Lithiation of N-alkyl-(o-tolyl)aziridine: Stereoselective synthesis of isochromans

Article abstract of DOI:10.1021/jo9011943

(Chemical Equation Presented) The lithiation reaction of o-tolylaziridine 1 has been investigated by using the aziridine ring capability to act as a directing metalation group. Trapped with electrophiles, the resulting o-aziridinyl benzyllithium 1-Li give

Full text of DOI:10.1021/jo9011943

pubs.acs.org/joc
o-lithiated depending upon the aziridine ring substitution,
Lithiation of N-Alkyl-(o-tolyl)aziridine:
Stereoselective Synthesis of Isochromans§
solvent, and temperature.2,3 Specifically, the previously de-
scribed directing-metalation ability of the aziridine group,
combined with its bias to give nucleophilic ring-opening, has
been successfully exploited for the preparation of phthalans.4,5
Six-membered-ring oxygen-bearing aromatic heterocycles
with isochroman and related skeletons occur in nature and
among bioactive compounds of interest, including drugs
(medicines, agrochemicals, etc.) and drug candidates.6
D1 dopaminergic agonists with 1,3-disubstituted isochro-
man skeletons are among the few D1 agonists known to
date. The synthesis of 1,3-disubstituted isochromans with an
aminomethyl substituent typically requires multistep oxa-
Pictet-Spengler cyclizations.7
Mariangela Dammacco,† Leonardo Degennaro,†
Saverio Florio,*,† Renzo Luisi,*,† Biagia Musio,† and
Angela Altomare‡
†Dipartimento Farmaco-Chimico, Universitaꢀ di Bari,
Consorzio Interuniversitario Nazionale Metodologie e
Processi Innovativi di Sintesi C.I.N.M.P.I.S., Via E. Orabona
4, I-70125-Bari, Italy, and ‡Istituto di Cristallografia
(IC-CNR), Via Amendola 122/o, I-70125 Bari, Italy
florio@farmchim.uniba.it; luisi@farmchim.uniba.it
Received June 8, 2009
In exploiting the lithiation-trapping sequence of arylaziri-
dines, we thought that 1-aminomethyl-3-alkyl(or aryl)-substi-
tuted isochromans could be prepared simply by lateral-
lithiation of o-tolyl-substituted N-alkyl-arylaziridines, trapping
with carbonyl compounds, and finally cyclization (Scheme 1).8
The reaction of 1-methyl-2-(o-tolyl)aziridine 1 with s-BuLi
in THF at -78 °C in the presence of TMEDA gave exclu-
sively the thermodynamically favored9,10 lithiated intermedi-
ate 1-Li as proved by trapping with D2O to furnish
deuterated derivative 2a (>98% D) (Table 1). Additionally,
lithiated intermediate 1-Li reacted with other electrophiles
(Table 1) to give ortho-functionalized aziridines 2b-j.
(3) Luisi, R.; Capriati, V.; Florio, S.; Musio, B. Org. Lett. 2007, 8, 1263–
1266.
(4) Capriati, V.; Florio, S.; Luisi, R.; Musio, B. Org. Lett. 2005, 7, 3749–
3752.
(5) (a) Snieckus, V. Chem. Rev. 1990, 879–933. (b) Gschwend, H. W.;
Rodriguez, H. R. Org. React. 1979, 26, 1. (c) Kizirian, J.-C. Chem. Rev. 2008,
108, 140–205.
(6) (a) Hsu, F. L.; Chen, J. Y. Phytochemistry 1993, 34, 1625–1627. (b)
Ralph, J.; Peng, J.; Lu, F. Tetrahedron Lett. 1998, 39, 4963–4964. (c)
Kashiwaba, N.; Morooka, S.; Kimura, M.; Ono, M.; Toda, J.; Suzuki, H.;
Sano, T. Nat. Prod. Lett. 1997, 9, 177–180.
The lithiation reaction of o-tolylaziridine 1 has been
investigated by using the aziridine ring capability to act
as a directing metalation group. Trapped with electro-
philes, the resulting o-aziridinyl benzyllithium 1-Li gives
access to several functionalized aziridines 2a-j. The
hydroxyalkylated derivatives 2d-j were converted into
important scaffolds such as isochromans 3a-d. A stereo-
selective preparation of isochromans (R)-3b, (1R,3S)-3d,
and (1R,3R)-3d has been developed starting from enan-
tioenriched o-tolylaziridine.
