LETTER
1,5-Stereocontrol in Bismuth-Mediated Reactions between Aldehydes and Allyl Bromides
577
Me
Me
Me
OR Me
Me
2 MeLi, CuCN
(OsO4, NMO)
48%
OR
OTIPS
19 R = H
21 R = Ts
23 R = TIPS
24 R = H
TBAF
90%
TsCl
91%
Me
Me
Me
OR Me
Me
2 MeLi, CuCN
(OsO4, NMO)
OR
OTIPS
20 R = H
22 R = Ts
TsCl
91%
25 R = TIPS
26 R = H
45%
TBAF
91%
Scheme 5 Stereoselective cuprate displacements
diastereomer 16 being detected. Hydrogenation of the diol mide 6, the additional stereogenic centres being intro-
13 was less stereoselective, but the major product was the duced by 1,5- and 1,2-diastereocontrol. Indeed this
syn-2,4-dimethylnonane-1,6-diol 17 as expected on the chemistry could be used for a diastereoselective synthesis
basis of Evans’ observations.13a In contrast, the major of racemic products.
product from the hydrogenation of the secondary allylic
alcohol 14 was the anti-dimethyl isomer 20 which was
isolated in a 56% yield (Scheme 4).
Acknowledgment
We thank Novartis for a Fellowship (to H.L.) and the EPSRC and
AstraZeneca for a CASE award (to S.D.).
The major product 15 from the hydrogenation of the pri-
mary alcohol 12 was assigned the syn configuration at C2
and C4 by analogy with Evans’ work.13a On desilyation
References and Notes
this gave the major product obtained from the hydrogena-
tion of the diol 13 which therefore was also assigned the
2,4-syn configuration as indicated in Scheme 4. However,
selective monosilylation of the primary hydroxy group of
diol 17 gave the minor product 19 obtained from hydroge-
nation of the secondary alcohol 14, and so the methyl
groups in the major product in this case were assigned the
anti relative configuration as shown in structure 20.
(1) Thomas, E. J. Chemical Rec. 2007, 7, 115.
(2) (a) Casteno, P.; Thomas, E. J.; Weston, A. Tetrahedron Lett.
2007, 48, 337. (b) Thomas, E. J.; Weston, A. Tetrahedron
Lett. 2007, 48, 341.
(3) Wada, M.; Ohki, H.; Akiba, K.-Y. Bull. Chem. Soc. Jpn.
1990, 63, 1738.
(4) (a) Donnelly, S.; Fielding, M.; Thomas, E. J. Tetrahedron
Lett. 2004, 45, 6779. (b) Donnelly, S.; Thomas, E. J.;
Arnott, E. A. Chem. Commun. 2003, 1460.
To access open-chain products with 1,3,5-disposed meth-
yl substituents, it remained to introduce the third methyl
substituent. This was carried out by treatment of the tolu-
ene p-sulfonates 21 and 22 prepared from alcohols 19 and
20 with a higher-order lithium cyanodimethylcuprate15
using osmium tetroxide in the workup to remove minor
elimination products. Higher-order cuprate displacements
of secondary sulfonates can be capricious,15 but the all-
syn- and anti,anti-products 23 and 25 were isolated from
the toluene p-sulfonates 21 and 22, respectively, albeit in
only moderate yields (Scheme 5). Desilylation of these
monotriisopropylsilyl ethers 23 and 25 then gave the all-
syn- and the anti,anti-2,4,6-trimethylnonan-1-ols 24 and
26, respectively. The structures of these alcohols were
consistent with spectroscopic data. In particular the three
methyl substituents were more shielded for the anti,anti-
isomer 26 (dC = 19.9, 19.5, 19.2 ppm) than for the all-syn-
epimer 24 (dC = 20.9, 20.4, 20.0 ppm) consistent with the
assigned stereochemistry.16
(5) Zhou, J.; Zhu, Y.; Burgess, K. Org. Lett. 2007, 9, 1391.
(6) (a) Herber, C.; Breit, B. Angew. Chem. Int. Ed. 2005, 44,
5267. (b) Herber, C.; Breit, B. Eur. J. Org. Chem. 2007,
3512.
(7) Zhu, G.; Liang, B.; Negishi, E.-i. Org. Lett. 2008, 10, 1099.
(8) ter Horst, B.; Feringa, B. L.; Minnaard, A. Org. Lett. 2007,
9, 3013.
(9) (R)-6: [a]D25 –13.9 (c 0.0046, CHCl3).
(10) Teerawutgulrag, A.; Thomas, E. J. J. Chem. Soc., Perkin
Trans. 1 1993, 2863.
(11) Zinc powder (30 mg, 0.46 mmol) was added to a solution of
bismuth(III) iodide (234 mg, 0.4 mmol) in THF (1.65 mL)
and the mixture stirred at r.t. for 1 h. The pent-2-enyl
bromide 6 (75 mg, 0.26 mmol) and benzaldehyde (27 mL,
0.26 mmol) in THF (0.6 mL) were added and the mixture
heated under reflux for 2 h. After cooling, the mixture was
filtered and concentrated under reduced pressure. Column
chromatography of the residue gave (1S,5R,3Z)-6-benzyl-
oxy-3,5-dimethyl-1-phenylhex-3-en-1-ol (9a, 8 mg, 10%),
as an oil. Rf = 0.28 (light PE–Et2O, 3:1). HRMS: m/z calcd
for C21H30O2N: 328.2271 [M]; found: 328.2273 [M + NH4].
IR: nmax = 3414, 1453, 1088, 1026, 752, 699 cm–1. 1H NMR
(300 MHz, CDCl3): d = 0.83 (3 H, d, J = 7 Hz, 5-CH3), 1.90
(3 H, d, J = 1 Hz, 3-CH3), 2.22 (1 H, dd, J = 14, 3 Hz, 2-H),
2.78 (1 H, dd, J = 14, 10 Hz, 2-H¢), 2.83 (1 H, m, 5-H), 3.18
(1 H, t, J = 9 Hz, 6-H), 3.41 (1 H, dd, J = 9, 5 Hz, 6-H¢), 4.55
and 4.58 (each 1 H, d, J = 12 Hz, OHCHPh), 4.87 (1 H, dd,
J = 10, 3 Hz, 1-H), 5.18 (1 H, dd, J = 10, 1 Hz, 4-H), 7.38
(10 H, m, ArH). 13C NMR (75 MHz, CDCl3): d = 17.6, 23.8,
This work has developed stereoselective syntheses of the
all-syn- and anti,anti-2,4,6-trimethylnonan-1-ols 24 and
26 which should be applicable to the syntheses of analo-
gous open-chain compounds. Although the stereoselectiv-
ities observed are somewhat less than those in other
approaches to compounds of this type,5–8 in the present
work, the only chiral reagent is the initial pentenyl bro-
Synlett 2010, No. 4, 575–578 © Thieme Stuttgart · New York
Bazar, Norazah
