Methyl 3-bromomethyl-3-butenoate as an isopentane building block for the stereoselective preparation of (S)-4-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde and (+)-faranal

Article abstract of DOI:10.1016/j.tetlet.2010.01.120

(S)-4-Methyl-3,6-dihydro-2H-pyran-2-carbaldehyde (3), the common intermediate in the syntheses of the C17-C27 subunit of laulimalide (4) and (+)-faranal (5), the trail pheromone of the pharaoh ant, Monomorium pharaonis, were obtained via transformation of

Full text of DOI:10.1016/j.tetlet.2010.01.120

Tetrahedron Letters 51 (2010) 1836–1839
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Tetrahedron Letters
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Methyl 3-bromomethyl-3-butenoate as an isopentane building block
for the stereoselective preparation of (S)-4-methyl-3,6-dihydro-
2H-pyran-2-carbaldehyde and (+)-faranal
*
Iryna V. Mineyeva, Oleg G. Kulinkovich
Department of Organic Chemistry, Belarusian State University, Nezavisimosti Av. 4, Minsk 220030, Belarus
a r t i c l e i n f o
a b s t r a c t
Article history:
(S)-4-Methyl-3,6-dihydro-2H-pyran-2-carbaldehyde (3), the common intermediate in the syntheses of
the C17–C27 subunit of laulimalide (4) and (+)-faranal (5), the trail pheromone of the pharaoh ant,
Monomorium pharaonis, were obtained via transformation of methyl 3-bromomethyl-3-butenoate (1)
into allylstannane 2 and subsequent allylation of (benzyloxy)acetaldehyde (6) in accordance with the
Keck procedure as the key steps.
Received 4 December 2009
Revised 19 January 2010
Accepted 29 January 2010
Available online 4 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Cyclopropanols
Allyl halides
(+)-Faranal
Ring opening
Asymmetric synthesis
3-Methylbut-2-enoic acid and its derivatives are widely used as
nucleophilic C5 buildings blocks via the generation of a carbanionic
centre by allylic deprotonation or metal–halogen exchange reac-
tions.1 The synthetic application of regioisomeric 3-methylbut-
3-enoic acid derivatives has not been studied in detail, and to
our knowledge, is limited to asymmetric allylation of aldehydes
with ethyl 3-[(tributylstannyl)methyl]but-3-enoate2 obtained in
turn by ethoxycarbonylation of 1,3-bis-(tributylstannyl)-2-meth-
ylenepropane.3 This allylating agent was successfully used for the
preparation of d-hydroxy-b-methylenealkanoic or (E)-d-hydroxy-
O
X
MeO
O
O
1, X = Br
2, X = SnBu3
3
OH
H
O
14
O
b-methyl-a,b-alkenoic esters after the displacement of the car-
27
bon–carbon double bond to a position conjugated to the carbonyl
group.2 Recently, we reported an effective preparation of a similar
allyl stannane 2 by zinc-mediated stannylation of methyl 3-bro-
momethyl-3-butenoate (1).4 Herein, compound 1 was exploited
for the stereoselective preparation of (S)-4-methyl-3,6-dihydro-
2H-pyran-2-carbaldehyde (3),5 a common intermediate in several
syntheses of the C17–C27 subunit of laulimalide (4),5a–i,k,6 as well
as in the synthesis of (+)-faranal, [(3S,4R,6E,10Z)-3,4,7,11-tetra-
methyl-6,10-tridecadienal] (5), the trail pheromone of the pharaoh
ant, Monomorium pharaonis7 (Scheme 1).
17
O
O
OH
H
H
O
5
4
The previously reported syntheses of aldehyde 3 from the
appropriate chiral precursors were based mainly on the formation
O
* Corresponding author. Tel.: +375 17 2095459; fax: +375 17 2265609.
E-mail addresses: kulinkovich@bsu.by, o.kulinkovich@gmail.com (O.G. Kulinko-
vich).
