Some unexpected results in Dondoni's one-carbon homologation procedure

Article abstract of DOI:10.1081/CAR-100108278

The formation of the unexpected secondary products (3 and 9) during Dondoni's one-carbon homologation of 6-deoxy-6-iodo-2,3:4,5-bis-O-isopropylidene-D-glucose (1) are described.

Full text of DOI:10.1081/CAR-100108278

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SOME UNEXPECTED RESULTS IN DONDONI'S ONE-
CARBON HOMOLOGATION PROCEDURE
José Marco-Contelles a & Elsa de Opazo a
a Laboratorio de Radicales Libres (CSIC) , C/Juan de la Cierva 3, Madrid, 28006, Spain
Published online: 16 Aug 2006.
To cite this article: José Marco-Contelles & Elsa de Opazo (2001) SOME UNEXPECTED RESULTS IN DONDONI'S ONE-CARBON
HOMOLOGATION PROCEDURE , Journal of Carbohydrate Chemistry, 20:7-8, 637-646
To link to this article: http://dx.doi.org/10.1081/CAR-100108278
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J. CARBOHYDRATE CHEMISTRY, 20(7&8), 637–646 (2001)
SOME UNEXPECTED RESULTS IN DONDONI’S
ONE-CARBON HOMOLOGATION PROCEDURE1
José Marco-Contelles* and Elsa de Opazo
Laboratorio de Radicales Libres (CSIC),
C/ Juan de la Cierva 3, 28006-Madrid, Spain
ABSTRACT
The formation of the unexpected secondary products (3 and 9) during Don-
doni’s one-carbon homologation of 6-deoxy-6-iodo-2,3:4,5-bis-O-isopropyli-
dene-D-glucose (1) are described.
INTRODUCTION
Dondoni’s one-carbon homologation procedure is one of the most successful
protocols described to date for the homologation of aldehydes.2 The mild and sim-
ple experimental conditions enhance the interest and synthetic potential of this ef-
ficient and reproducible process. In addition, the highly anti-stereoselective3 asym-
metric induction applied to ꢀ-alkoxy aldehydes has been used in a number of
synthetic approaches for the preparation of enantiomerically pure products.4 The
mechanism of this useful transformation has been discussed by Dondoni and co-
workers (Scheme 1).5
Very recently we wished to carry out a one-carbon homologation of 6-deoxy-
6-iodo-2,3:4,5-bis-O-isopropylidene-D-glucose (1) and we chose Dondoni’s
method.2 In this communication we describe in full the unexpected, secondary
products obtained in a three-step protocol for the addition of 2-trimethylsilylthia-
zole (2-TST) to the aldehyde carbonyl of 1.6
RESULTS AND DISCUSSION
Aldehyde 1 has been prepared in enantiomerically pure form and multigram
quantities from commercially available D-glucose diethyl dithioacetal.7 The reac-
637
Copyright © 2001 by Marcel Dekker, Inc.
www.dekker.com

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Scheme 1. Proposed mechanism for the 2-TST coupling with aldehydes (ref. 5).
tion of this compound with 2-TST under standard conditions3 afforded the ex-
pected 6-deoxy-6-iodo-2,3:4,5-bis-O-isopropylidene-1-(1ꢁ,3ꢁ-thiazol-2ꢁ-yl)-D-
glycero-D-gulose (2, 60%),7 and a secondary product (3aR,3bS,6aR,7aR)-
tetrahydro-2,2,5,5-tetramethyl-6aH-cyclopenta[1,2-d:3,4-dꢁ]bis[1,3]dioxole-6a-
carboxaldehyde (3) in 7% yield (Scheme 2). The structure of the latter product was
firmly established after inspection of the analytical and spectroscopic data. In the
1H NMR spectrum of 3 we observed a singlet aldehydic proton at 9.73 ppm (198.4
ppm for HMCO in the 13C NMR spectrum) and two significant protons at 2.50
ppm (dd, J5A,5Bꢂ 15.2 Hz, J4,5bBꢂ 2.9 Hz, 1 H, H5B) and 2.17 ppm (dd, J5A,5B
ꢂ 15.2 Hz, J4,5Aꢂ 6.2 Hz, 1 H, H5A) (C5: 39.9 ppm) forming the AB part of an
ABX system with a proton at 4.91 ppm (td, J4,5Bꢂ 2.9 Hz, J4,5Aꢂ 6.2 Hz, 1 H, H4).
In the IR spectrum of 3 no carbonyl band absorption was observed, the carbonyl
function being in the hydrated form. The absolute configuration at C1 was easily
assigned as R by NOE experiments. These data along with the elemental analysis
and the MS spectral results clearly pointed out that product 3 contained a cy-
Scheme 2. Reaction of 2-TST with ꢀ-alkoxy aldehyde 1.

