Enantioselective synthesis of (-)-(5R,6S)-6-acetoxyhexadecan-5-olide via tandem α-aminooxylation-Henry reaction

Article abstract of DOI:10.24820/ark.5550190.p010.635

novel enantioselective synthetic approach of (-)-(5R,6S)-6-acetoxyhexadecan-5-olide, an oviposition attractant pheromone of the mosquito Culex pipiens fatigans is presented, starting from n-dodecanal. The synthesis features tandem α-aminooxylation-Henry a

Full text of DOI:10.24820/ark.5550190.p010.635

The Free Internet Journal
for Organic Chemistry
Paper
Archive for
Organic Chemistry
Arkivoc 2018, part vii, 0-0
Enantioselective synthesis of (-)-(5R,6S)-6-acetoxyhexadecan-5-olide via tandem
α-aminooxylation-Henry reaction
Rachana Pandey,a Yuvraj Garg,a Ranjana Prakash,a* and Satyendra Kumar Pandeya,b*
aSchool of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala-147004, India
bDepartment of Chemistry, Institute of Science, Banaras Hindu University, Varanasi-221 005, India
Email: rprakash@thapar.edu, skpandey.chem@bhu.ac.in
Dedicated to Prof. Gordon W. Gribble in recognition of his seminal contributions
to so many aspects of organic chemistry
Received 05-23-2018
Accepted 07-30-2018
Published on line 08-25-2018
Abstract
A novel enantioselective synthetic approach of (-)-(5R,6S)-6-acetoxyhexadecan-5-olide, an oviposition
attractant pheromone of the mosquito Culex pipiens fatigans is presented, starting from n-dodecanal. The
synthesis features tandem α-aminooxylation-Henry and Yamaguchi-Hirao alkylation reactions as key steps.
Keywords: δ-lactone, (-)-(5R,6S)-6-acetoxyhexadecanolide, tandem α-aminooxylation-Henry reaction,
regioselective epoxide opening, Yamaguchi-Hirao reaction
DOI: https://doi.org/10.24820/ark.5550190.p010.635
Page 1
©ARKAT USA, Inc

Arkivoc 2018, vii, 0-0
Pandey, R. et al.
Introduction
Functionalized γ- and δ-lactone motifs possess intriguing biological activities and are important building blocks
to synthesize a variety of biologically active natural products.1-9 In 1982, Laurence and Pickett isolated (-)-
(5R,6S)-6-acetoxyhexadecanolide 1a, a functionalized δ-lactone, as a major constituent that forms on the
mosquito Culex pipens fatigans eggs.10 This mosquito is a possible vector of malaria, West Nile virus and filarial
infections.11 The (-)-(5R,6S)-6-acetoxyhexadecan-5-olide 1a attracts other gravid females of the identical and
few allied mosquitos tempting them to oviposit in the same place where the original eggs are found. Owing to
the potential of (-)-(5R,6S)-6-acetoxy-5-hexadecanolide 1a in controlling mosquito populations, several
enantioselective synthetic approaches for 1a and its unnatural isomer (+)-6-acetoxy-5-hexadecanolide 1b
(Figure 1) have been disclosed in the literature.12-29 As part of our research program aimed at developing the
asymmetric synthesis of bioactive natural compounds,30-37 we turned our attention to developing a flexible
and simple approach for the asymmetric synthesis of functionalized δ-lactones and its application to
asymmetric synthesis of (-)-(5R,6S)-6-acetoxyhexadecan-5-olide 1a. Herein, we report a new enantioselective
synthesis of (-)-(5R,6S)-6-acetoxyhexadecanolide 1a employing tandem α-aminooxylation-Henry reaction as
the source of chirality.
Figure 1. Structures of stereoisomers of 6-acetoxy-hexadecanolide.
