HRMS (ESI) [M+Na] found 382.2023. C H NO SiNa requires 382.2026.
1
7
33
5
1
3
Preparation
of
(E)-N-(tert-butyl(λ -oxidanyl)-λ -sulfanyl)-1-((4S,5R)-5-((R)-1-((tert-
butyldimethylsilyl)oxy)allyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methanimine (12): To a stirred
4

ACCEPTED MANUSCRIPT
solution of the amide 16 (0.8 g. 2.22 mmol) in THF (20 mL) at −78 °C, was added DIBAL-H (7.3 mL
of 1M, 7.23 mmol). The reaction mixture was stirred for 1 h at the same temperature. After
completion of the reaction, (TLC), the reaction mixture was diluted with Et O (10 mL) and
2
saturated aqueous solution of potassium sodium tartrate (10 mL) was added. The reaction mixture
was stirred vigorously at rt for 1.5 h. The organic layer was separated and the aqueous layer was
extracted with EtOAc (2×20 mL). The combined organic layer was washed with sat. solution of
brine (10 mL), and was dried over sodium sulphate. The crude aldehyde obtained after
evaporation of the solvent was used in the next step without further purification. The crude
aldehyde obtained above was dissolved in THF (20 mL), and (S)-tert-butanesulfinamide (0.385 g,
3
.17 mmol), Ti(OEt) (1 mL, 4.88 mmol) were added successively. The reaction mixture was
4
refluxed for 4h. After completion of the reaction (TLC), sat. solution of brine (5 mL) was added,
and stirred vigorously at rt for 15 min. The resulting solid cake filtered through a short pad of
celite. The crude residue obtained after evaporation of solvent was purified by silica gel column
chromatography using EtOAc:Hexane (1:9) as eluent to yield the compound 12 (0.71 g, 79% for 2
2
4
steps) as a colourless oil. Rf (1:9, EtOAc:Hexane) 0.6; [α] +126.4 (c 1.1, CHCl ); IR (Neat) 2955,
D
3
−1 1
2
1
1
0
8
4
858, 1741, 1622 cm ; H NMR (400 MHz, CDCl ) δ 8.10 (d, J = 4.0 Hz, 1H), 5.93 (ddd, J =16.8 Hz,
0.4 Hz, 5.6 Hz, 1H), 5.31 (d, J = 17.2 Hz, 1H), 5.22 (d, J = 10.8 Hz, 1H), 4.71 (dd, J =6.8 Hz, 4.0 Hz,
H), 4.31 (t, J =5.2 Hz, 1H), 4.11 (dd, J = 6.8 Hz, 4.4 Hz, 1H), 1.47 (s, 3H), 1.38 (s, 3H), 1.21 (s, 9H),
.90 (s, 9H), 0.08 (s, 3H), 0.06 (s, 3H); C NMR (100 MHz, CDCl ).δ: 168.2, 136.8, 116.9, 111.1,
2.4, 78.0, 73.1, 57.1, 26.7, 26.6, 25.8 (3C), 22.4 (3C), 18.3, −4.5, −4.9. HRMS(ESI) [M+Na] found
3
1
3
3
+
26.2109. C H NO SSiNa requires 426.2110.
1
9
37
4
Preparation of 1-tert-butyl-N-((S)-1-((4S,5R)-5-((R)-1-((tert-butyldimethylsilyl)oxy)allyl)-2,2-
1
3
dimethyl-1,3-dioxolan-4-yl)allyl)-1-( λ -oxidanyl)- λ -sulfanamine (17): To a stirred solution of
the imine 12 (0.07 g, 0.17 mmol) in THF (5 mL) at −78 °C, under argon atmosphere was added
dropwise a solution of vinylmagnesium bromide (0.2 M solution in THF, 1.5 mL, 0.3 mmol). The
resulting reaction mixture was stirred at the same temperature for 45 min. After completion of
the reaction (TLC), the reaction mixture was cautiously quenched by addition of aqueous solution
of NH Cl and was slowly warmed upto room temperature. The reaction mixture was extracted
4
with EtOAc (2×10 mL). Combined organic layer was washed with brine (5 mL) and dried over
sodium sulphate. Residue obtained after evaporation of the solvent was purified by silica gel
chromatography using EtOAc:Hexane (1:1) as eluent to yield the compound 17 (0.065 g, 89%) with
2
4
9
9:1 dr. Rf (1:1, EtOAc:Hexane) 0.4; [α] +28.0 (c 1.2, CHCl ); IR (Neat) 3308, 2931,1591, 1251
D
3
−1 1
cm ; H NMR (400 MHz, CDCl ) δ 5.91 (ddd, J = 17.2 Hz, 10.4 Hz, 6.4 Hz, 1H), 5.76 (ddd, J = 17.2
3
Hz, 10.4 Hz, 8.4 Hz, 1H), 5.40−5.18 (m, 4H), 4.28−4.17(m, 2H), 4.10 (quint, J = 4.4 Hz, 1H) 3.91 (d, J
=
8 Hz, 4 Hz, 1H), 3.81 (d, J = 4.4 Hz, 1H) 1.38 (s, 6H), 1.22 (s, 9H), 0.91 (s, 9H), 0.06 (s, 3H), 0.05 (s,
1
3
3
2
H), C NMR (100 MHz, CDCl ) δ 137.2, 134.0, 119.8, 116.8, 109.8, 80.2, 79.2, 74.0, 58.8, 55.8,
7.3, 27.0, 25.9 (3C), 22.6 (3C), 18.3, −4.5, −4.8. HRMS (ESI) [M+Na] found 454.2424.
