Carbohydrate auxiliaries in stereoselective syntheses of decahydroquinoline alkaloids

Article abstract of DOI:10.1007/s007060200030

Using tetra-O-pivaloyl-β-D-galactopyranosylamine as the chiral auxiliary, both trans- and cis-annelated decahydroquinoline alkaloids can be synthesized stereoselectively. This methodology of asymmetric synthesis is based on the effect that both enantiomers of 2,6-disubstituted piperidin-4-ones are selectively and alternatively accessible using the auxiliary as the identical stereodifferentiating tool. In addition, the carbohydrate auxiliary controls the stereoselective protonation of enolates formed by conjugate addition of cuprates to N-galactosyl octahydroquinolin-4-ones. The syntheses of trans-4a-epi-pumiliotoxin C and cis-4a-epi-perhydro-219A illustrate this concept of asymmetric synthesis of decahydroquinoline alkaloids.

Full text of DOI:10.1007/s007060200030

Monatshefte fuÈr Chemie 133, 571±587 ꢀ2002)
Carbohydrate Auxiliaries in Stereoselective
Syntheses of Decahydroquinoline Alkaloidsa
Markus Weymann, Martin Schulz-Kukula, Stephan Knauer,
Ã
and Horst Kunz

Institut fur Organische Chemie, Universitat Mainz, D-55099 Mainz, Germany
Summary. Using tetra-O-pivaloyl-ꢀ-D-galactopyranosylamine as the chiral auxiliary, both trans- and
cis-annelated decahydroquinoline alkaloids can be synthesized stereoselectively. This methodology of
asymmetric synthesis is based on the effect that both enantiomers of 2,6-disubstituted piperidin-4-
ones are selectively and alternatively accessible using the auxiliary as the identical stereodifferentiat-
ing tool. In addition, the carbohydrate auxiliary controls the stereoselective protonation of enolates
formed by conjugate addition of cuprates to N-galactosyl octahydroquinolin-4-ones. The syntheses of
trans-4a-epi-pumiliotoxin C and cis-4a-epi-perhydro-219A illustrate this concept of asymmetric
synthesis of decahydroquinoline alkaloids.
Keywords. Asymmetric synthesis; Decahydroquinoline alkaloids; Glycosylamine auxiliary; Domino
Mannich-Michael reactions; Conjugate curprate addition.
Introduction
In contrast to their extensive application as enantiopure starting materials in ex-
chiral-pool syntheses [1], the utility of carbohydrates as chiral auxiliaries in asym-
metric synthesis was recognized only during the past 10 years [2]. Owing to their
high content of stereogenic centers and functional groups, carbohydrates facilitate
arrangements of a reacting group relative to shielding or coordinating groups which
give rise to a distinct stereodifferentiation during the attack of a reagent.
In this sense, glycosylamines proved to be ef®cient chiral auxiliaries in reac-
tions of imines with nucleophiles, e.g. in Strecker syntheses of ꢁ-amino nitriles [3],
Ugi reactions [4, 5], syntheses of ꢁ-amino phosphonic acids [6], Mannich reactions
[7], and domino Mannich-Michael reaction sequences [8] by which glycosylimines
1 are converted into chiral piperidinone derivatives 2 ꢀScheme 1).
Taking advantage of the excellent stereocontrol in these reactions and sub-
sequent conjugate additions of cuprates to compounds 2, we have stereoselective-
ly synthesized alkaloids of the decahydroquinoline series. Such alkaloids have
been isolated from glandular secretions of South American frogs of the family
Dendrobates. Some of these compounds show marked biological effects, e.g. on
a
Dedicated to Professor Dr. Joachim Thiem on the occasion of his 60th birthday
Ã
Corresponding author. E-mail: hokunz@mail.uni-mainz.de

572
M. Weymann et al.
Scheme 1
Scheme 2
the transport of ions through membranes and on the transduction of stimuli in the
nervous system [9]. Interestingly, decahydroquinoline alkaloids from Dendrobates
pumilio such as pumiliotoxin C ꢀ3) [10] have a cis-annelated decahydroquinoline
structure, whereas those from Dendrobates histrionicus exclusively have trans-
con®guration, such as the alkaloid ꢀ ‡ )-219A ꢀ4) [11].
Stereoselective syntheses of natural ꢀÀ)-ꢀ3) and ꢀ ‡ )-pumiliotoxin C have
already been reported [12]. An auxiliary-controlled asymmetric synthesis of 3 was
achieved by Comins et al. [13] who applied nucleophilic addition reactions to N-
alkoxycarbonyl-3-trimethylsilyl-4-trimethylsilyloxy pyridinium salts derived from
8-phenylmenthol in the key step [13].
A stereoselective synthesis of alkaloid 219A ꢀ4) has also been described [14]. It
is based on a reductive conversion of an enol tri¯ate and subsequent hydrogenation
of the formed chiral alkene ꢀdiastereomeric ratio 87:13). Perhydro 219A and its cis-
annelated epimer 6 have been obtained from chiral trisubstituted cyclohexanes
[15].
We here describe an alternative and uniform concept for the stereoselective
syntheses of both cis- and trans-annelated decahydroquinoline alkaloids. In this
strategy, 2,3,4,6-tetra-O-pivaloyl-galactosylamine 7 [3, 7] as the auxiliary not only
controls the stereoselective formation of the stereogenic centers in 2-, 5-, and 8a-
position, but also the diastereoselective protonation of an enolate at position C-4a
which can be steered to either form the trans- or the cis-annelated bicyclic com-
pounds. The principle is demonstrated for the syntheses of epi-trans-pumiliotoxin
C [16] ꢀ5) and epi-cis-perhydro-219A ꢀ6), having opposite con®guration to each
other at C-2 and representing the cis-trans-annelated epimers of the natural
alkaloids 3 and 4, respectively.

Carbohydrate Auxiliaries in Alkaloid Synthesis
573
Results and Discussion
Stereoselective syntheses of both enantiomers of 2-propyl-octahydroquinolin-
4-one using the identical galactosylamine auxiliary 7
Using galactosylamine 7, both enantiomers of 2,6-cis-disubstituted piperidones can
selectively be obtained depending upon the choice of the aldehyde in the formation
of the imine 1 and the cuprate in the conjugate addition to product 2 [8].
Condensation of 7 with hex-5-enal gave the imine 8a, whereas the analogous
reaction with butyraldehyde formed the imine 8b [8]. Domino Mannich-Michael
reactions of imines 8 furnished the dehydropiperidiones 9a and 9b ꢀScheme 3).
Conjugate addition of the propylcuprate BF3 complex [17] to 9a resulted in
the formation of N-galactosyl-ꢀ2S,6R)-2-propyl-6-pentenyl-piperidone 10a with
excellent stereoselectivity. On the other hand, 1,4 addition of bis-ꢀ4-ꢀ1-ethoxy-
ethyloxy)-butyl)-cuprate to 9b in presence of trimethylchlorosilane and subsequent
treatment of the intermediate silyl enolether with ¯uoride gave ꢀ2R,6S)-2-propyl-
6-ꢀethoxyethyloxy)-butyl-piperidinone 10b in good diastereoselectivity. It should
be noticed that reactions of the enaminone 9b with pentenyl or functionalized
butylcuprate=BF3 complexes produced the 1,4 adducts in distinctly lower diastereo-
selectivity.
Oxidative cleavage of the ole®nic double bound of 10a using potassium
osmate=sodium periodate and subsequent cyclizing aldol condensation of the
formed aldehyde 11a furnished the octahydroquinoline 12a with ꢀ2S,8aR)-con-
®guration. In contrast, removal of the ꢀ1-ethoxy)-ethyl ꢀEE) group from 10b using
pyridinium p-toluenesulfonate ꢀPPTS) followed by oxidation of the alcohol with
tetrapropylammonium perruthenate ꢀTPAP) [18] gave aldehyde 11b, which under
aldol condensation yielded the N-galactosyl octahydroquinolinone 12b with oppo-
site enantiomeric con®guration of the N-heterocyclic system compared to that in
12a. These syntheses illustrate that both enantiomers of such hydroquinoline deri-
vatives can stereoselectively be obtained by this strategy using the identical glycosyl-
amine auxiliary.
It should be noted that, apart from usual chromatographic puri®cation, no
separation of a minor diastereomer was required during the synthesis to obtain the
pure diastereomers 11 and 12.
Stereoselective synthesis of trans-annelated decahydroquinolines:
trans-epi-4a-pumiliotoxin C ꢀ5)
For the conversion of the ꢀ2S)-propyl-octahydroquinolinone diastereomer 12a into
pumiliotoxin C ꢀ3), 1,4 addition of lithium dimethylcuprate to the enone in pres-
ence of trimethylsilyl chloride was carried out ꢀScheme 4). Cleavage of the inter-
mediate silyl enolether resulted in the formation of the adduct 13 with excellent
diastereoselectivity and the expected con®guration [13] at C-5 ꢀ5R).
However, 13 proved to be a trans-decahydroquinolinone derivative as was
0
con®rmed by the 1H NMR signal of H-8a ꢀꢂ ˆ 3.26 ppm ꢀdt, J8a,4a ˆ J8a;8 ˆ 11.2 Hz,
J8a,8 ˆ 3.5 Hz)) and by X-ray analysis [16]. This result was unexpected, since
Comins et al. [13] had carried out 1,4-methylcuprate addition to a octahydroqui-
nolinone analogous to 12a which carries a N-phenoxycarbonyl group instead of the

574
M. Weymann et al.
Scheme 3
N-galactosyl moiety and noted the formation of the cis-annelated decahydroquino-
linone with high preference ꢀ97:3). In order to clarify the contradictory situation, the
galactosyl auxiliary of 12a was cleaved off by treatment with dilute HCl in methanol
and substituted by the phenoxycarbonyl group ꢀ14). Compound 14 was identical
with the precursor of the optically active pumiliotoxin C described by Comins
et al. [13]. Conjugate addition of lithium dimethylcuprate to 14 in presence of

Carbohydrate Auxiliaries in Alkaloid Synthesis
575
Scheme 4
trimethylchlorosilane and subsequent ¯uoridolysis of the intermediate silyl
enolether preferentially yielded, in contrast to 13, the cis-annelated decahydro-
quinolinone 16.
To prove the hypothesis that the carbohydrate auxiliary actually steers the
protonation of the enolate during the cleavage of the intermediate silyl enolether
obtained by 1,4-addition of the cuprate to 12a, the galactosyl moiety was also
removed from product 13 and substituted by the phenoxycarbonyl ꢀ15a) or
benzyloxycarbonyl group ꢀ15b).

