(-)-8-Amino menthol-derived perhydrobenzoxazines as chiral templates and masked aldehydes in the diastereoselective intermolecular Pauson-Khand reaction

Article abstract of DOI:10.1016/j.tet.2012.08.006

Perhydro-1,3-benzoxazines derived from (-)-8-amino menthol behave as masked aldehydes and chiral templates in diastereoselective intramolecular Pauson-Khand reactions with norbornene and norbornadiene. The regioselectivity is excellent for unsubstituted o

Full text of DOI:10.1016/j.tet.2012.08.006

Tetrahedron 68 (2012) 9293e9300
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
(ꢀ)-8-Amino menthol-derived perhydrobenzoxazines as chiral templates and
masked aldehydes in the diastereoselective intermolecular PausoneKhand
reaction
*
ꢀ
ꢀ
Alicia Maestro, Rafael Pedrosa , Alfonso Perez-Encabo, Juan J. Perez-Rueda
ꢀ
Instituto CINQUIMA and Departamento de Química Organica, Facultad de Ciencias, Universidad de Valladolid, Dr. Mergelina s/n, 47011-Valladolid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 April 2012
Received in revised form 26 July 2012
Accepted 2 August 2012
Available online 5 September 2012
Perhydro-1,3-benzoxazines derived from (ꢀ)-8-amino menthol behave as masked aldehydes and chiral
templates in diastereoselective intramolecular PausoneKhand reactions with norbornene and norbor-
nadiene. The regioselectivity is excellent for unsubstituted or methyl-substituted acetylenes and mod-
erate with phenyl-substituted alkynes. The stereoselection is very poor or moderate depending also on
the substitution pattern of both the triple bond and the perhydrobenzoxazine nucleus. The hydrolysis of
the cycloadducts leads to 2- or 3-formylecyclopentenone derivatives.
Keywords:
Cyclopentenones
Ó 2012 Elsevier Ltd. All rights reserved.
Cobalt
Diastereoselective cyclization
Enantioselective synthesis
PausoneKhand reaction
1. Introduction
Chiral perhydrobenzoxazines, derived from (ꢀ)-8-amino men-
thol, are protected aldehydes as N,O-ketals, and more than a decade
PausoneKhand reaction (PKR) is a powerful reaction in terms of
molecular complexity and atom economy leading to 2-
cyclopentenone derivatives.1 The complexity of the resulting
cyclopentenone is dependent on the substituents of the alkene and
alkyne components of the reaction, and efforts to improve the
scope of the reaction have been done by using both functionalized
alkynes2 and alkenes3 with electron-donating and withdrawing
substituents. Interestingly, only few examples on the use of un-
saturated ketones have been reported,4 and no antecedents exist on
the use of formyl substituent, probably because it has been dem-
onstrated that aldehydes serve as a carbon monoxide source in
PausoneKhand-like reactions5 or as the alkene and CO components
of the process.6 On the contrary, ketals have been used as carbonyl
protecting groups in some interesting intramolecular PK reactions.7
A different and fundamental topic under development is related
with the stereoselectivity in the intermolecular PKR in order to
prepare enantioenriched cyclopentenone derivatives. In that way,
different approaches have been tested,1 but one of the most ex-
tended is based on the use of a chiral auxiliary attached to the
olefinic3 or acetylenic2g,8 component of the reaction.
ago we had demonstrated their ability to promote inter-9 and
intramolecular10 diastereoselective transformations. Now we con-
sider that these structures could act as chiral inductors in in-
termolecular PK reactions giving, after hydrolytic work up, formyl
cyclopentenone derivatives.11 To test that hypothesis, we have pre-
pared prehydro-1,3-benzoxazines 1aed by condensation of (ꢀ)-8-
amino menthol12 with propargylic aldehydes, and studied their re-
activity with norbornene (2) and norbornadiene (20) (Scheme 1).
Scheme 1. PausoneKhand reaction of perhydrobenzoxazines 1aed with norbornene
and norbornadiene.
* Corresponding author. Fax: þ34 983186324; e-mail address: pedrosa@qo.uva.es
(R. Pedrosa).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.006

9294
A. Maestro et al. / Tetrahedron 68 (2012) 9293e9300
Unsubstituted perhydrobenzoxazine 1a was used for reaction
7a. The hydrolysis into the final 2-formyl 2-cyclopentenone de-
rivatives allowed the assignation of the configuration for 5b and 50b
as S at C-3a and R at C-7a, and R at C-3a and S at C-7a for 6b and 60b.
Because the presence of a substituent at the nitrogen atom in the
perhydrobenzoxazine could improve the diastereoselection by
shielding one of the stereogenic cobalt atoms in the complex, we
prepared N-benzyl-substituted perhydrobenzoxazines 1c and 1d by
reaction of 1b or 2-ethynyl perhydrobenzoxazine with benzyl bro-
mide, respectively. The alkylation yielded the final perhydrobenzox-
azines asequimolarmixturesofepimers atC-2 intheheterocycle, and
these mixtures were used as starting materials without purification.
The PK reaction of 1c with 2 yielded a single regioisomer as
a mixture (79/21) of exo-diastereoisomers 5c and 6c, whereas the
reaction of 1c with norbornadiene (20) led to diastereoisomers 50c
and 60c in a ratio 60/40 (entries 6, 7 in Table 1). In the same way,
perhydrobenzoxazine 1d gave cyclopentenone derivatives 5d and 6d
when reacted with norbornene and a mixture of 50d and 60d by re-
action with norbornadiene in good yield, but very modest diaster-
optimization. First, the catalytic version of the PKR was tested by
heating at 60 ꢁC mixtures of 1a and 2 (10 equiv) with 5 mol % or
10 mol % of dicobalt octacarbonyl in DME and 20 mol % of cyclohexyl
amine under CO (1 atm) for 8 h. In both cases the yields of the cycli-
zation products were disappointly low (12% and 10%, respectively).
The yields improved to 33% when 1a was stirred, under nitrogen, with
5 equivof 2 in the presenceof 1.1 equivof Co2(CO)8 in DCM and 6 equiv
of TMANO,13 or to 50% in the same reaction conditions but using
10 equiv of 2. Inall these reactions importantamounts (10e30%)of the
semi-reduction of the triple bond of 1a were obtained.
A great improvement in the yields was observed when the re-
actions were carried out in air in the presence of 8 wt. equiv of
14
ꢁ
3 A mol sieves. These conditions were chosen as standard for all
the reactions, and the results are summarized in Table 1.
Table 1
0
ꢁ
PKR of perhydrobenzoxazines 1aed with 2 and 2 in DCM in the presence of 3 A mol.
sieves and TMANO
eoselection (entries 8,
9 in Table 1). Interestingly, all the
Entry Reagents Time (h) Temp (ꢁC) Yielda Products (ratio)
diastereoisomers have the S configuration at the N,O-acetal carbon in
the heterocycle, indicating that previous to the PKR, the complex
formed between the cobalt octacarbonyl and the perhydrobenzox-
azines 1c and 1d isomerized in a Nicholas-like transformation.
That fact can be explained by accepting that the transformation
of 1ced into the final PK adducts occurs by a tandem intra-
molecular Nicholas and PK reaction.17 The coordination of the
Co2(CO)8 to compounds 1ced leads to cobalt complexes derived
from a propargylic alcohol, which evolve to cobalt carbonyl stabi-
lized propargylic cations. That complexes can be intramolecularly
captured to the most stable intermediate (7) with configuration S at
C-2 in a Nicholas-like transformation.18 The subsequent PK re-
actions on the complexes 7 give the cyclization adducts 5ced and
6ced or 50ced and 60ced, respectively (Schemes 2 and 3).
All these diastereoisomers were separated by flash chromatog-
raphy, and the XR-diffraction analysis showed a configuration 3a-S,
7a-R for diastereoisomer 5c,16 and consequently 3a-R, 7a-S for 6c.
The stereochemistry for the other diastereoisomers (5d, 50ced, 6d,
and 60ced) was assigned by analogy.
Once isolated, the major diastereoisomers resulting from the
reaction of 1aec with norbornene 2 or norbornadiene 20 were
transformed into the 2- or 3-formyl cyclopentenone derivatives as
summarized in Scheme 2. The reaction was best performed by
treatment of the cycloadducts with a 2% solution of HCl in etha-
nolewater, giving the formyl cyclopentenones in good yields. The
hydrolytic cleavage also allowed the recovery of the (ꢀ)-8-amino
1
2
3
4
5
6
7
8
9
1a/2
1a/2
1a/20
1b/2
1b/20
1c/2
1c/20
1d/2
1d/20
3
8
3
3
3
3
3
3
3
25
0
90
83
86
70
80
78
65
88
75
3a(61) 4a(7) 5aþ6a(32)
3a(62) 4a(7) 5aþ6a(31)
30a(52) 40a(8) 50aþ60a(40)
5b(50) 6b(50)
25
25
25
25
25
25
25
50b(50) 60b(50)
5c(79) 6c(21)
50c(60) 60c(40)
5d(58) 6d(42)
50d(52) 60d(48)
a
Yields refer to pure and isolated compounds.
The reaction of the phenylpropargyl aldehyde-derived perhy-
drobenzoxazine (1a) with norbornene (2) at 25 ꢁC led to a mixture
of four isomeric tricyclic cyclopentenones in 90%. When the re-
action was carried out at 0 ꢁC similar results were obtained, al-
though at the expense of increased the reaction time (8 h, entry 2 in
Table 1). Excellent yields were also obtained in the reaction of 1a
with norbornadiene (20) (entry 3). The multiplicity and coupling
constants15 for protons at C-3a and C-7a indicate that all the
compounds are exo adducts. Otherwise, the four compounds are
grouped as two couples of regioisomers (3a/4a or 30a/40a vs 5a/6a
or 50a/60a), whereas the members of each couple (3a and 4a; 30a
and 40a; 5a and 6a; 50a and 60a) are diastereoisomers (pseudo-
enantiomers), which differ at the stereochemistry of the two cre-
ated stereogenic carbons (C-3a and C-7a).
