Iodomethylation of Chiral α-Amino Aldehydes by Means of Samarium/Diiodomethane. Application to the Synthesis of Various Enantiomerically Pure Compounds

Article abstract of DOI:10.1021/jo970318i

Chiral iodohydrins 2 have been obtained from α-amino aldehydes 1 and Sm/CH₂I₂. Treatment of compound 2 with acetic anhydride, NaH, or AgBF₄ affords, with high diastereoselectivity, O-protected 3-(dibenzylamino)-1-iodoalkan-2-ol 3, amino epoxides 4, or azetidinium salts 5, respectively. The synthesis of enantiomerically pure allylamines 6 is also described by metallation of 3 with zinc. The reaction of α-amino aldehydes 1 with Sm/CH₂I₂ and further treatment with organocuprates affords chiral amino alcohols 7 in a one-pot process.

Full text of DOI:10.1021/jo970318i

8902
J . Org. Chem. 1997, 62, 8902-8906
Iod om eth yla tion of Ch ir a l r-Am in o Ald eh yd es by Mea n s of
Sa m a r iu m /Diiod om eth a n e. Ap p lica tion to th e Syn th esis of
Va r iou s En a n tiom er ica lly P u r e Com p ou n d s
J ose´ M. Concello´n*
Departamento de Quı´mica Orga´nica e Inorga´nica and Instituto Universitario de Qu´ımica
Organometa´lica, Facultad de Quı´mica, Universidad de Oviedo, J ulia´n Claverı´a, 8, 33071 Oviedo, Spain
Pablo L. Bernad and J uan A. Pe´rez-Andre´s
Departamento de Quı´mica Orga´nica e Inorga´nica, Facultad de Qu´ımica, Universidad de Oviedo,
J ulia´n Claverı´a, 8, 33071 Oviedo, Spain
Received February 19, 1997
Chiral iodohydrins 2 have been obtained from R-amino aldehydes 1 and Sm/CH2I2. Treatment of
compound 2 with acetic anhydride, NaH, or AgBF4 affords, with high diastereoselectivity,
O-protected 3-(dibenzylamino)-1-iodoalkan-2-ol 3, amino epoxides 4, or azetidinium salts 5,
respectively. The synthesis of enantiomerically pure allylamines 6 is also described by metallation
of 3 with zinc. The reaction of R-amino aldehydes 1 with Sm/CH2I2 and further treatment with
organocuprates affords chiral amino alcohols 7 in a one-pot process.
In tr od u ction
formations into other functionalities such as aminoal-
kenes5 or R-amino aldimines.6
Chiral R-amino aldehydes are important compounds
widely used in organic synthesis owing to their ready
availability from R-amino acids1 and pronounced versatil-
ity. In recent years, several basic organic reactions using
R-amino aldehydes have been described to prepare enan-
tiomerically pure compounds such as organometallic
addition to carbonyl groups,2 aldol condensations,3 [4 +
2] cycloadditions with activated 1,3-dienes,4 and trans-
On the other hand, the halomethylation of carbonyl
compounds is known to be difficult to achieve under
ordinary reaction conditions due to the instability of
(halomethyl)lithium compounds.7 As an alternative, this
kind of reaction proceeds smoothly at room temperature
using samarium metal8 or samarium(II) iodide9 and
diiodomethane. However, to the best of our knowledge,
iodomethylation of chiral carbonyl compounds has not
been reported in the literature to date, and consequently,
there is no information about the utility of this methodol-
ogy in the synthesis of optically pure compounds.10
The halomethylation of chiral R-amino aldehydes
would afford iodohydrins, which could be easily trans-
formed into R-amino epoxides, azetidines, â-amino alco-
hols, or allylic amines. These compounds are important
because of their biological properties and synthetic ap-
plications. As examples, chiral R-amino epoxides are
highly useful intermediates in the synthesis of protease
inhibitors11 and other pharmaceutically interesting com-
pounds;12 the azetidine ring is present in an important
number of molecules with biological activity;13 â-amino
* To whom correspondence should be addressed. Fax: 34-8-510-
3446. E-mail: jmcg@sauron.quimica.uniovi.es.
X Abstract published in Advance ACS Abstracts, November 15, 1997.
(1) J urczak, J .; Golebiowski, A. Chem. Rev. 1989, 89, 149.
(2) (a) Reezt, M. T.; Drewes, M. W.; Schmitz, A. Angew. Chem., Int.
Ed. Engl. 1987, 26, 1141. (b) Hanson, G. J .; Lindberg, T. J . Org. Chem.
1985, 50, 5399. (c) Reezt, M. T.; Drewes, M. W.; Harms, K.; Reif, W.
Tetrahedron Lett. 1988, 29, 3295. (d) Reetz, M. T.; Reif, W.; Holdgru¨n
Heterocycles 1989, 28, 707. (e) Holladay, M. W.; Rich, D. H. Tetrahedron
Lett. 1983, 24, 4401. (f) Fray, A. H.; Kaye, R. L.; Kleiman, E. F. J .
Org. Chem. 1986, 51, 4828. (g) Newman, H. J . Am. Chem. Soc. 1973,
95, 4098. (h) Saitoh, Y.; Moriyama, Y.; Takahashi, T.; Khuong-Huu,
Q. Tetrahedron Lett. 1980, 21, 75.
(3) (a) Evans, D. A.; Nelson, J . V.; Taber, T. R. Top. Stereochem.
1983, 13, 1. (b) Heathcock, C. H. In Asymmetric Synthesis; Morrison,
J . D., Ed.; Academic Press: New York, 1984; Vol. 3B, p 111. (c) Narita,
M.; Otsuka, S.; Kobayashi, S.; Ohno, M.; Umezawa, Y.; Morishima,
H.; Saito, S; Takita, T.; Umezawa, H. Tetrahedron Lett. 1982, 23, 525.
(d) Hamada, Y.; Shioiri, T. Chem. Pharm. Bull. 1982, 30, 1921. (e)
Pyne, S. G.; Hensel, M. J .; Fuchs, P. L. J . Am. Chem. Soc. 1982, 104,
5719. (f) Ohfune, Y.; Nishio, H. Tetrahedron Lett. 1984, 25, 4133. (g)
Andersson, L.; Wolfenden, R. Anal. Biochem. 1982, 124, 150. (h) Reetz,
M. T. Wu¨nsch, T.; Harms, K. Tetrahedron Asymm. 1990, 1, 371.
(4) (a) Danishefsky, S.; Larson, E.; Askin, D.; Kato, N. J . Am. Chem.
