Comparative Study of the Diastereoselective Addition of Allenyl Zinc Reagents to α-Alkoxy (or Silyloxy) Aldehydes and Imines. A Straightforward Synthesis of Amino Alcohols from Imines

Article abstract of DOI:10.1021/jo005509r

The addition of allenylzinc bromides to α-chiral imines proceeds with very high diastereoselectivity. This result is in contrast with the addition to the corresponding aldehydes, leading to poor diastereoselectivity. The anti/anti adducts are explained by Felkin-Ahn and Gaudemar-Yamamoto models of the transition state.

Full text of DOI:10.1021/jo005509r

J . Org. Chem. 2000, 65, 6553-6560
6553
Com p a r a tive Stu d y of th e Dia ster eoselective Ad d ition of Allen yl
Zin c Rea gen ts to r-Alk oxy (or Silyloxy) Ald eh yd es a n d Im in es. A
Str a igh tfor w a r d Syn th esis of Am in o Alcoh ols fr om Im in es
J ean-Franc¸ois Poisson and J ean F. Normant*
Laboratoire de Chimie des Organoe´le´ments, Universite´ Pierre et Marie Curie,
4 place J ussieu-Tour 44-45, 75252 Paris ce´dex 05, France
normant@moka.ccr.jussieu.fr
Received April 26, 2000
The addition of allenylzinc bromides to R-chiral imines proceeds with very high diastereoselectivity.
This result is in contrast with the addition to the corresponding aldehydes, leading to poor
diastereoselectivity. The anti/anti adducts are explained by Felkin-Ahn and Gaudemar-Yamamoto
models of the transition state.
Sch em e 1
In tr od u ction
Little is known about double diastereoselection during
the addition of chiral allenylzinc reagents to chiral
electrophiles (aldehydes, imines...). The reaction of alle-
nylzinc reagents with simple aldehydes has been studied
extensively. As shown by Zweifel et al., an excellent anti/
syn ratio (>96:4) is achieved for the homopropargylic
alcohol thus formed.1 However, this selectivity depends
on the nature of the allenyl moiety substituent groups
and may drop (in the 70:30 range) so that the titanium
or boron reagents are considered more useful.2,3 For a
double diastereoselection, excellent results were obtained
by Marshall et al.4,5 when stannyl or indium6 reagents
were reacted with R-alkoxy or R-alkyl aldehydes.7 Re-
cently, the same group showed that nonracemic allenylz-
inc mesylates, derived from “umpolung” of propargylic
mesylates via a palladium intermediate, displayed little
mismatching during their addition to enantioenriched
R-chiral aldehydes: one enantiomer of the latter leads to
an anti/syn sequence while the other leads to the anti/
anti isomer.4,5
Sch em e 2
Sch em e 3
In a study of carbozincation,8 using allenylzinc bro-
mides derived from the corresponding lithium deriva-
tives, we were interested in knowing whether these
reagents would follow the same reactivity.
Resu lts a n d Discu ssion
We easily obtained the allenic zinc species 2 by means
of propargylic deprotonation using sec-BuLi in THF at
* To whom correspondence should be addressed. Fax: 01 44 27 75
67.
-40 °C, followed by standard transmetalation of the
lithium species using zinc (II) bromide (Scheme 1).
Reaction of 2a with 2-(N,N-dibenzylamino)-3-phenyl-
propionaldehyde,9 at 25 °C, gave an impure product with
many side products (Scheme 2). At -50 °C, 3 was
obtained as a mixture of two diastereomers with an
approximate d.r. of 85:15. However the aldehyde reacted
incompletely and unidentified side products were still
present.
(1) Zweifel, G.; Hahn, G. J . Org. Chem. 1984, 49, 4565-4567.
(2) Furuta, K.; Ishiguro, M.; Haruta, R.; Ikeda, N.; Yamamoto, H.
Bull. Chem. Soc. J pn. 1984, 57, 2768-2776.
(3) Ishiguro, M.; Ikeda, N.; Yamamoto, H. J . Org. Chem. 1982, 47,
2225-2227.
(4) (a) Marshall, J . A.; Adams, N. D. J . Org. Chem. 1998, 63, 3812-
3813. (b) Marshall, J . A.; J ohns, B. A. J . Org. Chem. 1998, 63, 7885-
7892.
(5) Marshall, J . A.; Adams, N. D. J . Org. Chem. 1999, 64, 5201-
5204.
(6) (a) Marshall, J . A.; Grant, C. M. J . Org. Chem. 1999, 64, 696-
697. (b) Marshall, J . A.; Grant, C. M. J . Org. Chem. 1999, 64, 8214-
8219.