5
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.01.120

I. V. Mineyeva, O. G. Kulinkovich / Tetrahedron Letters 51 (2010) 1836–1839
1837
p-TolSO2Na
DMF
MgBr2
O
O
OMs
Et2O, CHCl3
SO2C6H4Me-p
1
MeO
MeO
90%
ref. 4
9
8
O
BnO
6
(S)-BINOL/Ti(O-iPr)4, (10 mol%),
toluene, -15 ºC,7 d
H
Bu3SnH, AIBN
benzene
LiAlH4, Et2O
80%
O
O
OBn
2
67%
85%
7
1. Na, NH3, Et2O, -78 ºC
ZnCl2
1,2-dichloroethane
H
2. (COCl)2, DMSO
DIPEA, CH2Cl2
H
HO
HO
O
OBn
OR
3
75% over two steps
76%
10
11
R=Bn
12 R=H
Scheme 2.
NiCl2·6H2O, NaBH4,
H3BO3,THF, H2O
Pd(OH)2/C, H2
MeOH
TBSCl,
imidazole
7
OBn
OH
94%
O
O
O
O
83%
90%
14
13
Br
16
1. LiAlH4, Et2O
2. Me2C(OMe)2, PPTS, Me2CO
LDA, THF
OTBS
OTBS
O
O
73% over 2 steps
O
O
60%
17
15
1. PPTS, MeOH
2. PhI(OAc)2, MeOH
1. MsCl, Et3N, Et2O
2. LiAlH4, THF
O
O
O
O
5
74% over 2 steps
86% over 2 steps
HO
19
18
Scheme 3.
of a dihydropyran ring by a metathesis reaction.5b–k Its preparation
aldehyde 3 was obtained by transformation of ester 1 into
functionalized allyl stannane 2 followed by the addition of the lat-
ter to (benzyloxy)acetaldehyde 610 under Keck conditions11
(Scheme 2). When the reaction was carried out in dichloromethane
via the enantioselective cycloaddition of
a-functionalized alde-
hydes to isoprene8 or 4-methoxyisoprene9 in the presence of chiral
Cr or Co complexes as catalysts was also reported. In this work,

1838
I. V. Mineyeva, O. G. Kulinkovich / Tetrahedron Letters 51 (2010) 1836–1839
3. Keck, G. E.; Palani, A. Tetrahedron Lett. 1993, 34, 3223.
4. Mineeva, I. V.; Kulinkovich, O. G. Zh. Org. Khim. 2008, 44, 1277; Russ. J. Org.
Chem. (Engl. Trans.) 2008, 44, 1261.
in the presence of 10 mol % of (S)-BITIP catalyst, a complex mixture
of products was formed and the conversion of aldehyde 6 was less
than 50%. The allylation proceeded sufficiently faster and more
smoothly when toluene was used as the solvent.11 In this case,
the reaction was accompanied by lactonization of the intermediate
homoallylic alcohol and subsequent migration of the carbon–car-
bon double bond to a position conjugated to the carbonyl group
to afford lactone 7. For the preparation of allyl stannane 2, allyl
bromide 1, obtained via the cationic cyclopropyl-allyl isomeriza-
tion of the readily available cyclopropyl sulfonate 8,4,12 was con-
verted on treatment with p-TolSO2Na in N,N-dimethylformamide
(DMF) into sulfone 9. The latter was reacted with Bu3SnH in the
presence of AIBN13,14 to give 2. Reduction of lactone 7 with lithium
aluminium hydride, followed by treatment of the product diol 10
with zinc dichloride in boiling 1,2-dichloroethane15 led to dihydro-
5. (a) Ghosh, A. K.; Wang, Y. Tetrahedron Lett. 2000, 41, 2319; (b) Ghosh, A. K.;
Wang, Y.; Kim, T. K. J. Org. Chem. 2001, 66, 8973; (c) Dorling, E. K.; Öhler, E.;
Mulzer, J. Tetrahedron Lett. 2000, 41, 6323; (d) Ahmed, A.; Öhler, E.; Mulzer, J.