Soc. 1985, 42, 5045. (b) Garner, P.; Ramakanth, S. J . Org. Chem. 1986,
56, 2609. (c) Matsumoto, K.; Sera, A.; Uchida, T. Synthesis 1985, 1.
(d) Midland, M. M.; Alfonso, M. M. J . Am. Chem. Soc. 1989, 111, 4368.
(e) J urzak, J .; Golebiowsky, A.; Raczko, J . J . Org. Chem. 1989, 54,
2495. (f) Weinreb, S. M.; Staib, R. R. Tetrahedron 1982, 51, 2609. (g)
Danishefsky, S.; Kobayashi, S.; Kerwin, J . F., J r. J . Org. Chem. 1982,
47, 1981.
(5) (a) Reetz, M. T.; Ro¨hring, D. Angew. Chem., Int. Ed. Engl. 1989,
28, 1706. (b) Kozikowski, A. P.; Nieduzak, T. R.; Konoike, T.; Springer,
J . P. J . Am. Chem. Soc. 1987, 109, 5167. (c) Kozikowski, A. P.;
Nieduzak, T. R.; Springer, J . P. Tetrahedron Lett. 1986, 27, 819. (d)
Kozikowski, A. P.; Konoike, T.; Nieduzak, T. R. J . Chem. Soc., Chem.
Commun. 1986, 1350. (e) Itaya, T.; Fujii, T.; Evidente, A.; Randazzo,
G.; Surico, G.; Iacobellis, N. S. Tetrahedron Lett. 1986, 27, 6349. (f)
Sodano, G.; Spinella, A. Tetrahedron Lett. 1986, 27, 2505. (g) Ko-
miyama, K.; Urano, Y.; Kobayashi, S.; Ohno, M.; Tetrahedron Lett.
1987, 28, 3123. (h) Hensel, M. J .; Fuchs, P. L. Synth. Commun. 1986,
16, 1285. (i) Kogen, H.; Nishi, T. J . Chem. Soc., Chem. Commun. 1987,
311.
(6) Reetz, M. T.; J aeger, R.; Drewlies, R.; Hu¨bel, M. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 103.
(7) Aube´, J . In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: New York, 1991; p 260.
(8) (a) Imamoto, T.; Takeyama, T.; Koto, H. Tetrahedron Lett. 1986,
27, 3243. (b) Imamoto, T.; Hatajima, T.; Takiyama, W.; Takeyama, T.;
Kamiya, Y.; Yoshizawa, T. J . Chem. Soc., Perkin Trans. 1 1991, 3127.
(9) (a) Girard, P.; Namy, J . L.; Kagan, H. B. J . Am. Chem. Soc. 1980,
102, 2693. (b) Tabuchi, T.; Inanaga, J .; Yamaguchi, J . Tetrahedron Lett.
1986, 27, 3891. (c) For a recent review about reactions with samari-
um(II) iodide, see: Molander, G. A.; Harris, C. R. Chem. Rev. 1996,
96, 307.
(10) While this manuscript was being reviewed, preliminary results
about the reaction of diiodoalkanes with aldehydes using samarium
diiodide were reported, including two examples with chiral sub-
strates: Matsubara, S.; Yoshioka, M.; Utimoto, K. Angew. Chem., Int.
Ed. Engl. 1997, 36, 617. Synthetic applications of this reaction are
not described.
(11) (a) Pegorier, L.; Petit, Y.; Larcheveˆque, M. J . Chem. Soc., Chem.
Commun. 1994, 633. (b) Evans, E. V.; Rittle, E. K.; Homnicik, C. F.;
Springer, J . P.; Hirshfield, J .; Veber, D. F. J . Org. Chem. 1985, 50,
4615. (c) Luly, J . R.; Plattner; J . J .; Stein, H.; Yi, N.; Cohen, J .;
Tricarico, K.; Dellaria, J . F. Pharmacologist 1985, 27, 260.
(12) Luly, J . R.; Dellaria, J . F.; Plattner, J . J .; Soderquist, J . L.; Yi,
N. J . Org. Chem. 1987, 52, 1487.
S0022-3263(97)00318-6 CCC: $14.00 © 1997 American Chemical Society

Iodomethylation of Chiral R-Amino Aldehydes
J . Org. Chem., Vol. 62, No. 25, 1997 8903
Ta ble 1. Syn th esis of Com p ou n d s 3-6
Sch em e 1a
entry
R
producta
yieldb (%)
dec (%)
1
2
3
4
5
6
7
8
9
Me
iBu
Bn
Me
iBu
Bn
Me
iBu
Bn
Me
iBu
Bn
3a
3b
3c
4a
4b
4ce
5a
5b
5c
6a
6be
6c
72
65
70
81
81
79
81
82
77 (48d)
74
80 (61d)
81
62
60
81
80
82
59
10
11
12
87f
84f
82f
a
b
All reactions were carried out at room temperature. Isolated
yield after purification based on the starting R-amino aldehyde 1.
c Diastereomeric excess determined by 1H NMR (300 MHz) and/
a
Reagents and conditions: (i) Sm0/CH2I2, THF, 0 °C, 40 min,
then H3O+; (ii) Ac2O, pyridine, rt; (iii) NaH, CH2Cl2, rt; (iv) AgBF4,
Et2O, rt; (v) H2O.
or quantitative 13C NMR analysis of the crude products. Reaction
d
temperature -50 °C. e ee > 99% HPLC (Chiracel OD-H; 0.8 mL/
min; UV detector; 4c, 225 nm; 50:1 hexane/2-propanol; tR ) 17.15
min; 6b, 235 nm; 400:1 hexane/2-propanol; tR ) 6.15 min).
f Isolated yield after purification based on the starting compound
3.
alcohols are biologically important,14 and the allylic
amine moiety appears in many natural and bioactive
compounds.15 Moreover, R-amino epoxides,16 azetidines,17
and allylamines18 can be used as chiral building blocks
for a wide variety of compounds, and â-amino alcohols
can be used as chiral auxiliaries.19
In this paper, we describe the preparation of enantio-
merically pure, protected 3-amino-1-iodo 2-alcohols from
chiral R-amino aldehydes and Sm/CH2I2, which are
appropriate starting compounds for a simple and direct
entry to amino epoxides, 3-hydroxy azetidinium salts,
allylamines, and â-amino alcohols.
