Diastereoselective addition of alkenylchromium(III) reagents to Garner's aldehyde. The Nozaki-Hiyama-Kishi coupling approach to sphingosines and ceramides

Article abstract of DOI:10.2298/JSC130611067F

Intermolecular Nozaki-Hiyama-Kishi coupling between alkenylchromium( III) reagents, derived from either (E)-(2-bromoethenyl)benzene or (E)-1-iodo-1-pentadecene, and the conformationally rigid Garner's aldehyde resulted in the stereoselective formation of Felkin-type allylic alcohols in good yields, thus providing an easy access to sphingosines. In addition, when the protecting group in the Garner's aldehyde was changed (from Boc to N-octanoyl), a reversal of stereoselectivity was observed in the reaction with (E)- -1-pentadecenylchromium(III), probably as the result of hydrophobic interactions between the long carbon chains of the reaction partners.

Full text of DOI:10.2298/JSC130611067F

J. Serb. Chem. Soc. 79 (6) 627–636 (2014)
UDC 546.763–039.7+547.313–41:542.9:547.952
JSCS–4613
Original scientific paper
Diastereoselective addition of alkenylchromium(III) reagents to
Garner’s aldehyde. The Nozaki–Hiyama–Kishi coupling
approach to sphingosines and ceramides
1
2
*
1**
ZORANA FERJANČIĆ , RADOMIR MATOVIĆ and FILIP BIHELOVIĆ
1Faculty of Chemistry, University of Belgrade, Studentski trg 16, P. O. Box 158, 11000
Belgrade, Serbia and 2ICTM – Center for Chemistry, Njegoševa 12, 11000 Belgrade, Serbia
(Received 11 June, revised 18 June, accepted 19 June 2013)
Abstract: Intermolecular Nozaki–Hiyama–Kishi coupling between alkenyl-
chromium(III) reagents, derived from either (E)-(2-bromoethenyl)benzene or
(E)-1-iodo-1-pentadecene, and the conformationally rigid Garner’s aldehyde
resulted in the stereoselective formation of Felkin-type allylic alcohols in good
yields, thus providing an easy access to sphingosines. In addition, when the
protecting group in the Garner's aldehyde was changed (from Boc to N-octa-
noyl), a reversal of stereoselectivity was observed in the reaction with (E)-
-1-pentadecenylchromium(III), probably as the result of hydrophobic inter-
actions between the long carbon chains of the reaction partners.
Keywords: Nozaki–Hiyama–Kishi reaction; sphingosine; Garner’s aldehyde;
organochromium reagent.
INTRODUCTION
Nozaki–Hiyama–Kishi (NHK) coupling is a versatile carbon–carbon bond
forming reaction that involves nucleophilic addition of organochromium(III) spe-
1,2
cies to carbonyl compounds under very mild conditions. The NHK reaction
showed good tolerance to a range of functional groups in both reaction partners.
The great synthetic potential of the nickel-catalyzed addition of alkenylchromium
reagents to aldehydes was demonstrated in the syntheses of various natural pro-
3
4
5
6
ducts, including palytoxin, halichondrin, epothilone B and D, pestalotiopsin
7
8
A and abyssomicin C.
As alkenylchromium species are less basic than other organometallic rea-
gents, their addition to chiral aldehydes proceed without epimerization at the α
2c
carbon atom. While the stereochemical outcome of intermolecular NHK reac-
2,9
tions was thoroughly investigated with allylchromium species, less attention
has been paid to the stereoselectivity of the addition of alkenylchromium nuc-
Corresponding authors. E-mail: (*)zferjan@chem.bg.ac.rs; (**)filip@chem.bg.ac.rs
doi: 10.2298/JSC130611067F
627
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628
FERJANČIĆ, MATOVIĆ and BIHELOVIĆ
leophiles. Intermolecular additions, as well as intramolecular reactions on con-
formationally more flexible substrates, often result in mixtures of diastereo-
8,10
isomers, sometimes even with a complete lack of diastereoselectivity.
Garner’s aldehyde (tert-butyl (4S)-4-formyl-2,2-dimethyloxazolidine-3-car-
11
boxylate) (1) is a conformationally restricted α-nitrogen-substituted aldehyde,
which represents a good substrate for probing the stereochemical outcome of
alkenylchromium(III) addition. Nucleophilic additions of various organometallic
12,13
species to Garner’s aldehyde (1) are well studied.