Results and Discussion
Our retrosynthetic route to the synthesis of (-)-(5R,6S)-6-acetoxyhexadecanolide is displayed in Scheme 1. The
epoxy alcohol 2 was envisioned as a key intermediate from which δ-lactone 1 and 6-acetoxy-5-hexadecanolide
1a-1b could be synthesized via a Yamaguchi-Hirao alkylation reaction followed by standard organic
transformations. The key fragment 2 could in turn be prepared from the diol 3 in simple steps including
oxidation, reduction and epoxide formation. Subsequently, compound 3 could be envisaged from
commercially available n-dodecanal 4 via a tandem α-aminooxylation-Henry reaction.
Scheme 1. Retrosynthetic strategy for 6-acetoxy-hexadecanolide 1.
Page 2
©ARKAT USA, Inc

Arkivoc 2018, vii, 0-0
Pandey, R. et al.
As illustrated in Scheme 2, the synthetic endeavor towards (-)-(5R,6S)-6-acetoxyhexadecanolide 1a
commenced with commercially available n-dodecanal 4. Compound 4, on tandem α-aminooxylation-Henry
reaction38 in the presence of catalytic amount of D-proline and without ligand, furnished the syn-β,γ-
dihydroxynitrotridecane 3a along with its anti-diastereomer 3b in 1:1 ratio with 62% overall yield and
excellent enantioselectivities (>99% ees for both syn- and anti-diastereomers).39 Both (2S,3S)-syn 3a and
(2R,3S)-anti 3b diastereomers were carefully separated by silica gel column chromatography.
Scheme 2. Reagents and conditions: (a) i) PhNO, D-proline (30 mol%), DMSO, rt, 30 min, ii) CH3NO2, aq. NaOH,
MeOH, Cu(OAc)2·H2O, rt, 12 h, 62%.
Scheme 3. Reagents and conditions: (a) i) NaNO2, AcOH, DMSO, 35 oC, 24 h, ii) LiAlH4, THF, 0 oC to rt, 3 h, 62%
o
(over two steps); (b) i) TsCl, Bu2SnO, Et3N, CH2Cl2, 0 C to rt, 1 h; ii) K2CO3, MeOH, rt, 30 min, 76% (over two
o
o
steps); (c) NaH, BnBr, DMF, 0 C, 4 h, 92%; (d) n-BuLi, BF3·OEt2, HCCCO2Et, dry THF, -78 C, 2 h, 81%; (e) i) H2,
Pd/C (10%), MeOH, rt, 12 h; ii) p-TSA, benzene, reflux, 1 h, 91% (over two steps); (f) Ac2O, DMAP, DCM, 30
min, 95%.
Having anti-diastereomer (2R,3S)-anti 3b in hand, we then performed an oxidation using NaNO2/acetic acid in
DMSO to provide the acid40-41 which on immediate reduction with LiAlH4 afforded the triol derivative 5 in 62%
yield (Scheme 3). Our next goal was to achieve the synthesis of the terminal epoxide moiety. Towards this end,
triol 5 on regioselective monotosylation using TsCl/NEt3 in the presence of a catalytic amount of dibutyltin
oxide42-43 followed by base treatment, successfully furnished the terminal epoxide 6 in 76% yield, [α]D25 +16.4
(c 1.0, CHCl3); {lit.27 [α]D20 +16.2 [c 1.01, CHCl3]}. The free hydroxyl group of intermediate 6 was then alkylated
with benzyl bromide in the presence of sodium hydride as base to produce the benzyl ether derivative 7 in
92% yield. Next, regioselective ring opening of epoxide 7 with lithium salt of ethyl propiolate under the
Yamaguchi-Hirao conditions44 afforded homopropargylic alcohol derivative 8 in 81% yield. Subsequently, the
Page 3
©ARKAT USA, Inc

Arkivoc 2018, vii, 0-0
Pandey, R. et al.
lactone 9 was obtained from compound 8 via a two-step procedure involving catalytic (Pd/C, 10%)
hydrogenation and p-TSA catalyzed lactonization in 91% yield. Finally, treatment of alcohol 9 with acetic
anhydride and catalytic DMAP in dichloromethane at room temperature furnished (-)-(5R,6S)-6-
25
32
acetoxyhexadecanolide 1a in 95% yield; [α]D -36.89 (c 1.0, CHCl3); {lit.26 [α]D -36.8 (c 1.0, CHCl3)}. The
physical and spectroscopic data of (-)-(5R,6S)-6-acetoxyhexa-decanolide 1a were in full agreement with
literature data.