could be isolated and purified by flash column chroma-
tography (Scheme 1 and Table 1, entries 1-3). Despite
their instability, iodohydrins 2 could be converted to
different compounds using the crude product (see the
Experimental Section). Reaction of iodohydrins 2 with
NaH at room temperature led to erythro amino epoxides
4 (Scheme 1 and Table 1). The stereochemistry of amino
epoxides 4 was established unambiguously by comparison
of their NMR spectra with those previously reported.21
The iodomethylation of amino aldehydes 1 with Sm/CH2I2
took place with good diastereoselectivity. The diastere-
omeric excess (de) of compounds 4a -c was higher than
Resu lts a n d Discu ssion
Treatment of a mixture of diiodomethane and different
N,N-dibenzylated R-amino aldehydes 1 with samarium
metal at 0 °C gave, after hydrolysis, the corresponding
iodohydrins 2 (Scheme 1). When iodohydrins were taken
to dryness they became unstable and decomposed to a
mixture of several products. Therefore, these compounds
were identified by NMR spectroscopy of the crude reac-
tion mixture before the solvent was completely removed.20
In order to characterize compounds 2 they were trans-
formed into their O-acetyl derivatives 3 by treatment
with acetic anhydride at room temperature, and these
1
80%, as determined by 300-MHz H NMR and quantita-
tive 13C NMR spectroscopy. Interestingly, when the
reaction was carried out at lower temperature the de of
4b decreased (entry 5 in Table 1).22
Iodomethylation of 1 proceeds with no detectable
racemization. The enantiomeric purity of the major
diastereomer of compound 4c23 was determined by chiral
HPLC analysis (Chiracel OD-H) showing an enantiomeric
excess (ee) >99%; for comparison, a racemic mixture of
4c was prepared and HPLC analysis excluded the pos-
sibility of coelution of both enantiomers.
The observed stereochemistry of 4 can be explained by
assuming a nonchelation control model in the iodo-
methylation reaction of aldehyde 1. This diastereofacial
preference is the same as that previously reported for
the addition of other organometallic compounds to diben-
zylated amino aldehydes.21
Reaction of compounds 2 with AgBF4 at room temper-
ature afforded the corresponding azetidinium salts 5 with
high diastereoselectivity, in agreement with the de of
compounds 4 (Scheme 1 and Table 1, entries 7-9).
Configurational assignments of products 5 were estab-
(13) (a) Antibacterial: J acquet, J . P.; Bouzard, D.; Kiechel, J . R.;
Remuzon, P.; Tetrahedron Lett. 1991, 32, 1565. (b) Fungicidal: Isono,
K.; Asahi, K.; Suzuki, S. J . Am. Chem. Soc. 1969, 91, 7490. (c)
Monoamine oxidase inhibitory activity: Wells, J . N.; Tarwater, O. R.
J . Pharm. Bull. 1974, 22, 1490. (d) Actomyosin ATPase activating
activities: Takikawa, H.; Maeda, T.; Mori, K. Tetrahedron Lett. 1995,
36, 7689.
(14) Gladych, J . M. Z.; Hartley, D. In Comprehensive Organic
Chemistry; Barton, D., Ollis, W. D., Eds.; Pergamon: Oxford, 1979;
Vol. 2, p 99.
(15) Hutchins, R. O.; Wei, J .; Rao, S. J . J . Org. Chem. 1994, 59,
4007 and references cited therein.
(16) For applications of epoxides in organic synthesis, see: Behrens,
C. H.; Sharpless, K. B. Aldrichim. Acta 1993, 16, 67.
(17) For reactivity of azetidines: (a) Davies, D. E.; Stor, R. C. In
Comprehensive Heterocyclic Chemistry; Lwowski, W., Ed.; Pergamon:
Oxford, 1984; Vol. 7, pp 238-284. Other recent synthetic applications
of azetidines: (b) J ung, M. E.; Choi, Y. M. J . Org. Chem. 1991, 56,
6729. (c) Viallm, L.; Reinand, O.; Capdevielle, P.; Maumy, M. Tetra-
hedron Lett. 1995, 36, 4787.
(21) (a) Barluenga, J .; Baragan˜a, B.; Concello´n, J . M. J . Org. Chem.
1995, 60, 6696. (b) Reetz, M. T.; Binder, J . Tetrahedron Lett. 1989,
30, 5425.
(22) Similar diastereoselection temperature dependence has been
reported for other reactions induced by SmI2: (a) Kawatsura, M.;
Matsura, F.; Shirahawa, H. J . Org. Chem. 1994, 59, 6900. (b)
Kawatsura, M.; Hosaka, K.; Matsura, F.; Shirahawa, H. Synlett 1995,
729. (c) Kawatsura, M.; Dekura, F.; Shirahawa, H.; Matsura, F. Synlett
1996, 373. (d) Fallis, A. G.; Sturino, C. F. J . Am. Chem. Soc. 1994,
116, 7447.
(23) The high tendency of the N,N-dibenzylated aldehyde 4c (ob-
tained from phenylalanine) to racemize has been documented: Rittle,
K. E.; Homnick, C. F.; Ponciello, G. S.; Evans, B. E. J . Org. Chem.
1982, 47, 3016.
(18) For a review on the asymmetric isomerization of allylamines,
see: Akutagawa, S.; Tani, K. In Catalytic Asymmetric Synthesis; Ojima,
I., Ed.; VCH Publishers: New York, 1993; pp 41-61.
(19) Ager, D. J .; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96,
835.
(20) 13C-NMR of compounds 2 were recorded in the presence of THF
(20-50%). 2a : 130.9-128.2, 66.5 (CH), 59.0 (CH), 54.6 (CH2), 54.2
(CH2), 7.7 (CH3), 5.7 (CH2). 2b: 132.1-126.7, 66.5 (CH), 60.8 (CH) ,
55.0 (CH2), 54.5 (CH2), 31.8 (CH2), 29.2 (CH), 22.6 and 21.0 (2 × CH3),
7.2 (CH2).

8904 J . Org. Chem., Vol. 62, No. 25, 1997
Concello´n et al.
Sch em e 2
amino alcohols than direct reaction of R-amino aldehydes
with organolithium compounds or Grignard derivatives,
for instance, to obtain 7d ,e.27
In conclusion, iodomethylation of chiral carbonyl com-
pounds using Sm/CH2I2 is an easy, rapid, and mild
methodology for the transformation of R-amino aldehydes
into optically pure amino epoxides, 3-hydroxy azeti-
dinium salts, allylamines, and â-amino alcohols.
