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DOI: 10.1055/s-0030-1258248
Facile Synthesis of (-)-6-Acetoxy-5-hexadecanolide by Organocatalytic α-Oxygenation-Allylation-RCM Strategy
Publication History
Publication Date:
07 September 2010 (online)
Abstract
An asymmetric total synthesis of (-)-6-acetoxy-5-hexadecanolide has been accomplished by employing a seven-step sequence. Asymmetric α-benzoyloxylation of dodecanal followed by indium-mediated one-pot allylation produces the anti-1,2-diol. The six-membered lactone ring is constructed by RCM reaction.
Key words
allylation - α-benzoyloxylation - metathesis - organocatalysts - total synthesis
In the past few years organocatalysis, complementing bio- and metal-catalysis, has attracted much attention and it has been employed in numerous asymmetric synthesis. [¹] Considerable effort has also been devoted to the development of tandem reactions following the asymmetric organocatalytic reactions in a one-pot operation, thereby avoiding the isolation of reaction intermediates, for the synthesis of diverse chiral building blocks from simple precursors. For example, α-amino aldehydes have been further utilized in subsequent tandem reactions such as aldol, [²] Passerini, [³] Horner-Wadsworth-Emmons reactions, [4] and diazomethane homologation. [5] The allylation of the aldehyde intermediates has also been utilized to introduce 1,2-functionalized building blocks. [6]
Recently, the Maruoka [7a] and Hayashi [7b] groups have independently reported the organocatalytic α-benzoyloxylation of aldehydes with benzoyl peroxide catalyzed by pyrrolidine-type catalysts. Tandem allylation of the α-(benzoyloxy)aldehydes could readily generate monoprotected 1,2-diols which could serve as key intermediates in asymmetric synthesis. In continuation of our interest in exploring tandem reactions of organocatalytic reactions, [6b] we have developed a facile enantioselective synthesis of (-)-(5R,6S)-6-acetoxy-5-hexadecanolide (1), the mosquito oviposition attractant pheromone, which has been a synthetic target for several decades due to its physiological activity. [8]
Organocatalytic α-benzoyloxylation of dodecanal (4) with benzoyl peroxide catalyzed by chiral pyrrolidine followed by indium-mediated in situ allylation of the resulting α-(benzoyloxy)aldehyde 3 could afford the monoprotected 1,2-diol 2 as shown retrosynthetically in Scheme [¹] . Conversion of the homoallyl alcohol 2 into the corresponding acryl ester followed by ring-closing metathesis (RCM) and hydrogenation would generate the benzoyloxy derivative of 1. The overall synthetic route is expected to be highly efficient if the initial tandem reaction is successful.
Scheme 1 Retrosynthetic analysis for (-)-6-acetoxy-5-hexadecanolide (1)
Figure 1 A proposed transition state for the allylation reaction
First, we screened the reaction conditions for the one-pot α-benzoyloxylation-allylation sequence. After treating dodecanal (4) with 5-10 mol% of (S)-5 [9] and benzoyl peroxide (BzOOBz, 2 equiv) in the presence of hydroquinone (10 mol%) according to Maruoka’s procedure, [7a] the reaction mixture was diluted with tetrahydrofuran-water (5:1) and then reacted with indium powder (2 equiv) and allyl bromide (2 equiv) at room temperature for 12 hours (see Table [¹] ). The initial organocatalytic transformation step is highly enantioselective in tetrahydrofuran solution (Table [¹] , entry 6). The diastereoselectivities of the allylation reactions are uniformly good under different conditions and the 1,2-anti-isomer (anti/syn ˜86: 14) is formed predominantly. The anti preferences of indium-promoted allylations to α-oxy aldehydes in tetrahydrofuran-water solutions have been reported in the literature. [6a] [¹0] In tetrahydrofuran-water solution, the indium-chelation mode is less favorable, therefore, the Felkin-Anh transition state (with L = OBz) can explain the observed Cram product as shown in Figure [¹] .