To our delight, it was possible to determine the absolute ste-
reochemistry for the major compound 30a by XR-diffraction anal-
ysis16 as S at C-3a, and R at C-7a, and consequently to assign
configurations R at C-3a, and S at C-7a for diastereoisomer 40a for
the nature of the hydrolysis products (vide infra). Unfortunately, it
was not possible to establish the stereochemistry for the exo
regioisomers 5ae6a, and 50ae60a, but from the integrals of the 1H
NMR signals of their mixtures it was possible to determine 30% and
25% diastereomeric excesses, respectively.
It is interesting to note that, although the diastereoselection of
the reaction is good (90:10 dr for 3a/4a, and 87/13 for 30a/40a) the
regioselectivity is moderate (68/32 for the reaction of 1a with 2,
and 60/40 for the reaction with 20). It is noteworthy that the phenyl
group behaves as a bulkier group than the perhydrobenzoxazine
substituent because
were obtained as the major regioisomers. Looking to improve the
regioselectivity, the perhydrobenzoxazine 1b, with smaller
a-phenyl-substituted cyclopentenones 3 and 4
a
methyl substituent at the acetylenic terminus, was reacted with
norbornene (2) and norbonadiene (20) (entries 4 and 5 in Table 1).
As expected, only one regioisomer with the bulkiest perhy-
drobenzoxazine
a to the carbonyl group was obtained in those
Scheme 2. Isomerization and PK reaction of compounds 1ced.
reactions, but as an equimolar mixture of epimers at C-3a- and C-

A. Maestro et al. / Tetrahedron 68 (2012) 9293e9300
9295
it gave the same keto aldehyde (8) as compound 5c, whose ste-
reochemistry has been elucidated by XR-diffraction analysis. The
diastereomeric relationship between 6bec and 5bec was estab-
lished because they lead to enantiomeric 2-formyl cyclopentenones
8 and ent-8, respectively. Additionally, to test that the ester-
eochemical integrity of the products is maintained along the
elimination process of the chiral template, the enantiomeric purity
of the final products was determined for 7a by chiral HPLC.19
It is well documented that the regiochemistry of the PK reaction
is dependent on both the size of the substituents on the triple bond
and on their electronic nature. In general, the less sterically de-
manding substituent on the acetylenic bond is found
b to the car-
bonyl group in the formed cyclopentenone,20 but substituted
propiolates always lead to 3-alcoxycarbonyl cyclopentenones as
single or major regioisomer,8g,15a,21 as a consequence of polariza-
tion effects of the acetylenic carbons.22
In our case, contrary to that described for propiolates and in
agreement with the behavior of propargyl alcohols, the reaction of
unsubstituted (1d) or methyl-substituted (1b and 1c) perhy-
drobenzoxazines was completely regioselective leading to the
masked 1,3-dicarbonyl compounds. The PK reaction of 3-phenyl-
substituted perhydrobenzoxazine 1a was less regioselective, yield-
ing the 1,4-dicarbonyl derivatives as major reigioisomers, probably
because the perhydrobenzoxazine moiety is not able to polarize the
triple bond, and the regiochemistry is only dictated by steric effects.
A lot of experimental and theoretical23 studies have been done
to explain the stereochemistry associated to the PK reaction. The
chiral discrimination of the reaction can be explained assuming
that, after the formation of the hexacarbonyl dicobalt complex, the
olefin coordinates to the most accessible diastereotopic cobalt
atom. It is also generally accepted that the coordination of the
norbornene or norbornadiene occurs only from the exo face, and
that the most stable conformation is that where the methylene
bridge points away from the alkyne substituent. Taking into ac-
count these assumptions, the observed stereoselection in our case
could be explained as a consequence of the coordination of the
olefin to the cobalt atom in the side of the nitrogen (CoN) or to the
cobalt at the side of the oxygen atom (CoO) in the adduct 9 (Fig. 1),
Scheme 3. Hydrolysis of the adducts to 2- or 3-formyl-cyclopentenones.
menthol used as chiral auxiliary and masked aldehyde functional-
ity. That transformation also served to assign the stereochemistry
of the cycloadducts formed in the PKR. In fact, the enantiomeric
relationship between the ketoaldehydes (7a, 70a, and ent-7a, ent-
70a) obtained from 3a, 30a, and 4a, 40a indicates that those cyclo-
adduts are diastereoisomers, which differ at the configuration of
the stereocenters created in the PKR (C-3a, and C-7a).
The stereochemistry of compound 5b was also determined because
Fig. 1. Schematic representation for the formation of the regio- and diastereoisomers isolated in this work.

9296
A. Maestro et al. / Tetrahedron 68 (2012) 9293e9300
and it is dependent on the substitution pattern of the nitrogen
atom.
potassium carbonate (24 mmol), benzyl bromide (12 mmol), and
the corresponding perhydrobenzoxazine (10 mmol) in acetonitrile
(15 mL) was placed in a 25 mL flask and stirred at rt until the dis-
appearance of the perhydrobenzoxazine (TLC). The mixture was
filtrated and the solids were washed three times with EtOAc. The
solvents were eliminated under reduced pressure and the crude of
the reactions purified by flash chromatography the benzylated
perhydrobenzoxazines 1c (72%) and 1d (68%) as equimolar mix-
tures of epimers at C-2.
In fact, compounds 1c and 1d, with a bulky benzyl substituent at
the nitrogen atom lead to 5c and 50c or 5d and 50d as major di-
astereoisomers because the coordination of the olefins occurs by
the less hindered cobalt atom in the side of the oxygen (CoO). On
the contrary, the formation of 3a or 30a as major diastereoisomers
from perhydrobenzoxazine 1a, with a bulk substituent at the triple
bond (R1¼Ph) and small at the nitrogen atom (R2¼H) can be
explained by the preferred coordination of the olefin to the cobalt
atom at the nitrogen face of the complex (CoN). Perhydrobenzox-
azine 1b with an smaller substituent at the acetylenic bond
(R1¼Me) yielded and equimolar mixture of diastereoisomers. On
the other hand, compounds 1a and 1b are propargyl secondary
amines and could establish a hydrogen bond between the NH and
the CO substituent of the diastereotopic CoN in 9, helping to create
a coordination vacant, and facilitating the coordination of the olefin
to that cobalt atom.23c
In summary, perhydrobenzoxazines derived from (ꢀ)-8-amino
menthol behave as chiral inductors and masked propargyl alde-
hydes in diastereoselective intermolecular PKR with norbornene
and norbornadiene. Only the exo-cycloadducts were formed in high
yields and mild conditions, but the diastereoselection varies from
negligible to moderate (9:1) depending on the substitution pattern
of the triple bond and the nitrogen atom in the heterocycle. The
regioselectivity is also dependent on the nature of the substituents
at the acetylenic bond. The unsubstituted or methyl-substituted
2.2.1. Equimolar mixture of (2R,4aS,7R,8aR)- and (2S,4aS,7R,8aR)-N-
benzyl-2-(10-propinyl)-4,4,7-trimethyloctahydrobenz[e][1,3] oxazine
(1c). Yellowish oil. 1H NMR (300 MHz, CDCl3)
d: 0.89e1.19 (m, 5H);
0.97 (d, 3H, J¼6.6 Hz); 0.98 (d, 6H, J¼6.6 Hz); 1.23 (s, 3H); 1.26 (s,
6H); 1.29e1.63 (m, 6H); 1.69 (d, 3H, J¼1.7 Hz); 1.73e1.77 (m, 3H);
1.93 (d, 3H, J¼2.0 Hz); 1.96e2.01 (m, 2H); 3.54 (d, 1H, J¼14.4 Hz);
3.58 (dt, 1H, J1¼4.0 Hz, J2¼10.6 Hz); 3.87e3.95 (m, 2H); 4.08 (d, 1H,
J¼14.4 Hz); 4.55 (d, 1H, J¼17.0 Hz); 4.85 (d, 1H, J¼2.0 Hz); 5.56 (d,
1H, J¼1.7 Hz); 7.17e7.46 (m, 10H). 13C NMR (75 MHz, CDCl3)
d: 3.6
(CH3); 3.7 (CH3); 16.4 (CH3); 21.2 (CH3); 22.2 (CH3); 22.3 (CH3); 24.9
(CH2); 25.1 (CH2); 27.4 (CH3); 27.9 (CH3); 31.2 (CH); 31.4 (CH); 34.8
(CH2); 35.0 (CH2); 41.1 (CH2); 41.3 (CH2); 44.9 (CH); 48.2 (CH2); 48.6
(CH2); 49.9 (CH); 55.7 (C); 56.9 (C); 70.0 (CH); 76.3 (CH); 76.5 (CH);
76.8 (C^); 76.9 (C^); 79.6 (CH); 82.1 (C^); 83.3 (C^); 125.7
(CH]); 126.8 (CH]); 127.1 (2CH]); 127.8 (2CH]); 128.2 (2CH]);
128.3 (2CH]); 139.6 (C]); 144.4 (C]).
derivatives lead to
a
single regioisomer, but the phenyl-
2.2.2. Equimolar mixture of (2R,4aS,7R,8aR)- and (2S,4aS,7R,8aR)-N-
substituted derivative give a mixture (ca. 2:1) of regioisomeric
cycloadducts.
benzyl-2-(ethynyl)-4,4,7-trimethyloctahydrobenz[e][1,3]
oxazine
(1d). Yellowish oil. 1H NMR (300 MHz, CDCl3)
d: 0.90e1.21 (m, 5H);
Pure diastereoisomers can be obtained by flash chromatogra-
phy, and subjected to hydrolysis leading to enantioenriched 2- or 3-
formyl-cyclopentenone derivatives.
