Crossed acyloin condensation of aliphatic aldehydes

Article abstract of DOI:10.1002/1099-0690(200107)2001:14<2623::aid-ejoc2623>3.0.co;2-1

Crossed acyloins were efficiently prepared by the thiazolium-catalysed condensation of two different unhindered aldehydes, using one mol equivalent of one aldehyde with three mol equivalents of the other. Conversion into the corresponding nonsymmetrical 1

Full text of DOI:10.1002/1099-0690(200107)2001:14<2623::aid-ejoc2623>3.0.co;2-1

FULL PAPER
Crossed Acyloin Condensation of Aliphatic Aldehydes
[a]
[b]
[a]
[a]
´
´
Rainer Heck, Alistair P. Henderson, Berthold Köhler, Janos Retey,* and
Bernard T. Golding*[b]
Keywords: Condensation / Oximes / Aldehydes / Oxidation
Crossed acyloins were efficiently prepared by the thiazol-
ium-catalysed condensation of two different unhindered al- by oxidation with bismuth(III) oxide or the Dess−Martin
dehydes, using one mol equivalent of one aldehyde with
periodinane to give a 1,2-diketone that was then treated with
three mol equivalents of the other. Conversion into the cor- hydroxylamine to give the oxime.
responding nonsymmetrical 1,2-dioxime was achieved either
Introduction
ample of a symmetrically substituted acyloin 3g was also
prepared from a single aldehyde. Actually, Stetter and
Dämbkes did report the condensation of two aliphatic alde-
hydes,[4,5] but a common component of these reactions was
a hindered aldehyde, for example norbornene-2-carboxal-
dehyde, with which self-condensation is presumably sup-
pressed. We have found that the method of Stetter is effect-
ive even when two unhindered aldehydes are used. The
method has been validated with a representative set of alde-
hydes.
For the synthesis of supramolecular cobaloximes,[1,2]
which we have designed for modelling coenzyme B12-de-
pendent enzymatic reactions,[3] an efficient synthesis of
nonsymmetrical 1,2-dioximes 1 was required. We report a
route to these compounds via the corresponding crossed
acyloins, which are accessed by an efficient condensation of
two different aldehydes (see Scheme 1).
Scheme 1. Crossed acyloin condensation of two different aldehydes
Scheme 2. Reaction of the ylide derived from an aromatic aldehyde
with an aliphatic aldehyde
Stetter and co-workers[4Ϫ6] discovered a high yielding
crossed acyloin condensation[7] in which an aromatic alde-
hyde was treated with an excess of an aliphatic aldehyde in
the presence of triethylamine and a catalytic quantity of the
thiamine analogue 3-benzyl-5-(2-hydroxyethyl)-4-methylthi-
azolium chloride (2). This biomimetic process was ra-
tionalised as occurring by reaction of the more stable ylide,
derived from the aromatic aldehyde, with the more reactive
aliphatic aldehyde (Scheme 2).[8] However, we have found
that Stetter’s method can be applied to the preparation of
crossed acyloins 3aϪf from two aliphatic aldehydes selected
from 4aϪe, propanal and decanal, even though the relative
reactivities of the aldehyde functions are similar. An ex-
[a]
Fachbereich Biochemie, Institut für Organische Chemie,
Universität Karlsruhe,
Richard Willstätter Allee, 76128 Karlsruhe, Germany
[b]
Department of Chemistry, Bedson Building, University of
Newcastle upon Tyne,
Newcastle upon Tyne, NE1 7RU, UK
E-mail: b.t.golding@ncl.ac.uk
Eur. J. Org. Chem. 2001, 2623Ϫ2627
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0714Ϫ2623 $ 17.50ϩ.50/0
2623

´
R. Heck, A. P. Henderson, B. Köhler, J. Retey, B. T. Golding
FULL PAPER
Results and Discussion
alcohol function yielded aldehyde 4a (78%). Selective hy-
drolysis of 2-[2-(1,3-dioxolan-2-yl)ethyl]-1,3-dithiane with
Using the method of Stetter and Dämbkes,[4] we obtained 60% acetic acid (70 °C, 18 h) was used to access aldehyde
a yield of 71% for the symmetrically substituted acyloin 3g 4b.[9,10] Aldehyde 4c was synthesised by silylation of 7-hy-
starting from aldehyde 4e. To achieve the combination of droxyheptanal[11] with tert-butyldiphenylsilyl chloride in
two dissimilar aldehydes, Stetter and Dämbkes[4] used a 3:1 DMF with imidazole as base. All attempts to improve the
ratio of reactants, without commenting on this choice. We yield of 53% (variation of base and solvent) failed. Alde-
have also used this ratio (see Exp. Section for a description hyde 4d was prepared starting from 2-(3-hydroxy-2,2-di-
of the general procedure) and obtained yields of crossed methylpropyl)-1,3-dithiane.[12] First the hydroxyl group was
acyloin as high as 69% for 3aϪc,e,f (based on the minor converted into a 4-methoxybenzyl ether. In contrast to bu-
aldehyde; concerning acyloin 3d, see below). This at-first- tane-1,4-diol (see above) the neopentyl-like alcohol function
sight surprising outcome can be easily rationalised by a of 2-(3-hydroxy-2,2-dimethylpropyl)-1,3-dithiane could
statistical argument. Thus, an approximate 3:1 ratio of yl- only be protected in a moderate yield of 47% using catalytic
ides is exposed to a 3:1 ratio of aldehydes. Although this amounts of KI. Finally, removal of the dithiane function
necessarily leads primarily to a symmetrical acyloin from was achieved upon treatment of the thioacetal with HgO/
the major aldehyde, the minor aldehyde must give mainly a BF3·Et2O in wet THF to give aldehyde 4d in 50% yield.
