Stereo- and regiocontrolled construction of trisubstituted piperidines using a TpMo(CO)2(dihydropyridine) scaffold (Tp = hydridotrispyrazolylborate)

Article abstract of DOI:10.1021/jo0007128

Cationic TpMo(CO)₂(dihydropyridine) complexes (Tp = hydridotrispyrazolylborate), readily generated from 3-oxo-3,6-dihydro-2H-pyridine-1-carboxylic acid benzyl ester, represent scaffolds from which (by judicious choice of demetalation conditions

Full text of DOI:10.1021/jo0007128

J . Org. Chem. 2000, 65, 7445-7455
7445
Ster eo- a n d Regiocon tr olled Con str u ction of Tr isu bstitu ted
P ip er id in es Usin g a Tp Mo(CO) (Dih yd r op yr id in e) Sca ffold (Tp )
2
Hyd r id otr isp yr a zolylbor a te)
Alessandro F. Moretto and Lanny S. Liebeskind*
Sanford S. Atwood Chemistry Center, Emory University, 1515 Pierce Drive, Atlanta, Georgia 30322
CHEMLL1@emory.edu.
Received May 10, 2000
Cationic TpMo(CO) (dihydropyridine) complexes (Tp ) hydridotrispyrazolylborate), readily gener-
2
ated from 3-oxo-3,6-dihydro-2H-pyridine-1-carboxylic acid benzyl ester, represent scaffolds from
which (by judicious choice of demetalation conditions) either 2,3,6- or 2,5,6-trisubstituted-1,2,3,6-
tetrahydropyridines can be prepared in a regio- and stereodefined way.
In tr od u ction
set has rendered useful the functionalization of a variety
oxygen-containing heterocyclic systems.8
,23,26
Since the
The sequential, multistep, stereo- and regiocontrolled
functionalization-demetalation of stoichiometric transi-
tion metal π-complexes has received considerable atten-
tion as a means of producing highly substituted organic
molecules.1 Stoichiometric π-complexes of molybdenum
bound to polyene ligands are especially well suited to this
core units of a vast number of biologically active synthetic
and natural products are nitrogen-containing hetero-
cycles, the TpMo(CO) -based synthetic methodology
2
could prove of use in the stereocontrolled construction of
these systems, also. To that effect, we report herein the
synthesis, functionalization, and demetalation of a chiral,
27
-14
1
,15,16
task.
(
In this regard, hydridotris(1-pyrazolyl)borate
used in place of the more commonly studied
2
racemic TpMo(CO) (dihydropyridine) complex and its use
Tp)1
7-19
in the synthesis of 2,3,6-trisubstituted tetrahydro-
pyridines and piperidines. These studies represent a
prelude to current efforts to develop an enantiocontrolled
synthesis of substituted piperidines, the full details of
which will be reported in due course.
cyclopentadienyl (Cp) auxiliary ligand has significantly
extended the applicability of the molybdenum-based
methodology.6
,8,20-25
2
In particular, the TpMo(CO) ligand
*
To whom correspondence should be addressed. Tel no.: (404) 727-
6
604. FAX no.: (404) 727-0845.
Resu lts a n d Discu ssion
(
1) Liu, R.-S. Adv. Met.-Org. Chem. 1998, 6, 145-186.
(2) Kundig, E. P.; Bernardinelli, G.; Beruben, D.; Crousse, B.;
(η3-
F or m a tion of 2,3,6-Tr isu bstitu ted Tp Mo(CO)
2
Fretzen, A.; Ratni, H.; Schnell, B.; Xu, L.-H. ECHET98: Electron. Conf.
Heterocycl. Chem. 1998, 77-90.
a llyl) Com p lexes. Molybdenum π-allyl complex 2 was
derived from dihydropyridinone 1b (Scheme 1), which
was prepared from the known 1a by exchange of N-
protecting groups. Dihydropyridinone 1a was available
on large scale in three steps from commercially available
N-benzylglycine ethyl ester through a modification of a
(3) Kopach, M. E.; Kolis, S. P.; Liu, R.; Robertson, J . W.; Chordia,
M. D.; Harman, W. D. J . Am. Chem. Soc. 1998, 120, 6199-6204.
(
(
(
4) Harman, W. D. Chem. Rev. 1997, 97, 1953-1978.
5) Fretzen, A.; Kundig, E. P. Helv. Chim. Acta 1997, 80, 2023.
6) Pearson, A. J .; Neagu, I. B. J . Org. Chem. 1999, 64, 2890-2896.
(7) Pearson, A. J. In Iron Compounds in Organic Synthesis; Katritsky,
A. R., Meth-Cohn, O., Rees, R. W., Eds.; Academic Press: San Diego,
literature procedure.2
8,29
The previously described oxi-
(CO) to an enone followed
22
1
5
1
9
1
dative addition of Mo(DMF)
3
3
by O-methylation was used to generate molybdenum
complex 2 (the O-silylated material was too labile to be
of use, while O-acetylation gave a complex that could not
be converted into a cationic diene complex by hydride
abstraction). The robust O-methyl complex 2 proved to
be a useful starting point for the synthesis of a variety
substituted piperidines.
(
9) Yu, R. H.; McCallum, J . S.; Liebeskind, L. S. Organometallics
994, 13, 1476-1486.
(
10) Rubio, A.; Liebeskind, L. S. J . Am. Chem. Soc. 1993, 115, 891-
01.
(
11) Hansson, S.; Miller, J . F.; Liebeskind, L. S. J . Am. Chem. Soc.
990, 112, 9660.
(
(
(
12) Uemura, M. Rev. Heteroat. Chem. 1994, 10, 251-274.
13) Pearson, A. J . Synth. Lett. 1990, 10-19.
14) Solladi e´ -Cavallo, A. In Advances in Metal-Organic Chemistry;
(
(24) Ward, Y. D.; Villanueva, L. A.; Allred, G. D.; Payne, S. C.;
Semones, M. A.; Liebeskind, L. S. Organometallics 1995, 14, 4132-
4156.
(25) Villanueva, L. A.; Ward, Y. D.; Liebeskind, L. S. Organometal-
lics 1996, 15, 4190.
(26) The first general description of synthetically useful transforma-
2 2
tions of TpMo(CO) (η-3-allyl) and TpMo(CO) (η-4-diene) complexes is
documented within the Supporting Information for Ward, Y. D.;
Villanueva, L. A.; Allred, G. D.; Liebeskind, L. S. J . Am. Chem. Soc.
1996, 118, 897-898; Pearson, A. J .; Douglas, A. R. Organometallics
1998, 17, 1446-1448.
(27) Moody, C. J . Advances in Nitrogen Heterocycles; J AI Press:
London, 1996; Vol. 2.
(28) Ziegler, F. E.; Bennet, G. B. J . Am. Chem. Soc. 1973, 95, 7458.
(29) Chen, L.-C.; Wang, E.-C.; Lin, J .-H. Heterocycles 1984, 22, 2769.
(
1
0.1021/jo0007128 CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/03/2000

7
446 J . Org. Chem., Vol. 65, No. 22, 2000
Moretto and Liebeskind
Sch em e 1. Gen er a tion of Dih yd r op yr id in e
Com p lex 3 fr om Dih yd r op yr id on e 1b
F igu r e 1. 1H NMR Analysis of compound 23 substitution
pattern.
Ta ble 2. Syn th esis of 2,3,6-Tr isu bstitu ted
Dih yd r op yr id in yl Com p lexes
Ta ble 1. Nu cleop h ilic F u n ction a liza tion of
Dih yd r op yr id in e Com p lex 3
compd,
compd,
compd
R
yield (%)
R′M
yield (%)
4
5
methyl
ethyl
12 (90)
13 (94)
vinylMgBr
phenylMgBr
BnMgBr
EtMgBr
MeMgBr
19 (62)
20 (43)
21 (76)
22 (66)
23 (76)
24 (78)
25 (75)
26 (55)
27 (73)
28 (58)
29 (43)
30 (67)
31 (54)
compd
RM
yield (%)
6
7
benzyl
vinyl
14 (94)
15 (86)
4
5
6
7
8
9
MeMgBr
EtMgBr
BnMgBr
VinylMgBr
PhMgBr
83
71
77
67
66
52
69
EtMgBr
BnMgBr
8
9
phenyl
CH2CO2Et
allyl
16 (84)
17 (78)
18 (68)
vinylMgBr
EtMgBr
PhCtCLi
PhC(OLi)dCH2
PhCtCLi
PhC(OLi)dCH2
LiCH2CO2Et
AllylMgBr
1
0
1
0
Complex 2 underwent hydride abstraction using
Ph CPF and gave the cationic diene complex 3 in
3
6
The structures were determined through two-dimen-
sional H NMR analysis (vide infra).
quantitative yield (Scheme 1). In this hydride abstraction,
the exclusive formation of the cross-conjugated system
over the alternate linearly conjugated regioisomer is
consistent with Pearson’s earlier studies of stoichiometric
organoiron π-complexes, where frontier molecular orbital
1
Further functionalization of the dihydropyridine scaf-
fold was achieved through a selective second hydride
abstraction from tetrahydropyridinyl complexes 4-10,
which gave the corresponding cationic dienes 12-18
7
arguments were used to rationalize the selectivity. In
(
Table 2). In this second regiocontrolled hydride abstrac-
tion, only the C-H bond that is situated anti to the
TpMo(CO) moiety is properly oriented and accessible to
the present case, the regiochemistry of the hydride
abstraction was established through the examination of
2
1
H NMR coupling constants. The C-2 proton appears as
the triphenylcarbenium for abstraction. The derived
cationic diene complexes 12-18 underwent a second
nucleophilic addition with commercially available Grig-
nard reagents, two lithium enolates, and one lithium
acetylide, giving only a single isolable product in each
case. Although the yields for the second addition were
slightly reduced from those of the first, the remainder of
the mass balance was an intractable polar material that
was easily removed by basic alumina chromatography.
a broad singlet at 7.60 ppm, and the protons at C-4 and
C-5 are observed as a doublet (δ ) 5.60 ppm, J ) 8.4 Hz)
and an apparent doublet of doublets (δ ) 5.44 ppm, J )
8
.4 and 3.2 Hz), respectively.
Treatment of cationic complex 3 with various Grignard
reagents and a lithium enolate gave the anticipated
nucleophilic addition products 4-10 in good yield, along
3
with small amounts of the corresponding neutral η -
pentadienyl complex 11, formed by competitive deproton-
ation of 3 (Table 1). Although sensitive to silica gel, the
derived products 4-10 were readily purified by chroma-
tography using basic alumina. Consistent with earlier
Both termini of the coordinated dienes 12-18 are
available for nucleophilic attack. The site of the second
nucleophilic addition was determined through a study
of compound 23 (Figure 1) whose 1H NMR spectrum
showed doublets at both 1.43 and 1.42 ppm (rotamers)
with J ) 6.4 Hz, which were assigned to the methyl
substituent. The corresponding COSY spectrum allowed
identification of a doublet of quartets (J ) 6.4 and 2.4
Hz) at 4.56 and 4.48 ppm (rotamers) to which the doublet
was coupled. This methyne was in turn coupled to one
studies of the analogous Cp- and TpMo(CO)
2
(dihydro-
pyran) complexes,1
0,11,26
the addition of nucleophiles to
the dihydropyridinone complexes was regio- and stereo-
controlled, giving only the products from nucleophilic
attack at the end of the coordinated diene adjacent to
the N-heteroatom, and anti to the molybdenum moiety.

Construction of Trisubstituted Piperidines
J . Org. Chem., Vol. 65, No. 22, 2000 7447
Sch em e 2. Oxid a tive a n d P r otic Decom p lexa tion
of Dih yd r op yr id in yl Com p lexes
Sch em e 3. Regio- a n d Ster eocon tr olled
Decom p lexa tion s
of the terminal π-allyl protons, which was observed as a
doublet of doublets (J ) 8.4 and 2.4 Hz) at 3.98 and 3.92
ppm (rotamers). These data unambiguously confirm
addition of the nucleophile R to nitrogen not oxygen, and
consequently confirm the regiochemistry of the first
nucleophilic addition.
Sch em e 4 1H NMR An a lysis of Com p ou n d 23
Su bstitu tion P a tter n
Decom p lexa tion of 2,3,6-Tr isu bstitu ted Tp Mo-
3
(
CO)
2
(η -a llyl) Com p lexes. Three different decomplex-
ation protocols were explored: an oxidative decomplex-
ation,30 a photolytic protodemetalation,
31,32
and a reductive
+
decomplexation using CO f NO exchange to activate
the metal complex prior to hydride addition.26 Each of
these protocols gave a unique array of functionality, each
of which has potential utility for further synthetic
manipulations.
Oxidative decomplexation of compounds 21 and 29
with cupric chloride (6 equiv) gave the corresponding
enones 32 and 33 in moderate yield, as shown in Scheme
2
, but the procedure was not general. Attempted oxida-
tive decomplexation of other complexes led to decomposi-
tion or epimerization of the stereocenters. While direct
protodemetalation with TFA in CH Cl was not success-
2 2
ful, a photoinduced protodemetalation protocol gave the
desired tetrahydropyridines. Irradiation (350 nm lamp)
through Pyrex of a 0.005 M solution of compound 25 or
1
nation of the H NMR spectrum of 38 revealed a coupling
constant of 8.8 Hz between H2 and H3, which is con-
sistent with a trans diaxial relationship33 and implies a
chair conformation for 38 in which the phenyl group
occupies an equatorial position. If the ethyl group at the
6
-position is cis to the phenyl group, as expected, the
2
2 2
8 in CH Cl solution in the presence of 1 equiv of
protons at C2 and C6 should be 1,3-diaxial. To confirm
this an NOE difference spectrum was obtained. Irradia-
tion of H2 or H6 gave an 8% enhancement of the other,
supporting the assigned relative stereochemistry depicted
for compound 38 shown in Scheme 4.
trifluoroacetic acid gave the desired protodemetalation
products 34 and 35.
Treatment of a TpMo(CO)
3
2
(η -allyl) complex with ni-
trosonium tetrafluoroborate generates a cationic TpMo-
(
CO)(NO)(eta-3-allyl) complex that is susceptible to nu-
2
5,26
cleophilic attack.
Application of this activation
(dihydropyridinyl) complexes 20
and 27 followed by reduction of the intermediate cationic
Con clu sion s
procedure to TpMo(CO)
2
A strategy for the stereocontrolled placement of three
substituents around a π-coordinated dihydropyridinyl-
metal-ligand auxiliary has been described. This facile,
sequential introduction of substituents to a late, common
heterocyclic scaffold suggests that this methodological
sequence would be amenable to the generation of libraries
of analogous tetrahydropyridines and piperidines for use
in screening and structure-activity relationship studies.
Optimization of the reaction sequences, generalization
of the substituents beyond those demonstrated in this
work, and expansion of the methodology to the synthesis
of enantiomerically pure molybdenum complexes are
currently under active investigation. A general synthesis
of enantiomerically pure trisubstituted piperidines using
this methodology will be reported in due course.
3
η -allyl complex with NaBH
3
CN gave tetrahydropyridines
3
6 and 37 as shown in Scheme 3. Note that either of two
isomeric tetrahydropyridines can be prepared by applica-
tion of the pertinent decomplexation protocol (34 and 35
in Scheme 2 or 36 and 37 in Scheme 3).
Delivery of the hydride nucleophile at C3 of complexes
2
0 and 27 in Scheme 3 (adjacent to the methoxy sub-
1
1
stituent and anti to the molybdenum ) was rigorously
established through a careful examination of the coupling
constants of the trisubstituted piperidine 38. Piperidine
3
8 was produced from tetrahydropyridine 37 upon treat-
ment under one atmosphere of hydrogen in the presence
of 10 mol % of palladium on carbon (Scheme 4). Exami-
(
30) Eilbracht, P.; Hirschfeld, A. Synthesis 1996, 448.