0.97 (d, 3H, J¼6.5 Hz); 0.98 (d, 3H, J¼6.5 Hz); 1.24 (s, 6H); 1.28 (s,
6H); 1.31e1.67 (m, 6H); 1.74e1.78 (m, 3H); 1.95e2.02 (m, 2H); 2.42
(d, 1H, J¼1.5 Hz); 2.56 (d, 1H, J¼1.5 Hz); 3.55 (d, 1H, J¼14.4 Hz); 3.60
(dt, 1H, J1¼4.0 Hz, J2¼10.5 Hz); 3.92 (dt, 1H, J1¼4.2 Hz, J2¼10.6 Hz);
3.97 (d, 1H, J¼17.2 Hz); 4.14 (d, 1H, J¼14.4 Hz); 4.57 (d, 1H,
J¼17.2 Hz); 4.88 (d, 1H, J¼2.1 Hz); 5.62 (d, 1H, J¼1.5 Hz); 7.18e7.46
2. Experimental
2.1. General
(m, 10H). 13C NMR (75 MHz, CDCl3)
d: 16.3 (CH3); 21.3 (CH3); 22.2
(CH3); 22.3 (CH3); 24.8 (CH2); 25.0 (CH2); 27.1 (CH3); 27.9 (CH3);
31.2 (CH); 31.4 (CH); 34.7 (CH2); 35.0 (CH2); 41.0 (CH2); 41.2 (CH2);
44.8 (CH); 48.2 (CH2); 48.7 (CH2); 49.8 (CH); 55.9 (C); 57.0 (C); 69.8
(CH); 70.4 (CH); 73.6 (CH^); 75.5 (CH^); 76.2 (CH); 79.3 (CH); 80.6
(C^); 81.6 (C^); 125.9 (CH]); 126.9 (CH]); 127.0 (2CH]); 127.9
(2CH]); 128.3 (2CH]); 128.4 (CH]); 128.5 (CH]); 139.2 (C]);
143.9 (C]).
1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were
recorded on a Bruker ACe300 spectrometer in CDCl3. Chemical
shifts for protons are reported in parts per million from tetrame-
thylsilane with the residual CHCl3 resonance as internal reference.
Chemical shifts for carbons are reported in ppm from tetrame-
thylsilane and are referenced to the carbon resonance of the sol-
vent. Specific rotations were measured on a PerkineElmer digital
polarimeter using a 5-mL cell with a 1-dm path length, and a so-
dium lamp, and concentration is given in gram per 100 mL. Infrared
spectra were recorded on a PerkineElmer FTeIR spectrometer and
are reported in frequency of absorption. Melting points were ob-
tained with open capillary tubes and are uncorrected. Flash chro-
matography was carried out using silica gel (230e240 mesh). TLC
analysis was performed on glass-backed plates coated with silica
gel 60 and an F254 indicator, and visualized by either UV irradiation
or by staining with phosphomolybdic acid solution. Solvents were
2.3. PausoneKhand reaction. General procedure
A 25 ml flask was charged with 1.0 mmol of perhydrobenzox-
ꢁ
azine in 10 ml of dry DCM, eightfold (in weight) of 3 A mol sieves
and 1.1 mmol of Co2(CO)8 under argon atmosphere and the mixture
was stirred for 2 h at rt. Then, the flask was opened to the atmo-
sphere, 10.4 mmol of TMANO were added, and the stirring was
continued at rt until the reaction was finished (TLC). The reaction
mixture was filtered, the solids were washed 2e3 times with DCM
and the solvent was evaporated under vacuum. The residues were
purified by flash chromatography and mixtures of EtOAc/hexanes.
ꢁ
dried and stored over microwave-activated 4A molecular sieves.
Compounds 1a, and 1b have been previously described.24
2.2. Synthesis of perhydrobenzoxazines 1c and 1d. General
procedure
2.3.1. Adduct (3a). White solid. Mp 205e207 ꢁC (from hexane).
25
[a
]
¼ꢀ33.64 (CHCl3, c¼1.10). 1H NMR (300 MHz, CDCl3)
d:
D
0.84e1.00 (m, 2H); 0.92 (d, 3H, J¼6.5 Hz); 1.02e1.14 (m, 2H); 1.08 (s,
3H); 1.09 (s, 3H); 1.22e1.47 (m, 5H); 1.55e1.80 (m, 4H); 1.86 (m,
1H); 2.00 (m,1H); 2,31 (d,1H, J¼5.4 Hz); 2.49e2.52 (m, 2H); 2.99 (d,
1H, J¼5.4 Hz); 3.39 (dt, 1H, J1¼4.2 Hz, J2¼10.4 Hz); 5.24 (s, 1H);
A mixture of (ꢀ)-8-amino menthol12 (2.61 g, 10 mmol) and the
corresponding aldehyde (15 mmol), in toluene (50 ml) was refluxed
under nitrogen until the reaction was completed (TLC). The mixture
was filtered through a pad of Celite, and the Celite washed with
toluene. The solvent was evaporated, and the residue was subjected
7.29e7.40 (m, 3H); 7.53e7.57 (m, 2H). 13C NMR (75 MHz, CDCl3)
d:
18.9 (CH3); 22.2 (CH3); 25.4 (CH2); 28.5 (CH2); 29.4 (CH2); 30.1
(CH3); 31.3 (CH); 31.4 (CH2); 34.9 (CH2); 38.9 (CH); 39.6 (CH); 41.5
to N-benzylation without further purification.
A mixture of

A. Maestro et al. / Tetrahedron 68 (2012) 9293e9300
9297
(CH2); 48.0 (CH); 51.7 (CH); 52.0 (C); 53.8 (CH); 75.0 (CH); 81.3
(CH); 127.7 (2CH]); 128.0 (CH]); 129.6 (2CH]); 131.1 (C]); 143.7
(C]); 169.5 (C]); 209.6 (C]O). IR (Nujol dispersion): 3372; 2949;
1697. HRMS for C27H35NO2: calcd 405.2668, found 406.2734
(MþþH).
J¼5.2 Hz); 3.02 (s, 1H); 3.28 (s, 1H); 3.42 (dt, 1H, J1¼4.1 Hz,
J2¼10.4 Hz); 5.30 (s, 1H); 6.24 (dd, 1H, J1¼3.0 Hz, J2¼5.6 Hz); 6.36
(dd, 1H, J1¼3.0 Hz, J2¼5.6 Hz); 7.32e7.56 (m, 5H). 13C NMR (CDCl3)
d: 19.1 (CH3); 22.3 (CH3); 25.4 (CH2); 29.9 (CH3); 31.3 (CH); 34.9
(CH2); 41.6 (2CH2); 43.9 (CH); 44.1 (CH); 46.5 (CH); 51.9 (CH); 52.0
(C); 52.7 (CH); 75.0 (CH); 80.2 (CH); 128.0 (2CH]); 128.1 (CH]);
129.2 (2CH]); 130.8 (C]); 137.4 (CH]); 138.8 (CH]); 144.7 (C]);
167.8 (C]); 208.2 (C]O). IR (film): 3304; 3059: 2927; 1702. HRMS
for C27H33NO2: calcd 403.2511, found 404.2585 (MþþH).
25
2.3.2. Adduct (4a). Yellowish oil. [
NMR (CDCl3)
a
]
D
¼þ11.62 (CHCl3, c¼0.74). 1H
d
: 0.88e1.10 (m, 3H); 0.94 (d, 3H, J¼6.5 Hz); 1.03 (s,
3H); 1.10 (s, 3H); 1.13e1.48 (m, 6H); 1.55e1.68 (m, 4H); 1.95 (m,1H);
2.10 (m, 1H); 2.32 (d, 1H, J¼5.2 Hz); 2.50 (d, 1H, J¼3.1 Hz);
2.78e2.80 (m, 2H); 3.42 (dt, 1H, J1¼4.1Hz, J2¼10.4 Hz); 5.28 (s, 1H);
2.3.7. Adduct (50a) or adduct (60a). White solid. Mp 82e84 ꢁC (from
25
7.31e7.43 (m, 5H). 13C NMR (CDCl3)
d: 19.1 (CH3); 22.3 (CH3); 25.4
hexane).
[
a
]
D
¼þ221.66 (CHCl3, c¼0.90). 1H NMR (CDCl3)
d:
(CH2); 28.5 (CH2); 29.3 (CH2); 29.9 (CH3); 31.3 (CH); 31.5 (CH2); 34.9
(CH2); 38.6 (CH); 39.4 (CH); 41.6 (CH2); 47.3 (CH); 51.8 (C); 51.9
(CH); 53.9 (CH); 75.0 (CH); 80.2 (CH); 127.9 (2CH]); 128.0 (CH]);
129.3 (2CH]); 131.0 (C]); 144.0 (C]); 167.9 (C]); 209.5 (C]O).
IR (film): 3304; 3044; 2950; 1702; 1691. HRMS for C27H35NO2: calcd
405.2668, found 406.2726 (MþþH).
0.80e1.02 (m, 2H); 0.88 (d, 3H, J¼6.5 Hz); 1.06 (s, 3H); 1.08 (s, 3H);
1.11e1.26 (m, 2H); 1.28e1.42 (m, 3H); 1.60e1.66 (m, 2H); 1.82 (m,
1H); 2.46 (s, 1H); 2.48 (d, 1H, J¼5.4 Hz); 2.54 (broad s, 1H); 3.01 (s,
1H); 3.16 (d, 1H, J¼5.4 Hz); 3.34 (dt, 1H, J1¼4.1 Hz, J2¼10.5 Hz); 5.27
(s, 1H); 6.21e6.26 (m, 2H); 7.45e7.48 (m, 3H); 7.50e7.54 (m, 2H).
13C NMR (CDCl3)
d: 18.7 (CH3); 22.2 (CH3); 25.4 (CH2); 29.6 (CH3);
31.3 (CH); 34.8 (CH2); 41.4 (CH2); 41.9 (CH2); 42.9 (CH); 43.8 (CH);
50.9 (CH); 51.2 (CH); 51.4 (C); 53.0 (CH); 75.2 (CH); 78.2 (CH); 128.0
(2CH]); 128.4 (2CH]); 129.7 (CH]); 134.9 (C]); 137.7 (CH]);
138.2 (CH]); 141.5 (C]); 172.3 (C]); 207.8 (C]O). IR (KBr dis-
persion): 3312; 3050; 2953; 1694; 1633.