(7) (a) Michaelidis, M. R.; Schoenleber, R.; Thomas, S.; Yamamoto, D.
M.; Britton, D. R.; MacKenzie, R.; Kebabian, J. W. J. Med. Chem. 1991, 34,
2946–2953. (b) Hunteralt, B.; Heppert, U. D. Pharmazie 2001, 56, 445–447.
(c) Hunteralt, B.; Heppert, U. D. Pharmazie 2002, 57, 346–347.
(8) Some recent examples on lateral lithiation: (a) Aliyenne, A. O.;
Kraiem, J.; Kacem, Y.; Hassine, B. B. Tetrahedron Lett. 2008, 49, 1473–
1475. (b) Wilkinson, J. A.; Raiber, E. A.; Ducki, S. Tetrahedron 2008, 64,
6329–6333. (c) Clayden, J.; Turner, H.; Helliwell, M.; Moir, E. J. Org. Chem.
2008, 73, 4415–4423. (d) Hogan, A.-M. L.; Tricotet, T.; Meek, A.; Khokhar,
S. S.; O’Shea, D. J. Org. Chem. 2008, 73, 6041–6044. (e) Uchida, K.; Fukuda,
T.; Iwao, M. Tetrahedron 2007, 63, 7178–7186. (f) Sae-Lao, P.; Kittakoop, P.;
Rajivroongit, S. Tetrahedron Lett. 2006, 47, 345–348. (g) Burkhart, D. J.;
Zhou, P.; Blumenfeld, A.; Twamley, B.; Natale, N. R. Tetrahedron 2001, 57,
8039–8046. (h) Kowalczyk, B. A. Synthesis 2000, 1113–1116. (i) Wang, C.-C.;
Li, J. J.; Huang, H.-C.; Lee, L. F.; Reitz, D. B. J. Org. Chem. 2000, 65, 2711–
2715.
(9) It is likely that the nitrogen-induced stabilization in the six-membered
cyclic lithiated intermediated 1-Li, and Complex Induced Proximity Effect
could act sinergically making the lateral benzylic position the kinetically and
thermodynamically favored one, see: (a) Clayden J., In Organolithiums:
Selectivity for Synthesis; Pergamon: Oxford, UK, 2002; Chapter 2.
(b) Whisler, M. C.; MacNeil, S.; Snieckus, V.; Beak, P. Angew. Chem., Int.
Ed. 2004, 43, 2206–2225.
Synthesizing substituted aziridines and their derivatives by
using the lithiation/electrophile trapping sequence is a useful
synthetic methodology.1 Within this context, we have recently
reported that N-alkylarylaziridines are smoothly R- and/or
§ Dedicated to Professor Peter Stanetty of the Vienna University of Technology
for his 65th birthday.
(1) (a) Aziridines and Epoxides in Organic Synthesis; Yudin, A. K., Ed.;
Wiley-VCH: Weinheim, Germany, 2006. (b) Padwa, A. In Comprehensive
Heterocyclic Chemistry III; Katritzky, A. R., Ramsden, C. A., Scriven, E. F.
V., Taylor, R. J. K., Eds.; Elsevier: Oxford, UK, 2008; Vol. 1, pp 1-104. (c) Singh,
G. S.; D'hooghe, M.; De Kimpe, N. Chem. Rev. 2007, 107, 2080–2135. (d) Hu, X.
E. Tetrahedron 2004, 60, 2701–2743. (e) McCoull, W.; Davis, F. A. Synthesis
2000, 1347–1365.
(2) (a) Affortunato, F.; Florio, S.; Luisi, R.; Musio, B. J. Org. Chem.
2008, 73, 9214–9220. (b) Luisi, R.; Capriati, V.; Florio, S.; Di Cunto, P.;
Musio, B. Tetrahedron 2005, 61, 3251–3260.
(10) For other examples of nitrogen-assisted lithiation see: (a) Ross
Kelly, T.; Lebedev, R. L. J. Org. Chem. 2002, 67, 2197–2205. (b) Itami, K.;
Kamei, T.; Mitsudo, K.; Nokami, T.; Yoshida, J.-i. J. Org. Chem. 2001, 66,
3970–3976. (c) Flippin, L. A.; Muchowski, J. M.; Carter, D. S. J. Org. Chem.