Synthesis 2001, 2007; (e) Mulzer, J.; Öhler, E. Angew. Chem., Int. Ed. 2001, 40,
3842; (f) Mulzer, J.; Öhler, E. Angew. Chem. 2001, 113, 3961; (g) Mulzer, J.;
Öhler, E.; Enev, V. S.; Hanbauer, M. Adv. Synth. Catal. 2002, 344, 3026; (h)
Ahmed, A.; Hoegenauer, K.; Enev, V. S.; Hanbauer, M.; Kaehling, H.; Öhler, E.;
Mulzer, J. J. Org. Chem. 2003, 68, 3026; (i) Messenger, B. T.; Davidson, B. S.
Tetrahedron Lett. 2001, 42, 801; (j) Lee, H. W.; Yoon, S. H.; Lee, I.-Y. C.; Chung, B.
Y. Bull. Korean Chem. Soc. 2001, 22, 1179; (k) Sivaramakrishnan, A.; Nadolski, G.
T.; McAlexander, I. A.; Davidson, B. S. Tetrahedron Lett. 2002, 43, 213.
6. (a) Gollner, A.; Mulzer, J. Org. Lett. 2008, 10, 4701; (b) Gollner, A.; Altmann, K.-
H.; Gertsch, J.; Mulzer, J. Tetrahedron Lett. 2009, 50, 5790.
7. (a) Poppe, L.; Novák, L.; Kolonits, P.; Bata, A.; Szántay, C. Tetrahedron Lett. 1986,
27, 5769; (b) Poppe, L.; Novák, L.; Kolonits, P.; Bata, A.; Szántay, C. Tetrahedron
1988, 44, 1477; (c) Kobayashi, M.; Koyama, T.; Ogura, K.; Ritter, F. J.;
Brüggemann-Rotgans, I. E. M. J. Am. Chem. Soc 1980, 102, 6602; (d) Knight, D.
W.; Ojhara, B. A. J. Chem. Soc., Perkin Trans. 1 1983, 955; (e) Baker, R.; Billington,
D. C.; Ekanayake, N. J. Chem. Soc., Perkin Trans. 1 1983, 1387; (f) Mori, K.; Ueda,
H. Tetrahedron 1982, 38, 1227; (g) Mori, K.; Murata, N. Liebigs Ann 1995, 2089;
(h) Vasil’ev, A. A.; Engman, L.; Serebryakov, E. P. J. Chem. Soc., Perkin Trans. 1
2000, 2211.
pyran 11.16 After debenzylation of 11 with sodium in liquid ammo-
g–k, 9a, 17
nia, chiral alcohol 125a–c,
was obtained in 94% ee.18,19
Finally, Swern oxidation gave aldehyde 3 in 23% overall yield based
on allyl bromide 1.
8. (a) Wender, P. A.; Hilinski, M. K.; Soldermann, N.; Mooberry, S. L. Org. Lett. 2006,
8, 1507; (b) Wender, P. A.; Hegde, S. G.; Hubbard, R. D.; Zhang, L. J. Am. Chem.
Soc. 2002, 124, 4956.
9. (a) Paterson, I.; De Savi, C.; Tudge, M. Org. Lett. 2001, 3, 3149; (b) Paterson, I.;
Bergmann, H.; Menche, D.; Berkessel, A. Org. Lett. 2004, 6, 1293.