(31) Franck-Neumann, M.; Martina, D.; Brion, F. Angew. Chem.,
(33) Silverstein, R. M.; Bassler, G. C.; Morrill, T. C. In Spectrometric
Identification of Organic Compounds, 4th ed.; J ohn Wiley and Sons:
New York, 1981; p 235.
Int. Ed. Engl. 1978, 17, 690.
32) Donaldson, W. A.; J in, M. J . Tetrahedron 1993, 49, 8787-8794.
(

7
448 J . Org. Chem., Vol. 65, No. 22, 2000
Exp er im en ta l Section
Moretto and Liebeskind
at room temperature for 18 h, and then potassium hydrido-
trispyrazolylborate (7.05 g, 0.026 mol, 1.0 equiv) was added
as a solid. After stirring the resulting brown suspension at
room temperature for 0.5 h, tetrabutylammonium fluoride
trihydrate (22.05 g, 0.070 mol, 2.5 equiv) was added as a solid.
This was stirred for 0.5 h, methyl iodide (34.8 mL, 0.559 mol,
Gen er a l Meth od s. All reactions were performed under a
positive pressure of nitrogen, in flame-dried glassware. All
solvents were dried over 4 Å molecular sieves and titrated with
a Fisher Coulomatic Karl Fischer titrator prior to use. Solvents
were degassed by purging with nitrogen. Analytical thin-layer
chromatography (TLC) was performed on glass plates pre-
coated with Merck F254 silica gel 60, 0.25 mm thickness, and
visualized by UV light and a 5% solution of phosphomolybdic
acid in ethanol. Column chromatography was performed with
mixtures of hexane and ethyl acetate on Aldrich aluminum
oxide, activated basic, Brockman I, under a positive pressure
of nitrogen. P r esen ta tion of th e H a n d C NMR spectr a
of th e N-Cbz pr otected π-a llylm olybd en u m a n d ca tion ic
d ien e com plexes r equ ir es com m en t. These compounds show
multiple and sometimes broadened resonances because of
urethane a n d allylmolybdenum conformational isomers. There-
2
0.0 equiv) was added, and the mixture was allowed to stir
for 3 days. The resulting black suspension was filtered through
a large plug of basic alumina eluting with 50% ethyl acetate
in hexane, and the solvents were removed in vacuo. The
resulting brown residue was occluded onto Celite and purified
by basic alumina chromatography to give molybdenum com-
plex 2 as an orange, foamy solid (9.90 g, 0.016 mol, 63%). TLC
1
13
(silica gel, 25% ethyl acetate in hexanes, R
76 °C with decomp (THF/hexanes, 1:4); IR (CH
f
) 0.18); mp 173-
Cl , KBr,
cm ): 2486 (m), 1930 (sh, s), 1840 (sh, s), 1699 (sh, m). H
NMR ((CD SO, 400 MHz): δ 8.28 (d, J ) 1.6 Hz, 1 H), 7.89
d, J ) 1.6 Hz, 1 H), 7.87 (d, J ) 1.6 Hz, 1 H), 7.83 (d, J ) 1.6
1
2
2
-
1
1
3 2
)
(
1
13
Hz, 1 H), 7.66 (d, J ) 1.6 Hz, 2 H), 7.34 (m, 5 H), 6.34 (s, 1 H),
6.31 (s, 1 H), 6.29 (s, 1 H), 5.07 (br m, 2 H), 4.39 (d, J ) 16.0
Hz, 1 H), 4.25 (d, J ) 7.2 Hz, 1 H), 4.12 (dd, J ) 13.6, 2.8 Hz,
1 H), 3.76 (d, J ) 8.0 Hz, 2 H), 3.50 (br s, 1 H), 3.11 (s, 3 H).
C NMR ((CD ) SO, 100 MHz): δ 229.5, 227.4, 153.8, 145.7,
3 2
43.7, 140.6, 136.6, 136.5, 135.9, 134.8, 127.9, 127.2, 126.9,
05.6, 105.4, 105.3, 65.9, 56.2, 54.9, 44.2, 41.3, 41.2, 40.1 (only
fore, H NMR and C NMR spectra of all η-3 allylmolybdenum
complexes were run in DMSO-d
NMR spectra of all η-4 cationic diene complexes were run at
room temperature in CD
1
13
6
at 80 °C, H NMR and
C
1
2
Cl
2
, and H NMR spectra of all final
at 60 °C.
1
3
decomplexed organic products were run in DMSO-d
6
1
1
2
Depending on the structure, only partial coalescence was
sometimes achieved in spectra taken at 60-80 °C, and either
too many or two few (from significant broadening) signals were
observed. H NMR spectra of organic products (32-37) were
taken at 60 °C to achieve full coalescence of the urethane
3 of 25 signals were found). Anal. Calcd for C25
26 7 5
H N O BMo:
1
C, 49.12; H, 4.29; N, 16.04; O, 13.09; B, 1.77; Mo, 15.69.
Found: C, 49.12; H, 4.36; N, 16.13.
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(2R*,3R*,4R*,5S*)-(1-b en zyloxyca r b on yl) η-(2,3,4,5)-3-
m et h oxy-1,2-d ih yd r op yr id in e]m olyb d en u m H exa flu o-
r op h osp h a te, 3. To a 100 mL round-bottomed flask equipped
with a stirring bar were added complex 2 (5.82 g, 9.55 mmol,
(
rotamers that are present at room temperature.
[
Rea gen ts. Potassium hydridotris(1-pyrazolyl)borate was
3
4
3 3
prepared by the method of Trofimenko. (DMF) Mo(CO) was
3
5
prepared according to a literature procedure. Triphenylcar-
benium hexafluorophosphate was freshly prepared from tri-
phenylmethanol and hexafluorophosphoric acid following a
1
2 2
.0 equiv) and 10 mL of dry CH Cl . This solution was cooled
to -50 °C in a dry ice/acetone bath, and triphenylcarbenium
hexafluorophosphate (4.45 g, 11.46 mmol, 1.1 equiv) was added
all at once as a solid. The solution was allowed to warm slowly
to room temperature over 2 h. The resulting red/brown
7
literature procedure. Phenylacetylene and acetophenone were
purchased from Aldrich Chemical Co. and dried over 4 Å
molecular sieves. Nitrosonium tetrafluoroborate, sodium boro-
hydride, methylmagnesium bromide, ethylmagnesium bro-
mide, vinylmagnesium bromide, phenylmagnesium bromide,
and benzylmagnesium bromide were purchased from Aldrich
Chemical Co. and used as received.
suspension was diluted with 80 mL of Et
was removed from the resulting precipitate via filter-tip
cannulation. The solid was redissolved in 5 mL of CH Cl and
precipitated once again from solution by addition of 80 mL of
Et O. The solvent was again removed from the precipitate via
filter-tip cannulation, and the resulting solids were washed
three times with 10 mL portions of Et O. The product was
2
O, and the solvent
2
2
Ben zyl 1,6-Dih yd r o-3(2H )-p yr id in on e-1-ca r b oxyla t e,
b. To an oven-dried 100 mL round-bottomed flask equipped
2
1
with a magnetic stirring bar was added 1-benzyl-1,6-dihydro-
3
5
2
2
8,29
(2H)-pyridinone (1a )
(4.69 g, 25.19 mmol, 1.0 equiv) and
dried under vacuum to give cationic molybdenum complex 3
0 mL of dry CH Cl . The resulting solution was cooled to 0
2
2
as a red/brown powder (7.20 g, 9.55 mmol, 100%): mp 117-
°
5
C in an ice/water bath, and benzyl chloroformate (7.2 mL,
0.37 mmol, 2.0 equiv) was added via syringe. After warming
-1
1
(
8
)
1
2 2
22 °C with decomp; IR (CH Cl , KBr, cm ): 2506 (w), 2020
1
2 2
sh, s), 1956 (sh, s), 1723 (m). H NMR (CD Cl , 400 MHz): δ
slowly to room temperature, the mixture was stirred for an
additional 12 h. Solvent was removed in vacuo, and the
resulting oil was purified by medium-pressure chromatography
.39 (d, J ) 2.0 Hz, 1 H), 7.93 (d, J ) 2.0 Hz, 1 H), 7.85 (d, J
2.0 Hz, 1 H), 7.80 (d, J ) 2.0 Hz, 1 H), 7.66 (d, J ) 2.0 Hz,
H), 7.60 (br s, 1 H), 7.58 (br s, 1 H), 7.40 (m, 5 H), 6.46 (br
(
silica gel, 10-25% ethyl acetate in hexane) to give 1b as a
t, J ) 2.0 Hz, 1 H), 6.42 (br t, J ) 2.0 Hz, 1 H), 6.40 (br t, J
yellow oil (5.01 g, 23.43 mmol, 93%). TLC (silica gel, 50% ethyl
)
2.0 Hz, 1 H), 5.60 (br d, J ) 8.4 Hz, 1 H), 5.44 (dd, J ) 8.4,
-
1
acetate in hexanes, R
f
) 0.43); IR (CDCl
, 400 MHz): δ 7.36 (m, 5 H), 7.01 (br
m, 1 H), 6.19 (dt, J ) 10.8, 2.2 Hz, 1 H), 5.17 (s, 2 H), 4.31 (s,
3
, KBr, cm ): 1695
3
1
.2 Hz, 1 H), 5.25 (s, 2 H), 3.73 (A of AB quartet, J ) 14.8 Hz,
H), 3.61 (B of AB quartet, J ) 14.8 Hz, 1 H), 3.00 (s, 3 H).
1
(sh, s). H NMR (CDCl
3
13
2 2
C NMR (CD Cl , 100 MHz): δ 217.4, 146.4, 145.9, 143.8,
H), 4.20 (s, 2 H). 1 C NMR (CDCl
46.9, 136.0, 128.6, 128.4, 128.3, 128.1, 127.5, 67.8, 51.6, 51.2,
3.0. Anal. Calcd for C13 : C, 67.52; H, 5.67; N, 6.06;
3
, 100 MHz): δ 192.6, 154.9,
2
1
4
3
1
1
2
39.2, 138.6, 137.1, 135.4, 133.7, 129.8, 129.3, 129.2, 128.8,
26.8, 108.5, 107.9, 107.8, 94.8, 82.1, 69.9, 66.2, 56.3, 44.8 (only
H
13NO
3
3 of 25 signals were found). HRMS (FAB) calcd for C25
BMo: 612.1065. Found: 612.1064.
Syn th esis of 4-10 fr om Ca tion ic Com p lex 3. (η)-Di-
ca r bon yl[h yd r id otr is(1-p yr a zolyl)bor a to][(2S*,3R*,4R*,
H
25
O, 20.76. Found: C, 67.39; H, 5.70; N, 6.02.
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(3R*,4R*,5S*)-(1-ben zyloxycar bon yl)-η-(3,4,5)-3-m eth oxy-
,2,5,6-tetr ah ydr opyr idin -3-yl]m olybden u m , 2. To an oven-
dried 250 mL Schlenk tube equipped with a magnetic stirring
7 5
N O
(
[
1
5
1
S*)-(1-ben zyloxyca r bon yl) η-(3,4,5)-2-m eth yl-3-m eth oxy-
,2,5,6-tetr a h yd r op yr id in -3-yl]m olybd en u m , 4. To a 100
3
5
bar was added Mo(DMF)
and 90 mL of dry, degassed CH
suspension was added a solution of 1b (5.99 g, 0.026 mol, 1.0
equiv) in 5 mL of dry, degassed CH Cl , followed by addition
of tert-butyldimethylsilyl chloride (4.21 g, 0.026 mol, 1.0 equiv)
as a solid. The resulting deep red solution was allowed to stir
3
(CO)
3
(11.16 g, 0.026 mol, 1.0 equiv)
mL Schlenk tube equipped with a magnetic stirring bar were
added cationic complex 3 (2.0 g, 2.66 mmol, 1.0 equiv) and 25
mL dry THF. The resulting red/brown solution was cooled to
78 °C in a dry ice/acetone bath. To this cooled solution was
added a 3 M solution of methylmagnesium bromide in THF
0.97 mL, 2.92 mmol, 1.1 equiv) dropwise by syringe. The
2
2
Cl . To the resulting green
2
2
-
(
resulting mixture was allowed to stir at -78 °C for 0.5 h. The
cold reaction mixture was then poured over a plug of basic
alumina, which was then washed with 50% ethyl acetate in
hexane. The solvent was removed in vacuo, and the resulting
(
34) Trofimenko, S. J . Am. Chem. Soc. 1967, 89, 3170.
(35) Pasquali, M.; Leoni, P.; Sabatino, P.; Braga, D. Gazz. Chim.
Ital. 1992, 122, 275-277.

Construction of Trisubstituted Piperidines
J . Org. Chem., Vol. 65, No. 22, 2000 7449
53.4. Anal. Calcd for C32 BMo: C, 54.80; H, 4.60; N,
foamy orange solid was occluded onto Celite and purified by
32 7 5
H N O
basic alumina chromatography to give 4 as an orange solid
13.98; O, 11.41; B, 1.54; Mo, 13.68. Found: C, 54.57; H, 4.66;
N, 13.76.
(
1.37 g, 2.21 mmol, 83%). TLC (silica gel, 25% ethyl acetate in
hexane, R ) 0.30); mp 111-114 °C with decomp; IR (CH Cl
KBr, cm ): 2486 (w), 1932 (sh, s), 1840 (sh, s), 1695 (sh, m).
f
1
2
2
,
(()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
[(2S*,3R*,4R*,5S*)-(1-ben zyloxyca r bon yl) η-(3,4,5)-2-eth -
en yl-3-m eth oxy-1,2,5,6-tetr a h yd r op yr id in -3-yl]m olybd e-
n u m , 7. Complex 3 (0.250 g, 0.33 mmol, 1.0 equiv) in 25 mL
dry THF -78 °C was treated with a 1 M solution of vinyl-
magnesium bromide in THF (0.37 mL, 0.37 mmol, 1.1 equiv)
to give, after workup and basic alumina chromatography, 7
as an orange solid (0.141 g, 0.22 mmol, 67%). TLC (silica gel,
-
1
H NMR ((CD
.89 (s, 1 H), 7.88 (d, J ) 1.6 Hz, 1 H), 7.84 (d, J ) 2.0 Hz, 1
H), 7.76 (s, 2 H), 7.36 (m, 5 H), 6.34 (s, 1 H), 6.32 (s, 1 H), 6.29
s, 1 H), 5.13 (A of AB quartet, J ) 12.4 Hz, 0.4 H), 5.08 (A of
AB quartet, J ) 12.4 Hz, 0.6 H), 5.04 (B of AB quartet, J )
3 2
) SO, 400 MHz): δ 8.29 (d, J ) 1.6 Hz, 1 H),
7
(
1
4
0
2.4 Hz, 0.6 H), 4.95 (B of AB quartet, J ) 12.4 Hz, 0.4 H),
.55 (m, 1 H), 4.25 (d, J ) 8.0 Hz, 0.6 H), 4.21 (d, J ) 8.0 Hz,
.4 H), 4.06 (s, 0.4 H), 4.02 (s, 0.6 H), 3.75 (d, J ) 4.0 Hz, 0.6
25% ethyl acetate in hexanes, R ) 0.30); mp 100-104 °C with
f
-
1
decomp; IR (CH
(sh, s), 1699 (sh, m). H NMR ((CD ) SO, 400 MHz): δ 8.32 (s,
2 2
Cl , KBr, cm ): 2485 (w), 1932 (sh, s), 1844
1
H), 3.73 (d, J ) 4.0 Hz, 0.4 H), 3.56 (d, J ) 14.4 Hz, 0.6 H),
3 2
3
1
2
1
1
1
1
.48 (d, J ) 14.4 Hz, 0.4 H), 3.05 (s, 1.2 H), 2.98 (s, 1.8 H),
1 H), 7.92 (s, 1 H), 7.87 (s, 1 H), 7.84 (s, 1 H), 7.80 (s, 1 H),
7.77 (s, 1 H), 7.34 (m, 5 H), 6.35 (s, 1 H), 6.32 (s, 1 H), 6.28 (s,
1 H), 5.96 (m, 1 H), 5.11 (m, 5 H), 4.28 (d, J ) 8.0 Hz, 0.6 H),
4.23 (d, J ) 8.0 Hz, 0.4 H), 4.09 (s, 0.4 H), 4.05 (s, 0.6 H), 3.83
(t, J ) 6.6 Hz, 1 H), 3.56 (d, J ) 13.8 Hz, 0.4 H), 3.48 (d, J )
.35 (d, J ) 6.4 Hz, 3 H). 13C NMR ((CD
SO, 100 MHz): δ
3 2
)
29.9, 227.3, 153.4, 152.9, 145.6, 143.9, 140.6, 140.5, 140.0,
36.6, 136.0, 134.8, 128.4, 127.9, 127.3, 127.2, 127.1, 126.8,
05.7, 105.5, 105.4, 66.0, 65.7, 56.1, 54.9, 53.8, 53.2, 50.2, 49.9,
13.8 Hz, 0.6 H), 3.03 (s, 1.2 H), 2.95 (s, 1.8 H). 13C NMR ((CD
9.1. Anal. Calcd for C26
H
28
N
7
O
5
BMo: C, 49.94; H, 4.51; N,
3 2
) -
5.68; O, 12.79; B, 1.73; Mo, 15.34. Found: C, 49.88; H, 4.56;
SO, 100 MHz): δ 230.0, 227.4, 153.7, 153.0, 145.7, 144.0, 140.8,
140.6, 136.6, 136.0, 135.8, 135.4, 134.8, 131.5, 130.9, 127.9,
N, 15.46.