1993, 58, 2463–2467. (d) Tarnchompoo, B.; Thebtaranonth, C.; Thebt-
aranonth, Y. Tetrahedron Lett. 1990, 31, 5779–5780. (e) Ludt, R. E.;
Crowther, G. P.; Hauser, C. R. J. Org. Chem. 1970, 35, 1288–1296. (f) Jones,
F. N.; Zinn, M. F.; Hauser, C. R. J. Org. Chem. 1963, 28, 663–665.
DOI: 10.1021/jo9011943
r
Published on Web 07/17/2009
J. Org. Chem. 2009, 74, 6319–6322 6319
2009 American Chemical Society

Dammacco et al.
SCHEME 2. Acid-Catalyzed Cyclization to Isochromans
JOCNote
SCHEME 1. Retrosynthetic Approach to Isochromans
TABLE 2. Preparation of Isochromans 3
TABLE 1. Lithiation/Electrophile Trapping of o-Tolylaziridine 1
aziridine 2
2e
benzopyrane 3
R
R1
yield (%)a
3a
3bb
(R*,S*)-3c
(R*,R*)-3c
(R*,S*)-3d
(R*,R*)-3d
-(CH2)5-
80
98
80
80
85
60
aziridine 2
electrophile
D2O
CH3I
CH3(CH2)2I
acetone
cyclohexanone
benzophenone
propiophenone
t-BuCHO
4-Cl-C6H4CHO
furfural
yield (%)a
drb
2f
Ph
t-Bu
H
4-Cl-C6H4
Ph
H
(R*,R*)-2hc
(R*,S*)-2hd
(R*,R*)-2ic
(R*,S*)-2id
2a
2b
2c
2d
2e
2f
2g
2h
2i
95
95
95
57
21
73
t-Bu
H
4-Cl-C6H4
H
aCalculated by 1H NMR analysis of the crude. bSee ref 12.
cMajor diastereoisomer. dMinor diastereoisomer.
52c
82d
85d
80d
70/30
80/20
70/30
70/30
2j
b
aIsolated yield. Diastereomeric ratio calculated on the
1H NMR of the crude reaction mixture. cOnly the major di-
astereoisomer was isolated. dOverall yield of a separable
mixture of stereoisomers.
The reaction with carbonyl compounds gave hydro-
xyalkylated derivatives 2d-j with a low stereoselectivity.
Fortunately the diastereoisomers could be easily separated
by flash chromatography.
The results of the lithiation/trapping sequence above clearly
demonstrate the directing group ability of the aziridine ring. It
is, indeed, worth pointing out that the lithiation of the related
acyclic derivative, 2-N,N-dimethylaminomethyltoluene, is
comparatively much slower requiring more than 6 h at room
temperature for complete deprotonation.8f,9
FIGURE 1. Selected NOE interactions for stereochemical assignment.
The relative stereochemistry of isochromans (R*,S*)-3c,d
and (R*,R*)-3c,d was ascertained by selective 1D NOESY
experiments,13 the major isomers having an (R*,S*) relative
configuration (Figure 1).
As illustrated in Scheme 3, considering that the reaction
occurs exclusively with an SN2 mechanism,14 two possible
pathways could be hypothesized: the first involves nitrogen
protonation and ring-opening by nucleophilic addition of
the hydroxy group to the benzylic R-carbon (path a,
Scheme 3), and the second involves the intermediacy of an
acetate followed by nucleophilic displacement of acetic acid
by the hydroxy group (path b, Scheme 3).15
The ortho-hydroxyalkylated aziridines 2e-j were cyclized
to prepare a range of isochromans (Scheme 2).11
Several proton sources [TFA, (COOH)2, HCOOH,
H2SO4] and solvents (THF, CH3CN, Et2O, dioxane/H2O
4/1) were examined in order to find the best conditions.
Acetic acid either as proton source or reaction solvent at
room temperature proved to be superior with better yields
and cleaner reactions for the preparation of the isochromans
3a-d (Table 2). In the case of compounds 2h and 2i both
diastereoisomers were cyclized and the relative configura-
tions of the isochromans and the corresponding hydro-
xyalkylated aziridines were determined.12
These mechanistic pathways were distinguished by deter-
mining the stereochemistry of the major isomer 2i by X-ray
analysis.16 When diastereomerically pure (R*,R*)-2i was
(13) Neuhaus, D.; Williamson, M. In The Nuclear Overhauser Effect in
Structural and Conformational Analysis; VCH: New York, 1989; p 264.