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639
Scheme 3. Possible mechanisms for the intramolecular alkylation of ꢀ-alkoxy aldehyde 1.
clopentane ring system resulting from the intramolecular ꢀ-alkylation of the ꢀ-
alkoxy aldehyde 1. Additional proof of structure was obtained upon reduction of
compound 3 with sodium borohydride to give alcohol 4, which was then acetylated
to yield product 5 (Scheme 2).
Finally, we tested the direct alkylation of compound 1 with DBU (1.1 equiv)
as base, under the same experimental conditions (Scheme 3). Very interestingly, a
rapid reaction ensued (1 h) giving cleanly compound 3 in 75% isolated yield after
flash chromatography.
It is noteworthy that compounds 3–5 are densely functionalized, chiral cy-
clopentane derivatives with some of the structural and functional moieties present
in carbocyclic nucleosides8 and glycosidase inhibitors such as trehazolin aglycon
(Figure 1).9
The present reactivity was completely unexpected and unprecedented. As it
is well known, base-mediated alkylation of aldehydes is hampered by crotoniza-
tion or polymerization due to aldol condensation-like competitive reactions. A se-
ries of aldehyde derivatives (imines, hydrazones, oximes or enamines) have been
Figure 1.

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MARCO-CONTELLES AND DE OPAZO
used for this purpose,10 whereas a literature search for ꢀ-alkylation of ꢀ-alkoxy
aldehydes gave a limited number of examples.11 In addition, a recent synthesis of
chiral ꢀ-alkyl, ꢀ-trifluoromethyl ꢀ-alkoxy aldehydes used an indirect approach
from ketones,12a and an elegant synthesis of spirocyclopentenenones from ꢀ-
alkoxy aldehydes in furanose templates was only possible through enamine inter-
mediates.12b This is in sharp contrast with the ꢀ-alkoxy ketones which have proved
to be excellent intermediates for aldol reactions via the enol borinates.13
In Scheme 3 we show two possible mechanisms to explain these results: (a)
An intramolecular mechanism, where the presumed intermediate A, after proton
abstraction gives the trimethylsilyl enol ether B, the real precursor for the in-
tramolecular alkylation. Note that intermediate A can also yield the major product
(2) in this reaction,14 and (b) Alternatively, the intermolecular 2-TST mediated ab-
straction of the ꢀ-proton in compound 1 could also afford the reactive intermedi-
ate B leading to compound 3.
In any case ꢃ-elimination in intermediate B (Scheme 3) was not observed.
This is really exceptional, considering the experimental conditions used (room
temperature with 2-TST as the only reagent in the medium) compared with the nec-
essary controlled conditions [low temperature reaction (ꢄ78°C), LDA as base, co-
solvents such as HMPT or DMPU, and highly reactive alkylating agents] for the
intermolecular alkylation of tartaric acid derivatives described by Seebach.15 In the
present case, the stability of the enolate may also be due to the rigid acetonide
skeleton which precludes the optimal geometrical arrangement for ꢃ-elimination
to take place.15
In summary, we have reported the first example of an intramolecular alkyla-
tion of an ꢅ-iodo ꢀ-alkoxy aldehyde, by using basic, extremely simple and mild re-
action conditions. These results open the way for new exciting synthetic ventures
directed to the important, synthetic intermolecular alkylation of chiral ꢀ-het-
eroatom O or N-substituted aldehydes, as a new strategy for the synthesis of enan-
tiomerically pure molecules containing quaternary centers.16
Continuing with Dondoni’s protocol for the synthesis of aldehyde 7 from in-
termediate 2 (Scheme 4), we first O-benzylated the free alcohol 2 to give com-
pound 8,7 and then submitted it to sequential reactions2 with methyl iodide, sodium
borohydride and mercuric chloride to give the desired product 7, in 50% yield, and
compound 9, in 5% overall yield from product 8 (Scheme 4).
Scheme 4. Synthesis of compounds 7 and 9 from intermediate 8.