Curiously, there is no
report on alkenylchromium addition, although the addition of vinyl metals to
Garner’s aldehyde (1) represents a straightforward entry to sphingosines and
13c,d
14
ceramides (Fig. 1),
sphingolipid key metabolites.
These compounds
15
constitute a novel family of lipid second messengers that play important roles
in cell regulation and apoptosis, as well as in higher-order physiological
16
17
processes.
Fig. 1. Biologically important sphingosines and ceramides.
RESULTS AND DISCUSSION
Before exploring the diastereoselectivity of the addition of (E)-styrylchro-
18
mium(III) to Garner’s aldehyde (1), the focus was initially directed to opti-
mizing the reaction conditions. Attempts to use (E)-(2-iodoethenyl)benzene (6a)
as a precursor of alkenylchromium(III) species had limited success, as the coup-
ling products 7a and 7b were isolated in only 20 % yield (Scheme 1, Entry 1).
However, the yield was improved by using (E)-(2-bromoethenyl)benzene (6b) as
an (E)-styrylchromium(III) precursor (Scheme 1, Entry 2). Additionally, the
reaction yield was shown to be highly dependent on chromium(II) concentration
(Scheme 1, Entries 3 and 4) and tenfold excess of CrCl was found to be the
2
optimal loading. It is well known that, in practice, the NHK reaction requires the
2a
use of a large excess of CrCl .
2
19
Based on the available literature data, it was anticipated that the stereo-
chemistry of the addition would be in accordance with the non-chelated Felkin–
–Ahn Model (re-attack), thus favoring the formation of the anti product, due to
the pronounced voluminosity of the tert-butoxycarbonyl group. Indeed, when
performed at room temperature, the reaction stereoselectively provided allylic
20
alcohol 7a (anti:syn = 5:1). This selectivity could be improved to 8.5:1 by per-
forming the reaction at 0 °C, albeit with a drop in the reaction yield (Scheme 1,
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NOZAKI–HIYAMA–KISHI COUPLING APPROACH TO SPHINGOSINES AND CERAMIDES
629
Entry 5). The observed diastereoselectivity of the addition of (E)-styrylchro-
mium(III) to Garner’s aldehyde (1) was significantly higher than expected for an
2c
intermolecular NHK reaction (usually up to 3:1).
Scheme 1. Addition of (E)-styrylchromium(III) to Garner's aldehyde (1).
Next, attention was turned toward the most abundant sphingosine 2 in
nature, which could be obtained through the addition of (E)-1-iodo-1-pentadec-
21
ene (8) to Garner’s aldehyde (1, Scheme 2). With the previously optimized
chromium(II) loading, N,O-protected sphingosines 9a and 9b were obtained with
20,22
an even higher diastereoselectivity (anti:syn = 7:1).
Although the yield of
this product was moderate (46 %), the straightforwardness of the NHK approach,
coupled with its experimental simplicity, qualified it for synthetic application.
Scheme 2. Addition of (E)-1-pentadecenylchromium(III) to Garner’s aldehyde (1).
Diastereoselectivity in the addition of (E)-1-pentadecenylchromium(III) to
Garner’s aldehyde (1) was somewhat higher, as compared to other approaches to
sphingosines based on the addition of other vinylmetals (Li, Mg, Zn, Al; anti:syn
19,23
ratio from 5:1 to 1:6).
Fürstner et al. showed that rhodium-catalyzed addition
of 1-octenylboronic acid to Garner’s aldehyde proceeded with a moderate diaste-
13a
reoselectivity (4:1).
The diastereoselectivity in the addition of 1-(E)-alkenyl-
zirconocene-zinc reagents, according to Murakami et al., is superior to other
alkenylmetals (anti:syn ratio from 20:1 to 1:15). However in this method, diffe-
13c
rent additives were required (ZnBr for syn; Et Zn for anti).
2
2
Due to sensitivity of N-Boc-N,O-acetal moiety, aldehyde 10 (Scheme 3) was
subjected to further research, by supstituing the octanoyl group for Boc. This
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630
FERJANČIĆ, MATOVIĆ and BIHELOVIĆ
substrate is also expected to be conformationally restricted and, additionally, it
would allow for a direct synthesis of protected ceramides. Aldehyde 10 was pre-
pared from L-serine, according to Scheme 3. L-Serine was transformed into its
24
methyl ester 11, which was then acylated with octanoyl chloride, and the
25
resulting amide 12 was protected as N,O-acetal. After subsequent reduction of
ester moiety in 13, aldehyde 10 was finally obtained by the oxidation of the
intermediary alcohol 14 with Dess–Martin periodinane (DMP).