crossed acyloin (calculated yield based on the minor alde- Monosilylation of butane-1,4-diol with triisopropylsilyl
hyde ϭ 86%; i.e. 6/7 of the acyloins derived from the minor chloride, followed by DessϪMartin oxidation[13] of the in-
aldehyde, if all ylideϪaldehyde combinations occur at the termediate silyl-alcohol gave aldehyde 4e.
same rate, as expected for unhindered aldehydes; note that
two of the four possible combinations yield the crossed acy-
loin). This statistical argument was confirmed by a detailed
study of the system using the combination of propanal and
decanal. With a 3:1 ratio of propanal to decanal, 56% of
crossed acyloin 3e was obtained. When the ratio was re-
versed (i.e. 3:1 decanal/propanal) the yield of crossed acy-
loin 3e was in the same range (58%). The fact that the yield
of the crossed acyloins 3aϪc,e,f was always less than the
calculated yield can probably be explained by side reactions
such as aldehyde oligomerisation. In one experiment the to-
tal amount of acyloins derived from the minor aldehyde
was isolated and contained 76% crossed acyloin and 24%
symmetrical acyloin. The lower yield (29%) of acyloin 3d is
presumably due to steric hindrance in aldehyde 4d, which
reduces the efficiency of the crossed condensation. Indeed,
35% of aldehyde 4d was recovered from the reaction and it
did not yield any symmetrical acyloin.
Based on our experiences with the acyloin reactions de-
scribed, we recommend the following protocol: (i) The alde-
hyde which is more expensive (or time-consuming to synth-
Conversion of the acyloins into the corresponding diox-
esise) should be the minor aldehyde in the condensation re- ime was exemplified with acyloins 3a, 3b, 3f and 3g. Numer-
action. (ii) If the two different aldehydes are both easily ous methods were explored for oxidation of these acyloins
accessible, the aldehyde with the smaller molecular mass to the corresponding 1,2-diketone (5aϪd), but the best
should be the major aldehyde. Thus the amount of crude methods utilised either an excess of bismuth(III) oxide (3.5
product is reduced, facilitating the chromatographic frac- mol equiv.),[4,14] which was added to a 1.3  solution of the
tionation of the acyloins. (iii) If one aldehyde is a small acyloin (3a or 3b) in 2-ethoxyethanol/acetic acid (10:3, v/v)
molecule like propanal, the use of more than three equiva- at 105 °C, or the DessϪMartin periodinane[13] (acyloins 3f
lents might be advantageous because the corresponding and 3g). Under the conditions using bismuth oxide, oxida-
symmetrical acyloin can be removed under vacuum. (iv) If tion to the 1,2-diketone was complete within 35 minutes
both aldehydes are valuable one might choose a 2:1 or even and damage to the protecting groups was insignificant. The
1:1 ratio of aldehydes.
crude diketones 5a and 5b were immediately converted into
The aldehydes 4aϪe required for the preparation of acy- dioximes 1a and 1b (overall yield 77% and 69%, respect-
loins 3aϪd were prepared by standard methods. Aldehyde ively) with an excess of hydroxylamine in methanol (two
4a was accessed starting from commercially available bu- days at room temp.), with the pH maintained at 5 by peri-
tane-1,4-diol which was reacted with 0.25 equivalents of so- odic addition of 4-dimethylaminopyridine. Diketones 5c
dium hydride and then with 0.25 equivalents of 4-methox- and 5d were purified by medium pressure chromatography
ybenzyl chloride to give mainly the mono-O-4-methoxyben- and converted into the corresponding dioximes (1c and 1d)
zyl ether in 79% yield. Swern oxidation of the remaining with hydroxylamine in pyridine.
2624
Eur. J. Org. Chem. 2001, 2623Ϫ2627

Crossed Acyloin Condensation of Aliphatic Aldehydes
FULL PAPER
of m-Bn), 7.22Ϫ7.25 (m, 2 H, arom. H of o-Bn). Ϫ 13C NMR
(63 MHz, CDCl3): δ ϭ 7.28, 8.67, 23.48, 25.0, 26.44, 30.52, 30.80,
34.30, 54.95, 68.47, 69.14, 72.28, 75.78, 77.05, 113.52, 129.03,
130.08, 130.15, 158.95, 211.95, 212.80. Ϫ IR (film): ν˜ ϭ 3467, 2931,
2855, 1711, 1612, 1513, 1463, 1407, 1359, 1302, 1247, 1173, 1099,
1034, 984, 819 cmϪ1. Ϫ MS (EI): m/z (%) ϭ 266 (0.5) [Mϩ], 208
(2), 137 (10), 135 (2), 122 (14), 121 (100), 78 (2), 77 (3), 59 (3), 57
(2), 43 (4). Ϫ HRMS (EI): calcd. for C15H22O4 [Mϩ] 266.1518,
found 266.1524 Ϫ C15H22O4 (266.33): C 67.65, H 8.33; found C
67.94, H 8.14.