1
5
27.3, 127.0, 126.9, 116.7, 116.4, 105.8, 105.6, 105.4, 66.1, 65.9,
28 7 5
6.6, 56.4, 55.7, 54.9, 54.0, 53.3. Anal. Calcd for C27H N O -
(
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
[
3
(2S*,3R*,4R*,5S*)-(1-ben zyloxycar bon yl)- η-(3,4,5)-2-eth yl-
-m e t h o x y -1,2,5,6-t e t r a h y d r o p y r id in -3-y l]m o ly b d e -
BMo: C, 50.89; H, 4.43; N, 15.38; O, 12.55; B, 1.70; Mo, 15.05.
Found: C, 50.70; H, 4.55; N, 15.17.
n u m , 5. Complex 3 (1.0 g, 1.33 mmol, 1.0 equiv) in 15 mL dry
THF at -78 °C was treated with a 1 M solution of ethyl-
magnesium bromide in THF (1.46 mL, 1.46 mmol, 1.1 equiv)
to give, after workup and basic alumina chromatography, 5
as an orange solid (0.6044 g, 0.94 mmol, 71%). TLC (silica gel,
5% ethyl acetate in hexanes, R
decomp (THF/hexane, 1:4); IR (CH
931 (sh, s), 1842 (sh, s), 1693 (sh, m). H NMR ((CD ) SO,
(
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
[
(2S*,3R*,4R*,5S*)-(1-ben zyloxycar bon yl)- η-(3,4,5)-2-ph en -
yl-3-m et h yoxy-1,2,5,6-t et r a h yd r op yr id in -3-yl]m olyb d e-
n u m , 8. Complex 3 (0.250 g, 0.33 mmol, 1.0 equiv) in 5 mL of
dry THF -78 °C was treated with a 1 M solution of phenyl-
magnesium bromide in THF (0.37 mL, 0.37 mmol, 1.1 equiv)
to give, after workup and basic alumina chromatography, 8
as an orange solid (0.150 g, 0.22 mmol, 66%). TLC (silica gel,
2
f
) 0.38); mp 171-175 °C with
-1
2
Cl
2
, KBr, cm ): 2483 (m),
1
1
4
1
6
3 2
00 MHz): δ 8.28 (s, 1 H), 7.88 (m, 2 H), 7.84 (d, J ) 2.0 Hz,
H), 7.77 (d, J ) 2.4 Hz, 1 H), 7.74 (s, 1 H), 7.34 (m, 5 H),
.34 (s, 1 H), 6.32 (s, 1 H), 6.28 (s, 1 H), 5.10 (A of AB quartet,
2
5% ethyl acetate in hexanes, R ) 0.24); mp 194-198 °C with
f
-
1
2 2
decomp; IR (CH Cl , KBr, cm ): 2484 (w), 1935 (sh, s), 1844
1
(sh, s), 1695 (sh, m). H NMR ((CD
3
)
2
SO, 400 MHz): δ 8.36 (s,
J ) 12.4 Hz, 0.6 H), 5.06 (s, 0.8 H), 4.91 (B of AB quartet, J )
1
H), 7.99 (s, 1 H), 7.87 (s, 2 H), 7.82 (d, J ) 9.2 Hz, 1 H), 7.78
1
4
2.4 Hz, 0.6 H), 4.55 (br m, 1 H), 4.25 (d, J ) 8.2 Hz, 0.6 H),
.21 (d, J ) 8.2 Hz, 0.4 H), 4.13 (t, J ) 12.8 Hz, 1 H), 3.79 (t,
(
6
s, 2 H), 7.62 (d, J ) 7.6 Hz, 1 H), 7.34 (m, 8 H), 6.35 (s, 2 H),
.26 (s, 1 H), 5.59 (s, 0.46 H), 5.55 (s, 0.54 H), 5.06 (A of AB
J ) 7.8 Hz, 1 H), 3.60 (d, J ) 14.2 Hz, 0.4 H), 3.50 (d, J ) 14.2
quartet, J ) 12.4 Hz, 1 H), 4.96 (B of AB quartet, J ) 12.4
Hz, 0.54 H), 4.94 (B of AB quartet, J ) 12.4 Hz, 0.46 H), 4.44
(d, J ) 8.2 Hz, 0.54 H), 4.39 (d, J ) 8.2 Hz, 0.46 H), 4.12 (m,
2
1
1
1
1
5
Hz, 0.6 H), 3.01 (s, 1.2 H), 2.93 (s, 1.8 H), 1.99 (br m, 1.2 H),
1
1
1
1
5
.71 (br m, 0.8 H), 0.94 (t, J ) 7.6 Hz, 1.2 H), 0.89 (t, J ) Hz,
.6 H). C NMR ((CD ) SO, 100 MHz): δ 153.9, 153.4, 145.7,
3 2
43.9, 140.7, 140.5, 136.7, 136.0, 135.6, 134.9, 128.0, 127.9,
27.4, 127.3, 126.9, 105.7, 105.6, 105.5, 66.1, 65.8, 57.0, 55.2,
4.6, 53.6, 53.1, 27.9, 27.4, 10.3. Anal. Calcd for C27
BMo: C, 50.72; H, 4.73; N, 15.34; O, 12.51; B, 1.69; Mo, 15.01.
Found: C, 50.84; H, 4.82; N, 15.21.
(
1
3
3
6
H), 3.69 (s, 0.54 H), 3.65 (s, 0.46 H), 2.78 (s, 1.38 H), 2.68 (s,
.62 H). 13C NMR ((CD
SO, 100 MHz): δ 229.8, 227.5, 227.2,
3 2
)
53.5, 152.8, 145.8, 144.1, 140.7, 140.6, 140.5, 140.0, 136.6,
36.4, 136.3, 136.0, 134.8, 131.5, 131.0, 128.0, 127.8, 127.4,
27.3, 127.2, 127.1, 126.8, 126.7, 105.8, 105.6, 105.4, 66.2, 65.9,
8.3, 57.8, 57.7, 57.6, 54.5, 53.3, 52.7. Anal. Calcd for
30 7 5
H N O -
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
C
31
H
30
N
7
O
5
BMo: C, 54.17; H, 4.40; N, 14.26; O, 11.64; B, 1.57;
Mo, 13.96. Found: C, 54.16; H, 4.40; N, 14.27.
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(2S*,3R*,4R*,5S*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-2-eth -
oxycar bon ylm eth yl-3-m eth oxy-1,2,5,6-tetr ah ydr opyr idin -
-yl]m olybd en u m , 9. Lithioethyl acetate was generated:
[
(2S*,3R*,4R*,5S*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-2-ben -
zyl-3-m et h oxy-1,2,5,6-t et r a h yd r op yr id in -3-yl]m olyb d e-
n u m , 6. Complex 3 (1.0 g, 1.33 mmol, 1.0 equiv) in 15 mL dry
THF -78 °C was treated with a 1 M solution of benzyl-
magnesium bromide in THF (1.46 mL, 1.46 mmol, 1.1 equiv)
to give, after workup and basic alumina chromatography, 6
as an orange solid (0.721 g, 1.02 mmol, 77%). TLC (silica gel,
(
[
3
THF (10 mL) and diisopropylamine (0.94 mL, 6.73 mmol, 1.4
equiv) in a 25 mL round-bottomed flask at -78 °C were treated
with n-butyllithium (2.71 mL, 2.48 M in hexanes, 6.73 mmol,
2
5% ethyl acetate in hexanes, R
f
) 0.25); mp 111-113 °C with
-1
decomp (THF/hexanes, 1:4); IR (CH
2
Cl
932 (sh, s), 1842 (sh, s), 1694 (sh, m). H NMR ((CD
00 MHz): δ 8.26 (d, J ) 2.4 Hz, 1 H), 7.88 (d, J ) 2.0 Hz, 1
2
, KBr, cm ): 2484 (m),
1
.4 equiv). After 1 h at -78 °C, ethyl acetate (0.66 mL, 6.37
1
1
4
3 2
) SO,
mmol, 1.4 equiv) was added by syringe, and the mixture was
allowed to stir for 1 h at -78 °C. Then, the lithioethyl acetate
was cannulated into a solution of complex 3 (1.12 g, 1.49 mmol,
H), 7.84 (d, J ) 2.4 Hz, 1 H), 7.75 (s, 1 H), 7.24 (m, 12 H), 6.32
t, J ) 2.4 Hz, 1 H), 6.30 (t, J ) 2.4 Hz, 1 H), 6.28 (t, J ) 2.4
Hz, 1 H), 5.04 (A of AB quartet, J ) 12.8 Hz, 0.33 H), 4.97 (B
of AB quartet, J ) 12.8 Hz, 0.33 H), 4.79 (m, 2.68 H), 4.53 (B
of AB quartet, J ) 12.4 Hz, 0.66 H), 4.17 (d, J ) 8.4 Hz, 0.66
H), 4.10 (d, J ) 8.4 Hz, 0.33 H), 4.02 (dd, J ) 13.2, 2.4 Hz,
.66 H), 3.92 (d, J ) 14.0 Hz, 0.33 H), 3.76 (t, J ) 7.6 Hz, 1
3 2
H), 2.90 (m, 2 H), 3.00 (s, 1 H), 2.98 (s, 2 H). C NMR ((CD ) -
SO, 100 MHz): δ 153.6, 145.6, 144.0, 140.6, 137.6, 136.6,
36.3, 136.0, 134.8, 134.3, 129.4, 129.2, 127.9, 127.8, 127.7,
27.2, 126.9, 126.0, 105.7, 105.5, 65.9, 57.0, 56.1, 54.5, 54.3,
(
1
.0 equiv) in 40 mL of dry THF at -78 °C. The resulting
mixture was allowed to stir at -78 °C for 0.5 h. Workup and
basic alumina chromatography delivered 9 as an orange solid
(
1.751 g, 2.50 mmol, 52%). TLC (silica gel, 25% ethyl acetate
in hexanes, R ) 0.19); mp 135 °C with decomp; IR (CH Cl
KBr, cm ): 2483 (w), 1935 (sh, s), 1846 (sh, s), 1732 (sh, m),
f
2
2
,
0
-
1
13
1
1
7
699 (sh, m). H NMR ((CD
3 2
) SO, 400 MHz): δ 8.29 (s, 1 H),
3
6
.89 (d, J ) 2.4 Hz, 2 H), 7.85 (d, J ) 2.4 Hz, 1 H), 7.76 (s, 1
1
1
H), 7.74 (s, 0.44 H), 7.72 (s, 0.56 H), 7.34 (m, 5 H), 6.33 (t, J
2.4 Hz, 2 H), 6.29 (t, J ) 2.4 Hz, 1 H), 5.09 (A of AB quartet,
)
J ) 12.8 Hz, 0.56 H), 5.06 (A of AB quartet, J ) 12.8 Hz, 0.44
H), 5.04 (B of AB quartet, J ) 12.8 Hz, 0.56 H), 4.98 (B of AB
quartet, J ) 12.8 Hz, 0.44 H), 4.93 (t, J ) 6.0 Hz, 0.56 H),
36) 13C signals for the CO ligands were not found under the
conditions of the NMR experiment.
(

7
450 J . Org. Chem., Vol. 65, No. 22, 2000
Moretto and Liebeskind
4
.87 (t, J ) 6.0 Hz, 0.44 H), 4.30 (d, J ) 8.0 Hz, 0.56 H), 4.26
59.47, 58.99, 55.70, 55.57, 51.92, 51.41; Anal. Calcd for C25
24
H -
(
3
d, J ) 8.0 Hz, 0.44 H), 4.04 (m, 2.44 H), 3.93 (m, 0.56 H),
BMoN : C, 49.28; H, 3.97; N, 16.09. Found: C, 49.03; H,
7 5
O
.77 (d, J ) 8.0 Hz, 1 H), 3.57 (d, J ) 13.2 Hz, 0.44 H), 3.49
3.95, N, 16.05.
Gen er a tion of Ca tion ic Com p lexes 12-18.
(
d, J ) 13.2 Hz, 0.56 H), 2.92 (s, 1.32 H), 2.87 (s, 1.68 H), 2.68
(m, 2 H), 1.22 (t, J ) 7.2 Hz, 1.32 H), 1.14 (t, J ) 7.2 Hz, 1.68
(
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(2S*,3R*,4R*,5S*,6S*)-(1-ben zyloxyca r bon yl)- η-(3,4,5,6)-
-m et h yl-3-m et h oxy-1,2-d ih yd r op yr id in e]m olyb d en u m
1
3
3 2
H). C NMR ((CD ) SO, 100 MHz): δ 230.0, 229.6, 227.2,
[
2
2
1
1
5
4
26.8, 169.8, 169.7, 153.4, 153.1, 145.7, 144.0, 140.5, 136.8,
36.6, 136.4, 136.1, 134.9, 132.4, 132.2, 128.0, 127.4, 127.1,
26.9, 105.8, 105.7, 105.6, 66.3, 66.0, 59.8, 56.6, 54.8, 53.0, 52.9,
Hexa flu or op h osp h a te, 12. To a 100 mL round-bottomed
flask equipped with a stirring bar were added 4 (3.60 g, 5.78
mmol, 1.0 equiv) and 10 mL of dry CH Cl . This solution was
2 2
cooled to -50 °C in a dry ice/acetone bath and treated with
triphenylcarbenium hexafluorophosphate (2.47 g, 6.35 mmol,
2.6, 13.7, 13.6. Anal. Calcd for C29
32 7 7
H N O BMo: C, 49.95; H,
.63; N, 14.06; O, 16.06; B, 1.55; Mo, 13.76. Found: C, 50.16;
H, 4.64; N, 13.82.