25
2.3.3. Adduct (5a) or adduct (6a). Yellowish oil. [
a
]
¼þ261.23
D
(CHCl3, c¼1.46). 1H NMR (CDCl3)
d: 0.85e1.01 (m, 3H); 0.87 (d, 3H,
J¼6.5 Hz); 1.05 (s, 3H); 1.08 (s, 3H); 1.13e1.21 (m, 3H); 1.26e1.36
(m, 3H); 1.57e1.65 (m, 4H); 1.82 (m, 1H); 1.96 (s, 1H); 2.35 (d,
1H,J¼5.4 Hz); 2.49 (s, 1H); 2.82 (s, 1H); 3.00 (d, 1H, J¼5.4 Hz); 3.34
(dt, 1H, J1¼4.1 Hz, J2¼10.4 Hz); 5.29 (s, 1H); 7.43e7.46 (m, 3H);
2.3.8. Adduct (60a) or adduct (50a). Yellowish solid. Mp 90e92 ꢁC
25
7.50e7.53 (m, 2H). 13C NMR (CDCl3)
d
: 18.8 (CH3); 22.2 (CH3); 25.5
(from hexane). [
a]
¼ꢀ399.76 (CHCl3, c¼1.26). 1H NMR (CDCl3)
d:
D
(CH2); 28.6 (CH2); 29.0 (CH2); 29.6 (CH3); 31.3 (CH); 31.6 (CH2); 34.8
(CH2); 37.9 (CH); 39.1 (CH); 41.4 (CH2); 50.9 (CH); 51.3 (C); 51.5
(CH); 54.2 (CH); 75.1 (CH); 78.0 (CH); 128.1 (2CH]); 128.4 (2CH]);
129.6 (CH]); 135.1 (C]); 140.3 (C]); 172.1 (C]); 209.0 (C]O). IR
(film): 3308; 3055; 2952; 1690; 1631. HRMS for C27H35NO2: calcd
405.2668, found 406.2732 (MþþH).
0.82e1.06 (m, 2H); 0.91 (s, 3H); 0.92 (d, 3H, J¼6.4 Hz); 1.09 (s, 3H);
1.13e1.26 (m, 2H); 1.30e1.44 (m, 2H); 1.48 (m, 1H); 1.66 (m, 2H);
1.94 (m, 1H); 2.39 (d, 1H, J¼1.1 Hz); 2.42 (d, 1H, J¼5.3 Hz); 2.98 (d,
1H, J¼1.1 Hz); 3.17 (d, 1H, J¼5.3 Hz); 3.45 (dt, 1H, J1¼4.1 Hz,
J2¼10.4 Hz); 3.50 (broad s, 1H); 5.01 (s, 1H); 6.19e6.24 (m, 2H);
7.43e7.47 (m, 3H); 7.49e7.55 (m, 2H). 13C NMR (CDCl3)
d: 18.8
(CH3); 22.3 (CH3); 25.5 (CH2); 29.7 (CH3); 31.4 (CH); 34.9 (CH2); 41.5
(CH2); 41.9 (CH2); 42.9 (CH); 43.8 (CH); 50.3 (CH); 50.8 (CH); 51.0
(C); 53.1 (CH); 74.8 (CH); 78.9 (CH); 127.9 (2CH]); 128.6 (2CH]);
130.0 (CH]); 134.5 (C]); 137.7 (CH]); 138.1 (CH]); 139.8 (C]);
173.8 (C]); 208.7 (C]O). IR (film): 3315; 3048; 2955; 1691; 1630.
25
2.3.4. Adduct (6a) or adduct (5a). Yellowish oil. [
a]
¼ꢀ476.79
D
(CHCl3, c¼1.40). 1H NMR (CDCl3)
d: 0.87e1.04 (m, 3H); 0.91 (s, 3H);
0.92 (d, 3H, J¼7.3 Hz); 1.09 (s, 3H); 1.13e1.39 (m, 5H); 1.48e1.66 (m,
5H); 1.91e1.96 (m, 2H); 2.31 (d, 1H, J¼5.3 Hz); 2.47 (s, 1H); 3.02 (d,
1H, J¼5.3 Hz); 3.45 (dt, 1H, J1¼4.2 Hz, J2¼10.4 Hz); 3.70 (broad s,
1H); 5.02 (s, 1H); 7.43e7.48 (m, 3H); 7.51e7.54 (m, 2H). 13C NMR
25
2.3.9. Adduct (5b). Yellowish oil. [
NMR (CDCl3)
a
]
D
¼ꢀ79.12 (CHCl3, c¼1.36). 1H
(CDCl3)
d
: 18.8 (CH3); 22.2 (CH3); 25.5 (CH2); 28.7 (CH2); 28.8 (CH2);
d
: 0.86e0.97 (m, 3H); 0.90 (d, 3H, J¼6.5 Hz); 1.00e1.20
29.7 (CH3); 31.4 (CH); 31.5 (CH2); 34.9 (CH2); 37.9 (CH); 39.1 (CH);
41.5 (CH2); 50.7 (CH); 50.8 (C); 51.0 (CH); 54.3 (CH); 74.8 (CH); 78.8
(CH); 128.0 (2CH]); 128.5 (2CH]); 129.9 (CH]); 134.7 (C]);
138.7 (C]); 173.7 (C]); 210.0 (C]O). IR (film): 3310; 3051; 2953;
1686; 1626. HRMS for C27H35NO2: calcd 405.2668, found 406.2734
(MþþH).
(m, 2H); 1.12 (s, 6H); 1.21e1.33 (m, 3H); 1.51 (m, 1H); 1.58 (m, 1H);
1.64e1.73 (m, 3H); 1.86 (m, 1H); 2.13 (d, 1H, J¼3.6 Hz); 2.14 (s, 3H);
2.27 (d, 1H, J¼4.1 Hz); 2.41e2.43 (m, 2H); 3.01 (broad s, 1H); 3.46
(dt, 1H, J1¼4.2 Hz, J2¼10.4 Hz); 5.19 (s, 1H). 13C NMR (CDCl3)
d: 16.0
(CH3); 18.9 (CH3); 22.2 (CH3); 25.4 (CH2); 28.5 (CH2); 29.1 (CH2);
29.7 (CH3); 31.3 (CH); 31.4 (CH2); 34.9 (CH2); 37.3 (CH); 38.7 (CH);
41.4 (CH2); 51.0 (C); 51.1 (CH); 52.7 (CH); 53.8 (CH); 75.3 (CH); 77.8
(CH); 140.2 (C]); 174.7 (C]); 209.4 (C]O). IR (film): 3296; 2956;
1690; 1646. HRMS for C22H33NO2: calcd 343.2511, found 344.2587
(MþþH).
2.3.5. Adduct (30a). White solid. Mp 224e225 ꢁC (from hexane).
25
[
a]
¼ꢀ20.32 (CHCl3, c¼0.62). 1H NMR (CDCl3)
d: 0.86e0.98 (m,
D
2H); 0.92 (d, 3H, J¼6.5 Hz); 1.00e1.17 (m, 2H); 1.08 (s, 3H); 1.10 (s,
3H); 1.42e1.50 (m, 3H); 1.65e1.73 (m, 3H); 1.86 (m,1H); 2.44 (d,1H,
J¼5.4 Hz); 3.01 (s, 1H); 3.02 (s, 1H); 3.11 (d, 1H, J¼5.4 Hz); 3.41 (dt,
1H, J1¼4.1 Hz, J2¼10.4 Hz); 5.25 (s, 1H); 6.26 (dd, 1H, J1¼3.3 Hz,
J2¼5.5 Hz); 6.37 (dd, 1H, J1¼3.3 Hz, J2¼5.5 Hz); 7.30e7.41 (m, 3H);
25
2.3.10. Adduct (6b). Yellowish oil. [
a
]
¼þ31.29 (CHCl3, c¼1.40). 1H
D
NMR (CDCl3)
d
: 0.86 (d, 3H, J¼6.5 Hz); 0.90e1.04 (m, 5H); 1.07 (s,
6H); 1.10e1.29 (m, 3H); 1.46 (m, 1H); 1.55 (m, 1H); 1.60e1.84 (m,
3H); 2.01 (m, 1H); 2.08 (s, 3H); 2.09 (d, 1H, J¼5.3 Hz); 2.21 (d, 1H,
J¼3.6 Hz); 2.35 (d, 1H, J¼3.6 Hz); 3.39 (d, 1H, J¼5.3 Hz); 3.05 (broad
s, 1H); 3.43 (dt, 1H, J1¼4.2 Hz, J2¼10.4 Hz); 5.17 (s, 1H). 13C NMR
7.54e7.57 (m, 2H). 13C NMR (CDCl3)
d: 18.9 (CH3); 22.3 (CH3); 25.4
(CH2); 30.1 (CH3); 31.3 (CH); 34.9 (CH2); 41.5 (2CH2); 43.9 (CH); 44.1
(CH); 47.1 (CH); 51.8 (CH); 52.1 (C); 52.8 (CH); 75.1 (CH); 81.2 (CH);
127.8 (2CH]); 128.2 (CH]); 129.5 (2CH]); 130.9 (C]); 137.4
(CH]); 138.4 (CH]); 144.6 (C]); 169.2 (C]); 208.1 (C]O). IR
(Nujol dispersion): 3374; 3060; 2925; 1698. HRMS for C27H33NO2:
calcd 403.2511, found 404.2580 (MþþH)
(CDCl3) d: 16.0 (CH3); 18.8 (CH3); 22.2 (CH3); 25.4 (CH2); 28.4 (CH2);
29.1 (CH2); 29.6 (CH3); 31.3 (CH); 31.6 (CH2); 34.8 (CH2); 37.1 (CH);
38.6 (CH); 41.5 (CH2); 50.9 (C); 51.0 (CH); 52.7 (CH); 54.0 (CH); 75.0
(CH); 78.0 (CH); 139.9 (C]); 174.6 (C]); 209.3 (C]O). IR (film):
3312; 2956; 1690; 1647.