Experimental Section
General: NMR spectra were recorded on Bruker AC 250 or DRX
500 instruments. 1H and 13C chemical shifts are reported downfield
from Me4Si in ppm and were determined using residual nondeuter-
ated solvent or, when indicated, using Me4Si as an internal stand-
ard. IR spectra were recorded on Beckman Aculab 8 or Bruker
IFS 88 (FT) spectrometers. Mass spectra and high resolution mass
spectra were recorded on a Finnigan MAT 90 electron impact ma-
chine. Analytical thin layer chromatography was performed on
commercial Merck plates coated with silica gel 60F254. Column
chromatography was carried out on Merck silica gel 60. The solv-
ents used for chromatography were distilled before use. Ethanol
1-(1,3-Dithian-2-yl)-4-hydroxy-10-(tert-butyldiphenylsilanyloxy)-
decan-3-one (3c): This compound was prepared from 1 mol equiv.
4b and 3 mol equiv. 4c; yield based on 4b: 63%, colourless oil. Ϫ
1H NMR (500 MHz, CDCl3, Me4Si): δ ϭ 1.05 [s, 9 H, C(CH3)3],
1.24Ϫ2.17 [m, 14 H, 4 ϫ CH2, CH2CH(OH), SϪCH2ϪCH2,
SϪCH(S)ϪCH2], 2.40Ϫ2.50 and 2.64Ϫ2.75 (2 m, Σ 2 H, CH2ϪCϭ
O), 2.80Ϫ2.87 (m, 4 H, SϪCH2), 3.65 (t, J ϭ 6.4 Hz, 2 H,
CH2ϪOSi), 4.03 (t, J ϭ 6.9 Hz) and 4.06 (t, J ϭ 7.0 Hz, Σ 1 H,
SϪCHϪS), 4.17Ϫ4.18 [m, 1 H, CH(OH)CH2], 7.36Ϫ7.43 (m, 6 H,
arom. H of Si-Ph), 7.66Ϫ7.67 (m, 4 H, arom. H of Si-Ph). Ϫ 13C
NMR (126 MHz, CDCl3, Me4Si): δ ϭ 19.21, 23.52, 24.80, 25.52,
25.64, 25.72, 25.86, 25.92, 26.87, 28.87, 28.91, 29.19, 29.85, 30.18,
30.26, 30.53, 30.69, 32.29, 32.45, 33.73, 34.49, 37.77, 46.21, 46.92,
63.75, 63.84, 75.64, 76.51, 127.58, 129.50, 134.05, 134.09, 135.55,
211.17, 211.82. Ϫ IR (film): ν˜ ϭ 3470, 3134, 3070, 3047, 2998,
2931, 2857, 1711, 1589, 1472, 1462, 1428, 1390, 1361, 1276, 1243,
˚
was distilled from magnesium ethoxide and kept over 3 A molecu-
lar sieves. Triethylamine was distilled from, and kept over, KOH.
3-Benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium chloride, hy-
droxylamine hydrochloride and DMAP were purchased from
Fluka. Propanal and decanal were freshly distilled before use.
Glassware was dried by flaming or assembling straight from the
oven and flushing with argon.
General Procedure for Preparing Crossed Acyloins: One mol equiv.
of one aldehyde was mixed with 3 mol equiv. of the other aldehyde
in ethanol under argon (overall aldehyde concentration 1 ). The
condensation was initiated by addition of catalyst 2 (0.1 mol equiv.)
followed by triethylamine (0.6 mol equiv.). After heating the reac-
tion mixture at reflux for 16 h, addition of water and extraction
with ethyl acetate gave a crude product, which was fractionated
into crossed acyloin and symmetrical acyloins by flash chromato-
graphy on silica (elution with cyclohexane/ethyl acetate). According
to their spectroscopic data (see below) the acyloins were mixtures
of isomers R1CHOHCOR2 and R1COCHOHR2.
1187, 1112, 1008, 998, 938, 908, 824, 742, 704, 688, 622, 614 cmϪ1
.
Ϫ MS (EI): m/z (%) ϭ 544 (0.3) [Mϩ], 487 (10) [M Ϫ C4H9]ϩ, 311
(27), 276 (10), 275 (47), 200 (16), 199 (100), 183 (12), 147 (17), 139
(17), 135 (12), 132 (21), 131 (10), 119 (30), 69 (27). Ϫ HRMS (EI):
calcd. for C30H44O3S2Si [Mϩ] 544.2501, found 544.2534.