One of the most effective methods for the synthesis of (+)-far-
anal (5), the trail pheromone of the pharaoh ant, a foodstuff pest
and a dangerous infection carrier in hospitals,7d was elaborated
by Szántay and co-workers.7a,b The authors constructed the carbon
skeleton of the molecule via diastereoselective allylation of (3S)-
methyl valerolactone, which in turn was obtained by enzymatic
reduction of methyl glutaconicoate.7a,20 We found that lactone 7
could be successfully used to prepare (+)-faranal (5) by Szántay’s
modified procedure (Scheme 3). Diastereoselective reduction of
the carbon–carbon double bond in lactone 7 with sodium borohy-
dride in the presence of nickel chloride21 followed by deprotection
of the hydroxy group of unsaturated lactone 13 led to crystalline
cis-lactone 14 in 78% yield over two steps.22 The latter was recrys-
tallized twice from a mixture of diethyl ether–ethyl acetate to give
the product in greater than 99% ee.19,23
Silylation of the hydroxy group of 14 and subsequent treatment
of a mixture of compound 15 and (Z)-homogeranyl bromide
(16)7a,b,24 with LDA in tetrahydrofuran initially for 2 h at ꢀ78 °C
and then for 12 h at ꢀ30 °C7a,7b,25 led to allylation product 17
which was isolated as a single diastereomer in 60% yield.26 It is
noteworthy that the TBS-protecting group in lactone 15 had an
important influence on the alkylation process since lactone 13, un-
like 15, under the same conditions, yielded a complex mixture of
products. Reduction of alkylated lactone 17 with lithium alumin-
ium hydride, followed by transformation of the product formed
into acetonide derivative 18 and subsequent reductive elimination
of the hydroxy group of the latter gave 19. Hydrolysis of compound
19 and oxidative fragmentation of the formed vicinal diol with
phenyliodine(III) diacetate in methanol led to (+)-faranal (5) in
28% yield based on lactone 15.
10. Fatima, A.; Pilli, R. A. Arkivoc 2003, x, 118.
11. Kurosu, M.; Lorca, M. Synlett 2005, 1109.
12. Limbach, M.; Dalai, S.; de Meijere, A. Adv. Synth. Catal. 2004, 346, 760.
13. Ueno, Y.; Aoki, S.; Okawara, M. J. Chem. Soc., Chem. Commun. 1980, 683.
14. In comparison with the earlier reported one-step procedure,4 the advantage of
the described method in this two-step approach to the preparation of
functionalized allyl stannane 2 from allyl bromide 1 via sulfone 9 is that
equimolar quantities of the reagents are used and purification of the product
by column chromatography is easier.
15. Kim, S.; Chung, K. N.; Yang, S. J. Org. Chem. 1987, 52, 3917.
16. Experimental procedure: A solution of 1.08 g (5 mmol) of diol 10 and 0.8 g
(6 mmol) of anhyd ZnCl2 in 30 ml of dichloroethane was refluxed for 1.5 h.
After treatment with H2O (30 ml) and extraction with CH2Cl2 (3 ꢁ 25 ml), the
combined organic phase was washed with aq NaHCO3 (40 ml) and dried over
anhyd MgSO4. Following evaporation of the solvent, the residue was purified
by column chromatography on silica gel (eluent—petroleum ether/EtOAc),
yielding 0.76 g (76%) of 11 as a colourless oil. ½a D20
ꢂ
ꢀ75.7 (c 7.1, CHCl3); 1H NMR
(400 MHz, CDCl3) d 1.69 (s, 3H), 1.76–1.80 (m, 1H), 2.00–2.07 (m, 1H), 3.47 (dd,
J = 10.2, 3.8 Hz, 1H), 3.54 (dd, J = 10.2, 6.5 Hz, 1H), 3.73–3.79 (m, 1H), 4.17–4.21
(m, 2H), 4.57 (d, J = 12.3 Hz, 1H), 4.64 (d, J = 12.3 Hz, 1H), 5.42 (br s, 1H), 7.28–
7.37 (m, 5H); 13C NMR (100 MHz, CDCl3) d 23.0, 32.1, 65.8, 72.9, 73.0, 73.5,
119.8, 127.6, 127.8 (2 ꢁ C), 128.3 (2 ꢁ C), 131.2, 138.2; IR (CCl4) 1138,
1099 cmꢀ1; Anal. Calcd for C14H18O2: C, 77.03; H, 8.31. Found: C, 77.10; H, 8.28.
17. Lee, H. W.; Yeong, C.-S.; Yoon, S. H.; Choi Lee, I.-Y. Bull. Korean Chem. Soc. 2001,
22, 791.