576
M. Weymann et al.
Fig. 1. X-Ray analysis of trans-4a-epi-pumiliotoxin C ꢀ5)
Treatment of the thus obtained trans-annelated decahydroquinolinone 15a with
triethylamine=THF ꢀ1:200 v=v) caused epimerization to form the preferred cis-
annelated epimer 16 ꢀcis:trans ˆ 3:1, analytical HPLC) within 2 minutes. These
results suggest that the cis-annelated decahydroquinolinone 16 constitutes the
thermodynamically favoured epimer. It can be concluded that the carbohydrate
auxiliary obviously directs the enolate protonation even against the thermodyna-
mical preference in this simple cyclic system. Taking pro®t of this effect, the carbo-
hydrate auxiliary opens up the possibility to readily synthesize trans-annelated
decahydroquinolinone alkaloids usually requiring multistep procedures. In this
sense, we have converted the Z-protected trans-decahydroquinolinone 15b into
its dithiolane derivative 17. Treatment of 17 with hydrogen=Raney nickel resulted
in simultaneous removal of the Z group and desulfurization. The hydrochloride of
trans-4a-epi-pumiliotoxin C ꢀ5) was obtained in enantiomerically pure form. The
con®guration of 5 was con®rmed by X-ray analysis ꢀFig. 1).
Interpretation of the stereoselective enolate protonation
steered by the N-galactosyl auxiliary
The astonishing stereoselective protonation of the enolate A formed from the silyl
enolether to give the trans-annelated decahydroquinolinone can be rationalized by
stereoelectronic and steric effects.
The X-ray analysis of decahydroquinolinone 13 [16] gives evidence that the
exo-anomeric effect, i.e. the delocalization of the nitrogen lone pair into the
Ã
ꢃ -orbital of the ring C±O bond, stabilizes the N-galactosyl heterocycle in con-
formation A with carbohydrate and heterocyclic ring systems arranged almost per-
pendicular to each other. Approach of the proton from the front side reduces the
steric strain during ketone formation, since the carboxylic ring moves backwards,
i.e. away from the bulky 2-pivaloyloxy group. If this steric hindrance is not present
as in the case of the N-phenoxycarbonyl substituted enolate B, protonation pre-
ferentially leads to the cis-annelated decahydroquinoline 16.
The cis-annelated compound 16 is the weaker CH-acid since its H-4a is located
almost in the ꢃ-plane of the carboxyl group. In contrast, the C4a±H4a bond of the
Ã
trans-compound is located coaxial with the ꢄ -orbital of the carbonyl group and,

Carbohydrate Auxiliaries in Alkaloid Synthesis
577
Scheme 5
therefore, the compound is considerably more acidic. If the outlined interpretation
is correct, 1,4-cuprate additions to the enone in the N-galactosyl octahydroqui-
nolinone 12b should logically give cis-annelated decahydroquinolinones.
Stereoselective synthesis of cis-perhydro 219A
Reaction of N-galactosyl octahydroquinolinone 12b with propylcuprate in the
presence of trimethylsilyl chloride and subsequent cleavage of the intermediate
silyl enolether gave the cis-annelated decahydroquinolinone 18 as predicted
ꢀScheme 6).
The diastereoselectivity of the reaction was high, but the yield of 18 was only
moderate. Obviously, the addition reaction is sterically more hindered compared
to that with 12a ꢀScheme 4). In the H NMR spectrum of 18, the double triplet
1
with diaxial couplings Jh8a,H4a ˆ JH8a,8 ꢀ 11 Hz characteristic for H-8a in trans-
decahydroquinolinones is not observed. Instead, H-8a causes a multiplet at ꢂ ˆ
3.54 ppm which is not well structurized.
The galactosyl decahydroquinolinone 18 ꢀas well as 13) resists conversion into
a dithiolane. Since reduction with NaBH4 also failed, transformation to the
corresponding enol tri¯ate was applied. The only reagent to achieve this reaction was
N-tri¯uoromethanesulfonyl-5-chloro-pyrid-2-yl-tri¯uoromethanesulfonamide
ꢀClPyrNTf2) [19]. Unfortunately, the desired enol tri¯ate 19 was formed in a mixture
with its undesired regioisomer 20. Separation of 19 was achieved by chromato-
graphy. Hydrogenation of 19 followed by acidolytic cleavage of the N-glycosidic
bond gave the hydrochloride of cis-4a-epi-perhydro-219A ꢀ6). Comparison of the
NMR data of this hydrochloride and those of the free amine 6 with those reported
in the literature for the racemic [20] and optically active cis-perhydro-219A [15]
con®rm the structure of 6 and the correct stereochemistry at C-5.
The stereoselective syntheses of trans-epi-pumiliotoxin C ꢀ5) and cis-
epi-perhydro-219A ꢀ6) illustrate the versatility of the galactosylamine 7 as
the chiral auxiliary in stereoselective syntheses of trans- and of cis-annelated

578
M. Weymann et al.
Scheme 6
decahydroquinoline alkaloids. Moreover, cis-annulated decahydroquinolines of
enantiomeric con®guration opposite to 6 are also selectively accessible via the de-
tachment and epimerization pathway ꢀScheme 4). The value of this methodology
can be expanded even more if tri-O-pivaloyl-ꢀ-D-arabinopyranosylamine [21] is
applied as the virtual enantiomer of the D-galactopyranosyl amine 7. By this way,
enantiomers of trans-annelated decahydroquinolines, like 5, can selectively be
constructed.
Experimental
NMR spectra were recorded on Bruker AM 400 ꢀ400 MHz 1H, 100.6 MHz 13C) and Bruker WT 200
ꢀ200 MHz 1H, 50.3 MHz 13C) NMR spectrometers. Chemical shifts are given in ppm relative to TMS.
For N-galactosylated heterocyclic compounds, protons and carbons of the carbohydrate moiety are
marked with a superscribed dash, e.g. H-20. Analytical HPLC was carried out using a Pharmacia LBK
2150 unit with diode array detection. Columns: A: Eurospher 100, RP 18, 5 ꢅ, 250 Â 4 mm, Knauer
Eurochrom, B: Sperisorb ODS II, RP 18, 5 ꢅ, 250 Â 4 mm, Bischoff; ¯ow rate: 1 cm3=min. Thin layer
chromatography ꢀTLC) was performed on Merck silica gel 60F254, column chromatography on silica
gel 60 ꢀ0.06±0.2 mm, Baker). FAB and FD mass spectra were measured on a Finnigan MAT 95
spectrometer, optical rotations on a Perkin Elmer 241 polarimeter. Melting points were taken on a
Buchi Dr. Tottoli apparatus and are uncorrected. Elemental analysis data of new compounds were in
agreement with the calculated values.
Schiff bases 8 of commercially available galactosylamine 7 ꢀMerck-Schuchardt) were prepared
according to a described procedure [22]. The synthesis of compound 9b is described in Ref. [8].
/2R)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-2-/4-pentenyl)-
5,6-didehydropiperidin-4-one ꢀ9a; C36H57NO10)
9a was synthesized according to the general procedure described in Ref. [8] and puri®ed by
chromatography ꢀpetroleum ether:ethyl acetate ˆ 4:1).