5-Hydroxy-1-[(4-methoxyphenyl)methoxy]-11-(tert-butyldiphenyl-
silanyloxy)-2,2-dimethylundecan-4-one (3d): This compound was
prepared from 1 mol equiv. 4d and 3 mol equiv. 4c; yield based on
4d: 29%, colourless oil. Ϫ 1H NMR (250 MHz, CDCl3, Me4Si):
δ ϭ 0.98 and 1.02 [2 s, Σ 6 H, C(CH3)2], 1.04 [s, 9 H, C(CH3)3],
1.15Ϫ1.81 [m, 10 H, 4 ϫ CH2, CH2CH(OH)], 2.34Ϫ2.59 (m, 2 H,
CH2ϪCϭO), 3.19Ϫ3.30 (m, 2 H, CH2OPMB), 3.54 (d, J ϭ 5.0 Hz,
0.3 H, OH), 3.64 (t, J ϭ 6.4 Hz, 2 H, CH2ϪOSi), 3.79 (s, 3 H,
OCH3), 4.07Ϫ4.17 [m, 1 H, CH(OH)CH2], 4.21 (d, J ϭ 4.0 Hz, 0.7
H, OH), 4.40 and 4.46 (2 s, Σ 2 H, OCH2Ph), 6.85Ϫ6.90 (m, 2 H,
arom. H of m-Bn), 7.20Ϫ7.24 (m, 2 H, arom. H of o-Bn),
7.33Ϫ7.45 (m, 6 H, arom. H of Si-Ph), 7.65Ϫ7.69 (m, 4 H, arom.
H of Si-Ph). Ϫ MS (EI): m/z (%) ϭ 547 (3) [M Ϫ C4H9]ϩ, 409 (7),
311 (3), 249 (6), 231 (8), 199 (5), 122 (10), 121 (100), 109 (4). Ϫ
HRMS (EI): calcd. for C33H43O5Si [M Ϫ C4H9]ϩ 547.2880,
found 547.2859.
5-Hydroxy-1-[(4-methoxyphenyl)methoxy]-11-(tert-butyldiphenyl-
silanyloxy)undecan-4-one (3a): This compound was prepared from
1 mol equiv. 4a and 3 mol equiv. 4c; yield based on 4a: 69%, colour-
less oil. Ϫ 1H NMR (250 MHz, CDCl3): δ ϭ 1.01 [s, 9 H, C(CH3)3],
1.19Ϫ1.99 (m, 12 H, 6 ϫ CH2), 2.27Ϫ2.61 (m, 2 H, CH2ϪCϭO),
3.42 (t, J ϭ 5.4 Hz, 2 H, CH2OPMB), 3.37 and 3.63 (2 d, J ϭ
3.6 Hz, Σ 1 H, OH), 3.53 (t, J ϭ 5.4 Hz, 2 H, CH2OSi), 3.78 (s, 3
H, OCH3), 4.12 [m, 1 H, CH(OH)CH2], 4.38 and 4.40 (2 s, Σ 2 H,
OCH2Ph), 6.85 (d, J ϭ 8.9 Hz, 2 H, arom. H of m-Bn), 7.20 (m, 2
H, arom. H of o-Bn), 7.37 (m, 6 H, arom. H of Si-Ph), 7.63 (m, 4
H, arom. H of Si-Ph). Ϫ 13C NMR (63 MHz, CDCl3): δ ϭ 19.23,
23.53, 23.82, 24.90, 25.30, 25.58, 25.68, 26.89, 28.96, 29.23, 30.71,
32.34, 32.49, 33.69, 34.55, 37.82, 55.23, 63.79, 63.87, 69.38, 72.58,
76.17, 76.48, 113.79, 127.60, 129.29, 129.53, 130.38, 134.07, 135.57,
159.20, 212.40. Ϫ IR (film): ν˜ ϭ 2931, 2857, 1710, 1612, 1513,
1472, 1463, 1428, 1390, 1361, 1302, 1248, 1173, 1111, 1036, 1008,
998, 823, 741, 703, 687, 614 cmϪ1. Ϫ MS (EI): m/z (%) ϭ 519 (0.2)
[M Ϫ C4H9]ϩ Ϫ MS (ϩFAB/3-nitrobenzyl alcohol): m/z (%) ϭ 599
(0.9) [M ϩ Na]ϩ, 249 (5), 199 (12), 135 (13), 121 (100). Ϫ HRMS
(ϩFAB): calcd. for C35H48NaO5Si [M ϩ Na]ϩ 599.3169; found
599.3182. Ϫ C35H48O5Si (576.85): C 72.88, H 8.39; found C 72.71,
H 8.20.