(
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
1
.1 equiv) all at once as a solid. The solution was allowed to
warm slowly to room temperature over 2 h. The resulting red/
brown suspension was diluted with 80 mL of Et O, and the
[
(2S*,3R*,4R*,5S*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-2-(1-
p r op en yl)-3-m eth oxy-1,2,5,6-tetr a h yd r op yr id in -3-yl]m o-
2
lybd en u m , 10. Complex 3 (1.12 g, 1.49 mmol, 1.0 equiv) in
2
allylmagnesium bromide in THF (1.78 mL, 1.78 mmol, 1.2
equiv) to give, after workup and basic alumina chromatogra-
phy, 10 as an orange solid (0.666 g, 1.02 mmol, 69%). TLC
solvent was removed from the resulting precipitate via filter-
tip cannulation. The solid was the redissolved in 5 mL of
0 mL of dry THF -78 °C was treated with a 1 M solution of
CH
of 80 mL of Et
precipitate via filter-tip cannulation, and the resulting solids
were washed three times with 10 mL portions of Et O. The
2
Cl
2
and precipitated once again from solution by addition
2
O. The solvent was again removed from the
(silica gel, 25% ethyl acetate in hexanes, R
f
) 0.35); mp 85 °C
-
1
2
with decomp; IR (CH
2
Cl
2
, KBr, cm ): 2484 (w), 1932 (sh, s),
product was dried under vacuum to give 12 as a red/brown
powder (3.95 g, 5.20 mmol, 90%). mp 98-101 °C with decomp;
1
1
8
)
(
843 (sh, s), 1695 (sh, m). H NMR ((CD
.28 (t, J ) 2.0 Hz, 1 H), 7.89 (d, J ) 2.0 Hz, 1 H), 7.88 (d, J
2.0 Hz, 1 H), 7.84 (d, J ) 2.0 Hz, 1 H), 7.76 (m, 2 H), 7.36
m, 4 H), 7.32 (m, 1 H), 6.32 (m, 2 H), 6.28 (m, 1 H), 5.91 (dt,
3 2
) SO, 400 MHz): δ
-
1
IR (CH
(
2 2
Cl , KBr, cm ): 2506 (w), 2053 (sh, s), 2053 (m), 1935
1
sh, s), 1730 (m). H NMR (CD Cl , 400 MHz): δ 8.12 (br s, 1
2 2
H), 7.91 (br s, 1 H), 7.81 (br s, 2 H), 7.75 (br s, 1 H), 7.57 (br
s, 1 H), 7.50 (d, J ) 5.6 Hz, 1 H), 7.41 (m, 5 H), 6.40 (br s, 3
H), 5.45 (t, J ) 4.8 Hz, 1 H), 5.31 (s, 2 H), 5.04 (br s, 1 H),
J ) 10.0, 7.2 Hz, 0.42 H), 5.81 (dt, J ) 10.0, 7.2 Hz, 0.58 H),
5
4
.10 (A of AB quartet, J ) 12.4 Hz, 0.42 H), 5.01 (m, 3.16 H),
.92 (B of AB quartet, J ) 12.4 Hz, 0.42 H), 4.65 (t, J ) 6.4
4
.12 (q, J ) 6.4 Hz, 1 H), 3.30 (s, 3 H), 1.62 (d, J ) 6.4 Hz, 3
Hz, 0.42 H), 4.64 (t, J ) 6.4 Hz, 0.58 H), 4.26 (d, J ) 8.2 Hz,
13
H). C NMR (CD
2
Cl
43.5, 139.4, 138.2, 135.1, 129.5, 129.3, 129.2, 108.0, 100.2,
0.4, 69.3, 62.3, 58.7, 51.6, 21.3. Anal. Calcd for C26
: C, 40.60; H, 3.54; N, 12.75; O, 10.40; B, 1.41; Mo,
2.47; P, 4.03; F, 14.82. Found: C, 40.51; H, 3.49; N, 12.81.
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(2S*,3R*,4R*,5S*,6S*)-(1-ben zyloxyca r bon yl)- η-(3,4,5,6)-
-e t h yl-3-m e t h oxy-1,2-d ih yd r op yr id in e ]m olyb d e n u m
Hexa flu or op h osp h a te, 13. Complex 5 (0.545 g, 0.85 mmol,
.0 equiv) in 5 mL of dry CH Cl was treated with triphenyl-
2
, 100 MHz): δ 219.2, 152.8, 147.2, 144.5,
0
0
1
1
.58 H), 4.22 (d, J ) 8.2 Hz, 0.42 H), 4.11 (dd, J ) 9.2, 2.4 Hz,
.42 H), 4.07 (dd, J ) 9.2, 2.4 Hz, 0.58 H), 3.78 (t, J ) 8.4 Hz,
H), 3.62 (dd, J ) 14.0, 1.6 Hz, 0.42 H), 3.52 (dd, J ) 14.0,
.6 Hz, 0.58 H), 2.97 (s, 1.26 H), 2.90 (s, 1.74 H), 2.67 (m, 1
1
7
27 7 5
H N O -
BMoPF
1
6
1
3
H), 2.53 (m, 1 H). C NMR ((CD
3
)
2
SO, 100 MHz): δ 230.2,
(
2
1
1
6
30.0, 227.5, 227.2, 153.7, 153.3, 145.7, 144.0, 140.7, 140.5,
[
2
36.7, 136.5, 136.1, 134.9, 134.5, 134.4, 134.1, 133.7, 128.0,
27.9, 127.4, 127.3, 126.9, 117.3, 117.2, 105.8, 105.6, 105.5,
6.1, 65.8, 59.4, 57.0, 54.5, 54.3, 54.2, 53.9, 53.8, 53.3, 53.0.
1
2
2
Anal. Calcd for C28
O, 12.28; B, 1.66; Mo, 14.73. Found: C, 51.80; H, 4.67; N, 14.81.
30 7 5
H N O BMo: C, 51.63; H, 4.64; N, 15.05;
carbenium hexafluorophosphate (0.365 g, 0.94 mmol, 1.1 equiv)
and gave, after workup, 13 as a red/brown powder (0.623 g,
Ch a r a cter iza tion of Sid e-p r od u ct 11, (()-Dica r bon yl-
0
.80 mmol, 94%). mp 117-119 °C with decomp; IR (CH
2
Cl
2
,
[
h yd r id otr is(1-p yr a zolyl)bor a to][ 1S*,2S*,3R*)-(1-ben zyl-
-1
KBr, cm ): 2507 (w), 2052 (sh, s), 2006 (m), 1933 (sh, s), 1732.
oxyca r bon yl) η-(1,2,3)-4-m eth oxy-1,2-tetr a h yd r op yr id in -
2
1
H NMR (CD
2 2
Cl , 400 MHz): δ 8.11 (br s, 1 H), 7.90 (br s, 1
-yl]m olybd en u m . To a 100 mL Schlenk tube equipped with
H), 7.82 (br s, 1 H), 7.78 (br s, 1 H), 7.57 (d, J ) 5.2 Hz, 1 H),
a magnetic stirring bar were added 3 (2.0 g, 2.66 mmol, 1.0
equiv) and 25 mL of dry THF. The resulting red/brown solution
was cooled to -78 °C in a dry ice/acetone bath. To this cooled
solution was added a 3 M solution of methylmagnesium
bromide in THF (0.97 mL, 2.92 mmol, 1.1 equiv) dropwise by
syringe. The resulting mixture was allowed to stir at -78 °C
for 0.5 h. The cold reaction mixture was then poured over a
plug of basic alumina, which was then washed with 50% ethyl
acetate in hexane. The solvent was removed in vacuo, and the
resulting foamy orange solid was occluded onto Celite and
purified by basic alumina chromatography. Product 11 was
isolated by collection of the least polar orange band, giving a
bright orange solid (0.16 g, 0.27 mmol, 10%): mp ) 118-120
7
5
3
3
1
1
.51 (br s, 2 H), 7.42 (m, 5 H), 6.40 (br s, 3 H), 5.48 (br s, 1 H),
.34 (s, 2 H), 5.09 (br s, 1 H), 4.17 (app t, J ) 3.2 Hz, 1 H),
.26 (s, 3 H), 2.27 (m, 1 H), 2.03 (m, 1 H), 0.85 (t, J ) 7.6 Hz,
H). 13C NMR (CD
Cl , 100 MHz): δ 219.0, 153.0, 147.1, 144.4,
2 2
43.4, 139.4, 138.2, 135.1, 129.6, 129.4, 129.2, 129.1, 127.9,
27.7, 108.0, 101.0, 70.4, 70.3, 62.1, 58.6, 56.1, 27.4, 8.0. Anal.
Calcd for C27
0.21; F, 14.55; P, 3.95; B, 1.38; Mo, 12.25. Found: C, 41.29;
H, 3.69; N, 12.59.
29 7 5 6
H N O F PBMo: C, 41.40; H, 3.73; N, 12.52; O,
1
(()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
[(2S*,3R*,4R*,5S*,6S*)-(1-ben zyloxyca r bon yl)- η-(3,4,5,6)-
2-b en zyl-3-m et h oxy-1,2-d ih yd r op yr id in e]m olyb d en u m
Hexa flu or op h osp h a te, 14. Complex 6 (0.726 g, 1.04 mmol,
1.0 equiv) in 5 mL of dry CH Cl was treated with triphenyl-
2 2
carbenium hexafluorophosphate (0.484 g, 1.25 mmol, 1.1 equiv)
°
C (EtOAc/hexane); R ) 0.54 (EtOAc/hexane, 1:2); IR (KBr,
f
-
1
1
cm ): 1925 (s), 1832 (s), 1701 (s); H NMR (300 MHz, CDCl
δ 8.42 (d, J ) 2.1 Hz, 0.3 H), 8.21 (t, J ) 2.4 Hz, 0.7 H), 7.73
d, J ) 1.8 Hz, 0.5 H), 7.70 (d, J ) 2.1 Hz, 0.5 H), 7.68 (d, J )
.1 Hz, 0.25 H), 7.61 (d, J ) 2.4 Hz, 0.25 H), 7.59 (d, J ) 2.4
Hz, 0.25 H), 7.57 (d, J ) 2.1 Hz, 0.25 H), 7.53 (d, J ) 2.1 Hz,
3
)
(
2
and gave, after workup, 14 as a red/brown powder (0.823 g,
0.98 mmol, 94%): mp 100-103 °C with decomp; IR (CH
2
Cl
2
,
-1
KBr, cm ): 2512 (w), 2053 (sh, s), 2007 (m), 1936 (sh, s), 1729
1
1
7
7
6
5
3
H), 7.51 (d, J ) 1.8 Hz, 0.5 H), 7.48 (d, J ) 2.4 Hz, 0.5 H),
.46 (d, J ) 2.1 Hz, 0.5 H), 7.42 (d, J ) 2.1 Hz, 0.5 H), 7.40-
.37 (m, 2 H), 7.26-7.19 (m, 5 H), 6.26 (t, J ) 2.1 Hz, 0.5 H),
.20-6.17 (m, 1.5 H), 5.90-5.88 (m, 0.7 H), 5.72 (s, br, 0.3 H),
.40-5.26 (m, 2 H), 4.62 (dd, J ) 5.2 Hz, J ) 0.3 Hz, 1 H),
.64 (s, 1.5 H), 3.58 (s, 1.5 H), 2.84 (t, J ) 6.0 Hz, 0.5 H), 2.72
2 2
(m). H NMR (CD Cl , 400 MHz): δ 8.11 (br s, 1 H), 7.90 (br
s, 1 H), 7.82 (br s, 1 H), 7.78 (br s, 1 H), 7.57 (d, J ) 5.2 Hz,
1 H), 7.51 (br s, 2 H), 7.42 (m, 5 H), 7.35 (m, 5 H) 6.40 (br s,
3 H), 5.48 (br s, 1 H), 5.34 (s, 2 H), 5.09 (br s, 1 H), 4.17 (app
1
3
t, J ) 3.2 Hz, 1 H), 3.26 (s, 3 H), 2.70 (m, 2 H). C NMR
(CD Cl , 100 MHz): δ 218.7, 152.9, 147.1, 144.6, 143.2, 139.5,
2
2
1
3
(t, J ) 6.0 Hz, 0.5 H); C NMR (100 MHz, CDCl
3
) 229.93,
138.3, 135.1, 133.9, 130.2, 129.6, 129.5, 129.4, 129.3, 128.5,
127.9, 127.7, 108.0, 98.2, 70.7, 61.6, 58.3, 56.4, 39.7. Anal.
2
1
1
1
29.26, 223.17, 222.54, 153.48, 153.11, 151.46, 150.75, 146.36,
45.07, 143.89, 140.48, 140.32, 136.2, 136.17, 136.05, 136.00,
34.65, 129.37, 128.95, 128.85, 128.77, 128.48, 128.23, 106.02,
05.67 (2 carbons), 92.43, 92.34, 92.01, 90.91, 69.47, 68.52,
31 7 5 6
Calcd for C32H N O F BMoP: C, 45.47; H, 3.70; N, 11.60; O,
9.46; F, 13.48; B, 1.28; Mo, 11.35; P, 3.66. Found: C, 45.17;
H, 3.74; N, 11.45.

Construction of Trisubstituted Piperidines
J . Org. Chem., Vol. 65, No. 22, 2000 7451
(
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(2S*,3R*,4R*,5S*,6S*)-(1-ben zyloxyca r bon yl)- η-(3,4,5,6)-
-e t h e n y l-3-m e t h o x y -1,2-d ih y d r o p y r id in e ]m o ly b d e -
n u m Hexa flu or op h osp h a te, 15. Complex 7 (0.119 g, 0.19
mmol, 1.0 equiv) in 5 mL of dry CH Cl was treated with
triphenylcarbenium hexafluorophosphate (0.087 g, 0.23 mmol,
.1 equiv) and gave, after workup, 15 as a red/brown powder
0.116 g, 0.16 mmol, 86%). mp 99-101 °C with decomp; IR
Syn th esis of 19-31 fr om Ca tion ic Com p lexes 12-18.
(()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
[(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
2-m eth yl-3-m eth oxy-6-eth en yl-1,2,5,6-tetr a h yd r op yr id in -
3-yl]m olybd en u m , 19. To a 50 mL Schlenk tube equipped
with a magnetic stirring bar were added 12 (0.400 g, 0.52
mmol, 1.0 equiv) and 25 mL of dry THF. The resulting red/
brown solution was cooled to -78 °C in a dry ice/acetone bath.