Carbohydrate Auxiliaries in Alkaloid Synthesis
579
22
Yield: 68%; m.p.: 155±158ꢁC; ‰ꢁŠ ˆ À61:5 ꢀc ˆ 1, CHCl3); Rf ˆ 0.30 ꢀpetroleum ether:
D
EtOAc ˆ 3:1); d.r. ˆ 65:1 ꢀHPLC, column A; MeOH=H2O 4:1); 1H NMR ꢀ400 MHz, ꢂ, CDCl3): 1.09,
1.15 and 1.26 ꢀ4s, 4 Â 9H, piv-CH3), 1.41 ꢀm, 1H, CH2), 1.60 ꢀm, 2H, CH2), 1.88 ꢀm, 1H, CH2), 2.00
ꢀm, 2H, CH2), 2.34 ꢀd, 1H, Jgem ˆ 16.6 Hz, H-3ax), 2.60 ꢀdd, 1H, Jvic ˆ 6.3 Hz, Jgem ˆ 16.6 Hz, H-3eq),
0
0
0
0
0
0
0
3.70 ꢀm, 1H, H-2), 3.95 ꢀdd, 1H, J6a ,5 ˆ 6.9 Hz, J6a ,6b ˆ 10.5 Hz, H-6a ), 4.02 ꢀdd, 1H, J5 ,6a
ˆ
0
0
0
0
0
0
0
0
6.8 Hz, J5 ,6b ˆ 6.4 Hz, H-5 ), 4.14 ꢀdd, 1H, J6b ,5 ˆ 6.3 Hz, J6b ,6a ˆ 10.5 Hz, H-6b ), 4.54 ꢀd, 1H,
0
0
0
0
0
0
0
J1 ,2 ˆ 9.1 Hz, H-1 ), 4.96 ꢀm, 3H, H-5 and CHˆCH2), 5.16 ꢀdd, 1H, J3 ,4 ˆ 3.1 Hz, J3 ,2
ˆ
10.1 Hz, H-30), 5.41 ꢀd, 1H, J4 ,3 ˆ 3.0 Hz, H-4 ), 5.52 ꢀdd, 1H, J2 ,3 ˆ 9.8 Hz, J2 ,1 ˆ 9.5 Hz, H-2 ),
5.71 ꢀdddd, 1H, J1 ˆ 6.7 Hz, J2 ˆ 10.2 Hz, ÀCHˆCH2), 6.88 ꢀdd, 1H, J1 ˆ 0.9 Hz, J2 ˆ 7.7 Hz, H-6)
ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 25.08 ꢀCH2), 26.98, 27.08, 27.14 ꢀpiv-CH3), 30.22, 33.34
ꢀCH2), 38.65, 38.71, 38.85, 39.03 ꢀpiv-Cquart), 53.60 ꢀAlkyl-CHN), 60.81 ꢀC-60), 65.77, 66.52, 71.28,
72.88 ꢀC-20, C-30, C-40, C-50), 91.56 ꢀC-10), 99.96 ꢀC-5), 115.01, 137.85 ꢀÀCHˆCH2), 149.75 ꢀC-6),
176.42, 176.99, 177.03, 177.63 ꢀpivCˆO), 191.91 ꢀCˆO) ppm.
0
0
0
0
0
0
0
0
/2R,6S)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-2-/5-pentenyl)-
6-propyl-piperidin-4-one ꢀ10a; C39H65NO10)
10a was synthesized from 9a ꢀ0.66 g, 1 mmol) according to the general procedure for conjugate
addition of RCu Á BF3 described in Ref. [8] and puri®ed by column chromatography ꢀpetroleum
ether: EtOAc ˆ 4:1).
22
D
Yield: 0.57 g ꢀ81%); m.p.: 122ꢁC; ‰ꢁŠ ˆ À15:9 ꢀc ˆ 1, CHCl3); Rf ˆ 0.56 ꢀpetroleum
ether:EtOAc ˆ 3:1); d.r.ꢂ10:1; ꢀ1H NMR); 1H NMR ꢀ200 MHz, ꢂ, CDCl3): 0.86 ꢀt, 3H, J ˆ 6.8 Hz,
CH3), 1.10, 1.14, 1.15 and 1.24 ꢀ4s, 4 Â 9H, piv-CH3), 1.38 ꢀm, 7H, CH2), 1.61 ꢀm, 1H, CH2), 1.99
ꢀm, 2H, CH2), 2.26 ꢀdd, 1H, Jvic ˆ 7.0 Hz, Jgem ˆ 15.5 Hz, CH2CˆO), 2.35 ꢀd, 1H, Jgem ˆ 15.6 Hz,
CH2CˆO0), 2.61 ꢀdd, 1H, Jvic ˆ 5.6 Hz, Jgem ˆ 15.0 Hz, CH2CˆO), 2.69 ꢀdd, 1H, Jvic ˆ 6.6 Hz,
Jgem ˆ 15.4 Hz, CH2CˆO), 3.32 ꢀm, 1H, H-2), 3.46 ꢀm, 1H, H-6), 3.85±3.96 ꢀm, 2H, H-50, H-6a0),
0
0
0
0
0
0
0
0
4.09 ꢀdd, 1H, J6b ,5 ˆ 9.2 Hz, J6b ,6a ˆ 13.1 Hz, H-6b ), 3.88 ꢀd, 1H, J1 ,2 ˆ 9.2 Hz, H-1 ), 4.91±5.01
0
0
0
0
0
0
0
ꢀm, 2H, ole®n-CH2), 5.08 ꢀdd, 1H, J3 ,4 ˆ 2.9 Hz, J3 ,2 ˆ 9.9 Hz, H-3 ), 5.35 ꢀd, 1H, J4 ,3 ˆ 2.9 Hz,
H-40), 5.45 ꢀt, 1H, J ˆ 9.6 Hz, H-20), 5.71 ꢀddd, 1H, J1 ˆ 6.5 Hz, J2 ˆ 10.2 Hz, J3 ˆ 16.9 Hz,
CHˆCH2) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.91 ꢀCH3), 20.65, 25.75 ꢀCH2), 27.05, 27.16,
27.25 ꢀpiv-CH3), 33.59, 37.17 ꢀCH2), 38.71, 39.02 ꢀpiv-Cquart), 40.77 ꢀCH2), 44.12, 44.43 ꢀC-3, C-5),
61.66 ꢀC-60), 65.91, 67.22, 71.90, 72.55 ꢀC-20, C-30, C-40, C-50), 94.07 ꢀC-10), 114.99, 138.11
ꢀÀCHˆCH2), 176.66, 176.77, 177.37, 177.84 ꢀpiv-CˆO) ppm.
/2S,6R)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-2-/4-/1-ethoxyethyloxy)-
butyl)-6-propyl-piperidin-4-one ꢀ10b; C42H73NO12)
10b was prepared from 3.56 cm3 9b [8] ꢀ5.6 mmol) according to the general procedure for conjugate
addition of R2CuMgX in presence of Me3SiCl as described in Ref. [8] and puri®ed by column
chromatography ꢀpetroleum ether:EtOAc ˆ 5:1).
22
Yield: 3.19 g ꢀ73%); colorless oil; ‰ꢁŠ ˆ À11:8 ꢀc ˆ 1, CHCl3); Rf ˆ 0.61 ꢀpetroleum ether:
D
EtOAc ˆ 3:1); d.r. > 9:1 ꢀ1H NMR); 1H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.82 ꢀt, 3H, J ˆ 7.0 Hz, propyl-
CH3), 1.01±1.43 ꢀm, 48H, piv-CH3, CH2, EEO-CH3), 1.45±1.57 ꢀm, 4H, CH2), 2.19 ꢀdd, 1H,
Jvic ˆ 7.0 Hz, Jgem ˆ 15.5 Hz, CH2CˆO), 2.31 ꢀd, 1H, Jgem ˆ 15.4 Hz, CH2CˆO), 2.55 ꢀdd, 1H,
Jvic ˆ 5.9 Hz, Jgem ˆ 15.3 Hz, CH2CˆO0), 2.63 ꢀdd, 1H, Jvic ˆ 6.4 Hz, Jgem ˆ 15.2 Hz, CH2CˆO0),
3.27±3.60 ꢀm, 6H, H-2, H-6, RCH2O,0CH3CH2O), 3.81±3.89 ꢀm, 2H, H-50, H-6a0), 4.03 ꢀdd, 1H,
0
0
0
0
0
0
0
J6b ,5 ˆ 9.3 Hz, J6b ,6a ˆ 13.2 Hz, H-6b ), 4.33 ꢀd, 1H, J1 ,2 ˆ 9.3 Hz, H-1 ), 4.59 ꢀm, 1H, OCHO),
0
0
0
0
0
0
0
0
5.04 ꢀdd, 1H, J3 ,2 ˆ 9.9 Hz, J3 ,4 ˆ 3.0 Hz, H-3 ), 5.30 ꢀd, 1H, J4 ,3 ˆ 2.8 Hz, H-4 ), 5.38 ꢀt, 1H,
J ˆ 9.6 Hz, H-20) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.87 ꢀpropyl-CH3), 15.27 ꢀOCH2CH3),
19.66 ꢀCH2), 19.83 ꢀOCHOCH3), 24.13, 24.17 ꢀCH2), 27.03, 27.16, 27.21 ꢀpiv-CH3), 29.73, 29.84
ꢀCH2), 38.35, 38.65, 38.69, 39.00 ꢀpiv-Cquart), 44.00, 44.46 ꢀC-3, C-5), 52.02 ꢀNCHR), 60.60 ꢀC-60),