4-Hydroxytridecan-3-one (3e): This compound was prepared from
1 mol equiv. decanal and 3 mol equiv. propanal or 1 mol equiv.
propanal and 3 mol equiv. decanal; yield based on the minor alde-
hyde: 56% and 58%, respectively, colourless oil. Ϫ 1H NMR
(500 MHz, CDCl3): δ ϭ 0.86 [t, J ϭ 6.9 Hz, 6 H, 2 ϫ (CH2)8CH3],
0.92 [t, J ϭ 7.4 Hz, 3 H, CH(OH)CH2CH3], 1.10 (t, J ϭ 7.3 Hz, 3
H, CO-CH2CH3), 1.24Ϫ1.45 (m, 26 H, 13 ϫ CH2), 1.48Ϫ1.55 and
1.76Ϫ1.83 [2 m, 2 H, CH(OH)CH2(CH2)7], 1.55Ϫ1.62 and
1.86Ϫ1.91 [2 m, 4 H, CH(OH)CH2CH3, CO-CH2CH2], 2.38Ϫ2.56
4-Hydroxy-7-[(4-methoxyphenyl)methoxy]heptan-3-one (3b): This
compound was prepared from 1 mol equiv. 4a and 3 mol equiv.
propanal; yield based on 4a: 56%, colourless oil. Ϫ 1H NMR
(250 MHz, CDCl3, Me4Si): δ ϭ 0.92 (t, J ϭ 7.3 Hz) and 1.09 (t, J ϭ [m, 4 H, CO-CH2CH3, CO-CH2(CH2)7], 3.48Ϫ3.50 (br m, 2 H, 2
7.4 Hz, Σ 3 H, CH3CH2), 1.55Ϫ1.70 (2 m, Σ 2 H, CH2CH2OPMB), ϫ OH), 4.13Ϫ4.17 [m, 2 H, 2 ϫ CH(OH)]. Ϫ 13C NMR (126 MHz,
1.90Ϫ1.95 [2 m, Σ 2 H, CH2CH(OH)], 2.45Ϫ2.58 (2 m, Σ 2 H, CDCl3): δ ϭ 7.61, 8.86, 14.07, 22.65, 23.61, 24.81, 26.74, 29.24,
CH2ϪCϭO), 3.46 (t, J ϭ 5.9 Hz, 2 H, CH2OPMB), 3.50 (d, J ϭ 29.27, 29.34, 29.38, 29.46, 29.50, 31.06, 31.84, 31.86, 33.88, 37.88,
1.3 Hz, 1 H, OH), 3.80 (s, 3 H, OCH3), 4.15 [m, 1 H, CH(OH)CH2], 76.24, 77.17, 212.44, 212.90. Ϫ IR (film): ν˜ ϭ 3481, 2926, 2855,
4.40 and 4.43 (2 s, Σ 2 H, OCH2Ph), 6.86Ϫ6.89 (m, 2 H, arom. H 1713, 1463, 1407, 1379, 1352, 1262, 1115, 1095, 1037, 983, 723
Eur. J. Org. Chem. 2001, 2623Ϫ2627
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R. Heck, A. P. Henderson, B. Köhler, J. Retey, B. T. Golding
FULL PAPER
cmϪ1. Ϫ MS (EI): m/z (%) ϭ 214 (3) [Mϩ], 158 (3), 157 (49), 155
(77), 97 (40), 88 (11), 85 (13), 83 (100), 71 (30), 69 (53), 59 (100),
2 H, CH2ϪCϭO), 3.64 (t, J ϭ 6.1 Hz, 2 H, CH2ϪOSi). Ϫ 13C
NMR (500 MHz, CDCl3): δ ϭ 6.95, 12.01, 18.05, 26.47, 29.59,
˜
58 (22), 57 (81), 55 (58), 43 (53), 41 (48). Ϫ HRMS (EI): calcd. for 32.86, 62.28, 199.86, 200.25. Ϫ IR (cap film): ν ϭ 2943, 2892, 1714,
C13H26O2 [Mϩ] 214.1933, found 214.1944.
1463, 1109, 1070, 1013, 892 cmϪ1. Ϫ MS (ϩEI): m/z (%) ϭ 257
(100) [Mϩ Ϫ iPr], 243 (34), 213 (94), 173 (8), 103 (23), 57 (17). Ϫ
C16H32O3Si (300.51): C 63.95, H 10.73; found C 62.61, H 10.44;
contains 1/2 molecule of water.
4-Hydroxy-7-triisopropylsilanyloxyheptan-3-one (3f): This com-
pound was prepared from 1 mol equiv. 4e and 3 mol equiv. pro-
panal; yield based on 4e: 42%, colourless oil. Ϫ 1H NMR
(200 MHz, CDCl3): δ ϭ 0.82 (m, 24 H, TIPS ϩ CH3), 1.70 (m, 6 1,8-Bis(triisopropylsilanyloxy)octane-4,5-dione (5b): This compound
H, 3 ϫ CH2), 2.31 (m, 2 H, CH2-CH), 3.31 (d, J ϭ 4.6 Hz, 1 H, was prepared from 3g as a yellow oil, yield 94% Ϫ 1H NMR
CH-OH), 3.48 (m, 2 H, CH2ϪOSi), 3.98 (m, 1 H, CHϪOH). Ϫ (500 MHz, CDCl3): δ ϭ 0.97 (m, 42 H, 2 ϫ TIPS), 1.76 (q, J ϭ
13C NMR: (126 MHz, CDCl3) δ ϭ 8.50, 8.97, 12.04, 18.08, 26.94, 6.4, 4 H, 2 ϫ CH2), 2.79 (t, J ϭ 7.1 Hz, 4 H, 2 ϫ CH2ϪCϭO),
27.84, 30.62, 31.75, 34.29, 62.17, 62.85, 212.54, 213.32. Ϫ IR (cap
3.65 (t, J ϭ 6.4 Hz, 4 H, 2 ϫ CH2ϪOTIPS). Ϫ 13C NMR
(126 MHz, CDCl3): δ ϭ 11.98, 18.01, 26.42, 32.71, 62.30, 200.53.