3
+
C H NO SSiNa requires 454.2423.
2
1
41
4
5

ACCEPTED MANUSCRIPT
1
3
Preparation of (R)-1-((4S,5S)-5-((S)-1-((tert-butyl(λ -oxidanyl)- λ -sulfanyl)amino)allyl)-2,2-
dimethyl-1,3-dioxolan-4-yl)prop-2-en-1-ol (11): To a stirred solution of compound 17 (0.06 g, 0.15
mmol) in THF (3 mL) at 0 °C, under argon atmosphere was added TBAF in THF (1.0 M in THF, 0.2
mL, 0.19 mmol). The reaction mixture was stirred at room temperature for 45 min. After
completion of the reaction (TLC), it was concentrated under vacuum and the residue thus
obtained was purified by silica gel chromatography using EtOAc as eluent to yield 11 (0.041g, 93%)
2
4
as colourless oil. Rf (9:1, EtOAc:Hexane) 0.4; [α] : +58.4 (c 0.75, CHCl ); IR (Neat): 3462, 3437,
D
3
−1 1
1
592, 1219cm ; H NMR (400 MHz, CDCl ): δ 5.92 (ddd, J = 16.8 Hz, 10.4 Hz, 5.2 Hz, 1H), 5.76
3
(
ddd, J = 17.2 Hz, 10.4 Hz, 6.8 Hz, 1H), 5.47 − 5.22 (m, 4H), 4.33 (bs, 1H), 4.17 (d, J = 4.0 Hz, 1H)
.12 (dd, J = 6.8 Hz, 4.0 Hz, 1H), 4.04−3.91 (m, 2 H) 1.41 (s, 6H), 1.23 (s, 9H); C NMR (100 MHz,
1
3
4
CDCl ) δ 135.9, 135.2 , 119.1, 117.1, 109.6, 80.5, 79.0, 71.5, 60.0, 56.0, 27.1, 27.0, 22.7 (3C). HRMS
3
+
(
ESI) [M+Na] found 340.1556. C H NO SNa requires 340.1558.
15 27 4
1
3
Preparation of (3aS,4R,7S,7aS)-7-((tert-butyl(λ -oxidanyl)- λ -sulfanyl)amino)-2,2-dimethyl-
3
0
0
a,4,7,7a-tetrahydrobenzo[d][1,3]dioxol-4-ol (10): To a stirred solution of compound 11 (0.04 g,
nd
.12 mmol) in CH Cl (6 mL) under argon atmosphere was added Grubbs’-2 gen. catalyst (5 mg,
2
2
.006 mmol). The resulting solution was heated to reflux for 3 h. After completion of the reaction
(TLC), most of the solvent was evaporated and the crude residue thus obtained was purified by
silica gel column chromatography using EtOAc:MeOH (95:5) as eluent to yield the compound 10
−1 1
(
0.031g, 86% ) Rf (9:1, EtOAc: MeOH) 0.6; IR (Neat) 3583, 3449, 2926, 1586 cm ; H NMR (400
MHz, CDCl ) δ 5.99 (dd, J = 10.0 Hz, 4.8 Hz, 1H), 5. 90−5.75 (m, 1H), 4.40 (d, J = 8.0 Hz, 1H), 4.28 (s,
3
1
H), 3.95−3.75 (m, 2H), 3.61 (dd, J = 9.6 Hz, 4.4 Hz,1 H), 2.75 (s, 1H), 1.47 (s, 3H), 1.44 (s, 3H), 1.21
1
3
(s, 9H); C NMR (100 MHz, CDCl ) δ 133.9, 125.9, 111.0, 76.7, 75.8, 71.4, 56.0, 48.9, 27.1, 26.6,
3
+
2
2.5 (3C). HRMS (ESI) [M+Na] found 312.1247. C H NO SNa requires 312.1245.