580
M. Weymann et al.
61.65 ꢀRCH2O), 65.01 ꢀCH3CH2O), 66.03, 67.26, 71.96, 72.56 ꢀC-20, C-30, C-40, C-50), 94.20 ꢀC-10),
99.51 ꢀOCHO), 176.57, 176.62, 177.25, 177.72 ꢀpiv-CˆO), 210.00 ꢀCˆO) ppm.
/2R,6S)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-2-/4-oxy-butyl)-
6-propyl-piperidin-4-one ꢀ11a; C38H63NO11)
To a solution of 0.58 g ꢀ0.81 mmol) 10a in 20 cm3 oxygen-free 1,4-dioxane under Ar, a solution of
10 cm3 K2OsO4 Á 2H2O ꢀ3.5 mol%) in 5 cm3 oxygen-free H2O was added. The yellowish-brown solu-
tion was stirred for 15 min, and 0.87 g ꢀ4.1 mmol) NaIO4 were added. After stirring for 15 h, 20 cm3
diethyl ether and 40 cm3 H2O were added, and the aqueous layer was separated and extracted with
3 Â 30 cm3 diethyl ether. The combined organic solutions were washed with 2 Â 20 cm3 10% Na2SO3
solution and dried with Na2SO4. After evaporation of the solvent in vacuo, the crude product was
puri®ed by column chromatography ꢀpetroleum ether:EtOAc ˆ 3:1).
22
Yield: 0.43 g ꢀ73%); amorphous solid; ‰ꢁŠ ˆ À11:9 ꢀc ˆ 1, CHCl3); Rf ˆ 0.57 ꢀpetroleum ether:
D
EtOAc ˆ 2:1); 1H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.84 ꢀt, 3H, J ˆ 7.2 Hz, CH3), 1.07, 1.12 and 1.22 ꢀ4s,
4  9H, piv-CH3), 1.27 and 1.38 ꢀm, 5H, CH2), 1.51±1.74 ꢀm, 3H, CH2), 2.25 ꢀdd, 1H, Jvic ˆ 6.7 Hz,
Jgem ˆ 15.4 Hz, CH2CˆO), 2.33 ꢀd, 1H, Jgem ˆ 15.0 Hz, CH2CˆO0), 2.40 ꢀm, 2H, CH2CHO), 2.60±
2.70 ꢀm, 2H, H-3, H-5), 3.34 ꢀm, 1H, H-2), 3.460ꢀm, 1H, H-6), 3.84±3.92 ꢀm, 2H, H-50, H-6a0), 4.08
0
0
0
0
0
0
0
ꢀdd, 1H, J6b ,5 ˆ 9.2 Hz, J6b ,6a ˆ 13.0 Hz, H-6b ), 4.36 ꢀd, 1H, J1 ,2 ˆ 9.2 Hz, H-1 ), 5.07 ꢀdd, 1H,
0
0
0
0
0
0
0
0
J3 ,4 ˆ 2.9 Hz, J3 ,2 ˆ 9.9 Hz, H-3), 5.34 ꢀd, 1H, J4 ,3 ˆ 2.9 Hz, H-4 ), 5.44 ꢀt, 1H, J ˆ 9.6 Hz, H-2 ),
9.71 ꢀs, 1H, CHO) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.85 ꢀCH3), 19.16, 20.62 ꢀCH2), 27.06,
27.17, 27.24 ꢀpiv-CH3), 37.09 ꢀCH2), 38.69, 38.72, 39.03 ꢀpiv-Cquart), 40.67 ꢀCH2), 43.59, 44.14,
44.43 ꢀC-3, C-5, CH2CHO), 61.70 ꢀC-60), 66.01, 67.30, 72.09, 72.57 ꢀC-20, C-30, C-40, C-50), 94.34
ꢀC-10), 176.60, 176.69, 177.30, 177.78 ꢀpiv-CˆO), 201.22 ꢀCHO), 209.70 ꢀCˆO) ppm.
/2S,6R)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-2-/4-hydroxy-butyl)-
6-propyl-piperidin-4-one ꢀC38H65NO11)
To a solution of 2.93 g ꢀ3.73 mmol) 10b in dry 70 cm3 CH2Cl2, 15.6 g ꢀ62 mmol) pyridinium p-
toluenesulfonate were added in 5 portions after every 8 h. Monitoring by TLC is necessary in order to
terminate the reaction before cleavage of the N-glycosidic bond occurs ꢀ3 d, conversion about 85%).
200 cm3 CH2Cl2 were added, and the solution was extracted with 50 cm3 H2O, 50 cm3 sat. NaHCO3,
and 80 cm3 brine. After drying with Na2SO4 and evaporation of the solvent in vacuo, the remaining
residue was puri®ed by chromatography ꢀpetroleum ether:EtOAc ˆ 2:1).
22
Yield: 1.59 g ꢀ60%); amorphous solid; ‰ꢁŠ ˆ À18:3 ꢀc ˆ 1, CHCl3); Rf ˆ 0.15 ꢀpetroleum ether:
D
1
EtOAc ˆ 3:1); H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.85 ꢀt, 3H, J ˆ 7.2 Hz, CH3), 1.07±1.46 ꢀm, 42H,
piv-CH3, CH2), 1.52±1.62 ꢀm, 2H, CH2), 2.23 ꢀdd, 1H, Jvic ˆ 7.1 Hz, Jgem ˆ 15.4 Hz, CH2CˆO),
2.36 ꢀd, 1H, Jgem ˆ 15.6 Hz, CH2CˆO0), 2.62 ꢀdd, 1H, Jvic ˆ 5.4 Hz, Jgem ˆ 15.3 Hz, CH2CˆO),
2.70 ꢀdd, 1H, Jvic ˆ 6.7 Hz, Jgem ˆ 15.4 Hz, CH2CˆO0), 3.11 ꢀs, 1H, OH), 3.30 ꢀm, 1H, NCHR),
3.44 ꢀm, 1H, NCHR0), 3.57 ꢀdd, 2H, J1 ˆ 6.5 Hz, J2 ˆ 5.3 Hz, CH2OH), 3.87±3.92 ꢀm, 2H, H-50, H-
0
0
6a0), 4.08 ꢀdd, 1H, J6b ,5 ˆ 9.3 Hz, J6b ,6a ˆ 13.1 Hz, H-6b ), 4.37 ꢀd, 1H, J1 ,2 ˆ 9.2 Hz, H-1 ), 5.08
0
0
0
0
0
0
0
0
0
0
0
0
0
0
ꢀdd, 1H, J3 ,4 ˆ 3.0 Hz, J3 ,2 ˆ 9.9 Hz, H-3 ), 5.34 ꢀd, 1H, J4 ,3 ˆ 2.9 Hz, H-4 ), 5.42 ꢀt, 1H,
J ˆ 9.6 Hz, H-20) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.86 ꢀCH3), 19.60, 23.38 ꢀCH2), 27.04,
27.06, 27.18 ꢀpiv-CH3), 32.02, 37.93 ꢀCH2), 38.68, 38.73, 39.04 ꢀpiv-Cquart), 39.89 ꢀCH2), 44.19,
44.47 ꢀC-3, C-5), 47.50, 54.65 ꢀC-2, C-6), 61.62 ꢀCH2OH), 61.67 ꢀC-60), 66.38, 67.22, 71.97, 72.49
ꢀC-20, C-30, C-40, C-50), 94.15 ꢀC-10), 176.61, 177.30, 177.36, 177.80 ꢀpiv-CˆO) ppm.
/2S,6R)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-2-/4-oxo-butyl)-
6-propyl-piperidin-4-one ꢀ11b; C38H63NO11)
To a solution of 15 g ꢀ2.1 mmol) of the afore-described hydroxybutyl piperidone in 40 cm3 CH2Cl2,
Ê
molecular sieve ꢀ4 A, 5 g) was added. After stirring for 10 min, 0.5 g dry N-methylmorpholine