Exp er im en ta l Section
Sch em e 3a
Gen er a l Meth od s. Reactions requiring an inert atmo-
sphere were conducted under dry nitrogen, and the glassware
was oven dried (120 °C). THF and ether were distilled from
sodium/benzophenone ketyl immediately prior to use. All
reagents were purchased from Aldrich or Acros and were used
without further purification. Amino aldehydes 1 were pre-
pared according to literature procedures.2a Powdered zinc was
washed successively with aqueous HCl, H2O, MeOH, and ether
and then dried in vacuo. Pyridine was stored over NaOH.
Silica gel for flash chromatography was purchased from
Scharlau or Merck (200-450 mesh), and compounds were
visualized on analytical thin-layer chromatograms (TLC) by
UV light (254 nm). 1H NMR spectra were recorded at 200,
300, or 400 MHz. 13C NMR spectra and DEPT experiments
were determined at 50 or 75 MHz. Chemical shifts are given
in ppm relative to tetramethylsilane (TMS), which is used as
an internal standard, and coupling constants (J ) are reported
a
Reagents and conditions: (i) Sm/CH2I2, THF, 0 °C; (ii)
Me2CuLi, 0 °C or (CH2dCHCH2)CuCNMgBr or CH2dCHCH2MgBr,
-78 °C f rt; then NH4OH.
1
Ta ble 2. Syn th esis of Am in o Alcoh ols 7a -e
in Hz. The diastereomeric excesses were obtained using H-
NMR analysis of crude products or by inverse gated decoupling
experiments using chromium acetylacetonate (1 mg) as addi-
tive (namely quantitative 13C NMR). GC-MS and HRMS
were measured at 70 eV or using FAB conditions. When
HRMS could not be measured on the molecular ion the HRMS
of a significant fragment is given. Only the most important
IR absortions (in cm-1) and the molecular ions and/or base
peaks in MS are given. The enantiomeric purity was deter-
mined by chiral HPLC analysis using a Chiracel OD-H (0.46
× 25 cm, Diacel) column.
entry
R
R′
product
yielda (%)
deb (%)
1
2
3
4
5
6
Me
iBu
Bn
Me
Me
iBu
Mec
7a
7b
7c
7d
7d
7e
60
58
56
56
46
54
87
87
90
76
76
77
Mec
Mec
allyld
allyle
allyld
a
Isolated yield after purification based on the starting R-amino
aldehyde 1. Diastereomeric excess determined by 1H NMR (300
b
MHz) and/or quantitative 13C NMR analysis of the crude products.
Gen er a l P r oced u r e for th e P r ep a r a tion of P r otected
Iod oh yd r in s 3. Under a nitrogen atmosphere, samarium
powder (300 mg, 2 mmol) was placed in a Schlenk tube at 0
°C. A solution of CH2I2 (0.24 mL, 3 mmol) and the correspond-
ing amino aldehyde 1 (1 mmol) in THF (6 mL) were added
dropwise with stirring over 20 min. After stirring at the same
temperature for 20 min, the mixture was quenched with 1 M
HCl (30 mL) and extracted with CH2Cl2 (4 × 10 mL). The
combined organic layers were dried (Na2SO4), and to the
resulting solution were added pyridine (10 mL), acetic anhy-
dride (10 mL), and a catalytic amount of DMAP (5 mg). The
reaction mixture was then stirred at room temperature
overnight. Finally, the solution was carefully quenched with
water/ice. The organic layer was separated, and the aqueous
layer was extracted with ether (3 × 20 mL). The combined
extracts were dried over (Na2SO4) and the solvents removed
under reduced pressure (bath temperature 40 °C). Flash
column chromatography over silica gel (hexane/triethylamine
75/1) provided erythro-3-amino-1-iodo-2-acetoxyalkanes 3.
(2S,3S)-3-(N,N-Dib en zyla m in o)-1-iod ob u t a n -2-yl a c-
eta te (3a ): Rf ) 0.4 (hexane/ethyl acetate 10/1); [R]22D ) +4.74
(c 2.3, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 7.41-7.23 (10 H,
m), 4.89 (1 H, ddd, J ) 9.2, 6.7, 3.5), 3.81 and 3.43 (4 H, AB
syst, J ) 13.5), 3.68 (1 H, dd, J ) 6.7, 3.9), 3.29 (1 H, dd, J )
3.9, 3.5), 2.96 (1 H, dq, J ) 9.2, 6.7), 2.11 (3 H, s), 1.11 (3 H,
d, J ) 6.7); 13C NMR (CDCl3, 75 MHz) δ 170.11 (C), 139.0 (C),
128.7, 128.2 and 127.0 (3 × CH), 73.2 (CH), 55.8 (CH), 54.0
(CH2), 20.9 (CH3), 8.3 (CH3), 7.9 (CH2); IR (neat) 1742; MS
m/z 437.1 (M+, <1), 250.1 (22), 224.1 (95), 210.1 (92), 181.1
c Lithium dimethylcuprate was used. Magnesium allylcyanocu-
d
prate bromide was used. e Allylmagnesium bromide was used.
lished by NOESY experiments in the case of compound
5a , showing the trans relative configuration for methyl
and hydroxyl groups.
On the other hand, allylamines 6 were obtained by the
treatment of 3 with zinc powder in the presence of
aqueous acetic acid24 (Scheme 2 and Table 1, entries 10-
12). Compounds 6a -c were synthesized with no detect-
able racemization; chiral HPLC analysis of 6b using a
racemic mixture as reference indicated an ee of 99%. The
formation of these amines can be explained by formation
of the corresponding organozinc compounds that undergo
a â-elimination process to give the carbon-carbon double
bond.25
Finally, secondary amino alcohols were prepared in a
one-pot synthesis starting from R-amino aldehydes 1.
Succesive treatment of N,N-dibenzylated R-amino alde-
hydes 1 with Sm/CH2I2 and Grignard or organocuprate
reagents led to â-amino alcohols 7a -e (Scheme 3 and
Table 2). Diastereoisomeric excesses, between 76 and
1
87%, were determined using either 300 MHz H NMR
or quantitative 13C NMR spectroscopy of crude products.26
This methodology is a better strategy to prepare some
(60), 91.0 (100), 65.0 (42), 43.0 (38); HRMS calcd for C20H24
INO2 437.0852, found 437.0864.
-
(24) Florent, J . C.; Ughetto-Monfrin, J .; Monneret, C. J . Org. Chem.
1987, 52, 1051.
(25) House, H. O.; Ro, R. S. J . Am. Chem. Soc. 1958, 80, 182.