Scheme 2 Total synthesis of (-)-6-acetoxy-5-hexadecanolide (1)
With the monoprotected 1,2-diol 2 in hand, we next synthesized the lactone ring by RCM reaction [¹¹] (Scheme [²] ). Reaction of the homoallyl alcohol 2 with acryloyl chloride gave the diene 6, which was treated with 10 mol% Grubbs II catalyst (7) under dilution conditions (0.02 M in CH2Cl2) to produce 8 in 77%. [¹²] Catalytic hydrogenation of the unsaturated lactone 8 furnished the benzoyloxy derivative 9 in good yields. For the final conversion of 6-OBz group into 6-OAc, both the benzoyloxy and the lactone ring are hydrolyzed to give compound 10 which is then selectively cyclized to the six-membered lactone ring in the presence of excess acetic anhydride in pyridine solution. [¹³] The synthetic (-)-(5R,6S)-6-acetoxy-5-hexadecanolide (1) displayed spectral data and optical rotation {[α]D ²5 -35.1 (c 0.49, CHCl3)} consistent with those reported in the literature. [8]
In summary, we have completed a facile asymmetric total synthesis of (-)-(5R,6S)-6-acetoxy-5-hexadecanolide starting from dodecanal in seven steps. Tandem asymmetric α-benzoyloxylation and indium-mediated allylation sequence is utilized to prepare the monoprotected 1,2-diol intermediate for the first time. Construction of the six-membered lactone ring is performed by RCM reaction.
THF and Et2O were distilled from sodium benzophenone ketyl under nitrogen prior to use. CH2Cl2 and Et3N were dried over calcium hydride. Indium powder (˜100 mesh) was purchased from Aldrich. All reactions were performed under N2 atmosphere. All chromatographic purifications were performed on silica gel (230-400 mesh) using the indicated solvent systems. IR spectra were recorded as a thin film. NMR spectra were recorded with reference to TMS as an internal standard.
(4 R ,5 S )-4-Hydroxypentadec-1-en-5-yl Benzoate (2)
To a mixture of hydroquinone (30 mg, 0.27 mmol) and (-)-(S)-α,α-diphenylpyrrolidine-2-methanol trimethylsilyl ether [(S)-5, 44 mg, 0.14 mmol, 5 mol%] in THF (1 mL) was added dodecanal (4, 500 mg, 2.71 mmol) and BzOOBz (75%, remainder H2O; 963 mg, 2.98 mmol) in THF (13 mL) at 0 ˚C. The mixture was stirred at 0 ˚C for 6 h and treated with H2O (2.7 mL), indium powder (622 mg, 5.42 mmol), and allyl bromide (0.47 mL, 5.4 mmol). The mixture was stirred at r.t. for 12 h, quenched with sat. NaHCO3 (10 mL), and extracted with EtOAc (3 × 10 mL). The combined organic layers were dried (anhyd MgSO4), and the residue was chromatographed (silica gel, hexanes-EtOAc, 25:1) to give 2 (409 mg, 44%) as a colorless oil; R f = 0.4 (hexanes-EtOAc, 5:1). HPLC analysis: (Daicel Chiralcel IC, 272 nm, hexane-i-PrOH 99:1, flow rate 0.5 mL/min): t R = 21.5 (4R,5S), 24.2 min (4S,5R).
[α]D ²5 -7.2 (c 0.89, CHCl3).
IR (film) 3480, 3073, 2924, 2854, 1718, 1644, 1602, 1452, 1315, 1273, 1176, 1113, 1069, 1026 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 8.07-8.05 (m, 2 H), 7.60-7.44 (m, 3 H), 5.92-5.81 (m, 1 H), 5.19-5.12 (m, 3 H), 3.90-3.86 (m, 1 H), 2.42-2.22 (m, 2 H), 1.86-1.68 (m, 2 H), 1.35-1.23 (m, 16 H), 0.87 (t, J = 6.8 Hz, 3 H).
¹³C NMR (100.6 MHz, CDCl3): δ = 166.7, 134.5, 134.3, 133.2, 130.3, 129.8, 128.5, 118.5, 77.7, 72.3, 37.3, 32.0, 29.8, 29.7, 29.6, 29.4, 25.6, 22.8, 14.2.
HRMS: m/z [M + H]+ calcd for C22H35O3: 347.2508; found: 347.2579.