Scheme 3. Synthesis of aldehyde 10 from L-serine.
First, the reaction of the optically pure aldehyde 10 with (E)-1-pentadecenyl-
chromium(III) (Scheme 4, Entry 1) was examined. This time, unfortunately,
26
neither the yield (18 %) nor the diastereoselectivity (anti:syn = 1:2) reached
synthetically useful levels.
Scheme 4. Addition of alkenylchromium(III) to aldehyde 10.
It is interesting to note that this reaction proceeded with a reversal of diaste-
reoselectivity, with the predominant formation of the syn-product. The anti-Fel-
kin stereochemical outcome could be the result of a stabilizing hydrophobic
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NOZAKI–HIYAMA–KISHI COUPLING APPROACH TO SPHINGOSINES AND CERAMIDES
631
interaction between the two long, aliphatic chains of the reaction partners. Due to
this interaction, favored in polar media, alkenylchromium(III) species attack the
carbonyl group from the opposite, si-face (Fig. 2).
Fig. 2. si-Attack of (E)-1-pentadecenylchromium(III) on 10, which is favored by
hydrophobic interactions.
However, the treatment of aldehyde 10 with (E)-styrylchromium(III), pre-
pared in situ from (E)-(2-bromoethenyl)benzene (6b), resulted in a smooth con-
version, affording the desired products 16a and 16b in a good yield (Scheme 4,
1
Entries 2 and 3). Contrary to the H-NMR spectra of the diastereomeric mixtures
7a and b or 9a and b, it was difficult to determine directly the diastereomeric
1
ratio (dr) of 16a and b from the H-NMR spectrum, as it consisted of broad and
overlapping signals of rotamers, even at a higher temperature (60 °C). Therefore,
it was decided to modify the work-up procedure by in situ hydrolysis, con-
sequently leading to the formation of ceramides from aldehyde 10 in a single step
(Scheme 5). Once the reaction was completed, the reaction mixture was treated
25
with hydrochloric acid instead of sodium serinate, and the thus-obtained free
1
1
ceramides 5a and 5b were analyzed by H-NMR. Surprisingly, the H-NMR
analysis showed that the addition proceeded with almost complete lack of diaste-
reoselectivity (anti:syn = 1.2:1), possibly as a result of the smaller steric hind-
rance of the n-octanoyl group, as compared to that of the tert-butoxycarbonyl group.
Scheme 5. Direct synthesis of ceramides 5a and 5b from aldehyde 10.
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632
FERJANČIĆ, MATOVIĆ and BIHELOVIĆ
EXPERIMENTAL
General experimental
All chromatographic separations26 were performed on Silica 10–18, 60 Å, ICN
Biomedicals, using petroleum ether (b. p. 65–70 °C). Standard techniques were used for the
purification of the reagents and solvents.27 The NMR spectra were recorded on a Bruker
Avance III 500 (1H-NMR at 500 MHz, 13C-NMR at 125 MHz). The chemical shifts are
expressed in ppm (δ) using tetramethylsilane as an internal standard, coupling constants (J)
are in Hz. The IR spectra were recorded on a Nicolet 6700 FT instrument, and are expressed
in cm–1. The mass spectra were obtained on Agilent technologies 6210 TOF LC/MS
instrument (LC: series 1200). The optical rotations were measured on Rudolph Research
Analytical AUTOPOL IV automatic polarimeter.
Nozaki–Hiyama–Kishi couplings
Addition of (E)-styrylchromium(III) to Garner’s aldehyde 1. Commercial chromium(II)
chloride (113 mg; 0.924 mmol; 10 eq; 99.9 % purity) and anhydrous nickel(II) chloride (0.6
mg; 5 mol %) were suspended in freshly distilled and degassed dry DMF (0.4 mL), in a
glovebox, under an argon atmosphere. A solution of 1 (21 mg; 0.0924 mmol) and 6b (50 mg;
0.277 mmol; 3 eq) in DMF (0.4 mL) was added dropwise to the suspension, and the mixture
was stirred at room temperature for 1 h. The reaction mixture was treated with 1 M sodium
serinate (3 mL) and diethyl ether (10 mL) and vigorous stirring was continued for 1 h. The
layers were separated, the aqueous layer was extracted with diethyl ether (2×10 mL), and the
combined organic extract was washed with brine (2×5 mL), dried (MgSO4), filtered, and
concentrated under reduced pressure. Purification of the residue by column chromatography
(eluent, petroleum ether:ethyl acetate:triethylamine = 80:20:1) afforded 21 mg (69 %) of mix-
ture of allylic alcohols 7a and 7b (7a:7b = 5:1), as a colorless oil. The diastereoisomeric ratio
was determined by integrating signals in 1H-NMR spectrum (500 MHz, C6D6 at 60 °C,
δ / ppm): δ (isomer 7a) = 6.74 (1H, d, J = 16.0 Hz); δ (isomer 7b) = 6.62 (1H, d, J = 15.5 Hz).