(14) This assumption rises considering that the reaction on pure diaster-
eomers of (R*,R*)-2h,i and (R*,S*)-2h,i is highly stereospecific giving only
one isochroman. Likely, a mixture of diastereomeric isochromans should
have been obtained with an SN1 mechanism.
(11) Vaulx, R. L.; Jones, F. N.; Hauser, C. R. J. Org. Chem. 1964, 29,
1387–1391.
(15) Such hypothesis could be put forward since the GC-MS analysis of
the crude reaction mixture showed a side product deriving from the addition
of CH3COOH to the starting aziridine 2.
(16) CCDC 733354 contains the supplementary crystallographic data for
compound (R*,R*)-2i. These data have been deposited with the Cambridge
Crystallographic Data Centre and can be obtained free of charge via www.
ccdc.cam.ac.uk/data_request/cif.
(12) Following a referee’s suggestion, the one-pot cyclization was per-
formed by addition of 2 mL of acetic acid to the reaction mixture (1 mmol
scale) obtained after quenching of the lithiated intermediate with benzophe-
none. The complete conversion of 2f into 3b was observed and the isochro-
man was isolated with 40% yield.
6320 J. Org. Chem. Vol. 74, No. 16, 2009

Dammacco et al.
JOCNote
SCHEME 3. Reaction Pathways for the Intramolecular Cycli-
zation of Hydroxyalkylated Aziridines
SCHEME 4. Preparation of Optically Active o-Tolylaziridine (S)-1
SCHEME 5. Lateral Lithiation of Chiral o-Tolylaziridine (S)-1
dissolved in acetic acid only isochroman (R*,S*)-3d was
obtained, likely as the result of a single SN2 reaction with
one inversion of configuration (path a, Scheme 3). This
result, with NMR evidence, allowed the assignment of the
relative configuration (R*,R*) to the major isomers of the
hydroxyalkylated aziridines 2h-j.
Aware of the importance of the biological activities of
some isochroman derivatives,17 and that the control of their
stereochemistry could be an important goal in planning a
synthesis of such a scaffold, we turned our attention to the
chiral version of this lateral-lithiation/electrophile trapping
sequence.
The first step was the synthesis of the enantioenriched
aziridine (S)-4 ([R]D þ178 (c 1.5, CHCl3)),18 which was
obtained in >98:2 er starting from commercially available
(R)-(-)-styreneoxide (Scheme 4). Enantioenriched aziridine
(S)-4 was subjected to an ortho-lithiation/methylation
sequence to give enantioenriched o-tolylaziridine (S)-1.4
Surprisingly, when aziridine (S)-1 was subjected to lithiation
under the same conditions (s-BuLi/TMEDA THF, -78 °C,
30 min) used for (()-1, a completely racemic sample was
obtained upon quenching with
a deuterium source
(Scheme 5).
A possible explanation for the observed racemization
could be an aziridine ring-opening-promoted resonance
(Scheme 4).19 Reclosing to the aziridine might then occur
on both the enantiotopic faces of the double bond causing
racemization. In striking contrast, it was found that when the
same lithiation/electrophile trapping sequence was per-
formed in a less polar solvent such as hexane, no racemiza-
tion occurred and highly enantioenriched (S)-2a was
obtained. Likely the solvent could affect the nature and the
aggregation state of the lithiated intermediate disfavoring
racemization.20 The trapping reaction with carbonyl com-
pounds gave chiral derivatives (S)-2f, (1S,20S)-2i, and
(1R,20S)-2i which were subsequently converted into the
corresponding enantioenriched isochromans (R)-3b, (1R,-
3S)-3d, and (1R,3R)-3d.21
In conclusion, this work reports a new and convenient
methodology for the preparation of ortho-functionalized
aziridines based on the benzylic lithiation of simple and
easily available o-tolylaziridines. The role of the aziridine
ring as a directing group is significant in showing a higher
efficiency relative to open chain benzylamines. The useful-
ness of the hydroxyalkylated aziridines has been demon-
strated with the preparation of isochroman derivatives with
controlled stereochemistry and in highly enantioenriched
form.