˜
film): ν ϭ 3481, 2942, 2891, 2866, 1713, 1463, 1367, 1248, 1106,
1038, 1013 cmϪ1. Ϫ MS (ϩEI): m/z (%) ϭ 259 (71) [Mϩ Ϫ iPr],
Ϫ IR (cap film): ν ϭ 2943, 2891, 1714, 1463, 1107, 1069, 1038,
˜
241 (49), 217 (50), 111 (63), 103 (100), 75 (97), 61 (54). Ϫ 1013, 882 cmϪ1. Ϫ MS (ϩEI): m/z (%) ϭ 487 (33) [M ϩ H]ϩ, 443
C16H34O3Si (302.53): C 63.52, H 11.33; found C 60.09, H 10.81;
contains 1 molecule of water.
(25), 313 (42), 269 (100), 243 (62), 217 (40), 139 (42). Ϫ
C26H54O4Si2 (486.88): C 64.14, H 11.18; found C 62.54, H 11.07;
contains 1 molecule of water.
5-Hydroxy-1,8-bis(triisopropylsilanyloxy)octan-4-one (3g): This
1
compound was prepared from 4e; yield 71%, colourless oil. Ϫ H
11-(tert-Butyldiphenylsilanyloxy)-1-[(4-methoxyphenyl)methoxy]-
NMR (200 MHz, CDCl3): δ ϭ 1.02 (m, 42 H, 2 ϫ TIPS), 1.90 (m, undecan-4,5-dione Dioxime 1a: White solid, 77%, m.p. 54 °C. Ϫ 1H
6 H, 3 ϫ CH2), 2.60 (dt, J ϭ 2.2 and 5.1 Hz, 1 H, CHCH2), 3.69
NMR (500 MHz, CDCl3): δ ϭ 1.09 [s, 9 H, C(CH3)3], 1.38 [br m,
(m, 5 H, OH and 2 ϫ CH2ϪOSi), 4.20 (m, 1 H, CH-OH). Ϫ 13C 4 H, (CH2)2-(CH2)2ϪO], 1.52 [m, 2 H, CH2-(CH2)4ϪO], 1.60 [m,
NMR (50.3 MHz, CDCl3): δ ϭ 11.99, 18.04, 26.91, 28.35, 30.51, 2 H, NϭC-(CH2)4ϪCH2], 1.89 (quintet, J ϭ 7.5 Hz, 2 H,
˜
34.29, 62.25, 62.89, 212.50. Ϫ IR (cap film): ν ϭ 3483, 2943, 2892, CH2CH2OPMB), 2.63 [t, J ϭ 7.6 Hz, 2 H, NϭCϪCH2-(CH2)5],
2866, 2729, 1713, 1653, 1367, 1255, 1202, 1107, 1013 cmϪ1. Ϫ MS
2.75 [t, J ϭ 7.4 Hz, 2 H, NϭCϪCH2-(CH2)2], 3.51 (t, J ϭ 6.5 Hz,
(ϩEI): m/z (%) ϭ 489 (0.5) [M ϩ H]ϩ, 445 (4), 427 (5), 271 (100), 2 H, CH2OPMB), 3.68 (t, J ϭ 6.6 Hz, 2 H, CH2ϪOSi), 3.79 (s, 3
253 (22), 157 (14), 145 (29), 123 (32), 71 (14), 59 (10). Ϫ H, OCH3), 4.47 (s, 2 H, CH2Ph), 6.88 (d, J ϭ 8.6 Hz, 2 H, arom.
C26H56O4Si2 (488.90): C 63.88, H 11.55; found C 60.42, H 10.62; H of m-Bn), 7.29 (d, J ϭ 8.6 Hz, 2 H, arom. H of o-Bn), 7.40 (m,
contains 1 molecule of water.
6 H, arom. H of Si-Ph), 7.71 (m, 4 H, arom. H of Si-Ph), 9.17 (s,
1 H, NOH), 9.18 (s, 1 H, NOH). Ϫ 13C NMR (126 MHz, CDCl3):
δ ϭ 19.21, 20.63, 23.92, 25.53, 26.40, 26.90, 29.61, 32.48, 55.22,
64.08, 69.70, 72.38, 113.71, 127.60, 129.33, 129.52, 130.52, 134.09,
General Procedures for the Conversion of Acyloins into 1,2-Diox-
imes. Procedure A (acyloins 3a and 3b): To a 1.3  solution of the
acyloin in 2-ethoxyethanol and acetic acid (10:3, v/v) at 105 °C was
added bismuth(III) oxide (3.5 mol equiv.) in one portion. After 35
min. TLC showed complete consumption of starting material. The
mixture was filtered hot and the filter cake washed with chloro-
form. The filtrate was washed neutral with aq. NaHCO3 and water
and dried (MgSO4). The solvent was removed under reduced pres-
sure to leave a yellow oil which was immediately taken up in meth-
anol. After addition of H2NOH·HCl (5 mol equiv.), the pH was
˜
135.57, 157.58, 159.07. Ϫ IR (film): ν ϭ 3296, 3072, 2932, 2859,
1614, 1588, 1514, 1464, 1429, 1390, 1361, 1303, 1247, 1174, 1111,
1039, 989, 929, 905, 825, 741, 704, 687, 615 cmϪ1. Ϫ MS (EI): m/
z (%) ϭ 604 (0.1) [Mϩ], 587 (1) [M Ϫ OH]ϩ, 547 (2) [M Ϫ C4H9]ϩ.