Conclusions
In summary, we have demonstrated a general and flexible synthetic approach for functionalized δ-lactones
and its application to the asymmetric synthesis of (-)-(5R,6S)-6-acetoxyhexadecan-5-olide employing
asymmetric tandem α-aminooxylation-Henry reaction on the commercially available n-dodecanal. Further
extension of the tandem α-aminooxylation-Henry reaction strategy to biologically active molecules of more
structural complexity and diversity is in progress.
Experimental Section
General. All reactions were carried out under argon or nitrogen in oven-dried glassware using standard glass
syringes and septa. The solvents and chemicals were purchased from Merck and Sigma Aldrich chemical
company. Solvents and reagents were purified and dried by standard methods prior to use. Progress of the
reactions was monitored by TLC using precoated aluminium plates of Merck kieselgel 60 F254. Column
chromatography was performed on silica gel (60-120 and 100-200 mesh) using a mixture of n-hexane and
1
13
EtOAc. Optical rotations were measured on an automatic polarimeter, AA-65. H and C NMR spectra were
recorded in CDCl3 (unless otherwise mentioned) on JEOL ECS operating at 400 and 100 MHz, respectively.
Chemical shifts are reported in δ (ppm), referenced to TMS. HRMS were recorded on Agilent 6530 Accurate-
Mass Q-TOF using electrospray ionization. IR spectra were recorded on an Agilent resolution Pro 600 FT-IR
spectrometer, fitted with a beam-condensing ATR accessory.
syn-(2S,3S)-/anti-(2R,3S)-1-Nitrotridecane-2,3-diol (3a)/(3b). To a DMSO (15 mL) solution of aldehyde 4 (2.0
g, 10.80 mmol) was added nitrosobenzene (1.16 g, 10.8 mmol), followed by D-proline (375 mg, 3.26 mmol, 30
mol%) and the reaction mixture stirred for about 20-30 min at rt. The completion of the reaction was
monitored by its color change from green to orange or by TLC until all the nitrosobenzene was consumed and
used as such for the next step without further purification. To the above crude solution was added MeOH (15
mL), nitromethane (6.58 g, 5.8 mL, 108 mmol), aq. NaOH (650 mg, 16.2 mmol, 8M), and above synthesized α-
aminooxylated aldehyde were added. The reaction mixture was stirred for 30 min, then Cu(OAc)2·H2O (3.24 g,
16.2 mmol) was added and the mixture further stirred for additional 12 h at rt. After completion of the
reaction (monitored by TLC), the reaction mixture was evaporated, diluted with H2O, extracted with EtOAc (3 x
50 mL), dried over Na2SO4, and concentrated. The syn/anti diastereomers were separated and purified by
silica gel column chromatography (EtOAc/hexane, 1:9 v/v) as eluent, which furnished the syn-diastereomer 3a
25
1
(874 mg, 31%) as a white solid. [α]D +55.2 (c 0.20, CH2Cl2); H NMR (400 MHz, CDCl3) δ: 4.63-4.49 (m, 2H),
13
4.27-4.18 (m, 1H), 3.75-3.72 (m, 1H), 2.41 (br s, 2H), 1.56-1.20 (m, 18H), 0.86 (t, J 8.6 Hz, 3H); C NMR (100
Page 4
©ARKAT USA, Inc

Arkivoc 2018, vii, 0-0
Pandey, R. et al.
MHz, CDCl3) δ: 77.5, 73.1, 72.0, 33.0, 32.2, 29.9, 29.8, 29.7, 29.6, 25.9, 22.9, 14.4. HRMS (ESI) m/z calcd for
C13H27NO4 ([M-H]+) 260.1867; found 260.1872.