18. The ee value of alcohol 12 was determined by Mosher’s method.19 The signals
of the protons of the methoxy groups at d 3.57 and d 3.41 were used to
determine the enantiomeric purity. Major isomer of (R)-(+)-MTPA ester: 1H
NMR (400 MHz, CDCl3) d 1.68 (s, 3H), 1.75–1.80 (m, 1H), 1.95–2.05 (m, 1H),
3.57 (s, 3H), 3.75–3.85 (m, 1H), 4.09 (d, J = 16.0 Hz, 1H), 4.17 (d, J = 16.0 Hz,
1H), 4.37 (dd, J = 11.2, 6.0 Hz, 1H), 4.41 (dd, J = 11.2, 4.2 Hz, 1H), 5.41 (br s, 1H),
7.35–7.40 (m, 3H), 7.55–7.60 (m, 2H).
19. Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969, 34, 2543.
20. Horgan, D. J.; Stoops, J. K.; Webb, E. C.; Zerner, B. Biochemistry 1969, 8, 2000.
21. (a) Toshio, T.; Kenryo, N.; Shuichi, S. Chem. Pharm. Bull. 1971, 19, 817; (b)
Bekish, A. V.; Prokhorevich, K. N.; Kulinkovich, O. G. Eur. J. Org. Chem. 2006,
5069.
In summary, methyl 3-bromomethyl-3-butenoate (1) was suc-
cessfully used as a bifunctional isopentane building block in the
synthesis of (S)-4-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde
(3) and (+)-faranal 5. The Keck asymmetric condensation of (ben-
zyloxy)acetaldehyde 6 and allyl stannane 2, derived from allyl bro-
mide 1 was the key step in both syntheses.
22. Experimental procedure: 0.84 g of NaBH4 (22 mmol) was added in small
portions over 10 min each to
a stirred emulsion of 2.32 g (10 mmol) of
compound 7 in 50 ml THF–H2O (1:1) at 0 °C, containing 2.60 g (11 mmol) of
NiCl2ꢃ6H2O and 2.34 g (40 mmol) of H3BO3. After stirring for an additional
0.5 h, the reaction mixture was extracted with Et2O (4 ꢁ 25 mL). The combined
organic fraction was dried over Na2SO4 and concentrated under reduced
pressure. The residue was chromatographed on silica gel (eluent—petroleum
References and notes
ether/EtOAc) to give 13 (2.20 g, 94%) as
a colourless oil. The latter was
dissolved in 30 ml of absolute EtOH and stirred under H2 in the presence of
0.05 g of 10% Pd/C for 2 h. The mixture was filtered and the filtrate was
concentrated under reduced pressure. The residue was purified by column
chromatography on silica gel (eluent—petroleum ether/EtOAc), yielding
hydroxymethyl lactone 14 (1.34 g, 99% ee, 86%) as colourless crystals.
Crystallization (twice) from Et2O/EtOAc (10:1) gave 1.12 g (83%) of the
1. (a) Julia, M.; Arnold, D. Bull. Soc. Chim. Fr. 1973, 746; (b) Gedye, R. N.; Arora, P.;
Khalil, A. H. Can. J. Chem. 1975, 53, 1943; (c) Cardillo, G.; Orena, M.; Sandri, S.
Tetrahedron 1976, 32, 107; (d) Huisman, H. O. Pure Appl. Chem. 1977, 49, 1307;
(e) Dugger, R. W.; Heathcock, C. H. J. Org. Chem. 1980, 45, 1181; (f) Cainelli, G.;
Cardillo, G. Acc. Chem. Res. 1981, 14, 89; (g) Wang, Y.; Woo, W. S.; Hoef, I.;
Lugtenburg, J. Eur. J. Org. Chem. 2004, 2166; (h) Jeon, H.-S.; Yeo, J. E.; Jeong, Y. C.
Synthesis 2004, 2813; (i) Salman, M.; Babu, S. J.; Kaul, V. K.; Ray, P. R.; Kumar, N.