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641
The unexpected compound 9 was an extremely unstable product, and no reli-
able elemental analysis of the product could be obtained. However, the spectro-
scopic data strongly supported this structure. The IR spectrum of 9 contained a
strong carbonyl ester band at 1760 cm-1. In the 1H NMR spectrum of compound 9
we could assign the same protons, with similar chemical shifts, as those bonded to
carbons C3-C8, in compounds 7 or 8: the iodide atom and the two isopropylidene
groups were still present, but the thiazole nucleus was absent. The phenylmethyl
protons were more shifted in compound 9 (ca. 0.6 ppm) than in the precursor 8.7
These IR and 1H NMR data were supported in the 13C NMR spectrum plus the re-
sults from a DEPT experiment;9 a signal at 170.4 ppm was assigned to the ester
carbonyl group, and the methylene carbon bearing the iodide appeared at 1.4 ppm.
Finally, the mass spectrum of 9 showed an intense peak at m/z 461, suggesting that
the structure of compound 9 corresponded to the benzylic ester of the oxidized
form of aldehyde 1 (Scheme 2).
Looking very carefully at the three steps protocol for Dondoni’s homologa-
tion of product 8, we could see that this secondary product was already present in
the first step of the protocol, the reaction with methyl iodide, and that it survived
untouched the mild and quick reduction with sodium borohydride and the mercuric
mediated deprotection of the masked aldehyde. To the best of our knowledge a
similar product has not been documented in the reported Dondoni’s systematic ap-
plication of this method.2 In fact, it is difficult to rationalize the formation of this
molecule in the reaction with methyl iodide until formation of the quaternary salt!
In Scheme 5 we show a mechanism that we tentatively propose for the for-
mation of ester 9. Obviously, the equilibrium between 8 and 8ꢆ is displaced to the
Scheme 5. Possible mechanism for the formation of compound 9 from intermediate 8.

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MARCO-CONTELLES AND DE OPAZO
left, to the most stable aromatic “imine” 8. However, we think that enamine 8ꢆ may
react with small traces of water to give intermediate A, affording ester 9 after elim-
ination of thiazolidine B.
In summary, in this report we have described the successful homologation of
aldehyde 1 to aldehyde 7 using Dondoni’s method, showing also the formation of
some secondary, unexpected products (3 and 9) in this protocol. These results en-
hance the generality of the method, but also point out the possible formation of sec-
ondary products when designing synthetic schemes using this methodology.
EXPERIMENTAL
General Methods. Reactions were monitored by TLC using precoated sil-
ica gel aluminium plates containing a fluorescent indicator (Merck, 5539). Detec-
tion was done by UV (254 nm) followed by charring with sulfuric-acetic acid
spray, 1% aqueous potassium permanganate solution or 0.5% phosphomolybdic
acid in 95% EtOH. Anhydrous Na2SO4 was used to dry organic solutions during
work-ups and the removal of solvents was carried out under vacuum with a rotary
evaporator. Flash column chromatography was performed using silica gel 60
(230–400 mesh, Merck) and hexane/ ethyl acetate mixtures as eluent unless other-
wise stated. 1H spectra were recorded with a Varian VXR-300(400)S spectrome-
13
ter, using tetramethylsilane as internal standard and
recorded with a Bruker WP-200-SY.
C NMR spectra were
(3aR,3bS,6aR,7aR)-Tetrahydro-2,2,5,5-tetramethyl-6aH-cy-
clopenta[1,2-d:3,4-dꢁ]bis[1,3]dioxole-6a-carboxaldehyde (3). Method (A).
Compound 1 (197 mg, 0.53 mmol) dissolved in dry methylene chloride (1 mL) was
treated with 2-TST (0.094 mL, 0.58 mmol, 1.1 equiv) at 0°C, under argon. The re-
action mixture was warmed and stirred at room temperature for 18 h. The solvent
was removed, and the residue was treated with Bu4NF (0.53 mL, 1.1 M in THF)
until desilylation was complete. The solvent was evaporated, the residue diluted
with water and extracted with methylene chloride several times. The organic layer
was dried, filtered and concentrated. Flash chromatography (hexane/ethyl acetate
10%) gave compounds 27 (141.4 mg, 60%) and 3 (9.3 mg, 7%). Method (B). Alde-
hyde 1 (104.4 mg, 0.28 mmol) was dissolved in dry CH2Cl2 (1 mL, 0.3 M), cooled
at 0 °C and treated with DBU (0.05 mL, 0.31 mmol, 1.1 equiv). The mixture was
stirred and warmed at rt for 1 h. The solvent was removed and the crude product
was submitted to chromatography (hexane/ethyl acetate, 9/1) to give compound 3
(51 mg, 75%): oil; [ꢀ]D25 ꢄ 2 (c 0.7, CHCl3); IR (film) v 3470, 2986, 2942, 1744,
1644, 1376, 1254, 1166, 1060 cm-1; 1H NMR (300 MHz, CDCl3) ꢇ 9.73 (s, 1 H,
CHO), 4.91 (td, J4,5Bꢂ J4,3ꢂ 6.2 Hz, J4,5Aꢂ 2.9 Hz, 1 H, H4), 4.63 (d, J3,4ꢂ 6.2
Hz, 1 H, H3), 4.61 (s, 1 H, H2), 2.50 (dd, J5A,5Bꢂ 15.2 Hz, J4,5Aꢂ 2.9 Hz, 1 H,
H5A), 2.17 (dd, J5A,5Bꢂ 15.2 Hz, J4,5Bꢂ 6.2 Hz, 1 H, H5B), 1.52, 1.46, 1.38, 1.31
[4 s, 12 H, 2 ꢈ OC(CH3)2O]; 13C NMR (75 MHz, CDCl3) ꢇ 198.4 (CHO), 113.5,