13 23 4
Preparation of (1S,2S,3R,6S)-6-aminocyclohex-4-ene-1,2,3-triol [(+)-ent-conduramine F-1] (5): To
a stirred solution of compound 10 (0.020 g, 0.069 mmol) in THF (2 mL) was added a saturated
solution of HCl in MeOH (1mL) at 0 °C and was stirred for 2 h at room temperature. The reaction
mixture was quenched with sat. solution of NaHCO and concentrated. The crude residue thus
3
obtained was purified by silica gel column chromatography using CH Cl :MeOH (1:1) to yield (+)-
2
2
2
4
ent-conduramine F-1 (5) (6 mg) in 60% yield) Rf (1:1, MeOH:CH Cl ) 0.1: [α] +50.0 (c 0.2, MeOH)
2
2
D
9
b
−1 1
[
lit +50.8 ( c 1.3, MeOH)], IR (Neat): 3178, 2924, 1483, 1240, cm ; H NMR (400 MHz, CD OD) δ
3
5
.76 (dd, J = 8.4, Hz, 4.8 Hz, 1H), 5.68−5.58 (m, 1H) 3.92 (bs, 1H), 3.51−3.46 (m, 2H), 3.38 (bs, 1H),
1
3
+
C NMR (100 MHz, CD OD) δ 132.5, 129.2 ,73.7 (2C), 71.9, 51.5. HRMS (ESI) [M+H] found
3
1
46.0820. C H NO +H requires 146.0817.
6
11
3
Acknowledgements: K. R. P. thanks the Science and Engineering Research Board (SERB), New
Delhi for funding. V. A. R. thanks Indian Institute of Science (IISc) for a research fellowship.
References:
6

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2
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1
4
1574-11586. (c) Raghavan, S.; Chilveru, R. K.; Subramanian, S. G. J. Org. Chem. 2016, 81,
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6
7
.
.
Kim, J.-S.; Kang, J.-C.; Yoo, G.-H.; Jin, X.; Myeong, I.-S.; Oh, C.-Y.; Ham, W.-H. Tetrahedron
2
015, 71, 2772−2776.
8
9
1
.
For synthesis of γ-oxo-butyramides from the bis-amides of tartaric acid see: (a) Prasad, K.
R.; Chandrakumar, A. Tetrahedron 2007, 63, 1798. For selected application of γ-keto
amides derived from tartaric acid in natural product synthesis from our group see: (b) Bali,
A. K.; Sunnam, S. K.; Prasad, K. R. Org. Lett. 2014, 16, 4001. (c) Prasad, K. R.; Gholap, S. L. J.
Org. Chem. 2008, 73, 2.ꢀ
For prior asymmetric syntheses of conduramine F-1 see: (a) Pandey, G.; Tiwari, K. N.;
Puranik, V. G. Org. Lett. 2008, 10, 3611-3614. (b) Lu, P. H.; Yang, C. S.; Devendar, B.; Liao, C.
C. Org. Lett. 2010, 12, 2642-2645. (c) For synthesis of conduramine F-1 tetra acetate see:
Knapp, S.; Naughton, A. B. J.; Muralidhar, T. G. Tetrahedron Lett. 1992, 33, 1025-1028. and
references 4,5 and 7.
.
0.
Nugiel, D. A.; Jacobs, K.; Worley, T.; Patel, M.; Kaltenbach, R. F.; Meyer, D. T.; Jadhav, P. K.;
De Lucca, G. V.; Smyser, T. E.; Klabe, R. M.; Bacheler, L. T.; Rayner, M. M. Seitz, S. P. J. Med.
Chem. 1996, 39, 2156-2169.
1
1
1.
2.
Formation of minor amount (~5%) of known diketone resulting from the addition of
vinylmagnesium bromide to both the amides is observed.
The diastereomeric ratio could not be estimated at this stage. However, protection of the
alcohol as the TBS ether clearly indicated that the diastereomeric ratio is >99:1 estimated
1
within detectable limits by H NMR.
1
3.
For a review on the use of tert-butanesulfinamide in synthesis see: Robak, M. T.; Herbage,
M. A.; Ellman, J. A. Chem. Rev. 2010, 110, 3600-3740.
Formation of the other diastereomer was not seen within detectable limits by H NMR.
(a) Vougioukalakis, G. C.; Grubbs, R. H. Chem. Rev. 2010, 110 1746–1787. For a recent
review on the use of RCM and Grubbs catalyst in selected total synthesis see: Vanderwal,
C. D.; Atwood, B. R. Aldrichimica Acta, 2017, 50, 17-27.
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1
1
4.
5
7