Carbohydrate Auxiliaries in Alkaloid Synthesis
581
ꢀ4.1 mmol) and 74 cm3 tetrapropylammonium perruthenate ꢀTPAP) [18] ꢀ10 mol%) were added, and
the solution was stirred in the dark at room temperature. After 3 h, the catalyst was ®ltered off
through celite=silica gel and washed with 200 cm3 CH2Cl2. The solvent was evaporated from the
combined organic solutions, and the remainder was puri®ed by chromatography ꢀpetroleum ether:
EtOAc ˆ 5:2) to give pure 11b.
22
D
Yield: 1.23 g ꢀ83%); colorless amorphous solid; ‰ꢁŠ ˆ À10:2 ꢀc ˆ 1.1, CHCl3); Rf ˆ 0.14
ꢀpetroleum ether:EtOAc ˆ 3:1); 1H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.85 ꢀt, 3H, J ˆ 7.1 Hz, CH3), 1.07±
1.40 ꢀm, 42H, piv-CH3, CH2), 1.46±1.66 ꢀm, 2H, CH2), 2.22 ꢀdd, 1H, Jvic ˆ 6.9 Hz, Jgem ˆ 15.4 Hz,
CH2CˆO), 2.33±2.39 ꢀm, 3H, CH2CHO, CH2CˆO0), 2.61 ꢀdd, 1H, Jvic ˆ 5.7 Hz, Jgem ˆ 15.5 Hz,
CH2CˆO), 2.61 ꢀdd, 1H, Jvic ˆ 6.7 Hz, Jgem ˆ 15.5 Hz, CH2CˆO0), 3.31 ꢀm, 1H, NCHR), 3.47 ꢀm,
1H, NCHR0), 3.90 ꢀm, 2H, H-50, H-6a0), 4.08 ꢀdd, 1H, J6b ,5 ˆ 9.3 Hz, J6b ,6a ˆ 13.1 Hz, H-6b ), 4.36
0
0
0
0
0
0
0
0
0
0
0
0
0
ꢀd, 1H, J1 ,2 ˆ 9.3 Hz, H-1 ), 5.08 ꢀdd, 1H, J3 ,4 ˆ 3.0 Hz, J3 ,2 ˆ 9.9 Hz, H-3 ), 5.34 ꢀd, 1H,
J4 ,3 ˆ 2.9 Hz, H-4 ), 5.41 ꢀt, 1H, J ˆ 9.6 Hz, H-2 ), 9.71 ꢀt, 1H, J ˆ 1.5 Hz, CHO) ppm; 13C NMR
ꢀ100.6 MHz, ꢂ, CDCl3): 13.82 ꢀCH3), 19.61, 20.00 ꢀCH2), 27.01, 27.04, 27.16 ꢀpiv-CH3), 37.95 ꢀCH2),
38.66, 39.01 ꢀpiv-Cquart), 39.89 ꢀCH2), 43.46, 44.01, 44.38 ꢀC-3, C-5, CH2CHO), 61.62 ꢀC-60), 66.02,
67.21, 72.02, 72.46 ꢀC-20, C-30, C-40, C-50), 94.26 ꢀC-10), 176.54, 176.85, 177.25, 177.72 ꢀpiv-CˆO),
201.86 ꢀCHO), 209.65 ꢀCˆO) ppm.
0
0
0
0
/2S,8aR)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-2-propyl-4a,5-
didehydro-decahydroquinolin-4-one ꢀ12a; C38H61NO10)
In 40 cm3 benzene, 0.17 g ꢀ4.25 mmol) powdered NaOH and dibenzo [18] crown [6] were heated under
re¯ux. A solution of 1.4 g ꢀ1.97 mmol) 11a in 20 cm3 dry benzene was added, and the re¯ux was
continued until completion of the conversion ꢀ1.5 h). After cooling, the reaction mixture was poured
into 50 cm3 sat. NH4Cl solution and extracted with 200 cm3 diethyl ether. The organic layer was
washed with 40 cm3 sat. NaHCO3 solution and 60 cm3 brine, dried over MgSO4, and concentrated in
vacuo to 50% of its volume. After ®ltration and complete evaporation of the solvent, the remaining
residue was puri®ed by chromatography ꢀpetroleum ether:EtOAc ˆ 4:1).
22
Yield: 1.10 g ꢀ81%); colorless amorphous solid; ‰ꢁŠ ˆ À28:0 ꢀc ˆ 0.5, CHCl3); Rf ˆ 0.57
D
ꢀpetroleum ether:EtOAc ˆ 3:1); 1H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.81 ꢀt, 3H, J ˆ 6.8 Hz, CH3), 1.09,
1.12, 1.14, 1.24 ꢀ4s, 4 Â 9H, piv-CH3), 1.26±1.32 ꢀm, 4H, H-7, H-8), 1.40, 1.52, 1.71, 1.97 ꢀ4m,
4  1H, CH2), 2.24 ꢀm, 2H, H-6), 2.48 ꢀdd, 1H, Jvic ˆ 2.3 Hz, Jgem ˆ 16.4 Hz, H-3ax), 2.87 ꢀdd, 1H,
Jvic ˆ 4.8 Hz, Jgem ˆ 16.4 Hz, H-3eq), 3.36 ꢀm, 1H, H-2), 3.82±3.90 ꢀm, 3H, H-8a, H-50, H-6a0), 4.12
0
0
0
0
0
0
0
0
ꢀdd, 1H, J6b ,5 ˆ 9.5 Hz, J6b ,6a ˆ 13.6 Hz, H-6b ), 4.37 ꢀd, 1H, J1 ,2 ˆ 9.4 Hz, H-1 ), 5.06 ꢀdd, 1H,
0
0
0
0
0
0
0
0
0
J3 ,4 ˆ 3.0 Hz, J3 ,2 ˆ 9.9 Hz, H-3 ), 5.34 ꢀd, 1H, J4 ,3 ˆ 2.9 Hz, H-4 ), 5.43 ꢀt, 1H, J ˆ 9.6 Hz, H-2 ),
6.91 ꢀd, 1H, J ˆ 2.7 Hz, H-5) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.72 ꢀCH3), 19.62, 20.14, 25.87
ꢀCH2), 27.03, 27.07, 27.17, 27.25 ꢀpiv-CH3), 37.02 ꢀCH2), 38.67, 38.69, 38.72, 39.04 ꢀpiv-Cquart),
39.34 ꢀCH2), 43.27 ꢀC-3), 54.18 ꢀC-2), 61.35 ꢀC-60), 65.65, 67.25, 71.91, 72.80 ꢀC-20, C-30, C-40, C-50),
92.39 ꢀC-10), 135.65, 137.76 ꢀC-4a, C-5), 176.60, 176.67, 177.37, 177.77 ꢀpiv-CˆO), 198.13 ꢀCˆO)
ppm.
/2R,8aS)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-2-propyl-4a,5-
didehydro-decahydroquinolin-4-one ꢀ12b; C38H61NO10)
12b was obtained from 1.10 g ꢀ1.54 mmol) 11b according to the afore-described procedure for the
synthesis of its diastereomer 12a.
22
Yield: 0.78 g ꢀ73%); colorless amorphous solid; ‰ꢁŠ ˆ ‡37:6 ꢀc ˆ 1, CHCl3); Rf ˆ 0.50
D
ꢀpetroleum ether:EtOAc ˆ 3:1); 1H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.82 ꢀt, 3H, J ˆ 7.0 Hz, CH3), 1.07,
1.11, 1.13, 1.21 ꢀ4s, 9H, piv-CH3), 1.25±1.38 ꢀm, 4H, CH2), 1.51±1.59 ꢀm, 2H, CH2), 1.80, 1.93 ꢀ2m,
1H, CH2), 2.22 ꢀm, 2H, CH2), 2.29 ꢀd, 1H, Jgem ˆ 18.0 Hz, H-3ax), 2.85 ꢀd, 1H, Jgem ˆ 13.0 Hz, H-
3eq), 3.13 ꢀm, 1H, H-2), 3.87±3.98 ꢀm, 4H, H-8a, H-50, H-6a0, H-6b0), 4.39 ꢀd, 1H, J1 ,2 ˆ 9.2 Hz,
0
0

582
M. Weymann et al.
0
0
H-10), 5.01 ꢀdd, 1H, J3 ,4 ˆ 3.0 Hz, J3 ,2 ˆ 9.8 Hz, H-3 ), 5.28 ꢀt, 1H, J ˆ 9.5 Hz, H-2 ), 5.31 ꢀd, 1H,
0
0
0
0
J4 ,3 ˆ 2.7 Hz, H-4) , 6.66 ꢀd, 1H, J ˆ 2.9 Hz, H-5) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.70
ꢀCH3), 20.12, 21.39, 25.65 ꢀCH2), 26.92, 26.98, 27.03 ꢀpiv-CH3), 32.52, 38.32 ꢀCH2), 38.50, 38.56,
38.61, 38.87 ꢀpiv-Cquart), 43.81 ꢀC-3), 61.92 ꢀC-60), 66.70, 67.21, 71.50, 72.64 ꢀC-20, C-30, C-40, C-50),
94.45 ꢀC-10), 137.18 ꢀC-5.), 137.67 ꢀC-4a), 176.49, 176.73, 177.16, 177.70 ꢀpiv-CˆO), 198.73
ꢀCˆO) ppm.
0
0
0
/2S,4aR,5R,8aR)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-2-
propyl-5-methyl-decahydroquinolin-4-one ꢀ13; C39H65NO10)
To a suspension of 0.28 g ꢀ1.47 mmol) CuI in 10 cm3 dry THF under argon cooled to À28ꢁC, 1.8 cm3 of
a 1.6 M solution of methyllithium in diethyl ether ꢀ2.88 mmol) were added. After 30 min of stirring, the
now clear colorless solution was cooled to À78ꢁC. A solution of 0.5 g ꢀ0.72 mmol) of the enone 12a
and 0.73 cm3 ꢀ5.76 mmol) trimethyl chlorosilane in 25 cm3 dry THF was added. The color changed to
yellow. After 2±3 h ꢀTLC monitoring) the reaction was complete. A mixture of 15 cm3 conc.
NH4OH=NH4Cl ꢀ1:1 v=v) was added. The solution was warmed to room temperature, 100 cm3 diethyl
ether were added, and the separated organic layer was washed with conc. NH4OH=NH4Cl ꢀ1:1 v=v)
until the blue color in the aqueous layer vanished. The collected aqueous solutions were extracted with
2 Â 100 cm3 diethyl ether, and the combined organic solutions were washed with 50 cm3 brine and
dried over MgSO4. After removal of the solvent in vacuo, the crude silyl enolether ꢀRf ˆ 0.67,
petroleum ether:EtOAc ˆ 3:1, d.r. > 10:1, 1H NMR) was obtained; yield: 0.56 g ꢀquantitative),
yellowish amorphous solid.
In 3 cm3 THF, 0.10 g ꢀ0.128 mmol) of this silyl enolether were dissolved and cooled to À20ꢁC.
0.3 cm3 of a 1 M solution of tetrabutylammonium ¯uoride ꢀ0.3 mmol) in THF was added, and the
mixture was stirred for 36 h ꢀTLC monitoring). After addition of 2 Â 20 cm3 diethyl ether, the organic
solutions were washed with 40 cm3 brine and dried over MgSO4. After evaporation of the solvent, the
remaining compound 13 was puri®ed by chromatography ꢀpetroleum ether:EtOAc ˆ 5:1).
22
Yield: 73 mg ꢀ81%); m.p. 168ꢁC ꢀMeOH); ‰ꢁŠ ˆ À60:0 ꢀc ˆ 1, CHCl3); Rf ˆ 0.67 ꢀpetroleum
D
ether:EtOAc ˆ 3:1); d.r. > 15:1:0:0 ꢀ1H NMR); 1H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.77 ꢀd, 3H,
J ˆ 7.1 Hz, CH3), 0.82 ꢀt, 3H, J ˆ 6.8 Hz, propyl-CH3), 1.07±1.53 ꢀm, 45 H, piv-CH3, CH2), 2.04 ꢀm,
0
1H, CH2), 2.19 ꢀdd, 1H, Jvic ˆ 3.7 Hz, Jvic ˆ 12.0 Hz, H-4a), 2.47 ꢀd, 1H, Jgem ˆ 16.2 Hz, H-3ax),
0
2.63 ꢀm, 2H, H-3eq, H-5), 3.26 ꢀdt, 1H, J8a,8 ˆ 3.5 Hz, J8a,4a ˆ J8a,8 ˆ 11.2 Hz, H-8a), 3.36 ꢀm, 1H,
0
H-2), 3.64 ꢀm, 2H, H-50, H-6a0), 4.10 ꢀdd, 1H, J6b ,5 ˆ 9.5 Hz, J6b ,6a ˆ 13.2 Hz, H-6b ), 4.43 ꢀd, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
J1 ,2 ˆ 9.3 Hz, H-1 ), 5.04 ꢀdd, 1H, J3 ,4 ˆ 2.9 Hz, J3 ,2 ˆ 9.9 Hz, H-3 ), 5.34 ꢀd, 1H, J4 ,3 ˆ 3.0 Hz,
H-40), 5.35 ꢀt, 1H, J ˆ 9.5 Hz, H-20) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.62, 13.83 ꢀpropyl-
CH3, CH3), 19.59, 20.16 ꢀCH2), 27.08, 27.19, 27.25 ꢀpiv-CH3), 28.34 ꢀC-5), 32.12, 36.17 ꢀCH2),
38.69, 39.04 ꢀpiv-Cquart), 41.59 ꢀCH2), 44.22 ꢀC-3), 49.67 ꢀC-4a), 52.11, 54.23 ꢀH-8a, C-2), 61.81ꢀC-
60), 65.84, 67.47, 71.94, 72.86 ꢀC-20, C-30, C-40, C-50), 90.42 ꢀC-10), 176.64, 176.69, 177.41, 177.84
ꢀpiv-CˆO), 211.04 ꢀCˆO) ppm; X-ray: see Ref. [16].
/2S,8aR)-N-Phenoxycarbonyl-2-propyl-4a,5-didehydro-quinolin-4-one ꢀ14; C19H23NO3)
To a solution of 0.4 g ꢀ0.58 mmol) 12a in 5 cm3 MeOH, 1 cm3 of 1 M HCl was added, the mixture was
stirred at room temperature for 48 h, the MeOH was evaporated in vacuo, and 20 cm3 diethyl ether
were added to the remaining residue. This mixture was extracted ®ve times with 10 cm3 H2O. After
evaporation of the H2O, the hydrochloride of the quinolinone remained ꢀ133 mg, >95%), which was
dissolved in 5 cm3 H2O. 5 cm3 of sat. NaHCO3 solution were added, the mixture was stirred for 1 h, and
then 0.1 cm3 ꢀ0.68 mmol) phenyl chloroformate were added. After stirring for 2 h, the mixture was
extracted with 3 Â 30 cm3 diethyl ether. The organic layer was dried over MgSO4 and the solvent
removed in vacuo. The remaining crude 14 was puri®ed by chromatography ꢀpetroleum ether:
EtOAc ˆ 10:1).