(17) (a) Schoenleber, R. W.; DeNinno, M. P.; Basha, F. Z.; Ehrlich, P. P.;
Perner, R. J.; Meyer, M. D.; Campbell, J. R.; Martin, Y. C.; Stout, D. M.; De
Bernardis, J. F.; Morton, H. E.; Michaelides, M. Patent WO 96/38435, 1996.
(b) Len, C.; Pilard, S.; Lipka, E.; Vaccher, C.; Dubois, M. P.; Shrinska, Y.; Tran, V.;
Rabiller, C. Tetrahedron 2005, 61, 10583–10595. (c) TenBrink, R. E.; Bergh, C.
L.; Duncan, J. N.; Harris, D. W.; Huff, R. M.; Lahti, R. A.; Lawson, C. F.; Lutzke,
B. S.; Martin, I. J.; Rees, S. A.; Schlachter, S. K.; Sih, J. C.; Smith, M. W. J. Med.
Chem. 1996, 39, 2435–2437. (d) DeNinno, M. P.; Schoenleber, R. W.; Asin, K. E.;
MacKenzie, R.; Kababian, J. W. J. Med. Chem. 1990, 33, 2950–2952.
(18) Fujita, S.; Imamura, K.; Nozaki, H. Bull. Soc. Chem. Jpn. 1971, 44,
1975–1977.
(20) A NMR investigation could help to shed light on this isomerization
process; for a related example on the solvent effect, see: Capriati, V.; Florio,
S.; Luisi, R.; Mazzanti, A.; Musio, B. J. Org. Chem. 2008, 73, 3197–3204.
(21) The absolute configuration could be assigned considering that the
intramolecular cyclization is highly stereospecific (see infra).
(19) The resonance effect is often invoked for this kind of intermediate
even if their structures are still unknown, see: (a) Clark, R. D.; Jahangir, A.
Org. React. 1995, 47, 1–314. (b) Ito, Y.; Nakatsuka, M.; Saegusa, T. J. Am.
Chem. Soc. 1982, 104, 7609–7622.
J. Org. Chem. Vol. 74, No. 16, 2009 6321

Dammacco et al.
JOCNote
Experimental Section
column; hexane:iPrOH 99:1; flow 1.0 mL/min; for (()-2f t1 =
9.7 min, t2=10.9 min; for (S)-2f t=10.9 min) ([R]20D þ319 (c 1,
CH3CN)).
General Procedure for the Lithiation/Trapping Sequence of
Aziridine (S)-1. To a stirred solution of (o-tolyl)aziridine (S)-1
(100 mg, 0.68 mmol) and TMEDA (204.0 μL, 1.36 mmol) in
hexane (4 mL) at -78 °C was added dropwise a solution of
sec-BuLi (1.4 M in hexane, 972 μL, 1.36 mmol). After 30 min
at -78 °C the electrophile (1.36 mmol) was added neat if liquid
and in 2.0 mL of solvent if solid. After 2 h at -78 °C, the mixture
was allowed to warm slowly to room temperature and the
reaction mixture was poured into saturated aqueous NH4Cl
(10 mL) and extracted with Et2O (3 ꢀ10 mL). The combined
organic layers were dried (Na2SO4), filtered, and concentrated
in vacuo. Flash chromatography afforded the substituted azir-
idines 2.
General Procedure for the Preparation of Isochroman 3. The
hydroxyalkylated phenylaziridine 2 (1.0 mmol) in 3.0 mL of
acetic acid was stirred at room temperature until the disappear-
ance of the starting material (TLC monitoring, AcOEt/petro-
leum ether, 8/2). The resulting reaction mixture was poured into
20 mL of aqueous NaOH (10%) and extracted with CH2Cl2 (3 ꢀ
10 mL), then the combined organic extracts were dried (Na2SO4)
and evaporated in vacuo. The crude was purified by flash
chromatography (silica gel; CH2Cl2/MeOH, 9/1) to obtain the
pure isochroman 3.