After separating the syn-diastereomer, the quickly eluting anti-diastereomer 3b was then isolated
25
1
(EtOAc/hexane, 1:5 v/v) as a white solid (874 mg, 31%). [α]D +72.5 (c 1.0, CH2Cl2); H NMR (400 MHz, CDCl3)
13
δ: 4.62-4.48 (m, 2H), 4.25-4.21 (m, 1H), 3.59-3.51 (m, 1H), 1.61-1.20 (m, 18H), 0.86 (t, J 8.6 Hz, 3H); C NMR
(100 MHz, CDCl3) δ: 78.3, 71.4, 70.4, 33.2, 31.5, 29.3, 29.2, 29.1, 29.1, 29.0, 25.1, 22.3, 13.8.
(2R,3S)-Tridecane-1,2,3-triol (5). To a stirred solution of anti-diastereomer 3b (500 mg, 1.91 mmol) in DMSO
(5 mL) at 35 °C were added NaNO2 (396 mg, 5.75 mmol) and AcOH (1.1 mL, 19.0 mmol). After stirring for 24 h
at the same temperature, the reaction mixture was quenched with H2O and acidified with 10% aq solution HCl
(25 mL). The aqueous layer was extracted with Et2O (3 x 30 mL), dried over anhydrous Na2SO4, concentrated in
vacuo, and used as such for the next step without further purification. LiAlH4 (145 mg, 3.82 mmol) was added
to a solution of above crude material in THF (5 mL) at 0 oC under N2 atmosphere. After 5 min, the reaction was
allowed to reach rt and stirred for a further 3 h. Then the reaction mixture was quenched with 10% aq NaOH.
The aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic phases were dried with
Na2SO4 and the solvent was removed under reduced pressure. The residue was subjected to silica gel column
25
chromatography (EtOAc/hexanes, 4:1 v/v) to give triol 5 (274 mg, 62%) as a white solid. [Rf = 0.4, EtOAc]; [α]D
+40.4 (c 0.8, CHCl3); IR (CH2Cl2) ν: 3415, 2945, 2910, 2863, 1701, 1651 cm-1; 1H NMR (400 MHz, CDCl3) δ: 3.90-
3.48 (m, 3H), 2.64 (br, 1H), 2.74 (br, 1H), 2.26 (br, 2H) 1.70-1.10 (m, 18H), 0.93 (t, J 6.88 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ: 73.0, 67.5, 62.8, 33.8, 31.9, 29.6, 29.5, 29.3, 25.3, 22.6, 14.1; HRMS (ESI)+ m/z calcd for
C13H28O3Na+ [M+Na+] 255.1930; found 255.1929.
(S)-1-((R)-Oxiran-2-yl)undecan-1-ol (6). To a stirred solution of 5 (200 mg, 0.86 mmol) in CH2Cl2 (6 mL) under
N2 atmosphere at 0 oC were added Et3N (0.15 ml, 1.03 mmol), catalytic amount of Bu2SnO (21 mg, 0.09 mmol)
and TsCl (181 mg, 0.94 mmol). The resulting mixture was stirred at rt for 1 h. Then the reaction mixture was
quenched with H2O, extracted with CH2Cl2 and the extract dried over Na2SO4. The combined organic layers
were concentrated under reduced pressure to afford crude tosylate which was used for next step.
K2CO3 (237 mg, 1.72 mmol) was added to a solution of above crude product in MeOH (5 mL) at rt and stirred
for 30 min. The resulting mixture was diluted with H2O (10 mL) and EtOAc (20 mL). The organic layer was
separated, and aqueous layer was extracted with EtOAc (3 x 15 mL). The combined organic layers were dried
over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column
chromatography (EtOAc/hexane, 1:4) to give epoxide 6 (140 mg, 76%) as a colourless liquid. [Rf = 0.3,
EtOAc/hexane 1:4 v/v]; [α]D25 +16.4 (c 1.0, CHCl3); {lit.27 [α]D20 +16.2 [c 1.01, CHCl3]}; IR (CH2Cl2) ν: 3453, 2935,
1
2856, 1256, 1426 cm-1; H NMR (400 MHz, CDCl3) δ: 3.71-3.68 (m, 1H), 3.01-2.99 (m, 1H), 2.84-2.83 (m, 1H),
13
2.79-2.77 (m, 1H), 1.69-1.66 (m, 2H), 1.50-1.21 (m, 16H), 0.93 (t, J 7.6 Hz, 3H). C NMR (100 MHz, CDCl3) δ:
68.4, 54.5, 43.4, 33.4, 31.9, 29.7, 29.6, 29.5, 29.3, 25.3, 22.7, 14.1; HRMS (ESI)+ m/z calcd for C13H27O2+[M+H+]
215.2011; found 215.2012.