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DONDONI’S ONE-CARBON HOMOLOGATION
643
111.1 [2 ꢈ OC(CH3)2O], 97.3 (C1), 86.6, 83.6 (C2, C3), 81.2 (C4), 39.9 (C5),
27.5, 26.7, 25.9, 24.7 [2 ꢈ OC(CH3)2O]; MS (70 eV) m/z 243 (Mꢉ1ꢉ, 19), 227
(Mꢉ-15, 64), 43 (100).
Anal. Calcd for C12H18O5 (242.27): C, 52.94; H, 7.49. Found: C, 52.75;
H, 7.38.
(3aR,3bS,6aR,7aR)-Tetrahydro-2,2,5,5-tetramethyl-6aH-cy-
clopenta[1,2-d:3,4-dꢁ]bis[1,3]dioxole-6a-methanol (4). To a solution of com-
pound 3 (84.9 mg, 0.35 mmol) in methanol (2.1 mL, 0.17 M), cooled at 0°C,
sodium borohydride (20 mg, 0.52 mmol, 1.5 equiv) was added, and the mixture
was warmed at rt and stirred for 30 min. Acetone (0.5 mL) was added and the sol-
vents removed by evaporation. The crude product was diluted with methylene
chloride, washed with brine, dried and filtered. The solvent was evaporated and the
residue was submitted to chromatography (hexane/ethyl acetate, 4/1) to give alco-
hol 4 (73 mg, 85%): oil; [ꢀ]D25 ꢄ 13 (c 0.47, CHCl3); IR (film) v 3468, 2986, 2944,
1380, 1210, 1168, 1058 cm-1; 1H NMR (300 MHz, CDCl3) ꢇ 4.81 (ddd, J3,4ꢂ 5.9
Hz, J4,5Aꢂ 4.0 Hz, J4,5Bꢂ 2.9 Hz, 1 H, H4), 4.62 (d, J3,4ꢂ 5.9 Hz, 1 H, H3), 4.40
(s, 1 H, H2), 3.78 (dd, J1ꢁA,1ꢁBꢂ 12.1 Hz, J1ꢁA,OHꢂ 4.9 Hz, 1 H, H1ꢁA), 3.69 (dd,
J
J
1ꢁA,1ꢁBꢂ 12.1 Hz, J1ꢁB,OHꢂ 8.2 Hz, 1 H, H1ꢁB), 2.18 (dd, J1ꢁB,OHꢂ 8.2 Hz,
1ꢁA,OHꢂ 4.9 Hz, 1 H, OH), 2.16 (d, J5A,4ꢂ 4.0 Hz, 1 H, H5A), 2.10 (d, J5B,4ꢂ 2.9
Hz, 1 H, H5B), 1.48, 1.46, 1.37, 1.29 [4 s, 12 H, 2 ꢈ OC(CH3)2O]; 13C NMR (75
MHz, CDCl3) ꢇ 110.8, 109.8 [2 ꢈ OC(CH3)2O], 92.1, (C1), 84.7 (C2), 82.3 (C3),
80.2 (C4), 65.0 (C1ꢁ), 41.2 (C5), 28.1, 26.4, 26.0, 23.6 [2 ꢈ OC(CH3)2O]; MS (70
eV) m/z 229 (M-15ꢉ, 100), 213 (4), 155 (10), 111 (56), 99 (17), 43 (74).
Anal. Calcd for C12H20O5 (244.29): C, 59.00; H, 8.25. Found: C, 59.15;
H, 8.36.
(3aR,3bS,6aR,7aR)-Tetrahydro-2,2,5,5-tetramethyl-6aH-cy-
clopenta[1,2-d:3,4-dꢁ]bis[1,3]dioxole-6a-methyl Acetate (5). Alcohol 4 (32
mg, 0.13 mmol) was treated with a mixture of acetic anhydride/pyridine (1 mL,
1/1) at rt overnight. The solvent was evaporated and the crude product was sub-
mitted to chromatography (hexane/ethyl acetate, 83/17) to give acetate 5 (35 mg,
93%): oil; [ꢀ]D25 ꢄ 4 (c 0.51, CHCl3); IR (film) v 2989, 2938, 1747, 1382, 1211,
1
1169, 1062 cm-1; H NMR (300 MHz, CDCl3) ꢇ 4.79 (dt, J3,4ꢂ J4,5Bꢂ 5.6 Hz,
J4,5Aꢂ 1.5 Hz, , 1 H, H4), 4.59 (d, J3,4ꢂ 5.7 Hz, 1 H, H3), 4.37/4.15 (2 d, Jꢂ 12.1
Hz, 2 H, 2 H1ꢁ), 4.32 (s, 1 H, H2), 2.17 (br d, J5A,5Bꢂ 15.0 Hz, 1 H, H5A), 2.09
(s, 3 H, OCOCH3), 2.07 (dd, J5A,5Bꢂ 15.0 Hz, J5B,4ꢂ 5.6 Hz, 1 H, H5B), 1.44 (s,
6 H), 1.37, 1.29 [3 s, 12 H, 2 ꢈ OC(CH3)2O]; 13C NMR (75 MHz, CDCl3) ꢇ 170.1
(OCOCH3), 111.2, 109.9 [2 ꢈ OC(CH3)2O], 89.9, (C1), 85.0 (C2), 82.2 (C3), 80.2
(C4), 65.8 (C1ꢁ), 41.5 (C5), 27.9, 26.0 (2 C), 23.6 [2 ꢈ OC(CH3)2O], 20.9
(OCOCH3); MS (70 eV) m/z 286 (M, 1), 271 (M-15ꢉ, 72), 228 (8), 171 (10), 153
(34), 111 (66), 81 (33), 59 (20), 43 (100).
Anal. Calcd for C14H22O6 (286.32): C, 58.73; H, 7.74. Found: C, 58.65;
H, 7.63.