We then turned to R-oxygenated aldehydes, and stud-
ied silyl protected mandelaldehydes 4. They are prepared
(7) (a) Marshall, J . A.; Palovitch, M. R. J . Org. Chem. 1998, 64,
3701-3705. (b) Marshall, J . A.; Fitzgerald, R. N. J . Org. Chem. 1999,
64, 4477-4478.
(8) Meyer, C.; Marek, I.; Courtemanche, G.; Normant, J . F. J . Org.
Chem. 1995, 60, 863-871.
(9) Reetz, M. T.; Drewes, M. W.; Schmidtz, A. Angew. Chem., Int.
Ed. Engl. 1987, 26, 1141-1143.
10.1021/jo005509r CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/13/2000

6554 J . Org. Chem., Vol. 65, No. 20, 2000
Poisson and Normant
Sch em e 4
Ta ble 1. Ad d ition of Allen ylzin c Rea gen ts 2a ,b to Silyl
Sch em e 5
Der iva tives of Ma n d elic Ald eh yd e 4a -c
2
4
T (°C)
product
conversion (%)
d.r.
2a
2a
2a
2b
2b
4a
4b
4c
4b
4c
-50
-70
-50
-70
-70
5a
5b
5c
5b
5e
85
90
97
90
90
53:47
55:45
58:42
58:42
67:33
Ta ble 2. In flu en ce of Y in RZn -Y on th e
Dia ster eoselectivity
according to Leahy by a controlled DIBALH reduction of
the corresponding ethyl mandelate derivatives (Scheme
3).10c
Reaction of 2a with 4a , 4b, and 4c at -50 °C led this
time to a clean conversion to 5 (conversion of 85, 90, 97%,
respectively) consisting of two diastereomers, but still
with low diastereoselection (7, 9, and 17% respectively).
The same outcome was observed with zinc reagent 2b
with slightly better diastereoselection (Scheme 4 and
Table 1).
We then decided to use a lactaldehyde derivative. This
substrate was obtained by TIPS protection of the free
hydroxyl of cheap, commercially available, (S)-ethyl
lactate, racemization using LDA and DIBALH reduction
of the ester function. Upon reaction with 2a , a low
diastereoselection (57:43) was again observed.
We have no interpretation for the slight drop of
selectivity when the silicon protecting group is varied
from TBDPS to TBDMS or TIPS (Table 1, entries 1-3).
Our results are close to those obtained by Marshall et
al., who used R-methylated aldehydes, but our R-silyloxy
aldehydes displayed a higher diastereoselection. In an-
other connection, Tamaru,11 in early reports concerning
zinc reagents prepared by “umpolung” via a palladium
intermediate, found a notable difference of reactivity
between the in situ generated zinc species via a pal-
ladium intermediate and the “standard” alkylzinc bro-
mide species. Indeed, the diastereoselectivity of the
reaction of a 1,3-dimethylallylzinc reagent toward ben-
zaldehyde varied from >95% de, in the “umpolung” case,
to a 62:38 ratio in the “zinc bromide” case. The influence
of Y in RZnY derivatives has never been studied thor-
oughly. Preliminarily, we found that replacement of
entry
Y
conversion (%)
d.r.
1
2
3
4
5
6
7
Br
I
MeO
t-BuO
MeSO3
N(i-Pr)2
77
81
88
75
91
78
76
58:42
55:45
67:33
70:30
55:45
50:50
71:29
NMe(CH2)2NMe2
bromide, in reagent 2b, by different groups had a notable
influence on the diastereoselectivity of the addition to 4b
(Scheme 5 and Table 2).12
The diasteroselection varied with Y according to
Me2N(CH2)2NMe > t-BuO > MeO > Br > I ≈ MesO >
i-Pr2N and no difference in reactivity was observed. This
sequence is difficult to interpret, both in terms of bulki-
ness of Y and polarization of the Zn-Y bond.
Conversion of both diastereomers of 5d to the corre-
sponding cyclic carbonates 6 allowed us to assess the
relative configuration of the products by NOE. The major
diastereomer is of 2,3-anti relationship while the minor
diastereomer is of 2,3-syn relationship (Scheme 6). For
both isomers, we consider a common 1,2-anti relationship
as obvious, considering the previous studies realized by
Marshall et al.4,5
At this point, we suspected that the nucleophilicity of
allenylzinc bromides toward aldehydes was too great and
responsible for the low diastereoselection. Consequently,
we decided to use an aldehyde derivative of lower
electrophilicity: an imine.