(-)-(5R,6S)-6-Acetoxyhexadecan-5-olide (1a). To a stirred solution of the alcohol 9 (20 mg, 0.07 mmol) in
anhydrous CH2Cl2 (3.0 mL) under N2 atmosphere at rt were added DMAP (51 mg, 0.42 mmol) and Ac2O (43 mg,
0.42 mmol). The resulting mixture was stirred for 30 min. at rt. Next, the reaction mixture was quenched by
addition of cold H2O and extracted with EtOAc (3 x 5 mL). The combined organic layers were dried over
anhydrous Na2SO4 and solvent was removed in vacuo. Silica gel column chromatography of the resultant
residue furnished the target compound 1 (20 mg, 95%) as a colorless oil. [Rf = 0.4, EtOAc/hexane, 1:4 v/v];
[α]D25 -36.89 (c 1.0, CHCl3); {lit.26 [α]D32 -36.80 (c 1.0, CHCl3)}; IR (CH2Cl2) ν: 2935, 2844, 1740, 1361, 1236 cm-1;
1H NMR (400 MHz, CDCl3) δ: 4.99-4.95 (m, 1H), 4.38-4.31 (m, 1H), 2.65-2.57 (m, 1H), 2.50-2.41 (m, 1H), 2.08 (s,
13
3H), 2.00-1.79 (m, 2H), 1.72-1.56 (m, 4H), 1.38-1.20 (m, 16H), 0.88 (t, J 6.4 Hz, 3H); C NMR (100 MHz, CDCl3)
Page 5
©ARKAT USA, Inc

Arkivoc 2018, vii, 0-0
Pandey, R. et al.
δ: 170.9, 170.5, 80.5, 74.3, 31.9, 29.8, 29.7, 29.6, 29.5, 25.2, 23.5, 22.7, 21.0, 18.2, 14.1; HRMS (ESI)+ m/z calcd
for C18H33O4+[M+H] 313.2379; found 313.2395.
Acknowledgements
The authors (R.P. and S.K.P.) acknowledge the research grant No. 02(0309)/17/EMR-II facilitated by the
Council for Scientific and Industrial Research (CSIR), New Delhi, India for the carrying out the study. R. Pandey
thanks Thapar Institute of Engineering and Technology for the research associateship and Y.G. thanks UGC,
New Delhi for research fellowship.
Supplementary Material
Electronic supplementary information (ESI) available; copies of 1H and 13C NMR spectra of compounds 1a, Rac-
3, 3a, 3b and 5-9; HPLC of Rac-3, 3a, 3b, and HRMS of final compound 1a. This material can be found via the
“Supplementary Content” section of this article’s webpage.
References
1. Choi, J. H.; Horikawa, M.; Okumura, H.; Kodani, S.; Nagai, K.; Hashizume, D.; Koshino, H.; Kawagishi, H.
Tetrahedron 2009, 65, 221.
https://doi.org/10.1016/j.tet.2008.10.068
2. Reddy, P. P.; Yen, K. F.; Uang, B. J. J. Org. Chem. 2002, 67, 1034.
https://doi.org/10.1021/jo016216g
3. Alali, F. Q.; Rogers, L.; Zhang, Y.; McLaughlin, J. L. Tetrahedron 1998, 54, 5833.
https://doi.org/10.1016/S0040-4020(98)00286-5
4. Koch, S. S. C.; Chamberlin, A. R. In Enantiomerically Pure c-Butyrolactones in Natural Products Synthesis;
Atta-ur-Rahman, Ed.; Elsevier Science: Amsterdam, 1995; pp 687.