The spectroscopic data were fully consistent with those previously reported.13c
Addition of (E)-1-pentadecenylchromium(III) to Garner’s aldehyde (1). Commercial
chromium(II) chloride (80 mg; 0.654 mmol; 10 eq; 99.9 % purity) and anhydrous nickel(II)
chloride (0.4 mg; 5 mol %) were suspended in freshly distilled and degassed dry DMF (0.4
mL), in a glovebox, under an argon atmosphere. A solution of 1 (15.0 mg; 0.0654 mmol) and
8 (66 mg; 0.196 mmol; 3 eq) in DMF/THF (V/V = 1/1; 0.4 mL) was added dropwise to the
suspension, and the mixture was stirred at room temperature for 1 h. The reaction mixture was
treated with 1 M sodium serinate (3 mL) and diethyl ether (10 mL) and vigorous stirring was
continued for 1 h. The layers were separated, the aqueous layer was extracted with diethyl
ether (2×10 mL), and the combined organic extract was washed with brine (2×5 mL), dried
(MgSO4), filtered and concentrated under reduced pressure. Purification of the residue by
column chromatography (eluent, petroleum ether:ethyl acetate:triethylamine = 90:10:1)
afforded 13.3 mg (46 %) of a mixture of allylic alcohols 9a and 9b (9a:9b = 7:1), as a
1
colorless oil. The diastereoisomeric ratio was determined by integrating signals in the H-
NMR spectrum (500 MHz, C6D6 at 60 °C, δ / ppm): δ (isomer 9a) = 5.79 (1H, dt, J = 6.5 and
15.5 Hz); δ (isomer 9b) = 5.71 (1H, dt, J = 6.5 and 15.5 Hz). The spectroscopic data were
fully consistent with those previously reported.13c,19a
Addition of (E)-1-pentadecenylchromium(III) to aldehyde 10. Commercial chromium(II)
chloride (122 mg; 0.993 mmol; 12 eq; 99.9 % purity) and anhydrous nickel(II) chloride (0.5
mg; 5 mol %) were suspended in freshly distilled and degassed dry DMF (0.5 mL), in a
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NOZAKI–HIYAMA–KISHI COUPLING APPROACH TO SPHINGOSINES AND CERAMIDES
633
glovebox, under an argon atmosphere. A solution of 10 (21.0 mg; 0.0827 mmol) and 8 (83
mg; 0.248 mmol) in DMF/THF (V/V = 1/1; 0.6 mL) was added dropwise to the suspension,
and the mixture was stirred at room temperature for 1 h. The reaction mixture was treated with
1 M sodium serinate (2.1 mL) and diethyl ether (10 mL) and vigorous stirring was continued
for 1 h. The layers were separated, the aqueous layer was extracted with diethyl ether (2×10
mL), and the combined organic extract was washed with brine (2×5 mL), dried (MgSO4),
filtered, and concentrated under reduced pressure. Purification of the residue by column
chromatography (eluent, petroleum ether:ethyl acetate:triethylamine = 90:10:1) afforded 7.1
mg (18 %) of a mixture of allylic alcohols 15a and 15b, as a colorless oil.