To this cooled solution was added a 1 M solution of vinyl-
magnesium bromide in THF (0.63 mL, 0.63 mmol, 1.2 equiv)
dropwise by syringe. The resulting mixture was allowed to stir
at -78 °C for 0.5 h. The cold reaction mixture was then poured
over a plug of basic alumina, which was then washed with
50% ethyl acetate in hexane. The solvent was removed in
vacuo, and the resulting foamy orange solid was occluded onto
Celite and purified by basic alumina chromatography to give
19 as an orange solid (0.211 g, 0.32 mmol, 62%). TLC (silica
[
2
2
2
1
(
(
(
-
1
CH
2 2
Cl , KBr, cm ): 2506 (w), 2055 (sh, s), 2008 (m), 1935
1
sh, s), 1731 (m). H NMR (CD
H), 7.90 (br s, 1 H), 7.83 (br s, 1 H), 7.76 (br s, 1 H), 7.62 (m,
H), 7.58 (br s, 1 H), 7.40 (m, 5 H), 6.42 (br s, 3 H), 5.70 (m,
H), 5.54 (s, 1 H), 5.49 (s, 1 H), 5.46 (s, 1 H), 5.30 (s, 2 H),
2 2
.08 (br s, 1 H), 4.58 (br s, 1 H), 3.27 (s, 3 H). C NMR (CD Cl ,
00 MHz): δ 218.7, 161.0, 147.2, 144.8, 143.4, 139.5, 138.1,
35.0, 131.8, 129.6, 129.4, 129.2, 129.1, 127.9, 127.7, 122.9,
08.0, 100.1, 70.5, 66.2, 58.7, 57.2. HRMS (FAB) calcd for
2
2
Cl , 400 MHz): δ 8.15 (br s, 1
2
1
5
1
1
1
1
3
C
27
H
27
N
7
O
5
BMo: 638.1221. Found: 638.1412.
gel, 25% ethyl acetate in hexanes, R
f
) 0.35); mp 91-95 °C
-
1
(
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
with decomp; IR (CH
3 2
1840 (sh, s), 1694 (sh, m). H NMR ((CD ) SO, 400 MHz): δ
2 2
Cl , KBr, cm ): 2483 (w), 1933 (sh, s),
1
[
(2S*,3R*,4R*,5S*,6S*)-(1-ben zyloxyca r bon yl)- η-(3,4,5,6)-
-p h en yl-3-m et h oxy-1,2-d ih yd r op yr id in e]m olyb d en u m
Hexa flu or op h osp h a te, 16. Complex 8 (0.412 g, 0.60 mmol,
.0 equiv) in 5 mL of dry CH Cl was treated with triphenyl-
2
8.28 (s, 1 H), 7.89 (s, 2 H), 7.85 (s, 1 H), 7.77 (s, 1 H), 7.73 (s,
1 H), 7.36 (s, 4 H), 7.32 (s, 1 H), 6.34 (s, 1 H), 6.31 (s, 2 H),
6.05 (m, 1 H), 5.44 (d, J ) 17.2 Hz, 0.5 H), 5.32 (d, J ) 17.2
Hz, 0.5 H), 5.08 (m, 3 H), 4.78 (d, J ) 5.8 Hz, 0.5 H), 4.75 (d,
J ) 5.8 Hz, 0.5 H), 4.64 (m, 1 H), 4.28 (d, J ) 7.6 Hz, 0.5 H),
4.22 (d, J ) 7.6 Hz, 0.5 H), 3.80 (d, J ) 8.0 Hz, 1 H), 3.00 (s,
1.5 H), 2.93 (s, 1.5 H), 1.44 (d, J ) 6.8 Hz, 3 H). C NMR
3 2
((CD ) SO, 100 MHz): δ 231.0, 230.8, 227.3, 227.0, 153.4,
153.0, 145.7, 143.9, 141.6, 141.4, 140.7, 140.5, 136.7, 136.5,
136.0, 134.9, 128.0, 127.9, 127.4, 127.3, 127.1, 126.8, 115.9,
115.7, 105.7, 105.6, 105.5, 66.1, 65.9, 56.7, 56.0, 55.8, 54.7, 54.0,
1
2
2
carbenium hexafluorophosphate (0.256 g, 0.66 mmol, 1.1 equiv)
and gave, after workup, 16 as a red/brown powder (0.419 g,
0
.50 mmol, 84%): mp 194-198 °C with decomp; IR (CH
2
Cl
2
,
-1
13
KBr, cm ): 2506 (w), 2057 (sh, s), 2011 (m), 1937 (sh, s), 1732
1
(
m). H NMR (CD
s, 1 H), 7.85 (br s, 1 H), 7.80 (br s, 1 H), 7.69 (d, J ) 5.6 Hz,
H), 7.40 (m, 10 H), 7.32 (br s, 2 H), 6.43 (br s, 3 H), 5.87 (br
s, 1 H), 5.32 (br s, 1 H), 5.18 (s, 2 H), 4.97 (br s, 1 H), 2.94 (s,
2
Cl
2
, 400 MHz): δ 8.15 (br s, 1 H), 7.95 (br
1
1
3
3
1
1
6
H). C NMR (CD
2
Cl
2
, 100 MHz): δ 218.4, 165.3, 147.2, 144.7,
30 7 5
53.6, 50.5, 50.2, 23.1, 22.2. Anal. Calcd for C28H N O BMo:
C, 51.63; H, 4.64; N, 15.05; O, 12.28; B, 1.66; Mo, 14.73.
Found: C, 51.90; H, 4.71; N, 14.79.
44.4, 143.5, 139.7, 138.3, 135.9, 134.9, 130.1, 129.8, 129.6,
29.1, 129.0, 128.8, 127.9, 127.7, 126.8, 108.1, 99.0, 70.2, 70.0,
6.2, 61.9, 59.3, 58.5, 57.3. HRMS (FAB) calcd for C31
H
29
N
7
O
5
-
(()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
[(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
2-eth yl-3-m eth oxy-6-p h en yl-1,2,5,6-tetr a h yd r op yr id in -3-
yl]m olybd en u m , 20. Cationic complex 13 (0.400 g, 0.51 mmol,
1.0 equiv) in 25 mL dry THF at -78 °C was treated with a 1
M solution of phenylmagnesium bromide in THF (0.66 mL,
0.66 mmol, 1.3 equiv) and gave, after workup and basic
alumina chromatography, 20 as an orange solid (0.156 g, 0.22
BMo: 688.1378. Found: 688.1377.
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(2S*,3R*,4R*,5S*,6S*)-(1-ben zyloxyca r bon yl)- η-(3,4,5,6)-
-eth oxycar bon ylm eth yl-3-m eth oxy-1,2-dih ydr opyr idin e]-
m olybd en u m Hexa flu or op h osp h a te, 17. Complex 9 (1.107
g, 1.59 mmol, 1.0 equiv) in 5 mL of dry CH Cl was treated
(
[
2
2
2
with triphenylcarbenium hexafluorophosphate (0.740 g, 1.91
mmol, 1.1 equiv) and gave, after workup, 17 as a red/brown
powder (1.05 g, 1.24 mmol, 78%). mp 89-91 °C with decomp;
mmol, 43%). TLC (silica gel, 25% ethyl acetate in hexanes, R
f
-1
) 0.43); mp 120-123 °C with decomp; IR (CH
2485 (w), 1933 (sh, s), 1841 (sh, s), 1690 (sh, m). H NMR
((CD SO, 400 MHz): δ 8.30 (d, J ) 1.6 Hz, 0.65 H), 8.29 (d,
2 2
Cl , KBr, cm ):
-1
1
IR (CH
2
Cl
2
, KBr, cm ): 2507 (w), 2055 (sh, s), 2016 (m), 1939
1
(sh, s), 1734 (sh, s). H NMR (CD
2
Cl
2
, 400.MHz): δ 8.11 (br s,
3 2
)
1
H), 7.93 (br s, 1 H), 7.85 (br s, 1 H), 7.84 (br s, 1 H), 7.81 (br
J ) 1.6 Hz, 0.35 H), 7.98 (s, 0.65 H), 7.96 (s, 0.35 H), 7.92 (d,
J ) 1.6 Hz, 1 H), 7.88 (s, 1.05 H), 7.87 (s, 1.95 H), 7.78 (m, 3
H), 7.36 (m, 7 H), 6.35 (t, J ) 1.6 Hz, 1 H), 6.32 (t, J ) 1.6 Hz,
1 H), 6.31 (t, J ) 1.6 Hz, 1 H), 5.69 (d, J ) 1.6 Hz, 0.65 H),
5.56 (d, J ) 1.6 Hz, 0.35 H), 5.23 (A of AB quartet, J ) 12.4
Hz, 0.35 H), 5.16 (A of AB quartet, J ) 12.4 Hz, 0.65 H), 5.13
(B of AB quartet, J ) 12.4 Hz, 0.35 H), 4.94 (B of AB quartet,
J ) 12.4 Hz, 0.65 H), 4.58 (d, J ) 7.6 Hz, 0.35 H), 4.57 (d, J
) 7.6 Hz, 0.65 H), 4.54 (d, J ) 4.0 Hz, 0.35 H), 4.52 (d, J ) 4.0
Hz, 0.65 H), 4.14 (s, 0.65 H), 4.12 (s, 0.35 H), 3.02 (s, 1.05 H),
2.95 (s, 1.95 H), 1.72 (m, 0.7 H), 1.08 (m, 1.3 H), 0.67 (t, J )
s, 1 H), 7.80 (br s, 1 H), 7.56 (br s, 1 H), 7.42 (m, 5 H), 6.41 (br
s, 3 H), 5.57 (br s, 1 H), 5.35 (s, 2 H), 5.03 (br s, 1 H), 4.36 (t,
J ) 4.0 Hz, 1 H), 4.14 (q, J ) 7.2 Hz, 2 H), 3.22 (s, 3 H), 3.07
1
3
(
m, 2 H), 1.25 (t, J ) 7.2 Hz, 3 H). C NMR (CD
2 2
Cl , 100
MHz): δ 218.0, 169.0, 152.9, 147.2, 144.4, 143.4, 139.7, 138.3,
1
6
4
34.9, 129.5, 129.2, 129.1, 108.1, 99.3, 70.7, 70.6, 66.3, 62.1,
1.7, 58.7, 38.7, 14.4. Anal. Calcd for C29 PBMo: C,
1.40; H, 3.71; N, 11.65; O, 13.31; F, 13.55; P, 3.68; B, 1.28;
31 7 7 6
H N O F
Mo, 11.40. Found: C, 41.58; H, 3.83; N, 11.37.
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(2S*,3R*,4R*,5S*,6S*)-(1-ben zyloxyca r bon yl)-η-(3,4,5,6)-
-(1-p r op en yl)-3-m eth oxy-1,2-d ih yd r op yr id in e]m olybd e-
n u m Hexa flu or op h osp h a te, 18. Complex 10 (0.198 g, 0.30
mmol, 1.0 equiv) in 5 mL of dry CH Cl was treated with
triphenylcarbenium hexafluorophosphate (0.142 g, 0.37 mmol,
.2 equiv) and gave, after workup, 18 as a red/brown powder
0.165 g, 0.20 mmol, 68%). mp 92-95 °C with decomp; IR
(
[
2
7.6 Hz, 1.05 H), 0.54 (t, J ) 7.6 Hz, 1.95 H). 13C NMR ((CD
) -
3 2
SO, 100 MHz): δ 231.2, 227.5, 227.1, 154.8, 153.7, 145.6, 144.1,
143.6, 140.9, 140.8, 137.8, 136.7, 136.5, 136.3, 136.0, 134.9,
128.4, 127.9, 127.8, 127.7, 127.5, 127.0, 105.7, 105.5, 66.5, 66.3,
57.1, 56.9, 56.2, 55.9, 55.2, 54.7, 53.6, 53.1, 30.5, 30.4, 11.6,
2
2
1
34 7 5
11.4. Anal. Calcd for C33H N O BMo: C, 55.40; H, 4.79; N,
13.70; O, 11.18; B, 1.51; Mo, 13.41. Found: C, 55.47; H, 4.82;
N, 13.58.
(
(
(
-1
CH
2 2
Cl , KBr, cm ): 2509 (w), 2053 (sh, m), 2021 (sh, s), 1951
1
sh, s), 1717 (m). H NMR (CD
2
Cl
2
, 400 MHz): δ 8.11 (s, 1 H),
(()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
[(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
2-eth yl-3-m eth oxy-6-ben zyl-1,2,5,6-tetr a h yd r op yr id in -3-
yl]m olybd en u m , 21. Cationic complex 13 (0.400 g, 0.51 mmol,
1.0 equiv) in 25 mL of dry THF at -78 °C was treated with a
1 M solution of benzylmagnesium bromide in THF (0.66 mL,
0.66 mmol, 1.3 equiv) and gave, after workup and basic
alumina chromatography, 21 as an orange solid (0.282 g, 0.39
7
1
5
.90 (s, 1 H), 7.82 (s, 1 H), 7.75 (s, 1 H), 7.70 (s, 1 H), 7.54 (s,
H), 7.48 (d, J ) 5.4 Hz, 1 H), 7.42 (m, 5 H), 6.41 (br s, 3 H),
.64 (m, 1 H), 5.41 (t, J ) 5.4 Hz, 1 H), 5.34 (s, 2 H), 5.24 (d,
J ) 10.0 Hz, 1 H), 5.10 (d, J ) 17.2 Hz, 1 H), 5.02 (br s, 1 H),
4
.22 (br s, 1 H), 3.20 (s, 3 H), 2.95 (m, 1 H), 2.74 (m, 1 H). 13
NMR (CD Cl , 100 MHz): δ 218.7, 147.1, 144.5, 143.4, 139.6,
C
2
2
1
1
38.2, 135.0, 130.3, 129.6, 129.5, 129.3, 129.2, 128.6, 127.9,
27.7, 121.5, 108.0, 100.0, 70.7, 70.5, 66.3, 58.3, 55.4. HRMS
mmol, 76%). TLC (silica gel, 25% ethyl acetate in hexanes, R
) 0.38); mp 100-105 °C with decomp; IR (CH Cl , KBr, cm ):
2 2
f
-1
(FAB+) calcd for C28
H
29
N
7
O
5
BMo: 652.1378. Found: 652.1396.

7
452 J . Org. Chem., Vol. 65, No. 22, 2000
Moretto and Liebeskind
1
2
484 (w), 1933 (sh, s), 1841 (sh, s), 1692 (sh, m). H NMR
(CD SO, 400 MHz): δ 8.22 (s, 1 H), 7.88 (d, J ) 2.0 Hz, 1
H), 7.83 (d, J ) 2.0 Hz, 1 H), 7.78 (s, 1 H), 7.74 (s, 1 H), 7.34
m, 11 H), 6.30 (s, 3 H), 5.50 (A of AB quartet, J ) 12.4 Hz,
.5 H), 5.02 (A of AB quartet, J ) 12.4 Hz, 0.5 H), 4.95 (B of
AB quartet, J ) 12.4 Hz, 0.5 H), 4.94 (B of AB quartet, J )
2.4 Hz, 0.5 H), 4.52 (m, 2 H), 3.96 (m, 1 H), 3.77 (d, J ) 5.6
(()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
[(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
2-et h en yl-3-m et h oxy-6-et h yl-1,2,5,6-t et r a h yd r op yr id in -
3-yl]m olybd en u m , 24. Cationic complex 15 (0.400 g, 0.51
mmol, 1.0 equiv) in 25 mL of dry THF at -78 °C was treated
with a 1 M solution of ethylmagnesium bromide in THF (0.53
mL, 0.53 mmol, 1.2 equiv) and gave, after workup and basic
alumina chromatography, 24 as an orange solid (0.263 g, 0.40
(
3 2
)
(
0
1
Hz, 0.5 H), 3.75 (d, J ) 5.6 Hz, 0.5 H), 3.03 (m, 2 H), 3.03 (s,
.5 H), 2.96 (s, 1.5 H), 2.14 (m, 1 H), 1.77 (m, 1 H), 1.12 (t, J
7.6 Hz, 1.5 H), 0.99 (t, J ) 7.6 Hz, 1.5 H). C NMR ((CD
SO, 100 MHz): δ 231.0, 230.7, 227.4, 227.1, 154.0, 153.5, 145.7,
44.0, 139.4, 139.2, 138.6, 138.5, 137.4, 137.0, 136.7, 136.6,
36.4, 136.1, 134.9, 128.9, 128.8, 128.1, 128.0, 127.9, 127.8,
27.4, 127.3, 127.1, 126.1, 105.7, 105.5, 66.2, 66.1, 56.6, 55.9,
5.6, 54.7, 54.1, 53.7, 46.0, 45.4, 32.7, 32.5, 12.6, 12.4. Anal.