5. Warmerdam, E.; Tranoy, I.; Renoux, B.; Gesson, J. P. Tetrahedron Lett. 1998, 39, 8077.
https://doi.org/10.1016/S0040-4039(98)01786-9
6. Hanessian, S.; Grillo, T. A. J. Org. Chem. 1998, 63, 1049.
https://doi.org/10.1021/jo9713621
7. Buisson, D.; Azerad, R. Tetrahedron: Asymmetry 1996, 7, 9.
https://doi.org/10.1016/0957-4166(95)00408-4
8. Friesen, R. W.; Vanderwal, C. J. Org. Chem. 1996, 61, 9103.
https://doi.org/10.1021/jo961653u
9. Ye, Q.; Zeng, Lu.; Zhang, Y.; Zhao, G. X.; McLaughlin, J. L. J. Nat. Prod. 1995, 58, 1398.
https://doi.org/10.1021/np50123a010
10. Laurence, B. R.; Pickett, J. A. J. Chem. Soc., Chem. Commun. 1982, 59.
https://doi.org/10.1039/c39820000059
Page 6
©ARKAT USA, Inc

Arkivoc 2018, vii, 0-0
Pandey, R. et al.
11. Anderson, J. F.; Andeadis, T. G.; Vossbrinck, C. R.; Tirrell, S.; Waken, E. M.; French, R. A.; Garmendia, A. E.;
Van Kruiningen, H. J. Science 1999, 286, 2331.