Org. Proc. Res. Dev. 2005, 9, 302.
product, with ee >99%.23 Mp 80–81 °C; ½a D20
ꢂ
+11.7 (c 0.6 CHCl3); 1H NMR
(400 MHz, CDCl3) d 1.01 (d, J 6.1 Hz, 3H), 1.32–1.42 (m, 1H), 1.58 (br s, 1H),
1.80–1.85 (m, 1H), 1.96–2.07 (m, 2H), 2.58–2.67 (m, 1H), 3.60 (ddd, J = 12.3,
6.1, 5.4 Hz, 1H), 3.75 (ddd, J = 12.3, 7.4, 2.6, 1H), 4.34–4.39 (m, 1H); 13C NMR
(100 MHz, CDCl3) d 21.4, 26.2, 32.2, 37.9, 64.5, 81.1, 171.5; IR (CCl4) 3439,
2. (a) Keck, G. E.; Yu, T. Org. Lett. 1999, 1, 289; (b) Sanchez, C. C.; Keck, G. E. Org.
Lett. 2005, 7, 3053.

I. V. Mineyeva, O. G. Kulinkovich / Tetrahedron Letters 51 (2010) 1836–1839
1839
1732, 1259, 1087 cmꢀ1; Anal. Calcd for C7H12O3: C, 58.32; H, 8.39. Found: C,
58.37; H, 8.34.
25. (a) Posner, G. H.; Loomis, G. L. Chem. Commun. 1972, 892; (b) Herrmann, J. L.;
Schlessinger, R. H. Chem. Commun. 1973, 771.
23. The ee value of 14 was determined by Mosher’s method.19 The signals of the
protons of the methoxy groups at d 3.56 and d 3.41 were used to determine the
enantiomeric purity of 14. Major isomer of (R)-(+)-MTPA ester: 1H NMR
(400 MHz, CDCl3) d 1.02 (d, J = 6.1, 3H), 1.23–1.32 (m, 1H), 1.83–1.89 (m, 1H),
1.99–2.10 (m, 2H), 2.66 (ddd, J = 17.1, 4.9, 2.1 Hz, 1H), 3.56 (s, 3H), 4.38 (dd,
J = 11.8, 5.1 Hz, 1H), 4.41 (dd, J = 11.8, 3.6 Hz, 1H), 4.52–4.58 (m, 1H), 7.38–7.43
(m, 3H), 7.51–7.57 (m, 2H).
26. Compound 17. ½a D20
ꢂ
ꢀ6.1 (c 0.82, CHCl3); 1H NMR (400 MHz, CDCl3) d 0.06 (s, 6H),
0.88 (s, 9H), 0.94 (t, J = 7.7 Hz, 3H), 1.05 (d, J = 6.1 Hz, 3H), 1.37–1.46 (m, 1H), 1.63
(s, 3H), 1.65 (s, 3H), 1.85–1.93 (m, 2H), 1.97–2.08 (m, 6H), 2.13–2.19 (m, 1H), 2.41
(ddd, J = 15.1, 8.4, 4.6 Hz, 1H), 2.69 (dt, J = 15.1, 4.9 Hz, 1H), 3.64 (dd, J = 10.8,
5.6 Hz, 1H), 3.73 (dd, J = 10.8, 4.1 Hz, 1H), 4.21–4.27 (m, 1H), 5.02 (t, J = 6.4 Hz,
1H), 5.06 (t, J = 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) d ꢀ5.4 (2 ꢁ C), 12.8, 16.3,
18.3, 20.6, 22.8, 24.7, 26.1 (3 ꢁ C), 27.4, 29.6, 33.9, 40.1, 48.7, 65.3, 79.5, 120.2,
123.7, 137.2, 137.9, 173.3; IR (CCl4) 1716, 1450, 1268, 1104, 1004 cmꢀ1; Anal.
Calcd for C24H44O3Si: C, 70.53; H, 10.85. Found: C, 70.59; H, 10.82.
24. (a) Stotter, P. L.; Hornish, R. E. J. Am. Chem. Soc. 1973, 95, 4444; (b) Sen, S. E.;
Ewing, G. J. J. Org. Chem. 1997, 62, 3529; (c) Okochi, T.; Mori, K. Eur. J. Org. Chem.
2001, 2145.