Imines derived from aldehydes are easily available,13
and their electrophilicity can be finely tuned by a simple
variation of the nitrogen substituent. The addition of
allenylmetals (Ti, B, Al, Li) derived from 1-(trimethyl-
silyl)but-1-yne to simple imines has been described by
Yamamoto et al.14 With imines derived from aliphatic
(10) Lactic series. For OTBDMS, see: (a) Massad, S. K.; Hawkins,
L. D.; Baker, D. C. J . Org. Chem. 1983, 62, 5180-5182. For OBn, see:
(b) Hoppe, D.; Tarara, G.; Wilckens, M. Synthesis 1995, 723-725.
Mandelic series. For OTIPS, see: (c) Gardinier, K. M.; Leahy, J . W. J .
Org. Chem. 1997, 48, 7098-7099. For OTBDPS, see: (d) Raczko, J .
Tetrahedron: Asymmetry 1997, 8, 3821-3828. For OTBDMS, see: (e)
Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Ponzini, F. J .
Org. Chem. 1993, 58, 4746-4748. For OMOM, see: (f) Corey, E. J .;
Hannon, F. J .; Boaz, N. W. Tetrahedron 1989, 45, 545-555.
(11) (a) Tamaru, Y.; Tanaka, A.; Yasui, K.; Goto, S.; Tanaka, S.
Angew. Chem., Int. Ed. Engl. 1995, 34, 787-789. For an allenyl report
from the same author, see: (b) Tamaru, Y.; Goto, S.; Tanaka, A.;
Shimizu, M.; Kimura, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 878-
880. (c) Shimizu, M.; Kimura, M.; Tanaka, S.; Tamaru, Y. Tetrahedron
Lett. 1998, 39, 609-612.
(12) The aminozinc derivatives were prepared by displacement of
the bromide with the corresponding lithium amides. The alkoxyzinc
derivatives were prepared by hydrolysis of the diallenylzinc species
by 0.5 equiv of the corresponding alcohol. The iodide derivative was
prepared by transmetalation using zinc(II) iodide.
(13) (a) Midland, M. M.; Koops, R. W. J . Org. Chem. 1992, 57, 1158-
1161. (b) Kobayashi, Y.; Takemoto, Y.; Kamijo, T.; Harada, H.; Ito, Y.;
Terashima, S. Tetrahedron 1992, 48, 1853-1868. (c) Franz, T.; Hein,
M.; Veith, U.; J a¨ger, V.; Peters, E.-M.; Peter, K.; Von Schnering, H. G.
Angew. Chem., Int. Ed. Engl. 1994, 33, 1298-1300.

Synthesis of Amino Alcohols from Imines
J . Org. Chem., Vol. 65, No. 20, 2000 6555
Sch em e 6a
Ta ble 3. Ad d ition of Allen yl Rea gen ts 2b a n d 2a to th e
Ben zyl Im in e of Ma n d elic Ald eh yd e P r otected a s Silyl
Der iva tives or MOM Eth er
zinc
entry reagent imine T (°C) product yieldb (%) dea (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2a
2a
2a
7a
7b
7c
7c
7c
7d
7e
7f
7f
7f
7f
7f
7c
-70
-70
-70
-35
0
-60
-70
-60
-35
0
8a
8b
8c
8c
8c
8d
8e
8f
8f
c
90
70
85
93:7
>35:1
>35:1
96:4
68:32
>35:1
>35:1
>35:1
93:7
75 (68)
78 (70)
80
80 (74)
68 (52)
62 (55)
c
73 (61)
70
68
c
-70
-35
-70
8g
8g
8h
>35:1
93:7
>35:1
a
b
Determined by 1H NMR using the crude adduct. In paren-
theses, calculated from the aldehyde (two steps). c See text.
a
Key: (i) TBAF, THF; (ii) Cl3COCOCl, CH2Cl2, NEt(i-Pr)2.
filtration on a short pad of neutral alumina, or better by
washing the organic phase with a cold dilute solution of
NH4Cl, followed by drying on MgSO4. Even under argon
at 0 °C, they cannot be stored for days and are preferably
used immediately after preparation. Those imines were
reacted with zinc reagent 2b derived from 1-(trimethyl-
silyl)hex-1-yne and 2a derived from 1-(trimethylsilyl)but-
1-yne (Scheme 8). The results are quoted in Table 3.