https://doi.org/10.1126/science.286.5448.2331
12. Dong, H-B.; Yang, M-Y.; Zhang, X-T.; Wang, M-A. Tetrahedron: Asymmetry 2014, 25, 610.
https://doi.org/10.1016/j.tetasy.2014.03.006
13. Das, S.; Mishra, A. K.; Kumar, A.; Ghamdi, A. A. K. A.; Yadav, J. S. Carbohydrate Research 2012, 358, 7.
https://doi.org/10.1016/j.carres.2012.05.009
14. Park, Y.; Tae, J. Synthesis 2010, 21, 3627.
15. Singh, S.; Guiry, P. J. Eur. J. Org. Chem. 2009, 1896.
16. Quinn, K. J.; Curto, J. M.; McGrath, K. P.; Biddick, N. A. Tetrahedron Lett. 2009, 50, 7121.
https://doi.org/10.1016/j.tetlet.2009.09.179
17. Prasad, K. R.; Anbarasan, P. Tetrahedron: Asymmetry 2007, 18, 2479.
https://doi.org/10.1016/j.tetasy.2007.10.006
18. Ikishima, H.; Sekiguchi, Y.; Ichikawa, Y.; Kotsuki, H. Tetrahedron 2006, 62, 311.
https://doi.org/10.1016/j.tet.2005.08.111
19. Dhotare, B.; Goswami, D.; Chattopadhyay, A. Tetrahedron Lett. 2005, 46, 6219.
https://doi.org/10.1016/j.tetlet.2005.07.063
20. Sun, B.; Peng, L.; Chen, X.; Li, Y. Tetrahedron: Asymmetry 2005, 16, 1305.
https://doi.org/10.1016/j.tetasy.2005.02.017
21. Gao, X.; Hall, D. G. J. Am. Chem. Soc. 2003, 125, 9308.
https://doi.org/10.1021/ja036368o
22. Gallos, J. K.; Mihelakis, D. S.; Dellios, C. C.; Pozarentzi, M. E. Heterocycles 2000, 53, 703.
https://doi.org/10.3987/COM-99-8793
23. Couladouros, E. A.; Mihou, A. P. Tetrahedron Lett. 1999, 40, 4861.
https://doi.org/10.1016/S0040-4039(99)00895-3
24. Lohray, B. B.; Venkateswarlu, S. Tetrahedron: Asymmetry 1997, 8, 633.
https://doi.org/10.1016/S0957-4166(97)00011-6
25. Gravier-Pelletier, C.; Le Merrer, Y.; Depezay, J.-C. Tetrahedron 1995, 51, 1663.
https://doi.org/10.1016/0040-4020(94)01033-V
26. Kotsuki, H.; Kadota, I.; Ochi, M. J. Org. Chem. 1990, 55, 4417.
https://doi.org/10.1021/jo00301a038
27. Mori, K.; Otsuka, T. Tetrahedron 1983, 39, 3267.
https://doi.org/10.1016/S0040-4020(01)91574-1
28. Hurema, D.; Dudding, T. RSC Adv., 2015, 5, 101732.
https://doi.org/10.1039/C5RA19306K
29. Schmidt, B.; Petersen, M. H.; Braun, D. J. Org. Chem. 2018, 83, 1627.
https://doi.org/10.1021/acs.joc.7b02944
30. Kaur, A.; Prakash, R.; Pandey, S. K. ChemistrySelect 2018, 3, 105.
https://doi.org/10.1002/slct.201702732
31. Garg, Y.; Tiwari, A. K.; Pandey, S. K. Tetrahedron Lett. 2017, 58, 3344.
https://doi.org/10.1016/j.tetlet.2017.07.024
32. Garg, Y.; Sharma, P.; Pandey, S. K. Tetrahedron Lett. 2017, 57, 3493.
https://doi.org/10.1016/j.tetlet.2017.07.069
Page 7
©ARKAT USA, Inc

Arkivoc 2018, vii, 0-0
Pandey, R. et al.
33. Gahalawat, S.; Pandey, S. K. Org. Biomol. Chem. 2016, 14, 9287.
https://doi.org/10.1039/C6OB01775D
34. Garg, Y.; Pandey, S. K. RSC Adv. 2016, 6, 25913.
https://doi.org/10.1039/C6RA03915D
35. Gahalawat, S.; Garg, Y.; Pandey, S. K. Asian J. Org. Chem. 2015, 4, 1025.
https://doi.org/10.1002/ajoc.201500301
36. Garg, Y.; Gahalawat , S.; Pandey, S. K. RSC Adv. 2015, 5, 38846.
https://doi.org/10.1039/C5RA05987A
37. Garg, Y.; Pandey, S. K. J. Org. Chem. 2015, 80, 4201.
https://doi.org/10.1021/acs.joc.5b00480
38. Garg, Y.; Kaur, R.; Pandey, S. K. Eur. J. Org. Chem. 2017, 45, 6700.
https://doi.org/10.1002/ejoc.201701289
39. HPLC data of (2S,3S)-syn 3a: >99% ee, The enantiomeric purity (ee) was determined by HPLC analysis
using a Chirapak IA (4.6 x 250 mm) using mobile phase of (5:95 i-propanol:n-hexane, flow rate of 1
mL/min at 25 oC, UV detection at 210 nm): (R,R)-enantiomer: tr = 25.847 min, (S,S)-enantiomer: tr = 33.045
min. (2R,3S)-anti 3b: >99% ee, The enantiomeric purity (ee) was determined by HPLC analysis using a
Chirapak IA (4.6 × 250 mm) using mobile phase of i-propanol:n-hexane (5:95), flow rate of 1 mL/min at 25
oC, UV detection at 210 nm): (S,R)-enantiomer: tr = 20.995 min, (R,S)-enantiomer: tr = 23.045 min.
40. Lin, H.; Sun, X. W.; Lin, G. Q. Org. Lett. 2014, 16, 752.
https://doi.org/10.1021/ol403463h
41. Zhu, D.; Lu, M.; Chua, P. J.; Tan, B.; Wang, F.; Yang, X.; Zhong, G. Org. Lett. 2008, 10, 4585.
https://doi.org/10.1021/ol801864c
42. Yadav, J. S.; Sengupta, S. ; Yadav, N. N.; Chary, D. N.; Ghamdi, A. A. A. Tetrahedron Lett., 2012, 53, 5952.
https://doi.org/10.1016/j.tetlet.2012.08.112
43. Sabitha, G.; Reddy, K. P.; Reddy, S. P.; Yadav, J. S. Tetrahedron Lett., 2014, 55, 3227.
https://doi.org/10.1016/j.tetlet.2014.04.026
44. Yamaguchi, M.; Hirao, I. Tetrahedron Lett. 1983, 24, 391.
https://doi.org/10.1016/S0040-4039(00)81416-1
Page 8
©ARKAT USA, Inc