25
2.3.6. Adduct (40a). Yellowish oil. [
NMR (CDCl3)
a]
¼þ3.36 (CHCl3, c¼1.1). 1H
D
25
d
: 0.88e1.30 (m, 3H); 0.94 (d, 3H, J¼6.5 Hz); 1.05 (s,
2.3.11. Adduct (50b). Yellowish oil. [
NMR (CDCl3)
a
]
¼ꢀ58.18 (CHCl3, c¼1.1). 1H
D
3H); 1.12 (s, 3H); 1.34e1.46 (m, 4H); 1.65e1.69 (m, 2H); 1.95 (m,
1H); 2.43 (d, 1H, J¼5.2 Hz); 2.60 (broad s, 1H); 2.92 (d, 1H,
d
: 0.86e0.97 (m, 2H); 0.90 (d, 3H, J¼6.5 Hz); 1.02e1.26
(m, 2H); 1.12 (s, 6H); 1.28e1.46 (m, 2H); 1.53 (m, 1H); 1.67e1.69 (m,

9298
A. Maestro et al. / Tetrahedron 68 (2012) 9293e9300
2H); 1.85 (m, 1H); 2.15 (s, 3H); 2.25 (d, 1H, J¼5.2 Hz); 2.57 (d, 1H,
J¼5.2 Hz); 2.79 (s, 1H); 2.93 (s, 1H); 3.45 (broad s, 1H); 3.46 (dt, 1H,
J1¼4.2 Hz, J2¼10.4 Hz); 5.18 (s, 1H); 6.20 (dd, 1H, J1¼3.0 Hz,
(CH]); 137.8 (CH]); 142.5 (C]); 143.4 (C]); 176.3 (C]); 206.9
(C]O). IR (KBr dispersion): 3061; 2927; 1684; 1635. HRMS for
C
29H37NO2: calcd 431.2824, found 432.2892 (MþþH).
J2¼5.5 Hz); 6.25 (dd, 1H, J1¼3.0 Hz, J2¼5.5 Hz). 13C NMR (CDCl3)
d:
25
16.0 (CH3); 18.9 (CH3); 22.2 (CH3); 25.4 (CH2); 29.7 (CH3); 31.3 (CH);
34.8 (CH2); 41.3 CH2); 41.6 (CH2); 42.2 (CH); 43.4 (CH); 51.0 (C); 51.1
(CH); 52.1 (CH); 52.6 (CH); 75.3 (CH); 77.7 (CH); 137.6 (CH]); 137.9
(CH]); 141.0 (C]); 174.7 (C]); 208.1 (C]O). IR (film): 3312; 3063;
2927; 1686; 1647. HRMS for C22H31NO2: calcd 341.2355, found
342.2429 (MþþH).
2.3.16. Adduct (60c). Colorless oil. [
1H NMR (CDCl3)
a
]
¼þ180.49 (CHCl3, c¼1.22).
D
d
: 0.80e0.94 (m, 2H); 0.93 (d, 3H, J¼6.5 Hz);
0.95e1.27 (m, 3H); 1.15 (s, 3H); 1.20 (s, 3H); 1.42e1.49 (m, 2H); 1.61
(d,1H, J¼5.1 Hz); 1.70 (s,1H); 1.73 (s,1H); 1.78 (d,1H, J¼5.1 Hz); 1.88
(m, 1H); 2.01 (s, 3H); 2.54 (s, 1H); 2.79 (s, 1H); 3.24 (d, 1H,
J¼16.7 Hz); 3.43 (dt, 1H, J1¼4.2 Hz, J2¼10.5 Hz); 3.83 (d, 1H,
J¼16.7 Hz); 5.21 (s, 1H); 6.11 (m, 2H); 7.05 (m, 1H); 7.11e7.17 (m,
25
2.3.12. Adduct (60b). Yellowish oil. [
NMR (CDCl3)
a
]
D
¼þ24.28 (CHCl3, c¼0.7). 1H
4H). 13C NMR (CDCl3)
d: 14.7 (CH3); 17.5 (CH3); 22.2 (CH3); 25.1
d
: 0.85e0.98 (m, 1H); 0.90 (d, 3H, J¼6.5 Hz); 1.01e1.23
(CH2); 27.3 (CH3); 31.0 (CH); 34.8 (CH2); 41.4 (CH2); 41.6 (CH2); 41.9
(CH); 43.2 (CH); 47.9 (CH2); 49.5 (CH); 52.1 (2CH2); 57.2 (C); 74.9
(CH); 81.6 (CH); 125.7 (CH]); 126.7 (2CH]); 127.5 (2CH]); 137.4
(CH]); 137.9 (CH]); 142.5 (C]); 143.6 (C]); 179.0 (C]); 207.8
(C]O). IR (film): 3061; 2927; 1689; 1643. HRMS for C29H37NO2:
calcd 431.2824, found 432.2882 (MþþH).
(m, 3H); 1.12 (s, 6H); 1.27e1.38 (m, 2H); 1.46 (m, 1H); 1.67e1.70 (m,
2H); 1.87 (m, 1H); 2.15 (s, 3H); 2.27 (d, 1H, J¼5.2 Hz); 2.59 (d, 1H,
J¼5.2 Hz); 2.77 (s, 1H); 2.92 (s, 1H); 3.38 (broad s, 1H); 3.48 (dt, 1H,
J1¼4.2 Hz, J2¼10.4 Hz); 5.21 (s, 1H); 6.20 (dd, 1H, J1¼3.0 Hz,
J2¼5.5 Hz); 6.25 (dd, 1H, J1¼3.0 Hz, J2¼5.5 Hz). 13C NMR (CDCl3)
d:
16.1 (CH3); 18.8 (CH3); 22.2 (CH3); 25.4 (CH2); 29.6 (CH3); 31.3 (CH);
34.8 (CH2); 41.5 CH2); 41.8 (CH2); 42.1 (CH); 43.3 (CH); 51.0 (CHþC);
52.2 (CH); 52.9 (CH); 75.0 (CH); 78.1 (CH); 137.6 (CH]); 138.0
(CH]); 141.0 (C]); 174.6 (C]); 208.1 (C]O). IR (film): 3311; 3062;
2927; 1686; 1647. HRMS for C22H31NO2: calcd 341.2355, found
342.2425 (MþþH).
2.3.17. Adduct (5d). White solid. Mp 104.5e106.3 ꢁC (from hex-
¼þ10.00 (CHCl3, c¼0.88). 1H NMR (CDCl3)
d: 0.08 (d,
25
ane). [
a
]
D
1H, J¼10.8 Hz); 0.31 (d, 1H, J¼10.8 Hz); 0.89e0.95 (m, 2H); 0.94
(d, 3H, J¼6.6 Hz); 0.96 (s, 3H); 0.97e1.25 (m, 3H); 1.33 (s, 3H);
1.36e1.66 (m, 5H); 1.72 (m, 1H); 1.79 (d, 1H, J¼2.5 Hz); 1.92 (m,
1H); 2.08 (d, 1H, J¼5.1 Hz); 2.13 (s, 1H); 2.48 (s, 1H); 3.58 (dt, 1H,
J1¼3.9 Hz, J2¼10.5 Hz); 3.65 (d, 1H, J¼12.2 Hz); 3.96 (d, 1H,
J¼18.2 Hz); 5.49 (s, 1H); 7.07 (m, 1H); 7.17e7.22 (m, 2H);
7.27e7.30 (m, 2H); 7.48 (d, 1H, J¼2.5 Hz). 13C NMR (CDCl3, 333 K)
2.3.13. Adduct (5c). White solid. Mp 146.3e147.9 ꢁC (from hexane).
25
[
a]
¼þ22.61 (CHCl3, c¼1.3). 1H NMR (CDCl3)
d: ꢀ0.06 (d, 1H,
D
J¼10.8 Hz); 0.26 (d, 1H, J¼10.8 Hz); 0.94 (d, 3H, J¼6.8 Hz); 0.95 (s,
3H); 0.97e1.22 (m, 4H); 1.26 (s, 3H); 1.33e1.59 (m, 5H); 1.65e1.73
(m, 2H); 1.87 (s, 1H); 1.93 (m, 1H); 2.01 (d, 1H, J¼5.5 Hz); 2.17 (s,
1H); 2.26 (d, 1H, J¼5.5 Hz); 2.32 (s, 3H); 3.52 (dt, 1H, J1¼4.0 Hz,
J2¼10.4 Hz); 3.59 (d, 1H, J¼18.3 Hz); 3.85 (d, 1H, J¼18.3 Hz); 5.49 (s,
1H); 7.06 (m, 1H); 7.15e7.20 (m, 2H); 7.26e7.28 (m, 2H). 13C NMR
d
: 19.3 (CH3); 22.1 (CH3); 24.9 (CH2); 26.9 (CH3); 28.4 (CH2); 29.0
(CH2); 30.5 (CH2); 31.3 (CH); 35.0 (CH2); 37.7 (CH); 38.7 (CH);
41.5 (CH2); 46.6 (CHþCH2); 48.3 (CH); 54.3 (CH); 57.3 (C); 76.4
(CH); 81.9 (CH); 125.6 (CH]); 126.7 (2CH]); 127.6 (2CH]);
143.3 (C]); 147.7 (C]); 162.7 (CH]); 208.2 (C]O). IR KBr
(dispersion): 3031; 2951; 1698; 1637. HRMS for C28H37NO2: calcd
419.2824, found 420.2897 (MþþH).