(4 R ,5 S )-4-(Acryloyloxy)pentadec-1-en-5-yl Benzoate (6)
To a stirred soln of 2 (379 mg, 1.04 mmol) and DMAP (27 mg, 0.22 mmol) in CH2Cl2 (3 mL) was added Et3N (221 mg, 2.18 mmol) and acryloyl chloride (198 mg, 2.18 mmol) at 0 ˚C. The mixture was stirred at 0 ˚C for 5 h, quenched with sat. NH4Cl (10 mL), and extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried (anhyd MgSO4), and the residue was chromatographed (silica gel, hexanes-EtOAc, 99:1) to give 6 (319 mg, 73%) as a colorless oil; R f = 0.7 (hexanes-EtOAc, 5:1).
[α]D ²7 -3.1 (c 0.65, CHCl3).
IR (film) 2924, 2854, 1725, 1639, 1602, 1452, 1405, 1273, 1190, 1108, 1069 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 8.04-8.03 (m, 2 H), 7.57-7.42 (m, 3 H), 6.40-6.35 (m, 1 H), 6.14-6.07 (m, 1 H), 5.84-5.73 (m, 2 H), 5.36-5.32 (m, 1 H), 5.28-5.24 (m, 1 H), 5.13-5.05 (m, 2 H), 2.51-2.47 (m, 2 H), 1.79-1.67 (m, 2 H), 1.42-1.23 (m, 16 H), 0.86 (t, J = 6.8 Hz, 3 H).
¹³C NMR (100.6 MHz, CDCl3): δ = 166.0, 165.5, 133.3, 133.1, 131.1, 130.3, 129.8, 128.5, 118.1, 74.5, 73.7, 34.5, 32.0, 30.1, 29.7, 29.6, 29.5, 29.4, 25.5, 22.8, 14.2.
HRMS: m/z [M + H]+ calcd for C25H37O4: 401.2614; found: 401.2695.
( S )-1-[( R )-6-Oxo-3,6-dihydro-2 H -pyran-2-yl]undecyl Benzoate (8)
A mixture of 6 (319 mg, 0.796 mmol) and Grubbs II catalyst (7; 68 mg, 0.080 mmol, 10 mol%) in CH2Cl2 (400 mL, 0.02 M) was refluxed for 8 h. The mixture was evaporated and the residue was chromatographed (silica gel, hexanes-EtOAc, 12:1) to give 8 (228 mg, 77%) as a colorless oil (The minor syn diastereomer was separated in 15% (45 mg) as a colorless oil); R f = 0.1 (hexanes-CH2Cl2, 1:1).
[α]D ²5 +19.4 (c 0.92, CHCl3).
IR (film) 2920, 2854, 1727, 1637, 1601, 1585, 1452, 1381, 1314, 1270, 1110, 1069 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 8.05-8.03 (m, 2 H), 7.59-7.42 (m, 3 H), 6.91-6.87 (m, 1 H), 6.04-6.01 (m, 1 H), 5.34 (q, J = 5.6 Hz, 1 H), 4.61-4.56 (m, 1 H), 2.58-2.40 (m, 2 H), 1.85-1.81 (m, 2 H), 1.45-1.22 (m, 16 H), 0.87 (t, J = 6.8 Hz, 3 H).
¹³C NMR (100.6 MHz, CDCl3): δ = 165.9, 163.5, 144.8, 133.4, 129.8, 128.6, 122.5, 78.2, 74.2, 32.0, 30.1, 29.6, 29.5, 29.4, 25.6, 25.3, 22.7, 14.2.
HRMS: m/z [M + H]+ calcd for C23H33O4: 373.2301; found: 373.2372.
( S )-1-[( R )-6-Oxotetrahydro-2 H -pyran-2-yl]undecyl Benzoate (9)
To a soln of 8 (84 mg, 0.22 mmol) in Et2O (1 mL) was added 10% Pd/C (10 mg, 0.09 mmol). The mixture was stirred for 5 h under a H2 atmosphere (1.01 bar) at r.t. The mixture was filtered through a short pad of Celite and the residue was chromatographed (silica gel, hexanes-EtOAc, 6:1) to give 9 (74 mg, 90%) as a colorless oil: R f = 0.5 (hexanes-EtOAc, 2:1).
[α]D ²5 -11.5 (c 0.85, CHCl3).
IR (film) 2921, 2855, 1714, 1601, 1585, 1491, 1452, 1315, 1272, 1176, 1109, 1069, 1026 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 8.07-8.04 (m, 2 H), 7.60-7.43 (m, 3 H), 5.26-5.22 (m, 1 H), 4.52-4.46 (m, 1 H), 2.65-2.42 (m, 2 H), 2.03-1.68 (m, 6 H), 1.43-1.28 (m, 16 H), 0.87 (t, J = 6.8 Hz, 3 H).