(26) NMR data of 6a -c are available: Andre´s, J . M.; Barrio, M.;
Mart´ınez, M. A.; Pedrosa, R.; Pe´rez-Encabo, A. J . Org. Chem. 1996,
61, 4210.
(27) For example, allylmagnesium bromide (Table 2, entry 5) and
magnesium allylcyanocuprate bromide (Table 2, entries 4,6) are more
readily available than but-3-enyl-1-magnesium bromide (direct reaction
of R-amino aldehydes with organometallic compounds).

Iodomethylation of Chiral R-Amino Aldehydes
J . Org. Chem., Vol. 62, No. 25, 1997 8905
(2S,3S)-3-(N,N-Diben zyla m in o)-1-iod o-5-m eth ylh exa n -
and extracted with ether (3 × 10 mL). The combined organic
layers were dried (Na2SO4) and filtered in a flask covered with
aluminum foil. To the resulting solution was added AgBF4 (2
mmol, 0.40 g) with vigorous stirring under nitrogen. After
being stirred for 0.5 h, the mixture was quenched with H2O
(10 mL), and the solution was filtered, extracted with CH2Cl2
(5 × 20 mL), dried (Na2SO4), and concentrated. The resulting
oil was washed with ether (2 × 5 mL), and azetidinium salts
4 were obtained as colored solids.
2-yl a ceta te (3b): Rf ) 0.4 (hexane/ethyl acetate 10/1); [R]21
D
1
) -24.2 (c 2.41, CHCl3); H NMR (CDCl3, 300 MHz) δ 7.55-
7.20 (10 H, m), 5.31-5.22 (1 H, m), 3.69 (4 H, AB syst, J )
13.5), 3.45 and 3.31 (2 × 1 H, AB portion of ABX), 3.03-2.94
(1 H, m), 2.12 (3 H, s), 1.95-1.83 and 1.75-1.62 (2 × 1 H, m),
1.38-1.17 (1 H, m), 1.04 and 0.82 (2 × 3 H, d, J ) 6.4); 13C
NMR (CDCl3, 75 MHz) δ 170.2 (C), 139.5 (C), 128.9, 128.2 and
127.0 (3 × CH), 72.5 (CH), 57.4 (CH), 53.9 (CH2) 35.4 (CH2),
25.2 (CH), 23.1, 22.5 and 21.2 (3 × CH3), 7.05 (CH2); IR (neat)
1742; MS m/z 479.1 (M+, <1), 266.3 (100), 210.1 (84), 91.0 (96).
(2S,3S)-3-(N,N-Diben zyla m in o)-1-iod o-4-p h en ylbu ta n -
(2S,3R)-1,1-Diben zyl-3-h yd r oxy-2-m eth yla zetid in iu m
tetr a flu or obor a te (5a ): [R]20 ) +16.0 (c 1, acetone); 1H
D
NMR (DMSO-d6, 400 MHz) δ 7.93-7.81 (2 H, m), 7.70-7.51
(8 H, m), 6.36 (1 H, d, J ) 5.71), 4.87, 4.72, 4.61 and 4.18 (4 ×
1 H, d, J ) 13.15), 4.80-4.70 (1 H, m), 4.45 (1 H, dd, J ) 10.8,
7.04), 4.32-4.28 (1 H, m), 3.71-3.66 (1 H, m), 1.62 (3 H, d, J
) 7.04); 13C NMR (DMSO-d6, 75 MHz) δ 133.1, 133.0, 130.5,
130.3, 129.4, and 129.3 (6 × CH), 128.5, 128.4 (2 × C), 76.9
(CH), 63.7 (CH), 62.1, 61.4, 59.2 (3 × CH2), 11.5 (CH3); IR (KBr)
3441; MS (FAB) m/z 268.3 (M+, 100), 224.3 (12), 210.2 (22).
Anal. Calcd for C18H22NOBF4: C, 60.87; H, 6.24; N, 3.94.
Found: C, 60.78; H, 6.30; N, 3.90.
2-yl a ceta te (3c): Rf ) 0.4 (hexane/ethyl acetate 10/1); [R]22
D
1
) +1.54 (c 2.02, CHCl3); H NMR (CDCl3, 300 MHz) δ 7.50-
7.15 (15 H, m), 5.30-5.20 (1 H, m), 3.76 (2 H, d, J ) 13.3),
3.59-3.53 (3 H, m), 3.34-3.27 (1 H, m), 3.20-3.13 (2 H, m),
2.77 (1 H, dd, J ) 14.6, 6.9), 1.8 (3 H, s); 13C NMR (CDCl3, 75
MHz) δ 170.1 (C), 140.0, 138.8 (2 × C), 128.7, 128.2, 127.0
and 125.8 (4 × CH), 73.0 (CH), 61.2 (CH), 54.1 (CH2), 32.1
(CH2), 20.9 (CH3), 7.4 (CH2); IR (neat) 1740; MS m/z 513.1 (M+,
<1), 422.0 (30), 300.2 (63), 210.1 (10), 91.0 (100); HRMS calcd
for C19H21INO2 (M - C7H7) 422.0621, found 422.0617.
Gen er a l P r oced u r e for th e Syn th esis of Am in o Ep -
oxid es 4.21a A solution of CH2I2 (0.24 mL, 3 mmol) and the
corresponding amino aldehyde 1 (1 mmol) in THF (6 mL) was
added dropwise over 20 min to stirred samarium powder (300
mg, 2 mmol) at 0 °C. After being stirred for 20 min, the
mixture was quenched with 1 M HCl (30 mL) and extracted
with CH2Cl2 (4 × 10 mL), and the combined organic layers
were dried (Na2SO4). To the stirred resulting solution was
added NaH (0.24 g, 10 mmol) at room temperature under
nitrogen. After 30 min, the mixture was carefully quenched
with H2O (10 mL) and extracted with ether (3 × 20 mL). The
combined organic layers were dried (Na2SO4), and the solvents
were removed in vacuo. Column flash chromatography over
silica gel (hexane/triethylamine 75/1) provided erythro amino
epoxides 4.