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2-O-Benzyl-7-deoxy-7-iodo-3,4:5,6-bis-O-isopropylidene-D-glycero-D-
gulo-heptose (7) and Benzyl 6-deoxy-6-iodo-2,3:4,5-bis-O-isopropylidene-D-
gluconoate (9). Product 87 (930 mg, 1.7 mmol) was dissolved in acetonitrile (10
mL) and the solution treated with methyl iodide (0.53 mL, 9.5 mmol, 15 equiv) at
80 °C (bath temperature) for 24 h in a sealed tube. The reaction was cooled, the sol-
vent evaporated and the residue was dissolved in methanol (10 mL), cooled at 0°C
and treated with sodium borohydride (96.7 mg, 2.55 mmol, 1.5 equiv) under vig-
orous stirring for 30 min. Acetone was then added to destroy the excess of reagent,
the solvent was evaporated in vacuo, and the crude product was dissolved in
methylene chloride, washed with brine, dried, filtered, and the solvent was evapo-
rated. The residue was dissolved in acetonitrile (1 mL) and to this solution, a solu-
tion of mercuric chloride (562 mg, 2.04 mmol, 1.2 equiv) in a mixture of acetoni-
trile/water (7.4 mL, 4/1) was slowly added. The mixture was stirred at rt for 15 min.
The suspension was filtered over celite, which was washed with ethyl acetate. The
organic layer was washed with brine, dried, filtered, concentrated and the residue
was submitted to chromatography (hexane/ethyl acetate, 84/16) to give compounds
7 (420 mg, 50%) and 9 (30 mg, 5%).
1
7: oil; H NMR (300 MHz, CDCl3) ꢇ 9.71 (d, J1,2ꢂ 2.1 Hz, 1 H, H-1),
7.36/7.27 (m, 5 H, OCH2C6H5), 4.76/4.60 (AB system, Jꢂ 11.7 Hz, 2 H,
OCH2C6H5), 4.54 (q, J5,6ꢂ J6,7ꢂ J6,7ꢁꢂ 7.0 Hz, 1 H, H-6), 4.32 (dd, J3,4ꢂ 7.9 Hz,
J2,3ꢂ 5.9 Hz, 1 H, H-3), 4.13 (q, J4,5ꢂ 10.4 Hz, J3,4ꢂ 7.9 Hz, 1 H, H-4), 4.12 (dd,
J4,5ꢂ 10.4 Hz, J5,6ꢂ 7.0 Hz, 1 H, H-5), 3.88 (dd, J2,3ꢂ 5.9 Hz, J1,2ꢂ 2.1 Hz 1 H,
H-2), 3.37ꢄ3.34 (m, 2 H, 2 H-7), 1.50, 1.43, 1.37, 1.35 [4 s, 2 ꢈ OC(CH3)2O].
Anal. Calcd for C20H27IO6 (490.33): C, 48.99; H, 5.55. Found: C, 48.76;