¹³C NMR (100.6 MHz, CDCl3): δ = 171.0, 166.1, 133.3, 130.0, 129.9, 129.8, 128.6, 80.8, 75.0, 32.0, 29.79, 29.76, 29.65, 29.64, 29.5, 29.4, 25.4, 24.0, 22.8, 18.4, 14.2.
HRMS: m/z [M + H]+ calcd for C23H35O4: 345.2457; found: 375.2431.
(-)-(5 R ,6 S )-Acetoxy-5-hexadecanolide (1)
A soln of 7 (34 mg, 0.090 mmol) in EtOH (0.69 mL) and H2O (0.15 mL) with 1 M aq NaOH (0.45 mL) was stirred at r.t. for 5 h. The mixture was quenched with 2 M HCl (0.45 mL) and stirred for 1 h at r.t. The white solids were collected by filtration to give 10 (19 mg, 0.067 mmol, 75%). A soln of dried 10 (19 mg, 0.067 mmol) in pyridine (1.12 mL) and Ac2O (0.23 mL, 2.4 mmol) was stirred at 0 ˚C for 5 h. The mixture was quenched with sat. NH4Cl (10 mL) and extracted with EtOAc (3 × 10 mL) The combined organic layers were washed with sat. CuSO4, NaHCO3, H2O, and brine, and dried (anhyd MgSO4). The residue was chromatographed (silica gel, hexanes-EtOAc, 4:1) to give 1 (15 mg, 71%) as a colorless oil; R f = 0.4 (hexanes-EtOAc, 2:1).
[α]D ²5 -35.1 (c 0.49, CHCl3).
IR (film) 2928, 2854, 1730, 1464, 1373, 1240, 1052 cm-¹.
¹H NMR (400 MHz, CDCl3): δ = 4.99-4.95 (m, 1 H), 4.36-4.31 (m, 1 H), 2.63-2.40 (m, 2 H), 2.07 (s, 3 H), 1.98-1.87 (m, 2 H), 1.85-1.77 (m, 1 H), 1.65-1.57 (m, 3 H), 1.37-1.21 (m, 16 H), 0.87 (t, J = 6.8 Hz, 3 H).
¹³C NMR (100.6 MHz, CDCl3): δ = 171.0, 170.7, 80.7, 74.5, 32.0, 29.8, 29.7, 29.6, 29.5, 25.4, 23.7, 22.8, 21.2, 18.4, 14.3.
HRMS: m/z [M + H]+ calcd for C18H33O4: 313.2301; found: 313.2381.
- Supporting Information for this article is available online:
- Supporting Information
Acknowledgment
This work was supported by the Center for Bioactive Molecular Hybrids (MOST/KOSEF) at Yonsei University.
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Berkessel A.Gröger H. Asymmetric Organocatalysis Wiley-VCH; Weinheim: 2004. - 1b
Dalko PI. Enantioselective Organocatalysis Wiley-VCH; Weinheim: 2007. - 1c Special issue on organocatalysis
(guest editor: List, B.): Chem. Rev.