1
mmol, 78%). TLC (silica gel, 25% ethyl acetate in hexanes, R
f
1
3
-1
)
3
)
2
-
) 0.34); mp 89-94 °C with decomp; IR (CH
2486 (w), 1933 (sh, s), 1841 (sh, s), 1693 (sh, m). H NMR
((CD SO, 400 MHz): δ 8.29 (s, 1 H), 7.91 (s, 1 H), 7.87 (s, 1
2 2
Cl , KBr, cm ):
1
1
1
1
5
3 2
)
H), 7.84 (s, 1 H), 7.81 (s, 1 H), 7.76 (s, 1 H), 7.52 (m, 5 H), 6.33
(s, 2 H), 6.28 (s, 1 H), 5.89 (m, 1 H), 5.44 (d, J ) 17.2 Hz, 0.44
H), 5.09 (m, 4.44 H), 4.32 (d, J ) 8.2 Hz, 0.56 H), 4.27 (d, J )
8.2 Hz, 0.44 H), 4.22 (t, J ) 6.2 Hz, 0.56 H), 4.17 (t, J ) 6.2
Hz, 0.44 H), 3.81 (d, J ) 3.8 Hz, 0.56 H), 3.79 (d, J ) 3.8 Hz,
Calcd for C34
0.97; B, 1.48; Mo, 13.15. Found: C, 56.03; H, 4.99; N, 13.34.
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
-ben zyl-3-m eth oxy-6-eth yl-1,2,5,6-tetr a h yd r op yr id in -3-
yl-1-ca r boxyla te]m olybd en u m , 22. Cationic complex 14
0.250 g, 0.30 mmol, 1.0 equiv) in 10 of mL dry THF at -78
C was treated with a 1 M solution of ethylmagnesium bromide
36 7 5
H N O BMo: C, 55.98; H, 4.97; N, 13.44; O,
1
0
1
.44 H), 3.01 (s, 1.32 H), 2.91 (s, 1.68 H), 1.87 (m, 1.12 H),
(
.67 (m, 0.88 H), 1.00 (t, J ) 7.2 Hz, 1.68 H), 0.93 (t, J ) 7.2
[
2
1
3
3 2
Hz, 1.32 H). C NMR ((CD ) SO, 100 MHz): δ 230.2, 227.5,
1
1
1
5
53.9, 153.4, 145.7, 144.0, 140.7, 140.5, 138.7, 138.5, 136.5,
36.0, 134.8, 132.4, 131.8, 127.8, 127.2, 127.1, 127.0, 118.3,
17.9, 105.7, 105.5, 105.4, 65.9, 58.6, 57.7, 56.8, 56.4, 56.1, 54.5,
(
°
3.4, 53.2, 33.3, 33.1, 11.1. Anal. Calcd for C29
32 7 5
H N O BMo:
in THF (0.36 mL, 0.36 mmol, 1.2 equiv) and gave, after workup
and basic alumina chromatography, 22 as an orange solid
0.143 g, 0.20 mmol, 66%). TLC (silica gel, 25% ethyl acetate
C, 52.35; H, 4.85; N, 14.74; O, 12.02; B, 1.62; Mo, 14.42.
Found: C, 52.63; H, 4.95; N, 14.47.
(
(
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
in hexane, R ) 0.38); mp 107-111 °C with decomp; IR
f
-
1
[(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
2-eth en yl-3-m eth oxy-6-ben zyl-1,2,5,6-tetr a h yd r op yr id in -
(
(
(
CH
sh, m). H NMR ((CD
s, 0.44 H), 7.90 (s, 1 H), 7.84 (s, 2 H), 7.73 (s, 1 H), 7.51 (s, 1
2 2
Cl , KBr, cm ): 2487 (w), 1931 (sh, s), 1838 (sh, s), 1691
1
3 2
) SO, 400 MHz): δ 8.25 (s, 0.56 H), 8.24
3
-yl]m olybd en u m , 25. Cationic complex 15 (0.15 g, 0.19
mmol, 1.0 equiv) in 10 mL of dry THF at -78 °C was treated
with a 1 M solution of benzylmagnesium bromide in THF (0.23
mL, 0.23 mmol, 1.2 equiv) and gave, after workup and basic
alumina chromatography, 25 as an orange solid 0.103 g, 0.14
H), 7.28 (m, 10 H), 6.32 (d, J ) 2.0 Hz, 2 H), 6.20 (s, 1 H), 5.10
s, 0.9 H), 4.93 (s, 1.1 H), 4.82 (br m, 1 H), 4.33 (t, J ) 8.4 Hz,
.56 H), 4.29 (t, J ) 8.4 Hz, 0.44 H), 4.26 (t, J ) 6.8 Hz, 0.56
(
0
H), 4.20 (t, J ) 6.8 Hz, 0.44 H), 3.72 (d, J ) 2.8 Hz, 0.56 H),
mmol, 75%). TLC (silica gel, 25% ethyl acetate in hexanes, R
f
3
2
.70 (d, J ) 2.8 Hz, 0.44 H), 3.07 (m, 2 H), 2.80 (s, 1.33 H),
-1
)
0.35); mp 106-109 °C with decomp; IR (CH
486 (w), 1933 (sh, s), 1843 (sh, s), 1693 (sh, m). H NMR
(CD SO, 400 MHz): δ 8.27 (s, 1 H), 7.87 (s, 1 H), 7.84 (d, J
2.0 Hz, 2 H), 7.75 (s, 1 H), 7.33 (m, 11 H), 6.32 (t, J ) 2.0
2 2
Cl , KBr, cm ):
.77 (s, 1.67 H), 1.89 (m, 0.88 H), 1.77 (m, 1.22 H), 1.10 (t, J
1
2
)
7.2 Hz, 1.67 H), 1.00 (t, J ) 7.2 Hz, 1.33 H). 13C NMR ((CD
) -
3 2
(
3 2
)
SO, 100 MHz): δ 230.7, 227.4, 153.8, 153.5, 145.6, 143.7, 140.2,
)
1
1
5
39.7, 137.4, 137.0, 136.5, 136.2, 135.9, 134.8, 128.6, 128.4,
27.8, 127.5, 127.4, 127.2, 126.9, 125.4, 105.5, 66.4, 65.9, 57.1,
7.0, 55.9, 54.2, 53.8, 53.6, 45.8, 45.6, 33.2, 33.011.4. Anal.
Hz, 1 H), 6.30 (t, J ) 2.0 Hz, 2 H), 6.05 (m, 1 H), 5.40 (m, 2
H), 4.95 (m, 4 H), 4.46 (m, 1 H), 4.05 (dd, J ) 8.0, 2.0 Hz, 0.57
H), 4.01 (dd, J ) 8.0, 2.0 Hz, 0.43 H), 3.90 (d, J ) 7.8 Hz, 1
Calcd for C34
0.97; B, 1.48; Mo, 13.15. Found: C, 55.87; H, 5.01; N, 13.31.
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
36 7 5
H N O BMo: C, 55.98; H, 4.97; N, 13.44; O,
1
3
H), 3.09 (s, 1.71 H), 2.99 (s, 1.29 H), 3.01 (m, 1 H). C NMR
(CD SO, 100 MHz): δ 230.1, 227.4, 153.6, 153.0, 145.8,
44.1, 139.8, 139.4, 138.7, 138.6, 136.7, 136.4, 136.2, 134.9,
1
(
3 2
)
(
1
1
1
6
[
2
3
(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
-eth en yl-3-m eth oxy-6-m eth yl-1,2,5,6-tetr a h yd r op yr id in -
-yl]m olybd en u m , 23. Cationic complex 15 (0.05 g, 0.064
mmol, 1.0 equiv) in 25 mL of dry THF at -78 °C was treated
with a 1.0 M solution of methylmagnesium bromide in THF
0.02 mL, 0.071 mmol, 1.1 equiv) and gave, after workup and
basic alumina chromatography, 23 as an orange solid (0.032
g, 0.049 mmol, 76%). TLC (silica gel, 25% ethyl acetate in
) 0.32); mp 95-100 °C with decomp; IR (CH
KBr, cm ): 2484 (w), 1932 (sh, s), 1842 (sh, s), 1692 (sh, m).
32.1, 131.2, 128.8, 128.7, 128.1, 128.0, 127.9, 127.8, 127.3,
27.1, 127.0, 126.0, 125.9, 118.7, 118.2, 105.8, 105.6, 10.5, 66.2,
6.0, 57.7, 56.8, 56.5, 56.4, 56.2, 54.7, 54.1, 53.8, 46.1, 45.6.
Anal. Calcd for C34
O, 11.00; B, 1.49; Mo, 13.19. Found: C, 56.40; H, 4.82; N, 13.23.
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
34 7 5
H N O BMo: C, 56.14; H, 4.71; N, 13.48;
(
(
[
2
3
(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
-p h en yl-3-m eth oxy-6-eth en yl-1,2,5,6-tetr a h yd r op yr id in -
hexane, R
f
1
2
Cl
2
,
-yl]m olybd en u m , 26. Cationic complex 16 (0.15 g, 0.18
-
mmol, 1.0 equiv) in 10 mL of dry THF at -78 °C was treated
with a 1 M solution of vinylmagnesium bromide in THF (0.22
mL, 0.22 mmol, 1.2 equiv) and gave, after workup and basic
alumina chromatography, 26 as an orange solid (0.071 g, 0.1
mmol, 55%). TLC (silica gel, 25% ethyl acetate in hexanes, R
1
H NMR ((CD
.98 (d, J ) 2.0 Hz, 0.43 H), 7.96 (d, J ) 2.0 Hz, 0.57 H), 7.88
br s, 1 H), 7.85 (d, J ) 2.0 Hz, 1 H), 7.83 (d, J ) 2.0 Hz, 1 H),
3 2
) SO, 400 MHz): δ 8.30 (d, J ) 2.0 Hz, 1 H),
7
(
7
1
1
1
5
4
.77 (d, J ) 2.0 Hz, 1 H), 7.33 (m, 5 H), 6.33 (m, 2 H), 6.28 (m,
H), 5.93 (m, 1 H), 5.38 (d, J ) 17.2 Hz, 0.43 H), 5.25 (d, J )
0.4 Hz, 0.43 H), 5.20 (d, J ) 10.4 Hz, 0.57 H), 5.19 (d, J )
7.2 Hz, 0.57 H), 5.09 (A of AB quartet, J ) 14.8 Hz, 0.57 H),
.07 (br s, 1 H), 5.02 (A of AB quartet, J ) 10.4 Hz, 0.43 H),
.98 (B of AB quartet, J ) 10.4 Hz, 0.57 H), 4.96 (B of AB
f
-1
) 0.36); mp 116-119 °C with decomp; IR (CH Cl , KBr, cm ):
2
2
1
2486 (w), 1934 (sh, s), 1844 (sh, s), 1694 (sh, m). H NMR
((CD ) SO, 400 MHz): δ 8.34 (d, J ) 1.6 Hz, 1 H), 8.01 (s, 1
3 2
H), 7.88 (m, 2 H), 7.79 (m, 2 H), 7.69 (d, J ) 7.2 Hz, 1 H), 7.49
(m, 1 H), 7.31 (m, 8 H), 6.36 (m, 2 H), 6.26 (t, J ) 1.6 Hz, 1 H),
5.86 (m, 1 H), 5.78 (s, 0.5 H), 5.70 (s, 0.5 H), 5.24 (d, J ) 17.2
Hz, 0.5 H), 5.03 (m, 4 H), 4.87 (d, J ) 6.0 Hz, 0.5 H), 4.81 (d,
J ) 6.0 Hz, 0.5 H), 4.46 (dd, J ) 8.0, 2.0 Hz, 0.5 H), 4.37 (dd,
quartet, J ) 14.8 Hz, 0.57 H), 4.38 (m, 1 H), 4.33 (dd, J ) 8.0,
.2 Hz, 0.57 H), 4.28 (dd, J ) 8.0, 2.2 Hz, 0.43 H), 3.81 (d, J
8.0 Hz, 0.43 H), 3.79 (d, J ) 8.0 Hz, 0.57 H), 3.02 (s, 1.29
H), 2.92 (s, 1.71 H), 1.43 (d, J ) 6.4 Hz, 1.29 H), 1.42 (d, J )
2
)
1
3
J ) 8.0, 2.0 Hz, 0.5 H), 2.80 (s, 1.5 H), 2.66 (s, 1.5 H).
C
1
3
6
1
1
1
5
.4 Hz, 1.71 H). C NMR ((CD
3
)
2
SO, 100 MHz): δ 230.5, 227.5,
NMR ((CD SO, 100 MHz): δ 230.9, 227.2, 153.6, 153.3, 145.7,
3 2
)
53.5, 152.9, 145.8, 144.1, 141.0, 140.7, 138.9, 138.6, 136.7,
36.5, 136.1, 135.0, 131.4, 130.5, 128.0, 127.9, 127.4, 127.2,
26.9, 118.3, 117.9, 105.8, 105.5, 66.1, 65.9, 60.5, 59.6, 56.8,
144.2, 141.1, 140.9, 140.7, 140.5, 140.4, 136.7, 136.4, 136.1,
134.9, 131.2, 129.9, 128.5, 128.3, 127.9, 127.8, 127.6, 127.5,
127.4, 127.2, 126.8, 115.9, 115.7, 105.8, 105.6, 105.5, 66.5, 66.1,
6.4, 56.2, 54.7, 47.7, 25.9, 25.2. Anal. Calcd for C28
H
30
N
7
O
5
-
32 7 5
58.5, 58.4, 58.2, 57.3, 56.3, 54.5. Anal. Calcd for C33H N O -
BMo: C, 51.63; H, 4.64; N, 15.05; O, 12.28; B, 1.66; Mo, 14.73.
Found: C, 51.81; H, 4.83; N, 14.76.
BMo: C, 55.56; H, 4.52; N, 13.74; O, 11.21; B, 1.52; Mo, 13.45.
Found: C, 55.37; H, 4.64; N, 13.47.

Construction of Trisubstituted Piperidines
J . Org. Chem., Vol. 65, No. 22, 2000 7453
(
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
-p h en yl-3-m eth oxy-6-eth yl-1,2,5,6-tetr a h yd r op yr id in -3-
yl]m olybd en u m , 27. Cationic complex 16 (0.400 g, 0.48 mmol,
1
1
0
H), 7.89 (d, J ) 2.0 Hz, 1 H), 7.86 (s, 1 H), 7.77 (s, 1 H), 7.60
(m, 4 H), 7.34 (m, 4 H), 7.19 (m, 2 H), 6.32 (m, 3 H), 5.17 (dd,
J ) 8.4, 3.6 Hz, 0.45 H), 5.07 (m, 1.55 H), 5.00 (A of AB quartet,
J ) 13.2 Hz, 0.55 H), 4.87 (m, 0.9 H), 4.79 (B of AB quartet,
J ) 13.2 Hz, 0.55 H), 4.43 (dd, J ) 8.4, 2.4 Hz, 1 H), 4.09 (m,
3 H), 3.74 (m, 1 H), 3.72 (dd, J ) 8.4, 1.6 Hz, 1 H), 3.33 (dd, J
) 16.4, 4.8 Hz, 0.55 H), 3.28 (dd, J ) 16.4, 4.8 Hz, 0.45 H),
2.91 (s, 1.35 H), 2.90 (m, 1 H), 2.87 (s, 1.65 H), 1.25 (t, J ) 7.0
[
2
.0 equiv) in 25 mL of dry THF at -78 °C was treated with a
M solution of vinylmagnesium bromide in THF (0.53 mL,
.53 mmol, 1.1 equiv) and gave, after workup and basic
alumina chromatography, 27 as an orange solid (0.252 g, 0.35
mmol, 73%). TLC (silica gel, 25% ethyl acetate in hexane, R
Hz, 1.35 H), 1.17 (t, J ) 7.0 Hz, 1.65 H). 13C NMR ((CD
) SO,
f
3 2
-
1
)
0.43); mp 117-120 °C with decomp; IR (CH
483 (w), 1934 (sh, s), 1842 (sh, s), 1693 (sh, m). H NMR
(CD SO, 400 MHz): δ 8.32 (s, 1 H), 7.98 (d, J ) 2.4 Hz, 1
H), 7.88 (d, J ) 1.6 Hz, 2 H), 7.78 (m, 4 H), 7.55 (m, 1 H), 7.32
m, 7 H), 6.36 (s, 2 H), 6.26 (s, 1 H), 5.85 (s, 0.56 H), 5.77 (s,
.44 H), 5.17 (A of AB quartet, J ) 12.4 Hz, 0.44 H), 5.07 (A
of AB quartet, J ) 12.4 Hz, 0.56 H), 5.03 (B of AB quartet, J
2
Cl
2
, KBr, cm ):
100 MHz): δ 230.5, 230.2, 226.8, 226.4, 197.8, 197.6, 170.1,
169.9, 153.3, 152.8, 145.8, 143.9, 140.1, 140.0, 136.8, 136.6,
136.3, 136.2, 135.0, 133.4, 132.9, 132.7, 128.4, 127.9, 127.8,
127.4, 127.3, 127.1, 126.9, 126.5, 105.9, 105.7, 105.6, 66.3, 65.8,
63.2, 60.1, 59.6, 57.3, 57.1, 55.8, 55.6, 54.9, 54.3, 52.4, 52.3,
49.0, 48.7, 48.0, 47.6, 43.4, 42.413.9, 13.8. Anal. Calcd for
1
2
(
3 2
)
(
0
37 38 7 8
C H N O BMo: C, 54.50; H, 4.70; N, 12.02; O, 15.70; B, 1.33;
Mo, 11.76. Found: C, 54.22; H, 4.77; N, 12.30.