Ϫ HRMS (EI): calcd. for C35H48N2O5Si [Mϩ] 604.3353; found
604.3333 Ϫ C35H48N2O5Si (604.86): C 69.50, H 8.00, N 4.63; found
C 69.21, H 7.98, N 4.43.
adjusted to 5 by addition of DMAP. The mixture was stirred for 7-[(4-Methoxyphenyl)methoxy]heptan-3,4-dione
two days at room temp. with periodic addition of DMAP to main-
Dioxime
White solid, 69%, m.p. 108 °C). Ϫ H NMR (500 MHz, CD3OD):
tain the pH at 5. After addition of water and extraction with ethyl δ ϭ 0.92 (t, J ϭ 7.5 Hz, 3 H, CH2CH3), 1.68 (quintet, J ϭ 7.2 Hz,
(1b):
1
acetate the crude dioxime was purified by flash chromatography on
silica using cyclohexane/ethyl acetate as eluent.
2 H, CH2CH2CH2), 2.51 (q, J ϭ 7.5 Hz, 2 H, CH2CH3), 2.57 (t,
J ϭ 7.7 Hz, 2 H, NϭCϪCH2CH2), 3.36 (t, J ϭ 6.7 Hz, 2 H,
CH2OPMB), 3.68 (s, 3 H, OCH3), 4.31 (s, 2 H, CH2Ph), 6.78Ϫ6.80
(m, 2 H, arom. H of m-Bn), 7.15Ϫ7.17 (m, 2 H, arom. H of o-Bn),
Procedure B (acyloins 3f and 3g): To a solution of the Dess Martin
periodinane (1.2 mol equiv.) in dry dichloromethane was added
dropwise the acyloin (1.0 mol equiv.) in dry dichloromethane over 10.74 (s, 1 H, NOH), 10.81 (s, 1 H, NOH). Ϫ 13C NMR (126 MHz,
a 10 min. period. The resulting solution was stirred under N2 for
1 h. The yellow-coloured mixture was concentrated and the residue
chromatographed on silica gel eluting with ethyl acetate/petroleum
ether (5:95) to give the diketone as a yellow oil. To the diketone
(X, g) in dry ethanol (10X, mL) was added hydroxylamine hydro-
chloride (2X, g) and pyridine (2X, mL) and the resulting solution
was stirred for 2 h. After this time the solution was concentrated,
CD3OD): δ ϭ 11.7, 17.9, 21.4, 27.8, 55.9, 71.4, 73.6, 115.0, 130.9,
131.9, 157.7, 159.5, 161.0. Ϫ IR (diffuse reflection): ν˜ ϭ 3227, 3086,
2944, 2880, 1613, 1585, 1515, 1457, 1367, 1303, 1253, 1175, 1095,
1031, 969, 910, 901, 878, 851, 815 cmϪ1. Ϫ MS (EI): m/z (%) ϭ
277 (14) [Mϩ], 142 (9), 141 (78), 126 (5), 122 (9), 121 (100). Ϫ
HRMS (EI): calcd. for C15H21N2O3 [Mϩ] 277.1552; found
277.1541 Ϫ C15H21N2O3 (277.34): C 61.21, H 7.53, N 9.52; found
water was added and the solution extracted into ethyl acetate. The C 60.94, H 7.49, N 9.30.
extracts were combined, dried (MgSO4) and concentrated to give
7-Triisopropylsilanyloxyheptane-3,4-dione Dioxime (1c): This com-
the product as a white solid.
pound was prepared from 5a as a white solid, yield 69%. Ϫ 1H
NMR (500 MHz, [D6]DMSO): δ ϭ 1.03 (m, 24 H, TIPS ϩ CH3),
1.65 (quintet, J ϭ 7.3 Hz, 2 H, CH2), 2.56 (m, 4 H, 2 ϫ CH2ϪCϭ
7-Triisopropylsilanyloxyheptane-3.4-dione (5a): This compound was
prepared from 3f as a yellow oil, yield 69% Ϫ 1H NMR (500 MHz,
CDCl3): δ ϭ 0.95 (m, 24 H, TIPS ϩ CH3), 1.77 (quintet, 2 H, J ϭ N), 3.63 (t, J ϭ 7.1 Hz, 2 H, CH2ϪOSi), 11.31 (s, 1 H, NϪOH),
6.4 Hz, CH2), 2.70 (q, J ϭ 7.0, 2 H, CH2ϪCH3) 2.79 (t, J ϭ 7.0,
11.35 (s, 1 H, NϪOH). Ϫ 13C NMR (126 MHz, [D6]DMSO): δ ϭ
2626
Eur. J. Org. Chem. 2001, 2623Ϫ2627

Crossed Acyloin Condensation of Aliphatic Aldehydes
FULL PAPER
[2]
[3]
´
J. Retey, in Vitamin B12 and B12-Proteins (Eds.: B. Kräutler,
D. Arigoni, and B. T. Golding), Wiley-VCH, Weinheim, 1998,
chapter 18 (pp. 273Ϫ288).