2007,
107:
5413
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Pellissier H. Tetrahedron 2007, 63: 9267 - 1e
De Figueiredo RM.Christmann M. Eur. J. Org. Chem. 2007, 2575 - 1f
Dondoni A.Massi A. Angew. Chem. Int. Ed. 2008, 47: 4638 - 1g
Kotsuki H.Ikishima H.Okuyama A. Heterocycles 2008, 75: 493 - 1h
Kotsuki H.Ikishima H.Okuyama A. Heterocycles 2008, 75: 757 - 1i
Enders D.Narine AA. J. Org. Chem. 2008, 73: 7857 - 1j
Melchiorre P.Marigo M.Carlone A.Bartoli G. Angew. Chem. Int. Ed. 2008, 47: 6138 - 1k
Bertelsen S.Jørgensen KA. Chem. Soc. Rev. 2009, 38: 2178 - 1l
Bella M.Gasperi T. Synthesis 2009, 1583 - 1m
Grondal C.Jeanty M.Enders D. Nat. Chem. 2010, 2: 167 - 2
Ramachary DB.Barbas CF. Org. Lett. 2003, 5: 1685 - 3
Umbreen S.Brockhaus M.Ehrenberg H.Schmidt B. Eur. J. Org. Chem. 2006, 4585 - 4a
Kotkar SP.Chavan VB.Sudalai A. Org. Lett. 2007, 9: 1001 - 4b
Zhong G.Yu Y. Org. Lett. 2004, 6: 1637 - 5
Yang L.Liu R.-H.Wang B.Weng L.-L.Zheng H. Tetrahedron Lett. 2009, 50: 2628 - 6a
Kim S.-G. Synthesis 2009, 2418 - 6b
Lim A.Choi JH.Tae J. Tetrahedron Lett. 2008, 49: 4882 - 6c
Källström S.Erkkilä A.Pihko PM.Sjöholm R.Sillanpää R.Leino R. Synlett 2005, 751 - 6d
Zhong G. Chem. Commun. 2004, 606 - 7a
Kano T.Mil H.Maruoka K. J. Am. Chem. Soc. 2009, 131: 3450 - 7b
Gotoh H.Hayashi Y. Chem. Commun. 2009, 3083 - For recent synthesis and leading references, see:
- 8a
Quinn KJ.Curto JM.McGrath KP.Biddick NA. Tetrahedron Lett. 2009, 50: 7121 - 8b
Singh S.Guiry PJ. Eur. J. Org. Chem. 2009, 1896 - 8c
Garbe L.-A.Morgenthal K.Kuscher K.Tressl R. Helv. Chim. Acta 2008, 91: 993 - 8d
Prasad KR.Anbarsan P. Tetrahedron: Asymmetry 2007, 18: 2479 - 8e
Sabitha G.Swapna R.Reddy EV.Yadav JS. Synthesis 2006, 4242 - 8f
Ikishima H.Sekiguchi Y.Ichikawa Y.Kotsuki H. Tetrahedron 2006, 62: 311 - 8g
Dhotare B.Goswami D.Chattopadhyay A. Tetrahedron Lett. 2005, 46: 6219 - 8h
Sun B.Peng L.Chen X.Li Y.Yamasaki K. Tetrahedron: Asymmetry 2005, 16: 1305 - 9a
Hayashi Y.Gotoh H.Hayashi T.Shoji M. Angew. Chem. Int. Ed. 2005, 44: 4212 - 9b
Marigo M.Wabnitz TC.Fielenbach D.Jørgensen KA. Angew. Chem. Int. Ed. 2005, 44: 794 - 10a
Paquette LA.Mitzel TM.Isaac MB.Crasto CF.Schomer WW. J. Org. Chem. 1997, 62: 4293 - 10b
Paquette LA.Mitzel TM. J. Am. Chem. Soc. 1996, 118: 1931 - For reviews on olefin metathesis, see:
- 11a
Grubbs RH.Chang S. Tetrahedron 1998, 54: 4413 - 11b
Fürstner A. Angew. Chem. Int. Ed. 2000, 39: 3012 - 11c
Diver ST.Giessert AJ. Chem. Rev. 2004, 104: 1317 - 11d
Poulsen CS.Madsen R. Synthesis 2003, 1 - 13
Michaelakis A.Mihou APJ.Couladours EA.Zounos AK.Koliopoulos G. J. Agric. Food Chem. 2005, 53: 5225
References
At this point, the minor diastereomer is separated by column chromatography in 15% yield.
- For recent reviews on organocatalysis, see:
- 1a
Berkessel A.Gröger H. Asymmetric Organocatalysis Wiley-VCH; Weinheim: 2004. - 1b
Dalko PI. Enantioselective Organocatalysis Wiley-VCH; Weinheim: 2007. - 1c Special issue on organocatalysis
(guest editor: List, B.): Chem. Rev.