1-Methylaminomethyl-3,3-diphenyl-3,4-dihydro-1H-isochro-
mene (R)-3b: white solid, mp 123-126 °C, 77%; 1H NMR
(CDCl3, 400 MHz) δ 2.15 (br s, 1 H), 2.56 (s, 3 H), 3.04 (dd,
J=12.2, 8.5 Hz, 1 H), 3.15 (dd, J=12.2, 2.5 Hz, 1 H), 3.30 (d, J=
16.5 Hz, 1 H), 3.66 (d, J = 16.5 Hz, 1H), 4.68 (d, br, J = 7.7 Hz,
1 H), 6.9 (d, J=7.5 Hz, 1 H), 7.07-7.31 (m, 12 H), 7.37 (m, 1 H);
13C NMR (CDCl3, 100 MHz) δ 36.1, 39.4, 56.9, 71.0, 78.8,
123.9, 125.1, 126.2, 126.6, 126.7, 127.0, 127.9, 128.0, 128.1,
128.3, 133.5, 135.2, 141.6, 148.2; ESI-MS m/z (%) 330 [M -
H]þ (100); FT-IR (KBr, cm-1) 3430, 1600, 1447, 1073, 752, 700.
Anal. Calcd for C23H23NO: C, 83.85; H, 7.04; N, 4.25. Found:
C, 84.05; H, 7.07; N, 4.15. Enantiomeric purity of (R)-3b
determined by HPLC analysis (OD-H chiral column; hexane:
iPrOH 99:1; flow 0.5 mL/min; for (()-3b t1 = 55.1 min, t2 =
108.5 min; for (R)-3b t = 55.1 min); ([R]D -226.2 (c 0.5,
CHCl3)).
2-(2-Deuteriomethylphenyl)-1-methylaziridine (S)-2a: color-
less oil, 98% (98% D); 1H NMR (CDCl3, 400 MHz) δ 1.60 (d,
J=6.2 Hz, 1 H), 1.84 (d, J=3.7 Hz, 1 H), 2.33 (dd, J=3.5, 6.5 Hz,
1 H), 2.37 (t, CH2D, J=1.8 Hz, 2 H), 2.50 (s, 3 H), 7.10-7.24 (m,
4 H); 13C NMR (CDCl3, 100 MHz) δ 19.2 (t, JC-D=37 Hz),
37.6, 40.4, 48.0, 125.7, 125.9, 126.6, 129.5, 136.4, 138.0; GC-MS
m/z (%) 147 [Mþ, 100], 132 (45), 117 (19), 106 (16), 91 (9); FT-IR
(film, cm-1) 3025, 2967, 2944, 2848, 2779, 1491, 1454, 1383, 752,
732. Enantiomeric purity of (S)-2a determined by 1H NMR in
the presence of Mosher’s acid (er >99:1) ([R]20 þ104 (c 1.1,
D
CHCl3)).
2-[2-(1-Methylaziridin-2-yl)phenyl]-1,1-diphenylethanol (S)-
2f: white solid, mp 154-156 °C, 73%; H NMR (CDCl3, 400
1
MHz) δ 1.67 (d, J=6.6 Hz, 1 H), 2.14 (d overlapping s at 2.16
ppm, J=3.7 Hz, 1 H), 2.16 (s, 3 H), 2.46 (dd, J=3.6, 7.0 Hz, 1 H),
3.80 (s, 2 H), 6.16 (d, J=8.0 Hz, 1 H), 6.91 (t, J=8.0 Hz, 1 H),
7.08-7.18 (m, 3 H), 7.20-7.24 (m, 3 H), 7.33-7.34 (m, 4H), 7.70
(d, J=7.5 Hz, 2 H); 13C NMR (CDCl3, 150 MHz) δ 35.5, 42.2,
45.2, 45.5, 75.7, 124.8, 126.0, 126.1, 126.3, 126.6, 126.7, 127.5,
128.0, 128.7, 130.6, 136.7, 138.3, 147.1, 151.0; GC-MS m/z (%)
329 [Mþ, 1], 299 (17), 146 (100), 104 (35), 77 (14); FT-IR
(KBr, cm-1) 3424, 3063, 2940, 2850, 1447, 1080, 1059, 770,
755, 699. Anal. Calcd for C23H23NO: C, 83.44; H, 7.88; N, 4.05.
Found: C, 83.02; H, 7.75; N, 4.28. Enantiomeric purity of (S)-2f
(er >99:1) determined by HPLC analysis (OD-H chiral
Acknowledgment. This work was carried out under the
framework of the National Project “Stereoselezione in
Sintesi Organica. Metodologie ed Applicazioni” and
supported by the University of Bari.
Supporting Information Available: Experimental proce-
dures, spectra of the new compounds, and copies of 1D and
2D NMR experiments. This material is available free of charge
via the Internet at http://pubs.acs.org.
6322 J. Org. Chem. Vol. 74, No. 16, 2009