The thus-obtained alcohols 15a and 15b (7.1 mg; 0.0152 mmol) were dissolved in 70 %
acetic acid (0.5 mL) and the mixture was stirred overnight. The mixture was diluted with ethyl
acetate, washed with water and brine, dried (MgSO4), filtered and concentrated under reduced
pressure. Purification of the residue by column chromatography (eluent, petroleum ether:ethyl
acetate = 1:4) afforded 4.8 mg (73 %) of mixture of allylic alcohols 4a and 4b (4a:4b = 1:2),
1
as a white wax. The diastereoisomeric ratio was determined by integrating signals in the H-
-NMR spectrum (500 MHz, CDCl3, δ / ppm): δ (isomer 4a) = 6.26 (1H, d, J = 7.5 Hz);
δ (isomer 4b) = 6.13 (1H, d, J = 8.0 Hz). The spectroscopic data were fully consistent with
those previously reported.30
Addition of (E)-styrylchromium(III) to aldehyde 10. Commercial chromium(II) chloride
(173 mg; 1.41 mmol; 12 eq; 99.9 % purity) and anhydrous nickel(II) chloride (0.7 mg; 5 mol
%) were suspended in freshly distilled and degassed dry DMF (0.8 mL), in a glovebox, under
an argon atmosphere. A solution of 10 (30 mg; 0.117 mmol) and 6b (64 mg; 0.352 mmol;
3 eq) in DMF (0.4 mL) was added dropwise to the suspension, and the mixture was stirred at
room temperature for 1 h. Hydrochloric acid (3 M; 0.6 mL) was added to the reaction mixture
and stirring was continued for 1 h, before the resulting mixture was diluted with ethyl acetate,
and the layers were separated. The organic layer was washed with water and brine, dried
(MgSO4), filtered and concentrated under reduced pressure. Purification of the residue by
column chromatography (eluent, petroleum ether:ethyl acetate = 1:2) afforded 16.3 mg (43 %)
of a mixture of allylic alcohols 5a and 5b (5a:5b = 1.2:1), as a white wax. The diastereo-
1
isomeric ratio was determined by integrating signals in the H-NMR spectrum (500 MHz,
CDCl3, δ / ppm): δ (isomer 5a) = 6.48 (1H, d, J = 8.0 Hz); δ (isomer 5b) = 6.34 (1H, d, J = 8.0
Hz). The spectroscopic data were fully consistent with those previously reported.31
Preparation of aldehyde 10
Synthesis of (S)-methyl 3-hydroxy-2-octanamidopropanoate (12). To a cold solution (–15
°C) of L-serine (1.0 g, 9.6 mmol) in anhydrous methanol (20 mL), thionyl chloride (1.37 g,
11.52 mmol) was added slowly using a syringe. The solution was stirred at –15 °C for 30 min
and then at room temperature overnight. The reaction mixture was concentrated under reduced
pressure to afford 1.47 g (99 %) of crude L-serine methyl ester hydrochloride (11), as a white
powder, which was further used without purification.
L-Serine methyl ester hydrochloride (11, 1.47 g, 8.75 mmol) was added to a solution of
sodium bicarbonate (1.08 g, 17.49 mmol) in water (27 mL), followed by the addition of ethyl
acetate (27 mL). Octanoyl chloride (1.78 g, 10.94 mmol) was added to the vigorously stirred
reaction mixture and stirring was continued for 1 h. The reaction mixture was extracted with
ethyl acetate (3×20 mL) and the combined organic extract was washed with brine and dried
over MgSO4. After removal of the solvent under reduced pressure, the residue was purified by
dry-flash chromatography (eluent, petroleum ether:ethyl acetate = 1:1), to afford 1.81 g (85 %)
of 12 as a colorless, viscous oil.
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634
FERJANČIĆ, MATOVIĆ and BIHELOVIĆ
Synthesis of (S)-methyl 2,2-dimethyl-3-octanoyloxazolidine-4-carboxylate (13). A solu-
tion of 2,2-dimethoxypropane (8.9 g; 85.7 mmol), pyridinium p-toluenesulfonate (122 mg;
0.48 mmol) and the amide alcohol 12 (660 mg; 2.69 mmol) in toluene (11 mL) was heated at
90 °C for 20 h. The reaction mixture was diluted with dichloromethane, washed with saturated
NaHCO3 and water. The organic extract was dried over anh. MgSO4 and concentrated under
reduced pressure. Purification of the crude product by dry-flash chromatography
(eluent, petroleum ether:ethyl acetate = 85:15) afforded 530 mg (69 %) of compound 13, as a
colorless oil.
Synthesis of (R)-1-(4-(hydroxymethyl)-2,2-dimethyloxazolidin-3-yl)-1-octanone (14). A
solution of 13 (720 mg; 2.52 mmol) in methanol (5 mL) was treated with sodium borohydride
(429 mg; 11.34 mmol) for 1 h at room temperature. The reaction was quenched with saturated
NH4Cl and the resulting mixture was stirred for 5 min. After dilution with water, the reaction
mixture was extracted twice with dichloromethane and the extract was dried over anh.