(2S,3R)-1,1-Diben zyl-3-h yd r oxy-2-(2-m eth ylp r op yl)a ze-
tid in iu m tetr a flu or obor a te (5b): [R]20 ) +20.8 (c 1,
D
CHCl3); 1H NMR (DMSO-d6, 300 MHz) δ 7.72-7.41 (2 H, m),
7.40-7.21 (8 H, m), 6.43 (1 H, br s), 4.93-4.76 (3 H, m), 4.64
(1 H, d, J ) 12.7), 4.52-4.46 (1 H, m), 4.28-4.15 (2 H, m),
3.77-3.70 (1 H + residual DMSO, m), 2.20-2.13 (1 H, m),
1.90-1.65 (2 H, m), 1.04 and 0.95 (2 × 3 H, d, J ) 6.2); 13C
NMR (DMSO-d6, 75 MHz) δ 133.0, 132.9, 130.6, 130.2, 129.3
and 129.2 (6 × CH), 128.5 (C), 78.7 (CH), 63.6 (CH), 62.4, 61.6,
59.5 (3 × CH2), 34.4 (CH2), 24.2 (CH), 23.3 and 21.6 (2 × CH3);
IR (KBr) 3528; MS (FAB) m/z 310.3 (M+, 100), 220.2 (10), 133.0
(15). Anal. Calcd for C21H28NOBF4: C, 63.49; H, 7.10; N, 3.53.
Found: C, 63.38; H, 7.16; N, 3.57.
(2S,3R)-1,1,2-Tr iben zyl-3-h ydr oxya zetidin iu m tetr a flu -
or obor a te (5c): [R]20D ) +10.8 (c 1, CHCl3); 1H NMR (DMSO-
d6, 400 MHz) δ 8.02-7.81 (2 H, m), 7.73-7.55 (8 H, m), 7.51-
7.32 (5 H, m), 6.20 (1 H, d, J ) 6.6), 5.13-5.09 (2 H, m), 4.87-
4.82 (2 H, m), 4.53 (1 H, dd, J ) 10.5, 7.0), 4.43-4.22 (2 H,
m), 3.78-3.52 (2 H + residual DMSO, m), 3.43-3.40 (1 H, m);
13C NMR (DMSO-d6, 75 MHz) δ 134.5 (C), 133.2, 133.1, 130.6,
130.3, 129.5, 129.4, 129.3 and 128.9 (8 × CH), 128.4 (C), 127.2
(CH), 79.5 (CH), 63.5 (CH), 62.4, 61.7, 60.0 (3 × CH2), 32.1
(CH2); IR (KBr) 3520; MS (FAB) m/z 344.3 (M+, 100), 254.3
(26), 241.2 (75), 210.2 (15). Anal. Calcd for C24H26NOBF4: C,
66.84; H, 6.08; N, 3.25. Found: C, 66.69; H, 6.11; N, 3.28.
Gen er a l P r oced u r e for th e Syn th esis of Allyla m in es
6. To a stirred solution of 5 (1 mmol) in a mixture of THF (10
mL), acetic acid (2 mL), and H2O (2 mL) was added powdered
zinc at room temperature and the resulting solution stirred
overnight. The solution was decanted and extracted with ether
(3 × 20 mL). The organic layer was washed with a saturated
aqueous solution of Na2CO3, (2 × 10 mL), dried over Na2SO4,
and concentrated, yielding crude allylamines 6, which were
purified by column flash chromatography using hexane/ethyl
acetate (gradient of elution).
(2S)-[1′(S)-Diben zyla m in o)eth yl]oxir a n e (4a ): Rf ) 0.5
1
(hexane/ethyl acetate 10/1); [R]25 ) +9.3 (c 0.68, CHCl3); H
D
NMR (CDCl3, 200 MHz) δ 7.50-7.24 (10 H, m), 3.87 and 3.65
(2 × 2H, AB syst, J ) 14.0), 3.17-3.11 (1 H, m), 2.91-2.78 (1
H, m), 2.72 (1 H, dd, J ) 4.8, 4.1), 2.46 (1 H, dd, J ) 4.8, 2.9),
1.09 (3 H, d, J ) 6.7); 13C NMR (CDCl3, 50 MHz) δ 140.1 (C),
128.4, 128.1 and 126.8 (3 × CH), 54.2 (CH), 54.2 (CH2), 53.8
(CH), 44.8 (CH2), 8.9 (CH3); IR (neat) 3066; MS m/z 267.2 (M+,
2), 224.1 (8), 91.0 (100); HRMS calcd for C18H21NO 267.1623,
found 267.1629. Anal. Calcd for C18H21NO: C, 80.86; H, 7.92;
N, 5.24. Found: C, 80.71; H, 7.90; N, 5.29.
(2S)-[1′(S)-(Dib en zyla m in o)-3′-m et h ylb u t yl]oxir a n e
(4b): Rf ) 0.6 (hexane/ethyl acetate 10/1); [R]25 ) -14.1 (c
D
1
0.32, CHCl3); H NMR (CDCl3, 200 MHz) δ 7.45-7.20 (10 H,
m), 3.87 and 3.67 (2 × 2 H, AB syst, J ) 13.7), 3.04-3.11 (1
H, m), 2.84 (1 H, dd, J ) 5.1, 4.1), 2.53 (1 H, dd, J ) 5.1, 2.9),
2.53-2.43 (1 H, m), 1.96-1.80 (1 H, m), 1.72-1.53 (1 H, m),
1.39-1.15 (1 H, m), 0.88 and 0.69 (2 × 3 H, d, J ) 6.5); 13C
NMR (CDCl3, 50 MHz) δ 140.0 (C), 128.6, 128.1 and 126.8 (3
× CH), 56.4 (CH), 54.2 (CH2), 51.9 (CH), 46.0 (CH2), 36.9 (CH2),
24.3 (CH), 23.3 and 22.1 (2 × CH3); IR (neat) 3028; MS m/z
(2S)-N,N-Diben zylbu t-3-en -2-a m in e (6a ): Rf ) 0.4 (hex-
ane); [R]25D ) -11.6 (c 8.3, CHCl3); 1H NMR (CDCl3, 300 MHz)
δ 7.5-7.2 (10 H, m), 6.0 (1 H, ddd, J ) 17.5, 10.5, 6.4), 5.2 (1
H, d, J ) 10.5), 5.1 (1 H, d, J ) 17.5), 3.71 and 3.59 (4 H, AB
syst, J ) 14.0), 3.32 (1 H, m), 1.22 (3 H, d, J ) 6.7); 13C NMR
(CDCl3, 75 MHz) δ 139.7 (CH), 140.5 (C), 128.4, 128.1 and
126.6 (3 × CH), 115.6 (CH), 54.9 (CH), 53.4 (CH2), 14.6 (CH3);
IR (neat) 1603; MS m/z 251.1 (M+, 9), 236.1 (96), 224.1 (7),
91.0 (100); HRMS calcd for C18H21N 251.1674, found 251.1664.