Carbohydrate Auxiliaries in Alkaloid Synthesis
583
22
D
22
D
Yield: 110 mg ꢀ60%); colorless oil; ‰ꢁŠ ˆ À145:6 ꢀc ˆ 1, CHCl3) ꢀRef. [13]: ‰ꢁŠ ˆ À164
1
ꢀc ˆ 3, CHCl3)); Rf ˆ 0.49 ꢀpetroleum ether:EtOAc ˆ 3:1); H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.92 ꢀt,
3H, CH3), 1.16±1.52 ꢀm, 5H, CH2), 1.53±1.95 ꢀ3m, 3H, CH2), 2.32 ꢀdd, 2H, J1 ˆ 3.8 Hz, H-6), 2.49
ꢀdd, 1H, Jgem ˆ 17.6 Hz, Jvic ˆ 1.6 Hz, H-3a), 2.60 ꢀm, 1H, CH2), 2.74 ꢀdd, 1H, Jgem ˆ 16.7 Hz, H-
3eq), 4.68 ꢀm, 2H, H-2, H-8a), 6.91 ꢀd, 1H, H-5), 7.09 ꢀd, 2H, J ˆ 7.9 Hz, phenyl-H), 7.17 ꢀt, 1H,
J ˆ 7.3 Hz, phenyl-H), 7.34 ꢀt, 2H, J ˆ 7.0 Hz, phenyl-H) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3):
13.7 ꢀCH3), 19.64, 20.72, 20.92, 25.79, 36.49 ꢀCH2), 44.28 ꢀC-3), 50.41, 52.61 ꢀC-2, C-8a), 121.61,
125.22, 129.27, 129.54 ꢀphenyl), 134.33, 139.54 ꢀC-5, C-4a), 151.37 ꢀN±COO±Ph), 195.88 ꢀCˆO)
ppm.
/2S,4aR,5R,8aR)-N-Phenoxycarbonyl-2-propyl-5-methyl-decahydroquinolin-4-one
ꢀ15a; C20H27NO3)
Removal of the N-galactosyl group from 400 mg ꢀ0.56 mmol) quinolinone 13 was carried out as
described for 12a, as well as the subsequent acylation with phenyl chloroformate. Puri®cation of
the crude product by chromatography ꢀpetroleum ether:EtOAc ˆ 12:1) gave 15a ꢀd.r. 7ꢀtrans):
1ꢀcis):0:0).
22
Yield: 150 mg ꢀ82%); colorless oil; ‰ꢁŠ ˆ À160:3 ꢀc ˆ 1, CHCl3); Rf ˆ 0.48 ꢀpetroleum
D
1
ether:EtOAc ˆ 5:1); H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.96 ꢀd, 3H, J ˆ 7.0 Hz, CH3), 0.97 ꢀt, 3H,
J ˆ 7.1 Hz, propyl-CH3), 1.28 ꢀm, 1H, H-6), 1.49 ꢀm, 3H, H-8ax, CH2), 154±1.66 ꢀm, 4H, H-7, H-70,
H-6, CH2), 1.84 ꢀm, 1H, CH2), 2.48 ꢀdd, 1H, Jvic ˆ 1.5 Hz, Jgem ˆ 18.8 Hz, H-3ax), 2.64 ꢀdd, 1H,
Jvic ˆ 7.0 Hz, Jgem ˆ 19.0 Hz, H-3eq), 2.65±2.72 ꢀm, 2H, H-5, H-8eq), 2.73 ꢀdd, 1H, J4a,8a ˆ 12.0 Hz,
J4a,5 ˆ 3.2 Hz, H-4a), 4.02 ꢀdt, 1H, J8a,4a ˆ J8a,8 ˆ 11.5 Hz, J8a,8 ˆ 3.1 Hz, H-8a), 4.68 ꢀddt, 1H,
J2,3 ˆ 1.5 Hz, Jvic ˆ 7.6 Hz, H-2), 7.10 ꢀm, 2H, phenyl-H), 7.19 ꢀm, 1H, phenyl-H), 7.36 ꢀm, 2H,
phenyl-H) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.25, 13.85 ꢀpropyl-CH3, CH3), 20.22 ꢀCH2),
27.73 ꢀC-5), 32.19, 35.98, 39.39, 44.33 ꢀCH2), 51.34, 52.03, 53.93 ꢀC-2, C-4a, C-8a), 121.65, 125.36,
129.29 ꢀphenyl) 151.37 ꢀNCOOPh), 154.82 ꢀphenyl-O), 207.25 ꢀCˆO) ppm.
/2S,4aR,5R,8aR)-N-Benzylycarbonyl-2-propyl-5-methyl-decahydroquinolin-4-one
ꢀ15b; C21H29NO3)
15b was synthesized in a completely analogous manner to 15a from 0.4 g ꢀ0.58 mmol) 13 and
0.1 cm3 benzyl chloroformate ꢀ0.68 mmol) and puri®ed by chromatography ꢀpetroleum ether:
EtOAc ˆ 10:1).
22
Yield: 0.17 g ꢀ88%); colorless oil; ‰ꢁŠ ˆ À132:1 ꢀc ˆ 1, CHCl3); Rf ˆ 0.46 ꢀpetroleum
D
ether:EtOAc ˆ 5:1); FD-MS: m=z ˆ 342.9 [M ]; 1H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.9 ꢀt, 3H,
‡
J ˆ 7.3 Hz, propyl-CH3), 0.91 ꢀd, 3H, J ˆ 7.0 Hz, CH3), 1.19 ꢀm, 1H, CH2), 1.3±1.65 ꢀm, 7H, CH2,
CH), 1.75 ꢀm, 1H, CH2), 2.39 ꢀdd, 1H, Jcis ˆ 1.5 Hz, Jgem ˆ 19.5 Hz, H-3ax), 2.51 ꢀdd, 1H,
Jtrans ˆ 6.8 Hz, Jgem ˆ 19.5 Hz, H-3eq), 2.59 ꢀm, 2H, H-5, H-8), 2.66 ꢀdd, 1H, J4a,5 ˆ 3.6 Hz,
0
J4a,8a ˆ 11.3 Hz, H-4a), 3.91 ꢀdt, 1H, J8a,4a ˆ J8a,8 ˆ 11.3 Hz, J8a,8 ˆ 2.9 Hz, H-8a), 4.55 ꢀm, 1H, H-2),
5.12 ꢀm, 2H, benzyl-CH2), 7.33 ꢀm, 5H, phenyl-H) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.16,
13.75 ꢀpropyl-CH3, CH3), 27.59 ꢀCH-CH3), 32.12, 35.94, 39.13, 43.53, 44.21 ꢀCH2), 50.71, 51.51,
53.81, ꢀC-4a, C-2, C-8a), 67.18 ꢀbenzyl-CH2), 127.65, 127.9, 128.42 ꢀphenyl), 136.58 ꢀphenyl-ipso),
156.08 ꢀN±CO±O), 207.51 ꢀCˆO) ppm.
/2S,4aS,5R,8aR)-N-Phenyloxycarbonyl-2-propyl-5-methyl-decahydroquinolin-4-one
ꢀ16; C20H27NO3)
For the preparation of 16, of also Ref. [13].
To a stirred suspension of 0.28 g ꢀ1.47 mmol) CuI in 10 cm3 dry THF under argon at À30ꢁC,
1.8 cm3 of a 1.6 M solution of methyllithium in diethyl ether ꢀ2.88 mmol) were added. The clear