(CDCl3, 333 K)
d 17.0 (CH3); 17.4 (CH3); 22.1 (CH3); 24.9 (CH2); 27.0
(CH3); 28.6 (CH2); 29.0 (CH2); 30.5 (CH2); 31.2 (CH); 35.0 (CH2); 37.2
(CH); 38.4 (CH); 41.5 (CH2); 47.3 (CH2); 48.2 (CH); 53.5 (CH); 53.7
(CH); 57.4 (C); 75.6 (CH); 82.8 (CH); 125.6 (CH]); 126.5 (2CH]);
127.5 (2CH]); 141.2 (C]); 143.5 (C]); 176.6 (C]); 208.5 (C]O). IR
(KBr dispersion): 3061; 2955; 1691; 1642. HRMS for C29H39NO2:
calcd 433.2981, found 434.3065 (MþþH).
2.3.18. Adduct (6d). White solid. Mp 75.8e77.6 ꢁC (from hexane).
25
[a
]
¼þ148.78 (CHCl3, c¼0.90). 1H NMR (CDCl3)
d: 0.80e0.93 (m,
D
2H); 0.94 (d, 3H, J¼6.5 Hz); 0.98e1.02 (m, 2H); 1.08 (s, 3H);
1.11e1.88 (m, 3H); 1.35 (s, 3H); 1.42e1.59 (m, 5H); 1.64 (m, 1H);
1.72 (m, 1H); 1.93 (m, 1H); 2.04 (s, 1H); 2.08 (d, 1H, J¼3.3 Hz); 2.27
(s, 1H); 3.56 (dt, 1H, J1¼4.0 Hz, J2¼10.5 Hz); 3.64 (d, 1H, J¼17.2 Hz);
3.89 (d, 1H, J¼17.2 Hz); 5.45 (s, 1H); 7.08 (m, 1H); 7.14e7.26 (m,
25
2.3.14. Adduct (6c). Colorless oil. [
1H NMR (CDCl3)
a]
¼þ149.30 (CHCl3, c¼0.72).
D
d
: 0.75e0.88 (m, 2H); 0.93 (d, 3H, J¼6.5 Hz);
0.96e1.22 (m, 3H); 1.16 (s, 3H); 1.18 (s, 3H); 1.25e1.53 (m, 6H);
1.65e1.73 (m, 4H); 1.89 (m, 1H); 2.00 (s, 3H); 2.03 (s, 1H); 2.06 (s,
1H); 3.23 (d, 1H, J¼16.7 Hz); 3.44 (dt, 1H, J1¼4.1 Hz, J2¼10.5 Hz);
3.81 (d, 1H, J¼16.7 Hz); 5.24 (s, 1H); 7.07e7.16 (m, 5H). 13C NMR
4H); 7.29 (d, 1H, J¼2.3 Hz). 13C NMR (CDCl3)
d: 20.0 (CH3); 22.3
(CH3); 25.0 (CH2); 27.4 (CH3); 28.1 (CH2); 29.1 (CH2); 31.3
(CHþCH2); 35.0 (CH2); 37.9 (CH); 38.6 (CH); 41.4 (CH2); 46.3
(CH2); 46.6 (CH); 48.3 (CH); 53.9 (CH); 57.0 (C); 76.2 (CH); 81.2
(CH); 125.5 (CH]); 127.1 (2CH]); 127.7 (2CH]); 143.7 (C]);
148.0 (C]); 162.0 (CH]); 208.3 (C]O). IR (KBr dispersion): 3023;
2949; 1697; 1637. HRMS for C28H37NO2: calcd 419.2824, found
420.2903 (MþþH).
(CDCl3) d: 15.0 (CH3); 17.4 (CH3); 22.2 (CH3); 25.1 (CH2); 27.3 (CH3);
28.5 (CH2); 28.9 (CH2); 31.1 (CH); 31.3 (CH2); 34.8 (CH2); 36.9 (CH);
38.5 (CH); 41.4 (CH2); 47.8 (CH2); 49.4 (CH); 52.8 (CH); 53.4 (CH);
57.2 (C); 74.9 (CH); 81.7 (CH); 125.6 (CH]); 126.6 (2CH]); 127.5
(2CH]); 141.2 (C]); 143.7 (C]); 179.0 (C]); 209.1 (C]O). IR
(film): 3058; 2953; 1686; 1641.
2.3.19. Adduct (50d). White solid. Mp 152.0e153.9 ꢁC (from hex-
25
ane). [
a
]
D
¼þ12.56 (CHCl3, c¼1.6). 1H NMR (CDCl3)
d: 0.29 (d, 1H,
2.3.15. Adduct (50c). White solid. Mp 135.9e137.5 ꢁC (from hexane).
J¼9.7 Hz); 0.71 (d, 1H, J¼9.7 Hz); 0.75e1.27 (m, 3H); 0.93 (d, 3H,
J¼6.5 Hz); 0.96 (s, 3H); 1.32 (s, 3H); 1.39e1.73 (m, 4H); 1.92 (m, 1H);
2.17 (d, 1H, J¼5.0 Hz); 2.28 (s, 1H); 2.61 (s, 1H); 2.65 (s, 1H); 3.57 (dt,
1H, J1¼4.1 Hz, J2¼10.4 Hz); 3.63 (d, 1H, J¼18.3 Hz); 3.97 (d, 1H,
J¼18.3 Hz); 5.48 (s,1H); 6.05 (dd,1H, J1¼3.0 Hz, J2¼5.5 Hz); 6.12 (dd,
1H, J1¼3.0 Hz, J2¼5.5 Hz); 7.06 (m, 1H); 7.16e7.21 (m, 2H); 7.28 (m,
25
[
a]
¼þ39.02 (CHCl3, c¼0.82). 1H NMR (CDCl3)
d: 0.17 (d, 1H,
D
J¼9.6 Hz); 0.67 (d, 1H, J¼9.6 Hz); 0.83e1.20 (m, 3H); 0.94 (d, 3H,
J¼6.5 Hz); 0.96 (s, 3H); 1.26 (s, 3H); 1.52e1.60 (m, 2H); 1.65e1.73
(m, 2H); 1.93 (s, 1H); 2.12 (d, 1H, J¼5.3 Hz); 2.32 (s, 3H); 2.39 (s,1H);
2.40 (d, 1H, J¼5.3 Hz); 2.70 (s, 1H); 3.52 (dt, 1H, J1¼4.1 Hz,
J2¼10.5 Hz); 3.60 (d, 1H, J¼18.3 Hz); 3.87 (d, 1H, J¼18.3 Hz); 5.48 (s,
1H); 6.05e6.10 (m, 2H); 7.05 (m, 1H); 7.16 (m, 2H); 7.27 (m, 2H). 13C
2H); 7.50 (d, 1H, J¼2.4 Hz). 13C NMR (CDCl3, 333 K)
d: 19.2 (CH3);
22.1 (CH3); 24.9 (CH2); 26.8 (CH3); 31.3 (CH); 35.0 (CH2); 40.7 (CH2);
41.5 (CH2); 42.7 (CH); 43.5 (CH); 46.7 (CHþCH2); 47.8 (CH); 53.0
(CH); 57.3 (C); 76.4 (CH); 81.6 (CH); 125.6 (CH]); 126.7 (2CH]);
127.7 (2CH]); 137.1 (CH]); 138.3 (CH]); 143.2 (C]); 148.8 (C]);
162.5 (CH]); 206.6 (C]O). IR (KBr dispersion): 3053; 2922; 1698;
NMR (CDCl3, 333 K) d: 17.0 (CH3); 17.4 (CH3); 22.1 (CH3); 24.9 (CH2);
27.0 (CH3); 31.2 (CH); 35.0 (CH2); 40.8 (CH2); 41.5 (CH2); 42.2 (CH);
43.1 (CH); 47.3 (CH2); 48.2 (CH); 52.5 (CH); 52.8 (CH); 57.4 (C); 75.7
(CH); 82.6 (CH); 125.6 (CH]); 126.5 (2CH]); 127.6 (2CH]); 137.6

A. Maestro et al. / Tetrahedron 68 (2012) 9293e9300
9299
1638. HRMS for C28H35NO2: calcd 417.2668, found 418.2735
(CHCl3, c¼0.30). 1H NMR (CDCl3)
d
: 0.97e1.08 (m, 2H); 1.37 (m, 1H);
(MþþH).
1.58e1.81 (m, 3H); 2.30 (d, 1H, J¼5.5 Hz); 2.41 (d, 1H, J¼4.3 Hz);
2.49 (s, 3H); 2.51 (d, 1H, J¼4.3 Hz); 2.65 (d, 1H, J¼5.5 Hz); 9.97 (s,
2.3.20. Adduct (60d). White solid. Mp 141.7e143.3 ꢁC (from hex-
1H). 13C NMR (CDCl3)
d: 17.8 (CH3); 28.3 (CH2); 29.3 (CH2); 31.8
25
ane). [
a
]
D
¼þ134.69 (CHCl3, c¼1.28). 1H NMR (CDCl3)
d: 0.94 (d, 3H,
(CH2); 38.2 (CH); 39.1 (CH); 54.1 (CH); 54.2 (CH); 137.4 (C]); 189.1
(CH]O); 189.2 (C]); 208.0 (C]O). IR (film): 3051; 2953; 1689;
1643. Easily oxidized on standing, and the Mass spectra was reg-
istered for the acid. HRMS for C17H14O3: calcd 206.0943, found
229.0829 (MþþNa).