)
12.4 Hz, 0.56 H), 4.98 (B of AB quartet, J ) 12.4 Hz, 0.44
H), 4.42 (dd, J ) 8.4, 2.0 Hz, 0.44 H), 4.36 (dd, J ) 8.4, 2.0
Hz, 0.56 H), 4.28 (t, J ) 7.4 Hz, 0.44 H), 4.20 (t, J ) 7.4 Hz,
(()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
[(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
2-(1-pr open yl)-3-m eth oxy-6-ph en yleth yn yl-1,2,5,6-tetr ah y-
d r op yr id in -3-yl]m olybd en u m , 30. Cationic complex 18
(0.200 g, 0.25 mmol, 1.0 equiv) in 4 mL of dry THF was treated
with lithium phenylacetylide (generated from phenylacetylene
(0.033 mL, 0.30 mmol, 1.2 equiv) in 4 mL of THF and
n-butyllithium (0.13 mL, 2.42 M in hexanes, 0.30 mmol, 1.2
equiv) at -78 °C) to give, after workup and basic alumina
chromatography, 30 as an orange solid (0.126 g, 0.17 mmol,
0
.56 H), 4.17 (d, J ) 8.4 Hz, 0.56 H), 4.13 (d, J ) 8.4 Hz, 0.44
H), 2.86 (s, 1.68 H), 2.71 (s, 1.32 H), 1.77 (m, 0.88 H), 1.49 (m,
.12 H), 0.68 (t, J ) 7.4 Hz, 1.32 H), 0.55 (t, J ) 7.4 Hz, 1.68
1
1
3
H). C NMR ((CD
3
)
2
SO, 400 MHz): δ 230.7, 227.4, 154.0,
1
1
1
5
53.9, 145.7, 144.1, 141.5, 140.8, 140.5, 136.6, 136.4, 136.3,
36.0, 134.8, 131.6, 130.7, 128.2, 128.0, 127.9, 127.8, 127.6,
27.5, 127.5, 127.3, 127.1, 127.0, 105.7, 105.6, 105.5, 66.4, 66.1,
8.7, 58.5, 58.4, 57.6, 57.5, 56.7, 53.9, 53.5, 31.9, 10.7, 10.6.
Anal. Calcd for C33
O, 11.18; B, 1.51; Mo, 13.41. Found: C, 55.34; H, 4.82; N, 13.62.
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
H
34
N
7
O
5
BMo: C, 55.40; H, 4.79; N, 13.70;
67%). TLC (silica gel, 25%ethyl acetate in hexanes, R
f
) 0.45);
-
1
mp 103 °C with decomp; IR (CH
3 2
1936 (sh, s), 1846 (sh, s), 1699 (sh, m). H NMR ((CD ) SO,
2 2
Cl , KBr, cm ): 2484 (w),
1
(
[
(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
400 MHz): δ 8.28 (s, 1 H), 8.00 (s, 1 H), 7.91 (d, J ) 2.4 Hz,
1 H), 7.86 (d, J ) 2.4 Hz, 1 H), 7.78 (d, J ) 2.4 Hz, 1 H), 7.51
(d, J ) 2.4 Hz, 1 H), 7.35 (m, 10 H), 6.35 (t, J ) 2.4 Hz, 1 H),
6.32 (t, J ) 2.4 Hz, 1 H), 6.30 (t, J ) 2.4 Hz, 1 H), 6.01 (dt, J
) 17.0, 7.2 Hz, 0.38 H), 5.88 (dt, J ) 17.0, 7.2 Hz, 0.62 H),
5.21 (dd, J ) 10.8, 2.4 Hz, 1 H), 5.10 (A of AB quartet, J )
12.8 Hz, 1 H), 5.07 (d, J ) 14.0 Hz, 1 H), 4.97 (B of AB quartet,
J ) 12.8 Hz, 1 H), 4.92 (app t, J ) 9.6 Hz, 1 H), 4.71 (m, 1 H),
4.54 (dd, J ) 8.0, 2.4 Hz, 0.62 H), 4.50 (dd, J ) 8.0, 2.4 Hz,
0.38 H), 3.86 (d, J ) 8.0 Hz, 0.62 H), 3.84 (d, J ) 8.0 Hz, 0.38
2
1
-et h oxyca r b on ylm et h yl-3-m et h oxy-6-p h en ylet h yn yl-
,2,5,6-tetr a h yd r op yr id in -3-yl]m olybd en u m , 28. Cationic
complex 17 (0.200 g, 0.24 mmol, 1.0 equiv) in 4 mL of dry THF
at -78 °C was treated with lithium phenylacetylide (generated
from phenylacetylene (0.031 mL, 0.29 mmol, 1.2 equiv) in 4
mL of THF and n-butyllithium (0.12 mL, 2.42 M in hexanes,
0
.29 mmol, 1.2 equiv) at -78 °C) to give, after workup and
basic alumina chromatography, 28 as an orange solid (0.110
g, 0.14 mmol, 58%). TLC (silica gel, 25% ethyl acetate in
1
3
hexanes, R
f
) 0.20); mp 102-105 °C with decomp; IR (CH
2
Cl
2
,
H), 3.00 (s, 1.14 H), 2.95 (s, 1.86 H), 2.89 (m, 2 H). C NMR
((CD SO, 100 MHz): δ 230.8, 230.5, 226.9, 226.4, 153.7,
-
1
KBr, cm ): 2489 (w), 1939 (sh, s), 1850 (sh, s), 1731 (sh, m),
3 2
)
1
1
2
700 (sh, m). H NMR ((CD
.0 Hz, 1 H), 8.00 (s, 1 H), 7.91 (d, J ) 2.0 Hz, 1 H), 7.86 (d,
3
)
2
SO, 400 MHz): δ 8.30 (d, J )
152.8, 145.7, 144.1, 141.0, 136.9, 136.6, 136.2, 136.1, 135.7,
135.5, 135.0, 134.9, 131.0, 128.4, 128.0, 127.9, 127.6, 127.4,
126.8, 122.1, 116.3, 115.9, 105.9, 105.7, 92.1, 91.9, 82.7, 82.4,
66.6, 66.2, 56.6, 55.2, 54.8, 54.6 42.9, 42.5, 41.2. Anal. Calcd
J ) 2.0 Hz, 1 H), 7.78 (s, 1 H), 7.72 (s, 0.5 H), 7.70 (s, 0.5 H),
7
2
3
2
1
2
1
1
9
5
.40 (m, 10 H), 6.33 (m, 3 H), 5.13 (m, 4 H), 4.60 (dd, J ) 8.0,
.0 Hz, 0.5 H), 4.57 (dd, J ) 8.0, 2.0 Hz, 0.5 H), 4.02 (m, 2 H),
.89 (s, 0.5 H), 3.87 (s, 0.5 H), 2.99 (m, 2 H), 2.91 (s, 1.5 H),
.88 (s, 1.5 H), 1.21 (t, J ) 7.2 Hz, 1.5 H), 1.13 (t, J ) 7.2 Hz,
for C36
34 7 5
H N O BMo: C, 57.54; H, 4.56; N, 13.05; O, 10.65; B,
1.44; Mo, 12.77. Found: C, 57.35; H, 4.71; N, 12.98.
(()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
[(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
2-(1-pr open yl)-3-m eth oxy-6-(2-oxo-2-ph en yl-eth yl)-1,2,5,6-
tetr a h yd r op yr id in -3-yl]m olybd en u m , 31. Cationic complex
18 (0.200 g, 0.25 mmol, 1.0 equiv) in 4 mL of dry at -78 °C
was treated via cannula with lithioacetophenone (generated
by addition of acetophenone (0.41 mL, 0.35 mmol, 1.4 equiv)
to lithium diisopropylamide, prepared from diisopropylamine
(0.05 mL, 0.35 mmol, 1.4 equiv), 4 mL of THF, and n-
butyllithium (0.15 mL, 2.42 M in hexanes, 0.35 mmol, 1.4
equiv) at -78 °C). Workup and basic alumina chromatography
gave 31 as an orange solid (0.103 g, 0.14 mmol, 54%). TLC
1
3
3 2
.5 H). C NMR ((CD ) SO, 100 MHz): δ 230.4, 230.0, 226.5,
26.1, 169.7, 169.6, 153.2, 152.6, 145.8, 144.0, 140.9, 137.0,
36.4, 136.2, 136.0, 135.1, 133.8, 133.2, 131.4, 131.0, 128.4,
27.9, 127.4, 127.1, 126.9, 126.7, 122.0, 121.9, 105.9, 105.7,
1.5, 91.3, 82.8, 82.6, 66.8, 66.3, 59.7, 56.1, 55.1, 54.8, 53.0,
2.9, 43.0, 42.6, 42.0, 41.1, 13.7. Anal. Calcd for C37
36 7 7
H N O -
BMo: C, 55.73; H, 4.55; N, 12.29; O, 14.04; B, 1.36; Mo, 12.03.
Found: C, 55.85; H, 4.71; N, 12.31.
(
()-D ic a r b o n y l[h y d r id o t r is (1-p y r a zo ly l)b o r a t o ]-
(2S*,3R*,4R*,5S*,6R*)-(1-ben zyloxyca r bon yl)- η-(3,4,5)-
-et h oxyca r b on ylm et h yl-3-m et h oxy-6-(2-oxo-2-p h en yl-
[
2
et h yl)-1,2,5,6-t et r a h yd r op yr id in -3-yl]m olyb d en u m , 29.
Cationic complex 17 (0.200 g, 0.24 mmol, 1.0 equiv) in 4 mL
of dry THF at -78 °C was treated via cannula with lithio-
acetophenone (generated by addition of acetophenone (0.40
mL, 0.33 mmol, 1.4 equiv) to lithium diisopropylamide,
prepared from diisopropylamine (0.047 mL, 0.33 mmol, 1.4
equiv), 4 mL of THF, and n-butyllithium (0.14 mL, 2.42 M in
hexanes, 0.33 mmol, 1.4 equiv) at -78 °C). Workup and basic
alumina chromatography gave 29 as an orange solid (0.083 g,
(silica gel, 25% ethyl acetate in hexanes, R
f
) 0.33); mp 92 °C
-
1
with decomp; IR (CH
3 2
1842 (sh, s), 1696 (sh, m). H NMR ((CD ) SO, 400 MHz): δ
2 2
Cl , KBr, cm ): 2487 (w), 1934 (sh, s),
1
8.28 (d, J ) 1.6 Hz, 0.56 H), 8.26 (d, J ) 1.6 Hz, 0.44 H), 8.08
(s, 0.44 H), 8.07 (s, 0.56 H), 8.01 (s, 0.44 H), 8.00 (s, 0.56 H),
7.89 (d, J ) 2.0 Hz, 2 H), 7.85 (d, J ) 2.0 Hz, 1 H), 7.63 (m, 5
H), 7.28 (m, 5 H), 6.34 (t, J ) 2.0 Hz, 1 H), 6.31 (t, J ) 2.0 Hz,
1 H), 6.29 (m, 1 H), 6.04 (m, 0.44 H), 5.85 (m, 0.56 H), 5.03
(m, 5 H), 4.70 (q, J ) 6.0 Hz, 1 H), 4.36 (s, 0.44 H), 4.34 (s,
0.56 H), 3.79 (t, J ) 8.0 Hz, 0.44 H), 3.73 (d, J ) 4.8 Hz, 0.56
H), 3.71 (d, J ) 4.8 Hz, 0.44 H), 3.66 (t, J ) 8.0 Hz, 0.56 H),
3.35 (dd, J ) 16.0, 3.6 Hz, 0.56 H), 3.29 (dd, J ) 16.0, 3.6 Hz,
0.44 H), 3.00 (s, 0.87 H), 2.98 (s, 0.45 H), 2.94 (s, 1.11 H), 2.92
0
R
.10 mmol, 43%). TLC (silica gel, 25% ethyl acetate in hexanes,
) 0.17); mp 98-100 °C with decomp; IR (CH Cl , KBr,
cm ): 2487 (w), 1938 (sh, s), 1846 (sh, s), 1732 (sh, m), 1698
f
2
2
-
1
1
(
sh, m). H NMR ((CD
.55 H), 8.27 (d, J ) 2.0 Hz, 0.45 H), 8.10 (s, 0.45 H), 8.08 (d,
J ) 2.0 Hz, 0.55 H), 8.04 (s, 0.45 H), 8.02 (d, J ) 2.0 Hz, 0.55
3 2
) SO, 400 MHz): δ 8.29 (d, J ) 2.0 Hz,
0
(s, 0.57 H), 2.83 (m, 1 H), 2.66 (m, 1H). 13C NMR ((CD
100 MHz): δ 230.5, 227.5, 227.4, 227.1, 197.8, 197.7, 153.7,
3 2
) SO,

7
454 J . Org. Chem., Vol. 65, No. 22, 2000
Moretto and Liebeskind
1
1
1
1
4
53.1, 145.8, 144.0, 140.2, 140.0, 136.8, 136.6, 136.5, 136.3,
36.2, 135.1, 135.0, 134.4, 134.1, 133.7, 133.0, 128.5, 128.0,
27.8, 127.7, 127.6, 127.4, 127.1, 126.9, 126.6, 117.2, 116.1,
15.8, 105.9, 105.6, 66.3, 65.8, 58.0, 57.4, 57.0, 56.1, 55.9, 54.6,
Ben zyl Ester , 35. In a similar fashion, molybdenum complex
28 (0.043 g, 0.054 mmol, 1.0 equiv) in 15 mL of dry CH Cl
2 2
containing trifluoroacetic acid (0.006 g, 0.083 mmol, 1.0 equiv)
was irradiated for 24 h. The mixture was then occluded onto
silica and purified by silica MPLC (10% ethyl acetate in
hexanes) to give 35 as a colorless oil (0.023 g, 0.030 mmol,
8.8, 48.6, 48.0, 43.2, 42.7. Anal. Calcd for C36
36 7 6
H N O BMo:
C, 56.19; H, 4.72; N, 12.74; O, 12.48; B, 1.40; Mo, 12.47.
Found: C, 55.94; H, 4.90; N, 12.83.
55%). TLC (silica gel, 25% ethyl acetate in hexanes, R
f
) 0.48);
-
1
Decom p lexa tion Stu d ies.