584
M. Weymann et al.
solution was cooled to À78ꢁC, and 1.6 cm3 BF3 Á OEt2 ꢀ12 mmol) were added dropwise. After 20 min,
a solution of 11 mg ꢀ0.035 mmol) 15a in 2 cm3 THF was added, and the mixture was stirred for
30 min at À78ꢁC and for 2 h at À18ꢁC. At this temperature, 8 cm3 MeOH and, at room temp., 50 cm3
diethyl ether were added. The organic solution was washed with conc. NH4OH=NH4Cl ꢀ1:1, v=v)
solution until blue color vanished. The organic layer was washed with brine and dried over MgSO4.
After evaporation of the solvent, the crude product 16 was puri®ed by chromatography ꢀpetroleum
ether:EtOAc ˆ 15:1).
22
D
Yield: 7 mg ꢀ67%); colorless oil; ‰ꢁŠ ˆ ‡30:9 ꢀc ˆ 1, CHCl3); Rf ˆ 0.64 ꢀpetroleum ether:
EtOAc ˆ 3:1); d.r. ꢀ16:15a) ˆ 9:2:0:0; 1H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.91 ꢀt, 3H, J ˆ 7.3 Hz,
propyl-CH3), 1.03 ꢀd, 3H, J ˆ 7.3 Hz, CH3), 1.24±1.70 ꢀm, 9H, CH2), 1.93 ꢀd, 1H, J ˆ 9.4 Hz, H-
8endo), 2.34 ꢀdd, 1H, Jvic ˆ 2.1 Hz, Jgem ˆ 14.1 Hz, H-3eq), 2.60 ꢀm, 1H, H-5), 2.65 ꢀd, 1H,
J ˆ 6.5 Hz, H-4a), 2.78 ꢀdd, 1H, Jvic ˆ 8.2 Hz, Jgem ˆ 14.1 Hz, H-3eq), 4.71 ꢀm, 1H, H-2), 4.86 ꢀm,
1H, H-8a), 7.11 ꢀm, 2H, phenyl-H), 7.20 ꢀm, 1H, phenyl-H), 7.36 ꢀm, 2H, phenyl-H) ppm; 13C NMR
ꢀ100.6 MHz, ꢂ, CDCl3): 13.75, 18.36 ꢀpropyl-CH3, CH3), 18.08, 26.62 ꢀC-4a, C-5), 20.08, 20.28,
27.27, 36.60, 39.76, 43.66 ꢀCH2), 53.57, 54.22 ꢀC-2, C-8a), 121.68, 125.40, 129.30 ꢀphenyl), 151.44
ꢀNCOOPh), 154.17 ꢀphenyl-ipso), 208.84 ꢀCˆO) ppm.
Epimerization of 15a
To a solution of N-phenoxycarbonyl decahydroquinolin-4-one, 5 mg 15a ꢀtrans:cis ˆ 7:1) in 3 cm3
THF and two drops of triethylamine ꢀꢀ6 mg) were added. The mixture was stirred at room
temperature. After 2 min, an analytical sample was poured into a mixture of diethyl ether=1 M HCl.
The solvent was evaporated, and the remaining residue was investigated by analytical HPLC, column
B; ratio of diastereomers: 15aꢀtrans):16ꢀcis) ˆ 1:3; eluent: acetonitrile:water, gradient: 60=40!75=25
ꢀ0±20 min); Rtꢀ15a) ˆ 13.5 min, Rtꢀ16) ˆ 14 min.
/2S,4aR,5R,8aR)-N-Benzyloxycarbonyl-2-propyl-5-methyl-decahydroquinolin-
4-one-ethane-1,2-diyl dithioacetal ꢀ17; C23H33NO2S2)
To a solution of 160 mg ꢀ0.38 mmol) 15b and 0.1 cm3 ꢀ0.9 mmol) ethane dithiol in 5 cm3 dry CH2Cl2 at
0ꢁC, 0.3 cm3 borontri¯uoride etherate ꢀ2.5 mmol) were added dropwise. After 2 h at 0ꢁC the mixture
was stirred at room temperature for 15 h, diluted with 30 cm3 CH2Cl2, and washed with 2 Â 20 cm3 sat.
NaHCO3 solution and H2O. After drying over MgSO4, the solvent was evaporated in vacuo.
22
D
Yield: 120 mg ꢀ64%); colorless oil; ‰ꢁŠ ˆ À24:8 ꢀc ˆ 1, CHCl3); Rf ˆ 0.35 ꢀpetroleum ether:
‡
1
EtOAc ˆ 7:1); FD-MS: m=z ˆ 419.9 [M ]; H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.85 ꢀt, 3H, J ˆ 7.3 Hz,
propyl-CH3), 1.08 ꢀd, 3H, J ˆ 7.0 Hz, CH3), 1.26 ꢀm, 3H, CH2), 1.39±1.66 ꢀm, 6H, CH2), 1.91 ꢀdd,
1H, Jgem ˆ 13.5 Hz, Jcis ˆ 3.8 Hz, H-3eq), 2.09 ꢀdd, 1H, J4a,8a ˆ 12 Hz, J4a,5 ˆ 3.5 Hz, H-4a), 2.18 ꢀm,
1H, CH2), 2.62 ꢀm, 1H, H-5), 2.76 ꢀdd, 1H, Jgem ˆ 13.3 Hz, Jtrans ˆ 11.4 Hz, H-3ax), 3.22 ꢀm, 4H, S-
0
CH2), 4.10 ꢀdt, J8a,4a ˆ J8a,8 ˆ 11.7 Hz, J8a,8 ˆ 3.5 Hz, H-8a), 4.39 ꢀm, 1H, H-2), 5.16 ꢀm, 2H,
benzyl-CH2), 7.32 ꢀm, 5H, phenyl-H) ppm; 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.42, 13.81 ꢀpropyl-
CH3, CH3), 19.3, 20.57 ꢀCH2), 31.35 ꢀCH), 34.64, 34.97 ꢀCH2), 38.33, 38.67 ꢀS-CH2), 42.79 ꢀCH2),
49.33, 50.07, 54.29 ꢀCH, NCHR), 52.42 ꢀCH2), 66.89 ꢀbenzyl-CH2), 127.38, 127.59, 128.32 ꢀphenyl-
C), 137.29 ꢀquart. phenyl-C), 156.33 ꢀN±CO±O) ppm.
/2S,4aR,5R,8aR)-2-Propyl-5-methyl-decahydroquinoline hydrochloride
/trans-4a-epi-pumiliotoxin C) ꢀ5; C13H26NCl)
To a solution of 90 mg ꢀ0.22 mmol) of the dithioacetal 17 in 20 cm3 dry isopropanol, 1.5 g freshly
prepared and neutral washed Raney nickel were added. A gentle stream of hydrogen was passed
through the solution at room temperature for 2 h. After stirring for additional 14 h, the catalyst was