(3S)-N,N-Diben zyl-5-m eth ylh ex-1-en -3-a m in e (6b): Rf
309.1 (M+, 2), 266.1 (28), 91.0 (100); HRMS calcd for C21H27
-
NO 309.2093, found 309.2106. Anal. Calcd for C21H27NO: C,
81.51; H, 8.79; N, 4.53. Found: C, 81.32; H, 8.70; N, 4.59.
(2S)-[1′(S)-(Dib e n zyla m in o)-2′-p h e n yle t h yl]oxir a n e
(4c): Rf ) 0.36 (hexane/ethyl acetate 15/1); [R]25 ) +6.5 (c
D
1
0.8, CHCl3); H NMR (CDCl3, 200 MHz) δ 7.35-7.13 (15 H,
m), 3.91 and 3.81 (2 × 2 H, AB system, J ) 14.0), 3.25-3.21
(1 H, m), 3.13-3.05 (1 H, m), 2.97-2.72 (3 H, m), 2.59 (1 H,
dd, J ) 5.1, 2.8); 13C NMR (CDCl3, 50 MHz) δ 139.4 (C), 129.4,
128.3, 128.1, 128.0, 126.7 and 125.9 (6 × CH), 60.1 (CH), 54.0
(CH2), 51.9 (CH), 44.9 (CH2), 33.7 (CH2); IR (neat) 3051; MS
m/z 343.1 (M+, 1), 91.0 (100); HRMS calcd for C24H25NO
343.1936, found 343.1934.
) 0.5 (hexane); [R]25 ) -3.0 (c 8.2, CHCl3); 1H NMR (CDCl3,
D
300 MHz) δ 7.5-7.2 (10 H, m), 5.8 (1 H, ddd, J ) 17.2, 10.2,
8.6), 5.3 (1 H, dd, J ) 10.2, 1.6), 5.1 (1 H, dd, J ) 17.2, 1.6),
3.81 and 3.39 (2 × 2 H, AB syst, J ) 13.7), 3.11 (1 H, m), 1.82-
1.52 (2 H, m), 1.39-1.25 (1 H, m), 0.82 and 0.69 (2 × 3 H, d,
J ) 6.5); 13C NMR (CDCl3, 75 MHz) δ 140.5 (C), 136.7 (CH),
128.7, 128.0 and 126.6 (3 × CH), 117.3 (CH), 58.4 (CH), 53.5
(CH2), 41.3 (CH2), 24.3 (CH), 22.9 and 22.4 (2 × CH3); IR (neat)
1603; MS m/z 293.2 (M+, 1), 237.1 (38), 236.1 (100), 181.1 (7),
91.0 (99), 65.0 (13); HRMS calcd for C21H27N 293.2144, found
Gen er a l P r oced u r e for th e P r ep a r a tion of N,N-Diben -
zyla m in o Azetid in iu m Sa lts 5. In this case, the samarium-
promoted iodomethylation reaction was quenched with H2O
and then a saturated aqueous solution of NaHCO3 was added.
The resulting suspension was filtered through a pad of Celite

8906 J . Org. Chem., Vol. 62, No. 25, 1997
Concello´n et al.
293.2142. Anal. Calcd for C21H27N: C, 85.95; H, 9.27; N, 4.77.
Found: C, 85.98; H, 9.22; N, 4.80.
1.82-1.69 (1 H, m), 1.59-1.39 (1 H, m), 1.00 (3 H, t, J ) 7.3);
13C NMR (CDCl3, 75 MHz) δ 140.4 (C), 139.4 (C), 129.1, 128.4,
127.9, 126.6 and 126.5 (5 × CH), 72.6 (CH), 62.6 (CH), 54.5
(CH2), 31.6 (CH2), 27.4 (CH2), 10.6 (CH3); IR (neat) 3420; MS
m/z 300.2 (88), 268.1 (32), 181.1 (28), 91.0 (100). 65.0 (19);
HRMS calcd for C18H22NO (M - C7H7 ) 268.1701, found
268.1698. Anal. Calcd for C25H29NO: C, 83.52; H, 8.13; N,
3.90 Found: C, 83.49; H, 8.11; N, 3.93.
Gen er a l P r oced u r e for th e Syn th esis of Hom oa llylic
Am in o Alcoh ols 7d ,e. The procedure described for the
preparation of 2 was employed, but instead of H2O, magnesium
allylcyanocuprate29 was added via cannula at -78 °C. The
mixture was allowed to warm to room temperature overnight
and was quenched with a saturated aqueous solution of NH4-
OH (30 mL). After being stirred for 2 h, the mixture was
filtered through a pad of Celite and extracted with CH2Cl2 (3
× 20 mL). The organic layer was dried over Na2SO4 and
concentrated to give crude amino homoallyl alcohols 7d ,e,
which were purified by column chromatography using hexane/
ethyl acetate (10:1).
(2S)-N,N-Diben zyl-1-p h en ylbu t-3-en -2-a m in e (6c): Rf )
0.7 (hexane/ethyl acetate 25:1); [R]19D ) +10.0 (c 0.58, CHCl3);
1H NMR (CDCl3, 300 MHz) δ 7.2-7.1 (15 H, m), 5.9 (1 H, ddd,
J ) 17.2, 10.3, 8.2), 5.2 (1 H, d, J ) 10.3), 5.02 (1 H, d, J )
17.2), 3.85 and 3.42 (2 × 2 H, AB syst, J ) 14.0), 3.37 (1 H,
m), 3.02 and 2.81 (2 × 1 H, dd, J ) 13.8, 7.3); 13C NMR (CDCl3,
75 MHz) δ 135.7 (CH), 140.0 (C), 129.5, 128.4, 128.0, 127.9,
126.6 and 125.8 (6 × CH), 117.9 (CH), 62.0 (CH), 53.4 (CH2),
38.1 (CH2); IR (neat) 1603; MS m/z 237.1 (20), 236.1 (100), 91.0
(92), 65.0 (7); HRMS calcd for C17H18N (M - C7H7) 236.1439,
found 236.1440. Anal. Calcd for C24H25N: C, 88.03; H, 7.69;
N, 4.28. Found: C, 87.89; H, 7.76; N, 4.30.