H, 5.67.
9: oil; [ꢀ]D25 ꢄ 21 (c 0.34, CHCl3); IR (film) v 2987, 2936, 1760, 1498, 1456,
1381, 1214, 1100, 1062 cm-1; 1H NMR (300 MHz, CDCl3) ꢇ 7.37ꢄ7.32 (m, 5 H,
CO2CH2C6H5), 5.26/5.23 (2 d, Jꢂ 12.1 Hz, 2 H, CO2CH2C6H5), 4.57 (d, J2,3ꢂ 8.1
Hz, 1 H, H2), 4.53 (q, J5,6Aꢂ J5,6Bꢂ J5B,4ꢂ 7.0 Hz, 1 H, H5), 4.33 (dd, J3,4ꢂ 1.5
Hz, J4,5ꢂ 6.7 Hz, 1 H, H4), 4.25 (dd, J3,4ꢂ 1.5 Hz, J3,2ꢂ 8.0 Hz, 1 H, H3), 3.39
(dd, J6A,6Bꢂ 10.1 Hz, J6A,5ꢂ 6.7 Hz, 1 H, H6A), 3.33 (dd, J6A,6Bꢂ 10.1 Hz, J6B,5
ꢂ 7.7 Hz, 1 H, H5B), 1.49, 1.48 1.42, 1.36 [3 s, 12 H, 2 ꢈ OC(CH3)2O]; 13C NMR
(75 MHz, CDCl3) ꢇ 170.4 (CO2CH2C6H5), 135.3ꢄ128.5 (CO2CH2C6H5), 111.9,
109.6 [2 ꢈ OC(CH3)2O], 77.8, (C5), 76.8 (C3), 75.7 (C2), 75.2 (C4), 67.1
(CO2CH2C6H5), 26.8, 26.6, 25.9, 25.5 [2 ꢈ OC(CH3)2O], 1.4 (C6); MS (70 eV)
m/z 461 (M-15ꢉ, 63), 283 (17), 235 (38), 183 (18), 91 (100).
HRMS: m/z Calcd for C19H25IO6: 476.0695. Found: 476.0643.
ACKNOWLEDGMENTS
We thank Professor A. Dondoni for useful interchange of information and
discussion. This was supported by COST Action No. D12 (European Union) and
Mizutani Foundation for Glycoscience. E. de O. is a fellow of the Consejería de
Eduación (CAM).

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REFERENCES
1. Dedicated to Prof. J. Thiem on the occasion of his 60th birthday.
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14. Intermediates of type A (Scheme 3) have been proposed by Dondoni in the mecha-
nism of the thiazole-carbonyl coupling (see reference 5).
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also: (d) Ladner, W. Stereoselektive Synthese von ꢀ-Alkyl-ꢀ,ꢃ-dihydroxy-carbon-
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16. Martin, S.F. Methodology for the Construction of Quaternary Carbon Centers. Tetra-
hedron 1980, 36, 419–460.
Received February 5, 2001
Accepted July 19, 2001

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