Carbohydrate Auxiliaries in Alkaloid Synthesis
585
®ltered off. The catalyst was dissolved in aqueous HCl, neutralized with conc. aq. ammonia, and the
solution was extracted with 2 Â 30 cm3 CHCl3. The organic layer was extracted with aq. HCl, and
the acidic aq. solution was evaporated to dryness in vacuo. Impurities were removed from the crude
hydrochloride 5 by silica layer chromatography with EtOAc as the eluent.
22
Yield: 11 mg ꢀ22%); m.p. 256±258ꢁC; ‰ꢁŠ ˆ À11:3 ꢀc ˆ 0.5, CHCl3); FD-MS: m=z ˆ 195.8
D
‡
1
[M-Cl] ; H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.82 ꢀd, 3H, J ˆ 7.3 Hz, CH3), 0.88 ꢀt, 3H, J ˆ 7.3 Hz,
propyl-CH3), 1.2±2.0 ꢀm, 14H, m CH2), 2.05, 2.36 ꢀ2m, 2H, CH), 2.87 ꢀm, 2H, N-CHR) ppm; 13C
NMR ꢀ100.6 MHz, ꢂ, CDCl3): 12.68, 13.73 ꢀpropyl-CH3, CH3), 18.79, 19.0, 30.31 ꢀCH2), 31.96
ꢀCH), 32.16, 35.1 ꢀCH2), 41.45 ꢀC-4a), 56.85, 58.25 ꢀC-2, C-8a) ppm; X-ray analysis: P212121
Ê
Ê 3
ꢀorthorhombic), a ˆ 7.2852ꢀ2), b ˆ 8.7387ꢀ3), c ˆ 22.0953ꢀ5) A, V ˆ 1406.67ꢀ7) A , z ˆ 4,
Fꢀ000) ˆ 512, Cu-Kꢁ, SIR-92, SHELXL-97 [23].
/2R,4aR,5S,8aS)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-
2,5-di-propyl-decahydroquinolin-4-one ꢀ18; C41H69NO10)
To 0.34 g ꢀ1.6 mmol) CuBr Á SMe2 in 20 cm3 dry THF at À78ꢁC under argon, 1.2 cm3 of a 2 M solution
of n-propyl magnesium chloride in diethyl ether ꢀ3.2 mmol) were added. The pale yellow suspension
was warmed to À55ꢁC within 60 min and became clear. This solution was cooled again to À78ꢁC, and
a solution of 0.39 g ꢀ0.56 mmol) enone 12b and 0.85 cm3 trimethylchlorosilane ꢀ0.67 mmol) in 20 cm3
dry THF was added through a syringe. The color of the reaction mixture changed ®rst to deep red and
then to orange. After 45 min stirring, only traces of the starting material could be detected ꢀmonitoring
by TLC). After 1.5 h, 20 cm3 of conc. NH4OH=NH4Cl ꢀ1:1, v=v) were added. The mixture was warmed
up to room temperature, 140 cm3 diethyl ether were added, and the organic layer was extracted with
conc. NH4OH=NH4Cl ꢀ1:1, v=v) as long as a blue color occurred in the aqueous layer. The collected
aq. solutions were extracted with 2 Â 130 cm3 diethyl ether, the combined organic solutions were
washed with 70 cm3 brine, dried over MgSO4, and the solvent was evaporated in vacuo. The remaining
crude silyl enolether was dissolved in 7 cm3 THF, cooled to À20ꢁC, and 0.8 cm3 ꢀ0.8 mmol) of a 1 M
solution of tetrabutylammonium ¯uoride in THF were added. After 24 h the solvent was evaporated,
and the remaining residue was dissolved in 55 cm3 diethyl ether and washed with 60 cm3 H2O. The aq.
layer was extracted with 2 Â 25 cm3 diethyl ether. The combined organic solutions were washed with
50 cm3 brine and dried over MgSO4. After evaporation of the solvent in vacuo, the crude 18 was
puri®ed by chromatography ꢀpetroleum ether:EtOAc ˆ 7:1).
22
Yield: 0.18 g ꢀ43%); colorless amorphous solid; ‰ꢁŠ ˆ À46:7 ꢀc ˆ 1.1, CHCl3); Rf ˆ 0.51
D
ꢀpetroleum ether:EtOAc ˆ 5:1); d.r. > 10:1:0:0 ꢀ1H NMR); 1H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.87 ꢀt, 6H,
0
J ˆ 6.9 Hz, CH3, CH3 ), 1.08±1.42 ꢀm, 48 H, piv-CH3, CH2), 1.54 ꢀm, 1H, CH2), 1.65 ꢀm, 1H, CH2),
0
2.25 ꢀdd, 1H, Jvic ˆ 9.7 Hz, Jvic ˆ 16.6 Hz, H-3ax), 2.44 ꢀm, 1H, H-5), 2.43 ꢀm, 2H, CH2CˆO,
CHCˆO), 3.28, 3.54 ꢀ2m, 1H, H-2, H-8a), 3.93 ꢀm, 2H, H-50, H-6a0), 4.10 ꢀdd, 1H, J6b ,5 ˆ 9.5 Hz,
0
0
0
0
0
0
0
0
0
0
J6b ,6a ˆ 13.6 Hz, H-6b ), 4.38 ꢀd, 1H, J1 ,2 ˆ 9.4 Hz, H-1 ), 5.09 ꢀdd, 1H, J3 ,4 ˆ 3.2 Hz,
0
0
0
0
0
0
0
0
0
0
J3 ,2 ˆ 10.0 Hz, H-3 ), 5.38 ꢀd, 1H, J4 ,3 ˆ 3.4 Hz, H-4 ), 5.38 ꢀdd, 1H, J2 ,1 ˆ 9.3 Hz, J2 ,3 ˆ 9.9 Hz,
13
H-20) ppm; C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 14.00, 14.07 ꢀCH3, CH3 ), 20.83, 20.92, 25.07 ꢀCH2),
0
27.04, 27.10, 27.23, 27.29 ꢀpiv-CH3), 32.13 ꢀC-5), 33.40, 35.00 ꢀCH2), 38.70, 38.74, 39.03 ꢀpiv-Cquart),
40.27 ꢀCH2), 44.29 ꢀC-3), 54.44, 56.23 ꢀC-2, H-8a), 61.46 ꢀC-60), 66.04, 67.28, 72.12, 72.69 ꢀC-20,
C-30, C-40, C-50), 176.73, 176.82, 177.32, 177.79 ꢀpiv-CˆO), 211.34 ꢀCˆO) ppm.
/2R,4aR,5S,8aS)-N-/2,3,4,6-Tetra-O-pivaloyl-ꢀ-D-galactopyranosyl)-2,5-di-propyl-
4-tri¯uoromethane-sulfonyloxy-3,4-didehydro-decahydroquinoline ꢀ19; C42H68NO12SF3)
To a solution of 0.15 g ꢀ0.20 mmol) 18 in 6 cm3 dry THF at 78ꢁC, 0.3 cm3 ꢀ3.0 mmol) of a 1 M
solution of sodium hexamethyldisilazane ꢀNaHMDS) in THF were added. After stirring for 1 h,
0.86 cm3 ꢀ0.43 mmol) of a 0.5 M solution of 5-chloro-pyridine-2-N,N-bis-tri¯uoromethanesulfoni-
ꢁ
Ê
mide ꢀdried with molecular sieve 4 A) were added, and stirring was continued for 2 h at À78 C. After

586
M. Weymann et al.
additional stirring at À20ꢁC for 12 h, 5 cm3 sat. NH4Cl solution was added, followed by addition of
50 cm3 diethyl ether at room temperature. The organic layer was washed with 30 cm3 brine and dried
over MgSO4. The solvent was evaporated in vacuo. Column chromatography with petroleum
ether:EtOAc ˆ 8:1 gave 25 mg of the starting material, 41 mg of the regioisomer 20, and the product
19.
22
Yield: 71 mg ꢀ41%); oil containing traces of impurities; ‰ꢁŠ ˆ ‡4:82 ꢀc ˆ 0.5, CHCl3); Rf ˆ 0.59
D
1
0
ꢀpetroleum ether:EtOAc ˆ 5:1); H NMR ꢀ400 MHz, ꢂ, CDCl3): 0.81±0.91 ꢀm, 6H, CH3, CH3 ), 1.07±
1.61 ꢀm, 50 H, piv-CH3, CH2), 2.14 ꢀm, 1H, CH2), 2.82 ꢀbr s, 1H, H-4a), 3.43 ꢀm, 1H, H-8a), 3.80 ꢀdd,
0
0
0
0
0
0
0
0
00
0
1H, J5 ,6a ˆ 6.9 Hz, J5 ,6b ˆ 6.4 Hz, H-5 ), 3.89 ꢀm, 2H, H-6a , H-1 ), 4.03 ꢀdd, 1H, J6b ,5 ˆ 6.6 Hz,
0
0
0
0
0
0
J6b ,6a ˆ 17.6 Hz, H-6b ), 4.23 ꢀm, 1H, H-2), 5.08 ꢀdd, 1H, J3 ,4 ˆ 3.3 Hz, J3 ,2 ˆ 10.0 Hz, H-3 ), 5.34
ꢀd, 1H, J4 ,3 ˆ 3.4 Hz, H-4 ), 5.48 ꢀt, 1H, J ˆ 9.6 Hz, H-2 ), 5.69 ꢀt, 1H, J ˆ 3.0 Hz, H-3) ppm; 13C
0
0
0
0
0
NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.88, 14.14 ꢀCH3, CH3 ), 20.17, 20.87 ꢀCH2), 27.07, 27.11, 27.24,
27.28 ꢀpiv-CH3), 30.14 ꢀCH2), 33.20 ꢀC-5), 34.09 ꢀCH2), 38.33, 38.65, 38.73, 39.01 ꢀpiv-Cquart), 43.94
ꢀC-4a), 61.20 ꢀC-60), 65.48, 67.22, 72.06, 72.51 ꢀC-20, C-30, C-40, C-50), 96.10 ꢀC-10), 119.21 ꢀC-3),
148.66 ꢀC-4), 176.64, 176.84, 176.94, 177.20 ꢀpiv-CˆO) ppm.
/2R,4aR,5S,8aS)-2,5-Di-propyl-decahydroquinoline /cis-4a-epi-/ ‡ )-
perhydro 219A) ꢀ6; C15H29N)
To a solution of 50 mg ꢀ0.57 mmol) of enol tri¯ate 19 in 10 cm3 dry MeOH, 100 mg lithium carbonate
and 10 mg palladium on charcoal ꢀ5%) were added. The mixture was vigorously stirred under
hydrogen at room temperature for 24 h. After ®ltration through celite and washing of the solid with
50 cm3 MeOH, the solvent was evaporated from the combined MeOH solutions. The remaining
residue was dissolved in 30 cm3 diethyl ether, washed with 25 cm3 H2O and 25 cm3 brine, and dried
over MgSO4. After evaporation of the solvent, the residue was dissolved in 3 cm3 MeOH; sub-
sequently, 0.1 cm3 1 N HCl were added, and the mixture was stirred for 24 h at room temperature. After
evaporation of the solvents, 15 cm3 diethyl ether were added to the residue, and the solution was
extracted with 5 Â 10 cm3 H2O. Evaporation of H2O in vacuo gave 14 mg of the crude hydrochloride 6.
The residue was stirred with 0.5 cm3 sat. Na2CO3 solution and extracted with 3 Â 10 cm3 CH2Cl2 to
give the free amine 6 ꢀyield: 9 mg, 74%). NMR spectroscopic data of both the free amine 6 and its
hydrochloride are in agreement with those reported in Refs. [15] and [20].
22
Hydrochloride of 6: ‰ꢁŠ ˆ ‡12:2 ꢀc ˆ 0.7, MeOH); 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 13.81,
D
0
14.42 ꢀCH3, CH3 ), 18.75, 19.21, 20.66, 23.39, 25.02, 29.13, 31.11, 31.43, 34.71, 35.10, 38.89 ꢀCH2),
58.64, 60.27 ꢀC-2, C-8a) ppm.
Free amine 22: 13C NMR ꢀ100.6 MHz, ꢂ, CDCl3): 14.09, 14.46 ꢀCH3, CH3 ), 18.99, 19.11, 21.03,
0
26.64, 27.09, 31.55, 32.01, 32.99, 35.46, 39.29 ꢀ9CH2, CH), 40.27 ꢀC-4a), 56.24, 57.78 ꢀC-2, C-8a)
ppm.
Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft and by the Fonds der Chemischen
Industrie.
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Ruck-Braun K ꢀ1993) Angew Chem Int Ed Engl 32: 336

Carbohydrate Auxiliaries in Alkaloid Synthesis
587
[3] Kunz H, Sager W ꢀ1987) Angew Chem Int Ed Engl 26: 557
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[23] Further details are available on request from the Cambridge Crystallographic Data Center
quoting the deposit number CCDC 170250
Received September 7, 2001. Accepted October 16, 2001