10.88, 11.41, 17.83, 19.75, 29.51, 29.56, 63.17, 155.25, 156.95. Ϫ
˜
IR (KBr disc): ν ϭ 3283, 2944, 2868, 1461, 1075, 1041, 1029, 909,
882 cmϪ1. Ϫ MS (ϩEI): m/z (%) ϭ 287 (11) [Mϩ Ϫ iPr], 198 (100),
131 (30), 103 (54), 75 (75), 61 (54). Ϫ C16H34N2O3Si (330.54): C
58.14, H 10.37, N 8.47; found C 58.22, H 10.79, N 8.47.
For a review, see: B. T. Golding, W. Buckel, in Comprehensive
Biological Catalysis (Ed.: M. L. Sinnott), Academic Press, Lon-
don, 1997, chapter 33 (pp. 239Ϫ259).
[4]
[5]
[6]
[7]
H. Stetter, G. Dämbkes, Synthesis 1977, 403Ϫ404.
H. Stetter, G. Dämbkes, Synthesis 1980, 309Ϫ310.
H. Stetter, R. Y. Rämsch, Synthesis 1981, 477Ϫ478.
For the acyloin condensation of esters, see: K. Rühlmann, H.
Seefluth, H. Becker, Chem. Ber. 1967, 100, 3820Ϫ3824.
Concerning the mechanism of the thiazolium-promoted acy-
loin condensation, see K. Motesharei, D. C. Myles, J. Am.
Chem. Soc. 1997, 119, 6674Ϫ6675 and references cited therein.
S. D. Burke, T. H. Powner, M. Kageyama, Tetrahedron Lett.
1983, 24, 4529Ϫ4532.
A. Murai, M. Ono, T. Masamune, J. Chem. Soc., Chem. Com-
mun. 1977, 573Ϫ574.
T. S. Burton, M. P. L. Caton, E. C. J. Coffee, T. Parker, K.
A. J. Stuttle, G. L. Watkins, J. Chem. Soc., Perkin Trans. 1
1976, 2550Ϫ2556.
J. Uenishi, Y. Kawachi, S. Wakabayashi, J. Chem. Soc., Chem.
Commun. 1990, 1033Ϫ1034.
D. B. Dess, J. C. Martin, J. Am. Chem. Soc. 1991, 113,
7277Ϫ7287.
W. Rigby, J. Chem. Soc. 1951, 793Ϫ795.
Vogel’s Textbook of Practical Organic Chemistry, 5th ed., Lon-
don; New York: Longman, 1989.
1,8-Bis(triisopropylsilanyloxy)octane-4,5-dione Dioxime (1d): This
compound was prepared from 5b as a white solid, yield 57%. Ϫ 1H
NMR (500 MHz, CDCl3): δ ϭ 1.00 (m, 42 H, 2 ϫ TIPS), 1.62
(quintet, J ϭ 7.4 Hz, 4 H, 2 ϫ CH2), 2.54 (t, J ϭ 7.3 Hz, 4 H, 2
ϫ CH2ϪCϭN), 3.60 (t, J ϭ 7.0 Hz, 4 H, 2 ϫ CH2ϪOTIPS), 11.30
(s, 2 H, 2 ϫ OH). Ϫ 13C NMR (126 MHz, CDCl3): δ ϭ 11.36,
[8]
˜
17.83, 19.71, 29.58, 63.15, 155.24. Ϫ IR (KBr): ν ϭ 3342, 2962,
[9]
2946, 2867, 1606, 1461, 1118, 1072, 1027, 1019, 883 cmϪ1. Ϫ MS
(ϩEI): m/z (%) ϭ 499 (2.7) [Mϩ Ϫ OH], 473 (46), 299 (44), 198
(75), 145 (77), 103 (81), 89 (52), 75 (100). Ϫ C26H56N2O4Si2
(516.91): C 60.41, H 10.92, N 5.42; found C 60.88, H 10.92, N 5.24.
[10]
[11]
Acknowledgments
[12]
[13]
We thank the European Commission, EPSRC, the Deutsche For-
schungsgemeinschaft and the Fonds der Chemischen Industrie for
financial support. R. H. thanks the Land Baden-Württemberg for
a scholarship for graduate students.
[14]
[15]
[1]
M. Knauer, B. Köhler, W. Clegg, M. R. J. Elsegood, B. T. Gold-
ing, J. Retey, Angew. Chem. Int. Ed. Engl. 1995, 34, 2389Ϫ2390.
Received August 17, 2000
´
[O00430]
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2627