J¼6.5 Hz); 0.98e1.07 (m, 2H); 1.10 (s, 3H); 1.14e1.28 (m, 3H); 1.34
(s, 3H); 1.41e1.53 (m, 2H); 1.63e1.74 (m, 3H); 1.93 (m, 1H); 2.18 (s,
1H); 2.59 (s, 1H); 2.79 (s, 1H); 3.56 (dt, 1H, J1¼4.0 Hz, J2¼10.5 Hz);
3.66 (d, 1H, J¼17.1 Hz); 3.93 (d, 1H, J¼17.1 Hz); 5.42 (s, 1H); 6.06 (dd,
1H, J1¼3.0 Hz, J2¼5.5 Hz); 6.15 (dd, 1H, J1¼3.0 Hz, J2¼5.5 Hz); 7.05
(m, 1H); 7.14e7.26 (m, 4H); 7.33 (d, 1H, J¼1.9 Hz). 13C NMR (CDCl3)
2.4.6. (3aS,4R,7S,7aR)-2-Formyl-3-methyl-3a,4,5,6,7,7a-hexahydro-
25
d
: 19.8 (CH3); 22.3 (CH3); 25.0 (CH2); 27.5 (CH3); 31.3 (CH); 35.0
4,7-methanoinden-1-one (ent-8). Yellowish oil (64%). [
(CHCl3, c¼0.60).
a]
¼þ39.33
D
(CH2); 41.4 (CH2); 41.5 (CH2); 42.8 (CH); 43.3 (CH); 46.4 (CH2); 46.7
(CH); 47.9 (CH); 52.7 (CH); 57.0 (C); 76.2 (CH); 81.0 (CH); 125.6
(CH]); 127.2 (2CH]); 127.7 (2CH]); 136.9 (CH]); 138.4 (CH]);
143.6 (C]); 149.5 (C]); 162.1 (CH]); 207.3 (C]O). IR (Nujol dis-
persion): 3027; 2940; 1698. HRMS for C28H35NO2: calcd 417.2668,
found 418.2736 (MþþH).
2.4.7. (3aR,4S,7R,7aS)-2-Formyl-3-methyl-3a,4,7,7a-tetrahydro-4,7-
25
methanoinden-1-one (80). Yellowish oil (70%).
[
a
]
¼ꢀ63.46
D
(CHCl3, c¼0.26). 1H NMR (CDCl3)
: 1.21 (d, 1H, J¼9.6 Hz); 1.45
d
(d, 1H, J¼9.6 Hz); 2.41 (d, 1H, J¼5.4 Hz); 2.50 (s, 3H); 2.80 (d,
1H, J¼5.4 Hz); 2.93 (s, 1H); 3.05 (s, 1H); 6.25e6.34 (m, 2H); 9.96
2.4. Hydrolysis of the perhydrobenzoxazines nucleous. Syn-
thesis of 2- or 3-formyl ciclopentenones. general procedure
(s, 1H). 13C NMR (CDCl3)
d: 17.8 (CH3); 41.7 (CH2); 43.3 (CH);
43.9 (CH); 52.9 (CH); 53.8 (CH); 137.9 (C]); 138.1 (CH]); 138.3
(C]); 188.6 (C]); 189.1 (CH]O); 206.4 (C]O). IR (film): 3060;
2973; 1689; 1653.
To a solution of the corresponding adduct (1 mmol) in ethanol
(2 mL) was added a 2% HCl solution in water (7.5 mL) and the
mixture was refluxed until the reaction was completed (TLC). After
cooling, the mixture was extracted with Et2O (3ꢂ25 mL), the or-
ganic phase was washed with brine and dried over anhydrous
MgSO4. After filtration, the solvent was evaporated and the oily
residues were purified by flash chromatography on silica gel and
DCM as a solvent.
2.4.8. (3aS,4R,7S,7aR)-2-Formyl-3-methyl-3a,4,5,6,7,7a-hexahydro-
25
4,7-methanoinden-1-one (ent-80). Yellowish oil (60%). [
(CHCl3, c¼0.32).
a]
¼þ68.75
D
Acknowledgements
We acknowledge financial support by the Spanish MICINN
(CTQ2008-03960/BQU and CTQ 2011-28487) and Junta de Castilla y
2.4.1. (3aR,4S,7R,7aS)-3-Formyl-2-phenyl-3a,4,5,6,7,7a-hexahydro-
25
4,7-methanoinden-1-one (7a). Yellowish oil (62%). [
a
]
¼ꢀ72.11
ꢀ
Leon (Project GR 168). J.J.P.R. also thanks the MEC for a pre-doctoral
D
(CHCl3, c¼0.52).1H NMR (CDCl3)
d: 1.01e1.10 (m, 2H); 1.32e1.52 (m,
fellowship (FPU program).
2H); 1.58e1.80 (m, 2H); 2.46 (d,1H, J¼5.6 Hz); 2.49 (d, 1H, J¼3.8 Hz);
2.56 (d, 1H, J¼3.8 Hz); 2.99 (d, 1H, J¼5.6 Hz); 7.36e7.43 (m, 2H);
Supplementary data
7.46e7.53 (m, 3H); 10.14 (s, 1H). 13C NMR (CDCl3)
d: 28.4 (CH2); 29.1
(CH2); 31.7 (CH2); 38.4 (CH); 40.1 (CH); 45.8 (CH); 54.2 (CH); 128.3
(CH]); 128.5 (2CH]); 129.9 (3CH]); 154.0 (C]); 160.3 (C]); 192.1
(CH]O); 210.5 (C]O). IR (film): 3058; 2960; 1704; 1676. HRMS for
C17H16O2: calcd 252.1150, found 307.1295 (MþþMeOHþNa). Chiral
HPLC (Chiralpack AD-H, hexane/isopropanol 95:5, 1.0 mL/min,
Supplementary data associated with this article, including
copies of 1H NMR and 13C NMR spectra for all new compounds and
ORTEP representation of XR structures for compounds 30a and 5c
can be found on the online version. Supplementary data related to
this article can be found online at http://dx.doi.org/10.1016/
j.tet.2012.08.006.
l
¼220 nm); tR¼12.1 min) showed ee>99%.19
2.4.2. (3aS,4R,7S,7aR)-3-Formyl-2-phenyl-3a,4,5,6,7,7a-hexahydro-
References and notes
25
4,7-methanoinden-1-one (ent-7a). Yellowish oil
(CHCl3, c¼0.26).
[
a
]
D
¼þ78.46
1. For recent reviews see: (a) Lee, H. W.; Kwong, F. Y. Eur. J. Org. Chem. 2010, 789;
(b) Shibata, T. Adv. Synth. Catal. 2006, 348, 2328; (c) Strubing, D.; Beller, M.
€
Top. Organomet. Chem. 2006, 18, 165; (d) Laschat, S.; Becheanu, A.; Bell, T.;
Baro, A. Synlett 2005, 2547; (e) Rivero, M. R.; Adrio, J.; Carretero, J. C. Synlett
2005, 26; (f) Gibson, S. E.; Mainolfi, N. Angew. Chem., Int. Ed. 2005, 44, 3022; (g)
Blanco-Urgoiti, J.; Anorbe, L.; Perez-Serrano, L.; Domínguez, G.; Perez-Castells, J.
Chem. Soc. Rev. 2004, 33, 32; (h) Alcaide, B.; Almendros, P. Eur. J. Org. Chem.
2004, 3377; (i) Gibson, S. E.; Stevenazzi, A. Angew. Chem., Int. Ed. 2003, 42, 1800;
(j) Brummond, K. M.; Kent, J. L. Tetrahedron 2000, 53, 3263.
2.4.3. (3aR,4S,7R,7aS)-3-Formyl-2-phenyl-3a,4,7,7a-tetrahydro-4,7-
25
methanoinden-1-one (70a). Yellowish oil (71%).
[
a
]
¼ꢀ37.02
D
(CHCl3, c¼1.04). 1H NMR (CDCl3)
d
: 1.25 (d, 1H, J¼9.5 Hz); 1.48 (d,
~
ꢀ
ꢀ
1H, J¼9.5 Hz); 2.57 (d, 1H, J¼5.4 Hz); 2.99 (s, 1H); 3.07 (s, 1H); 3.10
(d, 1H, J¼5.4 Hz); 6.25 (dd, 1H, J1¼3.1 Hz, J2¼5.6 Hz); 6.40 (dd, 1H,
J1¼3.1 Hz, J2¼5.6 Hz); 7.38e7.42 (m, 2H); 7.43e7.52 (m, 3H); 10.13
ꢀ
ꢂ
2. See as examples: (a) Lledo, A.; Sola, J.; Verdaguer, X.; Riera, A.; Maestro, M. A.
ꢂ
Adv. Synth. Catal. 2007, 349, 2121; (b) Sola, J.; Riera, A.; Verdaguer, X.; Maestro,
M. A. J. Am. Chem. Soc. 2005, 127, 13629; (c) Rios, R.; Moyano, A.; Pericas, M. A.
Tetrahedron Lett. 2002, 43, 1023; (d) Pagenkopf, B. L.; Belanger, D. B.; OMahony,
(s, 1H). 13C NMR (CDCl3)
d: 41.7 (CH2); 43.3 (CH); 44.7 (CH); 45.3
ꢂ
ꢀ
(CH); 53.2 (CH); 128.2 (CH]); 128.6 (2CH]); 129.9 (2CH]); 130.0
(CH]); 136.9 (CH]); 139.3 (CH]); 154.6 (C]); 160.0 (C]); 192.0
(CH]O); 208.9 (C]O). IR (film): 3061; 2983; 1708; 1678. HRMS for
C17H14O2: calcd 250.0994, found 305.1136 (MþþMeOHþNa).
D. R. R.; Livinghouse, T. Synthesis 2000, 1009; (e) Hiroi, K.; Watanabe, T. Tet-
rahedron Lett. 2000, 41, 3935; (f) Witulski, B.; Go
1879; (g) Montenegro, E.; Moyano, A.; Pericas, M. A.; Riera, A.; Alvarez-Larena,
b
mann. Chem. Commun. 1999,
ꢂ
A.; Piniella, J.-F. Tetrahedron: Asymmetry 1999, 10, 457.
3. (a) Rodríguez Rivero, M.; de la Rosa, J. C.; Carretero, J. C. J. Am. Chem. Soc. 2003,
125, 14992; (b) Rodríguez Rivero, M.; Alonso, I.; Carretero, J. C. Chem.dEur. J.
2004, 10, 5443; (c) Rodríguez Rivero, M.; Adrios, J.; Carretero, J. C. Eur. J. Org.