Gen er a l P r oced u r e for th e Syn th esis of Am in o Alco-
h ols 7a -c.26 The procedure described for the preparation of
2 was employed, but instead of H2O, lithium dimethylcuprate28
was added at the same temperature. After being stirred for 3
h, the reaction was quenched with a saturated aqueous
solution of NH4Cl (20 mL), the stirring was maintained for 2
h, and then 1 M HCl (20 mL) was added. The mixture was
filtered through a pad of Celite, extracted with CH2Cl2 (3 ×
20 mL), dried over Na2SO4, and concentrated to give crude
amino alcohols 7a -c. Column flash chromatography over
silica gel (10:1 hexane-ethyl acetate) provided the pure amino
alcohols 7.
(2S,3R)-4-(N,N-Diben zyla m in o)h ep t-6-en -3-ol (7d ): Rf
) 0.3 (hexane/ethyl acetate/triethylamine 10/1/1); [R]19
)
D
+18.9 (c 2.01, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 7.50-
7.35 (10 H, m), 5.96-5.82 (1 H, m), 5.12-5.01 (2 H, m), 3.83
and 3.51 (4 H, AB syst, J ) 13.75), 3.69-3.62 (1 H, m), 2.82-
2.73 (1 H, m), 2.28-1.32 (3 H, m), 1.18 (3 H, d, J ) 6.4); 13C
NMR (CDCl3, 75 MHz) δ 139.8 (C), 138.6 (CH), 128.6, 128.1
and 126.7 (3 × CH), 114.5 (CH2), 72.8 (CH), 57.0 (CH), 54.7
(CH2), 33.2 and 30.0 (2 × CH2), 8.4 (CH3); IR (neat) 3420, 1639,
1603; MS m/z 224.1 (71), 181.0 (11), 178.0 (19), 91.0 (100).
(4S ,5R )-4-(N ,N -Dib e n zyla m in o)-2-m e t h yln on -8-e n -
(2S,3R)-2-(N,N-Diben zyla m in o)p en ta n -3-ol (7a ): Rf )
0.2 (hexane/ethyl acetate 10/1); [R]18 ) +44.5 (c 2.8, CHCl3);
D
1H NMR (CDCl3, 300 MHz) δ 7.51-7.23 (10 H, m), 3.79 and
3.50 (4 H, AB syst, J ) 13.4), 3.52 (1 H, m), 2.75 (1 H, m),
1.93-1.69 (2 H, m), 1.42-1.23 (1 H, m), 1.11 (3 H, d, J ) 6.9),
0.89 (3 H, d, J ) 7.3); 13C NMR (CDCl3, 75 MHz) δ 140.0 (C),
128.7, 128.2 and 126.8 (3 × CH), 75.1 (CH), 57.0 (CH), 54.7
(CH2), 27.1 (CH2), 10.3 (CH3), 8.6 (CH3); IR (neat) 3320; MS
m/z 266.2 (40), 224.1 (98), 181.1 (65), 132.0 (32), 91.0 (100),
65.0 (42); HRMS calcd for C19H24N (M+ - OH) 266.1897, found
266.1909.
5-ol (7e): Rf ) 0.3 (hexane/ethyl acetate); [R]20 ) +8.34 (c
D
1
2.8, CHCl3); H NMR (CDCl3, 300 MHz) δ 7.51-7.19 (10 H,
m), 5.93-5.80 (1 H, m), 5.11-5.00 (2 H, m), 3.92-3.70 (5 H,
m), 2.81-2.74 (1 H, m), 2.38-2.24 (1 H, m), 2.17-2.14 (1 H,
m), 1.86-1.72 (1 H, m), 1.68-1.42 (2 H, m), 1.33-1.22 (2 H,
m), 0.95 and 0.80 (2 × 3 H, d, J ) 6.9); 13C NMR (CDCl3, 75
MHz) δ 140.0 (C), 138.4 (CH), 128.8, 128.2 and 126.9 (3 × CH),
114.8 (CH2), 69.8 (CH), 58.3 (CH), 55.0 (CH2), 34.3, 33.5 and
30.7 (3 × CH2), 24.6 (CH), 22.9 and 22.8 (2 × CH3); IR (neat)
3433, 1639, 1602; MS m/z 267.2 (66), 266.2 (100), 210.1 (20),
181.1 (18), 91.0 (93); HRMS calcd for C20H24NO (M - C4H9)
294.1858, found 294.1858. Anal. Calcd for C24H33NO: C,
82.00; H, 9.46; N, 3.98. Found: C, 81.84; H, 9.57; N, 4.01.
(3R,4S)-4-(N,N-Dib en zyla m in o)-6-m et h ylh ep t a n -3-ol
(7b): Rf ) 0.2 (hexane/ethyl acetate 10/1); [R]32 ) +13.8 (c
D
1
0.8, CHCl3); H NMR (CDCl3, 300 MHz) δ 7.45-7.22 (10 H,
m), 3.68 (5 H, m), 2.74 (1 H, td, J ) 6.9, 3.9), 1.84-1.73 (1 H,
m), 1.66-1.19 (4 H, m), 0.98-0.92 (6 H, m), 0.74 (3 H, d, J )
6.4); 13C NMR (CDCl3, 75 MHz) δ 140.1 (C), 128.9, 128.2 and
126.9 (3 × CH), 72.1 (CH), 58.1 (CH), 55.0 (CH2), 34.3 (CH2),
27.5 (CH2), 24.6 (CH), 23.1, 22.6 and 11.0 (3 × CH3); IR (neat)
3433; MS m/z 266.2 (40), 210.1 (12), 181.1 (15), 91.0 (98). Anal.
Calcd for C22H31NO: C, 81.18; H, 9.60; N, 4.30. Found: C,
81.03; H, 9.68; N, 4.22.
Ack n ow led gm en t. We are thankful for the financial
support received from the Direccio´n General de Inves-
tigacio´n Cient´ıfica y Te´cnica (DGICYT, PB92-1005).
(2S,3R)-2-(N,N-Dib en zyla m in o)-1-p h en ylp en t a n -3-ol
(7c): Rf ) 0.2 (hexane/ethyl acetate 10/1); [R]20D ) +23.2 (c 1,
CHCl3); 1H NMR (CDCl3, 200 MHz) δ 7.45-7.12 (15 H, m),
3.65-3.62 (5 H, m), 3.13-3.05 (2 H, m), 2.96-2.85 (1 H, m),
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectral data of 3-7 (34 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
(28) Whitesides, G. M.; Fischer, W. F., J r.; San Filippo, J ., J r.; Bashe,
R. W.; House, H. O. J . Am. Chem. Soc 1969, 91, 4871.
(29) Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J . A.; Parker, D. J .
Org. Chem. 1984, 49, 3928.
J O970318I