2007,
107:
5413
- 1d
Pellissier H. Tetrahedron 2007, 63: 9267 - 1e
De Figueiredo RM.Christmann M. Eur. J. Org. Chem. 2007, 2575 - 1f
Dondoni A.Massi A. Angew. Chem. Int. Ed. 2008, 47: 4638 - 1g
Kotsuki H.Ikishima H.Okuyama A. Heterocycles 2008, 75: 493 - 1h
Kotsuki H.Ikishima H.Okuyama A. Heterocycles 2008, 75: 757 - 1i
Enders D.Narine AA. J. Org. Chem. 2008, 73: 7857 - 1j
Melchiorre P.Marigo M.Carlone A.Bartoli G. Angew. Chem. Int. Ed. 2008, 47: 6138 - 1k
Bertelsen S.Jørgensen KA. Chem. Soc. Rev. 2009, 38: 2178 - 1l
Bella M.Gasperi T. Synthesis 2009, 1583 - 1m
Grondal C.Jeanty M.Enders D. Nat. Chem. 2010, 2: 167 - 2
Ramachary DB.Barbas CF. Org. Lett. 2003, 5: 1685 - 3
Umbreen S.Brockhaus M.Ehrenberg H.Schmidt B. Eur. J. Org. Chem. 2006, 4585 - 4a
Kotkar SP.Chavan VB.Sudalai A. Org. Lett. 2007, 9: 1001 - 4b
Zhong G.Yu Y. Org. Lett. 2004, 6: 1637 - 5
Yang L.Liu R.-H.Wang B.Weng L.-L.Zheng H. Tetrahedron Lett. 2009, 50: 2628 - 6a
Kim S.-G. Synthesis 2009, 2418 - 6b
Lim A.Choi JH.Tae J. Tetrahedron Lett. 2008, 49: 4882 - 6c
Källström S.Erkkilä A.Pihko PM.Sjöholm R.Sillanpää R.Leino R. Synlett 2005, 751 - 6d
Zhong G. Chem. Commun. 2004, 606 - 7a
Kano T.Mil H.Maruoka K. J. Am. Chem. Soc. 2009, 131: 3450 - 7b
Gotoh H.Hayashi Y. Chem. Commun. 2009, 3083 - For recent synthesis and leading references, see:
- 8a
Quinn KJ.Curto JM.McGrath KP.Biddick NA. Tetrahedron Lett. 2009, 50: 7121 - 8b
Singh S.Guiry PJ. Eur. J. Org. Chem. 2009, 1896 - 8c
Garbe L.-A.Morgenthal K.Kuscher K.Tressl R. Helv. Chim. Acta 2008, 91: 993 - 8d
Prasad KR.Anbarsan P. Tetrahedron: Asymmetry 2007, 18: 2479 - 8e
Sabitha G.Swapna R.Reddy EV.Yadav JS. Synthesis 2006, 4242 - 8f
Ikishima H.Sekiguchi Y.Ichikawa Y.Kotsuki H. Tetrahedron 2006, 62: 311 - 8g
Dhotare B.Goswami D.Chattopadhyay A. Tetrahedron Lett. 2005, 46: 6219 - 8h
Sun B.Peng L.Chen X.Li Y.Yamasaki K. Tetrahedron: Asymmetry 2005, 16: 1305 - 9a
Hayashi Y.Gotoh H.Hayashi T.Shoji M. Angew. Chem. Int. Ed. 2005, 44: 4212 - 9b
Marigo M.Wabnitz TC.Fielenbach D.Jørgensen KA. Angew. Chem. Int. Ed. 2005, 44: 794 - 10a
Paquette LA.Mitzel TM.Isaac MB.Crasto CF.Schomer WW. J. Org. Chem. 1997, 62: 4293 - 10b
Paquette LA.Mitzel TM. J. Am. Chem. Soc. 1996, 118: 1931 - For reviews on olefin metathesis, see:
- 11a
Grubbs RH.Chang S. Tetrahedron 1998, 54: 4413 - 11b
Fürstner A. Angew. Chem. Int. Ed. 2000, 39: 3012 - 11c
Diver ST.Giessert AJ. Chem. Rev. 2004, 104: 1317 - 11d
Poulsen CS.Madsen R. Synthesis 2003, 1 - 13
Michaelakis A.Mihou APJ.Couladours EA.Zounos AK.Koliopoulos G. J. Agric. Food Chem. 2005, 53: 5225
References
At this point, the minor diastereomer is separated by column chromatography in 15% yield.
Scheme 1 Retrosynthetic analysis for (-)-6-acetoxy-5-hexadecanolide (1)
Figure 1 A proposed transition state for the allylation reaction
Scheme 2 Total synthesis of (-)-6-acetoxy-5-hexadecanolide (1)