MgSO4. Concentration under reduced pressure, followed by purification of the residue by dry-
-flash chromatography (eluent, petroleum ether:ethyl acetate = 1:1) gave alcohol 14 (490 mg;
75%), as a colorless, viscous oil.
Synthesis of (S)-2,2-dimethyl-3-octanoyloxazolidine-4-carboxaldehyde (10). Dess–
Martin periodinane (1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one, 372 mg; 0.87
mmol) was added to a solution of alcohol 14 (30 mg; 0.19 mmol) in dichloromethane (3 mL)
and the reaction mixture was stirred for 30 min at room temperature. The reaction mixture was
diluted with dichloromethane and washed with 10% Na2S2O3 and saturated NaHCO3. The
organic extract was dried over anh. MgSO4 and concentrated under reduced pressure.
Purification of the crude product by dry-flash chromatography (eluent, petroleum ether:ethyl
acetate = 1:1) afforded 26 mg (87 %) of the title compound, as a colorless oil.
The physical and spectral data for aldehyde 10 and the isolated intermediates in its
preparation 12–14 are given in the Supplementary material to this paper.
CONCLUSIONS
In conclusion, it was shown that alkenylchromium(III) species add to confor-
mationally rigid Garner’s aldehyde (1) in a stereoselective manner. The predo-
minant formation of Felkin-type products is in accordance with non-chelation
control in the transition state. In addition, it was shown that a nonpolar inter-
action between two long, aliphatic chains of the reaction partners may play an
important role in diastereofacial selectivity, thus favoring the formation of the
anti-Felkin product. Therefore, Nozaki–Hiyama–Kishi reaction with Garner’s
aldehyde (1) offers an alternative synthetic route toward sphingosines. This coup-
ling approach also allows for a direct, but non-stereoselective preparation of aro-
matic ceramide analogue 5, in a good yield.
SUPPLEMENTARY MATERIAL
The physical and spectral data for aldehyde 10 and the isolated intermediates 12–14 are
available electronically from http://www.shd.org.rs/JSCS/, or from the corresponding author
on request.
Acknowledgments. Financial support of the Ministry of Education, Science and Tech-
nological Development of the Republic of Serbia is acknowledged (Project No. 172027). We
are grateful to Prof. Radomir N. Saicic (Faculty of Chemistry, University of Belgrade, Serbia)
for helpful discussions.
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NOZAKI–HIYAMA–KISHI COUPLING APPROACH TO SPHINGOSINES AND CERAMIDES
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И З В О Д
ДИЈАСТЕРЕОСЕЛЕКТИВНЕ АДИЦИЈЕ АЛКЕНИЛХРОМ(III) РЕАГЕНАСА НА ГАРНЕРОВ
АЛДЕХИД. СИНТЕЗА СФИНГОЗИНА И ЦЕРАМИДА НОЗАКИ–ХИЈАМА–КИШИJЕВИМ
КУПЛОВАЊЕМ
ЗОРАНА ФЕРЈАНЧИЋ1, РАДОМИР МАТОВИЋ2 и ФИЛИП БИХЕЛОВИЋ1
1
Хемијски факултет Универзитета у Београду, Студентски трг 12–16, п. пр. 158, 11 000 Београд и
2
ИХТМ-Центар за хемију, Универзитет у Београду, Његошева 12, 11 000 Београд
У
интермолекулском Нозаки–Хијама–Кишиjевом купловању алкенилхром(III)
реагенаса, изведених из (Е)-2-бромстирена или (Е)-1-јод-1-пентадецена, и конформа-
ционо ригидног Гарнеровог (Garner) алдехида стереоселективно се добијају алилни
алкохоли Фелкиновог (Felkin) типа у добрим приносима, што омогућује лак приступ
сфингозинима. Такође, промена заштитне групе у Гарнеровом алдехиду (из терц-
-бутоксикарбонил- у октаноил-), резултује обрнутом дијастереоселективношћу у случају
(Е)-1-пентадеценилхрома(III), вероватно као последица хидрофобних интеракција
између дугих угљоводоничних ланаца реакционих партнера.
(Примљено 11. јуна, ревидирано 18. јуна, прихваћено 19. јуна 2013)
REFERENCES
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