Chem. 2002, 2881; (d) Carretero, J. C.; Adrio, J. Synthesis 2001, 1888; (e)
Carretero, J. C.; Adrio, J. J. Am. Chem. Soc. 1999, 121, 7411; (f) Ahmar, M.; Antras,
B.; Cazes, B. Tetrahedron Lett. 1999, 40, 5503; (g) Costa, M.; Mor, A. Tetrahedron
Lett. 1995, 36, 2867.
2.4.4. (3aS,4R,7S,7aR)-3-Formyl-2-phenyl-3a,4,7,7a-tetrahydro-4,7-
25
methanoinden-1-one (ent-70a). Yellowish oil (69%) [
(CHCl3, c¼1.00).
a
]
¼þ28.80
D
2.4.5. (3aR,4S,7R,7aS)-2-Formyl-3-methyl-3a,4,5,6,7,7a-hexahydro-
4. (a) Hoye, T. R.; Soriano, J. A. J. Org. Chem. 1993, 58, 1659; (b) Gybin, A. S.; Smit,
W. A.; Caple, R.; Veretenov, A. L.; Shashkov, A. S.; Vorontsova, L. G.; Kurella, M.
25
4,7-methanoinden-1-one (8). Yellowish oil (76%). [
a]
¼ꢀ43.33
D

9300
A. Maestro et al. / Tetrahedron 68 (2012) 9293e9300
ꢀ
G.; Chertkov, V. S.; Carapetyan, A. A.; Kosnikov, A. Y.; Alexanyan, M. S.;
8570; (f) Andres, C.; Maestro, G.; Nieto, J.; Pedrosa, R.; García-Granda, S.;
ꢀ ~
Perez-Carreno, E. Tetrahedron Lett. 1997, 38, 1463.
11. Vazquez-Romero, A.; Cardenas, L.; Blasi, E.; Verdaguer, X.; Riera, A. Org. Lett.
Lindeman, S. V.; Panov, V. N.; Maleev, A. V.; Struchkov, Y. T.; Sharpe, S. M. J. Am.
Chem. Soc. 1992, 114, 5555; (c) Veterenov, A. L.; Smit, W. A.; Vorontsova, L. G.;
Kurella, M. G.; Caple, R.; Gybin, A. S. Tetrahedron Lett. 1991, 32, 2109.
ꢀ
ꢀ
2009, 11, 3104.
5. (a) Ikeda, K.; Morimoto, T.; Kakiuchi, K. J. Org. Chem. 2010, 75, 6279; (b) Kwong,
F. Y.; Lee, H. W.; Qiu, L.; Lam, W. H.; Li, Y. M.; Kwong, H. L.; Chan, A. S. C. Adv.
Synth. Catal. 2005, 347, 1750; (c) Jeong, N.; Kim, D. H.; Choi, J. H. Chem. Commun.
2004, 1134; (d) Fuji, K.; Morimoto, T.; Tsutsumi, K.; Kakiuchi, K. Angew. Chem.,
Int. Ed. 2003, 42, 2409; (e) Morimoto, T.; Fuji, K.; Tsutsumi, K.; Kakiuchi, K. J. Am.
Chem. Soc. 2002, 124, 3806; (f) Shibata, T.; Toshida, N.; Takagi, K. Org. Lett. 2002,
4, 1619; (g) Shibata, T.; Toshida, N.; Takagi, K. J. Org. Chem. 2002, 68, 7446.
12. He, X. C.; Eliel, E. L. Tetrahedron 1987, 43, 4979.
13. (a) Jeong, N.; Chung, Y. K.; Lee, B. Y.; Lee, S. H.; Yoo, S. E. Synlett 1991, 204; (b)
Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetrahedron Lett. 1990, 31, 5289.
ꢀ
ꢀ
14. Perez-Serrano, L.; Casarrubios, L.; Domínguez, G.; Perez-Castells, J. Org. Lett.
1999, 1, 1187.
ꢂ
15. (a) Fonquerna, S.; Moyano, A.; Pericas, M. A.; Riera, A. Tetrahedron 1995, 51,
4239; (b) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.; Foreman, M. I. J.
Chem. Soc., Perkin Trans. 1 1973, 977.
6. Park, K. H.; Jung, G.; Chung, Y. K. Org. Lett. 2004,ˇ 6, 1183.
7. (a) Kim, D. E.; Lee, B. H.; Rajagopalasarma, M.; Genet, J.-P.; Ratovelomanana-Vidal,
V.; Jeong, N. Adv. Synth. Catal. 2008, 350, 2695; (b) Lanver, A.; Schmalz, H. G.
Eur. J. Org. Chem. 2005, 1444; (c) Velcicky, J.; Lanver, A.; Lex, J.; Prokop, A.;
Wieder, T.; Schmalz, H. G. Chem.dEur. J. 2004, 10, 5087; (d) Velcicky, J.; Lex, J.;
Schmalz, H. G. Org. Lett. 2002, 4, 565; (e) Stolle, A.; Becker, H.; Salaun, J.;
de Meijere, A. Tetrahedron Lett. 1994, 35, 3521; (f) Jeong, N.; Lee, B. Y.; Lee, S. H.;
Chung, Y. K.; Lee, S. G. Tetrahedron Lett. 1993, 34, 4023.
16. CCDC 861634 for 30a and CCDC 861635 for 5c contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/data_request/cif.
17. (a) Quintal, M. M.; Closser, K. D.; Shea, K. M. Org. Lett. 2004, 6, 4949; (b) Jamison,
T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc. 1997, 119,
4353; (c) Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem.
Soc. 1994, 116, 5505.
ꢀ
ꢀ
8. (a) Ji, Y.; Riera, A.; Verdaguer, X. Org. Lett. 2009, 11, 4346; (b) Sola, J.; Reves, M.;
18. For some reviews on Nicholas reaction see: (a) Omae, I. Appl. Organomet. Chem.
€
Riera, A.; Verdaguer, X. Angew. Chem., Int. Ed. 2007, 46, 5020; (c) Sola, J.; Riera,
2007, 21, 318; (b) Teobald, B. J. Tetrahedron 2002, 58, 4133; (c) Muller, T. J. J. Eur.
ꢂ
A.; Pericas, M. A.; Verdaguer, X.; Maestro, M. A. Tetrahedron Lett. 2004, 45, 5387;
J. Org. Chem. 2001, 2021; (d) Green, J. R. Curr. Org. Chem. 2001, 5, 809; (e)
(d) Shen, L.; Hsung, R. P. Tetrahedron Lett. 2003, 44, 9353; (e) Marchueta, I.;
Nicholas, K. M. Acc. Chem. Res. 1987, 20, 207.
19. See Supplementary information.
ꢂ
Montenegro, E.; Panov, D.; Poch, M.; Verdaguer, X.; Moyano, A.; Pericas, M. A.;
ꢀ
Riera, A. J. Org. Chem. 2001, 66, 6400; (f) Balsells, J.; Vazquez, J.; Moyano, A.;
20. Kraft, M. E.; Romero, R. H.; Scott, I. L. Synlett 1995, 577.
21. Kraft, M. E.; Romero, R. H.; Scott, I. L. J. Org. Chem. 1992, 57, 5277.
22. (a) Robert, F.; Milet, A.; Gimbert, Y.; Konya, D.; Greene, A. E. J. Am. Chem. Soc.
2001, 123, 5396; (b) Bruin, T. J. M.; Milet, A.; Robert, F.; Gimbert, Y.; Greene, A. E.
J. Am. Chem. Soc. 2001, 123, 7184.
ꢂ
Pericas, M. A.; Riera, A. J. Org. Chem. 2000, 65, 7291; (g) Fonquerna, S.; Rios, S.;
ꢂ
Moyano, A.; Pericas, M. A.; Riera, A. Eur. J. Org. Chem. 1999, 3459; (h) Verdaguer,
ꢀ
X.; Vazquez, J.; Fuster, G.; Bernardes-Genisson, V.; Greene, A. E.; Moyano, A.;
ꢂ
Pericas, M. A.; Riera, A. J. Org. Chem. 1998, 63, 7037; (i) Fonquerna, S.; Moyano,
ꢂ
ꢂ
A.; Pericas, M. A.; Riera, A. J. Am. Chem. Soc. 1997, 119, 10225.
23. (a) Fjermestad, T.; Pericas, M. A.; Maseras, F. Chem.dEur. J. 2011, 17, 10050; (b)
ꢀ
~ꢀ
9. Andres, C.; Nieto, J.; Pedrosa, R.; Villamanan, N. J. Org. Chem. 1996, 61, 4130.
Bruin, T. J. M.; Milet, A.; Greene, A. E.; Gimber, Y. J. Org. Chem. 2004, 69, 1075; (c)
ꢀ
ꢂ
10. (a) Pedrosa, R.; Andres, C.; de las Heras, L.; Nieto, J. Org. Lett. 2002, 4, 2513;
Pericas, M. A.; Balsells, J.; Castro, J.; Marchueta, I.; Moyano, A.; Riera, A.;
ꢀ
ꢀ
ꢀ
(b) Pedrosa, R.; Andres, C.; Nieto, J. J. Org. Chem. 2000, 65, 831; (c) Andres,
C.; Duque-Soladana, J. P.; Pedrosa, R. J. Org. Chem. 1999, 64, 4273; (d)
Vazquez, J.; Verdaguer, X. Pure Appl. Chem. 2002, 74, 167; (d) Yamanaka, M.;
Nakamura, E. J. Am. Chem. Soc. 2001, 123, 1703.
ꢀ
ꢀ
ꢀ
Andres, C.; Duque-Soladana, J. P.; Pedrosa, R. J. Org. Chem. 1999, 64, 4282;
24. Maestro, A.; Pedrosa, R.; Perez-Encabo, A.; Perez-Rueda, J. J. Eur. J. Org. Chem.
2012, 1202.
ꢀ
(e) Andres, C.; Nieto, J.; Pedrosa, R.; Vicente, M. J. Org. Chem. 1998, 63,