IR (CH
(w), 2941 (w), 2908 (w), 2853 (w), 1730 (sh, s), 1699 (sh, s). H
NMR ((CD SO, 400 MHz): δ 7.35 (m, 10 H), 5.47 (d, J ) 5.2
2 2
Cl , KBr, cm ): 3071 (w), 3037 (w), 2984 (w), 2961
1
(
()-(2S*,6R*)-6-Ben zyl-2-et h yl-3-oxo-3,6-d ih yd r o-2H -
p yr id in e-1-ca r boxylic Acid Ben zyl Ester , 32. To a 10-mL
round-bottomed flask equipped with a stirring bar were added
molybdenum complex 21 (0.081 g, 0.11 mmol, 1.0 equiv) and
3 2
)
Hz, 1 H), 5.20 (A of AB quartet, J ) 12.8 Hz, 1 H), 5.12 (B of
AB quartet, J ) 12.8 Hz, 1 H), 4.89 (d, J ) 6.0 Hz, 1 H), 4.82
(app t, J ) 6.4 Hz, 1 H), 4.00 (m, 2 H), 3.52 (s, 3 H), 3.20 (m,
1 H), 2.89 (app t, J ) 5.2 Hz, 1 H), 2.59 (m, 1 H), 2.37 (dd, J
1
2 2
mL dry CH Cl . Cupric chloride (0.066 g, 0.67 mmol, 6.0
equiv) was added as a solid, and the reaction mixture was
allowed to stir at room temperature for 15 min. The resulting
green suspension was added directly to a flash silica gel
column and eluted with 25% ethyl acetate in hexanes to give
enone 32 as a colorless oil (0.021 g, 0.06 mmol, 53%). TLC
) 16.6, 6.4 Hz, 1 H), 1.14 (m, 3 H). 13C NMR (CDCl
, 100
3
MHz): δ 171.5, 171.0, 155.9, 155.6, 153.6, 136.7, 136.5, 132.0,
131.7, 128.8, 128.7, 128.6, 128.5, 128.3, 128.2, 128.1, 128.0,
126.6, 123.2, 123.0, 90.3, 89.8, 89.4, 82.5, 81.1, 67.8, 67.6, 60.5,
54.9, 54.7, 52.3, 50.9, 44.8, 29.4, 27.6, 14.4. HRMS (EI) calcd
(silica gel, 25% ethyl acetate in hexanes, R
f
) 0.68); IR (CDCl
3
,
-
1
KBr, cm ): 3091 (w), 3068 (w), 3034 (w), 2973 (w), 2936 (w),
2
for C26
5
H27NO : 433.1889. Found: 433.1895.
1
879 (w), 1685 (sh, s). H NMR ((CD
3
)
2
SO, 400 MHz): δ 7.40
(()-(2S*,3R*,6S*)-2-Eth yl-3-m eth oxy-6-p h en yl-3,6-d ih y-
d r o-2H-p yr id in e-1-ca r boxylic Acid Ben zyl Ester , 36. To
a 10 mL round-bottomed flask equipped with stirring bar was
added the molybdenum complex 20 (0.077 g, 0.108 mmol, 1.0
(
(
(
m, 5 H), 7.26 (m, 5 H), 6.85 (dd, J ) 10.8, 4.4 Hz, 1 H), 6.04
dd, J ) 10.8, 2.4 Hz, 1 H), 5.15 (m, 2 H), 4.87 (m, 1 H), 4.42
app t, J ) 8.0 Hz, 1 H), 3.19 (m, 1 H), 2.91 (dd, J ) 12.8, 10.4
1
3
Hz, 1 H), 1.68 (m, 2 H), 0.92 (m, 3 H). C NMR (CDCl
3
, 100
2 2
equiv) and 1 mL of dry CH Cl . The solution was cooled to 0
MHz): δ 195.4, 155.4, 155.2, 148.2, 147.1, 137.3, 136.1, 134.4,
°C in an ice/water bath and treated with nitrosonium tet-
rafluoroborate (0.038 g, 0.32 mmol, 3.0 equiv). The reaction
mixture was allowed to stir at 0 °C for 1 h, and then a solution
of sodium cyanoborohydride (0.024 g, 0.38 mmol, 3.5 equiv)
in 1 mL of THF was added by cannula. The resulting mixture
was allowed to warm to room temperature, stirred for 1.5 h,
and then filtered through a plug of silica gel eluting with 50%
ethyl acetate in hexanes. The resulting crude product was
1
1
6
30.3, 129.8, 129.6, 129.5, 129.2, 129.0, 128.9, 128.8, 128.7,
28.5, 128.3, 128.2, 128.1, 127.5, 127.4, 127.3, 125.0, 124.8,
8.4, 68.2, 67.9, 64.1, 61.9, 61.4, 55.0, 42.9, 28.8, 10.9, 10.8.
HRMS (EI) calcd for C22
()-(2S*,6R*)-2-Eth oxyca r bon ylm eth yl-3-oxo-6-(2-oxo-
-ph en yl-eth yl)-3,6-dih ydr o-2H-pyr idin e-1-car boxylic Acid
Ben zyl Ester , 33. In a similar fashion, molybdenum complex
9 (0.096 g, 0.12 mmol, 1.0 equiv) in 1 mL of dry CH Cl was
3
H23NO : 349.1678. Found: 349.1682.
(
2
2
2
2
purified by medium-pressure chromatography (SiO
acetate in hexanes) to give 36 as a colorless oil (0.027 g, 0.077
mmol, 71%). TLC (silica gel, 25% ethyl acetate in hexanes, R
2
, 25% ethyl
treated with cupric chloride (0.070 g, 0.71 mmol, 6.0 equiv).
Flash silica gel chromatography (25% ethyl acetate in hexanes)
gave enone 33 as a colorless oil (0.024 g, 0.06 mmol, 47%).
f
-
1
) 0.64); IR (CDCl
3
, KBr, cm ): 3091 (w), 3068 (w), 3037 (w),
TLC (silica gel, 25% ethyl acetate in hexanes, R
f
) 0.34); IR
, KBr, cm ): 1731 (sh, s), 1686 (sh, s). H NMR ((CD
SO, 400 MHz): δ 7.97 (d, J ) 7.6 Hz, 2 H), 7.67 (tt, J ) 7.6,
.2 Hz, 1 H), 7.54 (t, J ) 7.6 Hz, 2 H), 7.30 (m, 5 H), 7.22 (dd,
J ) 10.4, 4.8 Hz, 1 H), 6.12 (dd, J ) 10.4, 2.0 Hz, 1 H), 5.29
dtd, J ) 9.2, 4.5, 2.0 Hz, 1 H), 5.10 (s, 2 H), 4.95 (t, J ) 6.8
Hz, 1 H), 4.03 (q, J ) 7.2 Hz, 2 H), 3.68 (dd, J ) 17.3, 9.2 Hz,
H), 3.51 (dd, J ) 17.2, 3.8 Hz, 1 H), 2.85 (dd, J ) 14.7, 7.0
Hz, 1 H), 2.75 (dd, J ) 14.7, 7.2 Hz, 1 H), 1.16 (t, J ) 7.2 Hz,
2970 (w), 2936 (w), 2880 (w), 2094 (w), 2824 (w), 1687 (sh, s).
-1
1
1
(CDCl
3
3
)
2
-
3 2
H NMR ((CD ) SO, 400 MHz): δ 7.30 (m, 10 H), 6.28 (br d, J
) 8.8 Hz, 1 H), 6.14 (ddd, J ) 8.8, 6.0, 2.0 Hz, 1 H), 5.67 (br
s, 1 H), 5.20 (A of AB quartet, J ) 12.8 Hz, 1 H), 5.12 (B of AB
quartet, J ) 12.8 Hz, 1 H), 4.46 (br t, J ) 7.2 Hz, 1 H), 3.64
(d, J ) 5.2 Hz, 1 H), 3.25 (s, 3 H), 1.24 (m, 2 H), 0.55 (br s, 3
1
(
H). 13C NMR (CDCl
, 100 MHz): δ 157.1, 156.8, 141.7, 137.1,
3
1
136.6, 131.2, 128.6, 128.4, 128.1, 127.8, 127.5, 123.7, 77.4, 74.3,
73.9, 67.5, 56.5, 56.1, 54.8, 54.0, 53.4, 25.9, 25.6, 11.0, 10.8.
1
3
3
1
1
H). C NMR (CDCl
3
, 100 MHz): δ 197.2, 193.3, 170.2, 170.3,
25 3
HRMS (EI) calcd for C22H O N: 351.1834. Found: 351.1826.
54.8, 150.1, 149.3, 136.3, 135.8, 133.9, 129.3, 129.0, 128.8,
28.5, 128.3, 68.2, 61.4, 57.3, 49.1, 44.6, 43.7, 39.7, 39.0, 14.3.
(()-(2S*,3R*,6R*)-6-E t h yl-3-m et h oxy-2-p h en yl-3,6-d i-
h yd r o-2H-p yr id in e-1-ca r boxylic Acid Ben zyl Ester , 37.
In a similar fashion, molybdenum complex 27 (0.050 g, 0.070
HRMS (EI) calcd for C25
()-(2S*,6S*)-2-Ben zyl-5-m eth oxy-6-eth en yl-3,6-dih ydr o-
H-p yr id in e-1-ca r boxylic Acid Ben zyl Ester , 34. To a 25-
6
H25NO : 435.1682. Found: 435.1675.
(
2 2
mmol, 1.0 equiv) in 1 mL of dry CH Cl at 0 °C was treated
2
with nitrosonium tetrafluoroborate (0.025 g, 0.21 mmol, 3.0
equiv). Treatment with sodium cyanoborohydride (0.015 g, 0.25
mmol, 3.5 equiv) in 1 mL of THF followed by workup and
chromatography (25% ethyl acetate in hexanes) gave 37 as a
colorless oil (0.015 g, 0.044 mmol, 63%). TLC (silica gel, 25%
mL resealable Pyrex Schlenk tube were added molybdenum
complex 25 (0.060 g, 0.083 mmol, 1.0 equiv), 15 mL of dry
CH
equiv). The flask was placed in a UV reactor equipped with
50 nm lamps and irradiated for 24 h. The mixture was then
occluded onto silica and purified by medium-pressure chro-
matography (SiO , 10% ethyl acetate in hexanes) to give 34
as a colorless oil (0.019 g, 0.054 mmol, 65%). TLC (silica gel,
0% ethyl acetate in hexanes, R ) 0.46); IR (CDCl , KBr,
cm ): 3089 (w), 3068 (w), 3032 (w), 2957 (w), 2940 (w), 2907
2 2
Cl , and trifluoroacetic acid (0.0094 g, 0.083 mmol, 1.0
-
1
3
ethyl acetate in hexanes, R
f
) 0.50); IR (CH
2 2
Cl , KBr, cm ):
3032 (w), 2968 (w), 2932 (w), 2875 (w), 2819 (w), 1688 (sh, s).
H NMR ((CD ) SO, 400 MHz): δ 7.33 (m, 10 H), 6.20 (ddd, J
3 2
1
2
) 10.4, 5.6, 2.8 Hz, 1 H), 6.02 (dd, J ) 10.4, 3.6 Hz, 1 H), 5.69
(s, 1 H), 5.24 (A of AB quartet, J ) 12.8 Hz, 1 H), 5.19 (B of
1
f
3
-
1
AB quartet, J ) 12.8 Hz, 1 H), 4.28 (dd, J ) 5.4, 1.4 Hz, 1 H),
1
13
(
w), 2857 (w), 2839 (w), 1686 (sh, s). H NMR ((CD
3
)
2
SO, 400
4.27 (m, 1 H), 3.21 (s, 3 H), 0.89 (m, 2 H), 0.62 (s, 3 H).
C
MHz): δ 7.27 (m, 10 H), 5.88 (ddd, J ) 17.0, 10.3, 6.8 Hz, 1
NMR (CDCl
128.6, 128.5, 128.3, 128.1, 128.0, 127.6, 122.2, 72.5, 68.2, 67.6,
56.8, 54.9, 54.1, 53.3, 27.4, 11.4, 11.2. Anal. Calcd for C22
NO : C, 75.19; H, 7.17; N, 3.99; O, 13.66. Found: C, 74.92; H,
7.02; N, 4.06.
(()-(2S*,3R*,6R*)-6-Eth yl-3-m eth oxy-2-p h en yl-p ip er i-
d in e, 38. In a 25 mL round-bottomed flask, a solution of
compound 37 (0.062 g, 0.18 mmol, 1 equiv) in 10 mL of
anhydrous ethanol and 10% palladium on carbon (0.019 g,
0.017 mmol, 0.10 equiv) was purged with hydrogen gas for 10
min. The reaction mixture was then allowed to stir under 1
atm of hydrogen overnight. The solid catalyst was then
3
, 100 MHz): δ 140.6, 136.9, 133.2, 128.8, 128.7,
H), 5.19 (d, J ) 14.8 Hz, 1 H), 5.15 (d, J ) 8.8 Hz, 1 H), 5.12
(
2
s, 2 H), 4.81 (m, 2 H), 4.55 (q, J ) 7.2 Hz, 1 H), 3.21 (s, 3 H),
25
H -
.80 (m, 2 H), 2.22 (ddt, J ) 16.4, 6.8, 2.8 Hz, 1 H), 1.98 (dd,
3
1
3
3
J ) 17.8, 5.0 Hz, 1 H). C NMR (CDCl , 100 MHz, significant
broadening of some absorptions precluded an accurate signal
count): δ 155.6, 151.9, 139.6, 136.8, 136.1, 129.5, 129.0, 128.7,
1
4
3
28.6, 128.3, 128.2, 126.5, 118.3, 89.7, 67.5, 55.2, 54.7, 50.8,
0.7, 24.4. HRMS (EI) calcd for C23
63.1832.
3
H25NO : 363.1834. Found:
(
()-(2S*,6S*)-6-E t h oxyca r b on ylm et h yl-5-m et h oxy-2-
ph en yleth yn yl-3,6-dih ydr o-2H-pyr idin e-1-car boxylic Acid

Construction of Trisubstituted Piperidines
J . Org. Chem., Vol. 65, No. 22, 2000 7455
removed by filtration, and the solvent evaporated to give 38
as a colorless oil (0.033 g, 0.14 mmol, 85%). TLC (silica gel,
General Medical Sciences, DHHS. We are particularly
grateful for the assistance of Dr. Helena Malinakova in
proofreading and suggesting modifications to this manu-
script.
2
5% ethyl acetate in hexanes, R
f
3
) 0.48); IR (CDCl , KBr,
-
1
1
cm ): 3155 (sh, m), 2983 (w), 2934 (w), 2899 (w). H NMR
CDCl , 400 MHz): δ 7.35 (m, 5 H), 3.47 (d, J ) 8.8 Hz, 1 H),
(
3
3
.16 (ddd, J ) 10.4, 8.8, 4.4 Hz, 1 H), 3.02 (s, 3 H), 2.56 (app
ddd, J ) 17.1, 6.4, 2.4 Hz, 1 H), 2.27 (dq, J ) 10.4, 4.0 Hz, 1
H), 1.81 (dq, J ) 8.4, 3.2 Hz, 1 H), 1.75 (m, 4 H), 0.90 (t, J )
7
1
1
Su p p or tin g In for m a tion Ava ila ble: Photocopies of H
and 13C NMR spectra of compounds 3, 15, 16, 18, 32-38. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
3
.6 Hz, 3 H). C NMR (CDCl3, 100 MHz): δ 143.9, 129.2, 129.1,
28.4, 83.3, 68.7, 59.7, 58.3, 31.9, 31.7, 30.4, 11.7. HRMS (EI)
calcd for C14H21ON: 219.1623. Found: 219.1615.
Ack n ow led gm en t. This work was supported by
grant #GM43107, awarded by the National Institute of
J O0007128