To our delight, at -70 °C, only one diastereomer is
formed (except for entry 1), as is the case at -35 °C with
the TBDMS protection (entry 4). Even at 0 °C, a
significant diastereoselection occurs (entry 5). It must be
noted that the strongly chelating OMOM substituent also
allows for excellent diastereoselection (entry 6). With
reagent 2b, benzyl imines 7e and 7f, derived from
lactaldehyde led to a similar diastereoselection (Scheme
8 and Table 3). At -70 °C, 7e gives one diastereomer
(entry 7). At -60 °C or -35 °C, 7f gives a slightly lower
yield of a single diastereomer 8f (entries 8 and 9),
whereas at 0 °C, 7f delivers four diastereomers (1.1/0.5/
5.5/0.4). An attempt at reversing the diastereoselectivity
of the reaction, by precomplexing imine 7f with MgBr2‚
OEt2, led to a slight drop of selectivity, furnishing an
adduct with 97:3 dr of the same major isomer (see
structure determination). Unfortunately, an analogous
attempt with 7d led to the decomposition of the imine.
In the case of 2a , similar high selectivity (a single
isomer formed at -70 °C) and similar isolated yield are
obtained with both mandelic and lactic derivatives, thus
showing that a methyl or a primary alkyl group on the
allenic species are equally diastereodiscriminating in this
reaction (entries 11-13 in Table 3).
Sch em e 7a
Key: M ) Ti, B, Al, Li; R2 ) alkyl, R1 ) benzyl or alkyl.
a
aldehydes the exclusive formation of an anti product was
observed (Scheme 7).
The addition of allenylzinc derivatives to simple imines
derived from benzaldehyde15 has also been reported and
led to the major formation of the anti product, but to our
knowledge,16 the use of imines derived from aliphatic
aldehydes either simple or R-substituted has never been
reported. On the other hand, the reaction of allylic zinc
reagents with imines derived from aliphatic R-substituted
aldehydes is well documented17 and gives rather low
diastereomeric excesses as compared to the allylic tita-
nium and boron reagents.17d,k,l
For our first attempts, we selected benzyl imines of
mandelaldehyde blocked as silyl or MOM ethers. They
are formed quantitatively by simply adding the desired
primary amine to a suspension of the aldehyde and
magnesium sulfate in toluene at 0 °C, as already re-
ported.18 They are unstable on silica gel, and the slight
excess of amine must be removed either by a rapid
(14) Yamamoto, Y.; Ito, W.; Maruyama, K. J . Chem. Soc., Chem.
Comun. 1984, 1004-1005.
(15) (a) Moreau, J . L.; Gaudemar, M. Bull. Soc. Chem. Fr. 1975,
1211-1215; (b) Bull. Soc. Chem. Fr. 1973, 2549-2554.
(16) For an example where the diastereoselection was not studied,
see: Leboutet, L.; Courtois, G.; Miginiac, L. J . Organomet. Chem. 1991,
420, 155-161.
Str u ctu r e Deter m in a tion
(17) For generality, see: (a) Kleinman, E. F.; Volkmann, R. A. In
Comprehensive Organic Synthesis; Trost, B., Fleming, I., Eds.; Perga-
mon Press, New York, 1991; Vol. 2, p 984. (b) Bloch, R. Chem. Rev.
1998, 1407-1438. (c) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 2207-
2293. With allyltitanium, see: (d) Enders, D.; Reinhold, U. Tetrahe-
dron: Asymmetry 1997, 8, 1895-1946. For allylzinc, see: (e) Baside,
T.; Bocum, A.; Savoia, D.; Umani-ronchi, A. J . Org. Chem. 1994, 59,
7766-7773. (f) Dembele, Y. A.; Beland, C.; Hitchcock, P.; Villieras, J .
Tetrahedron: Asymmetry 1992, 8, 351-354. (g) Nyzam, V.; Beland, C.;
Zammatio, F.; Villieras, J . Tetrahedron: Asymmetry 1996, 8, 1835-
1843. (h) Chtara, R. A.; Moreau, J . L.; Gaudemar, M. C. R. Acad. Sci.
Ser. C 1975, 280, 1157-1159. (i) Yamamoto, Y.; Nishii, S.; Maruyama,
K.; Komatsu, T.; Ito, W. J . Am. Chem. Soc. 1986, 108, 7778-7786. (j)
Yamamoto, Y.; Komatsu, T.; Maruyama, K. J . Chem. Soc., Chem.
Commun. 1985, 814-816. For allyl Boron see: (k) Yamamoto, Y.;
Komatsu, T.; Muruyama, K. J . Am. Chem. Soc. 1984, 106, 5031-5033.
(l) Yamamoto, Y.; Komatsu, T.; Muruyama, K. J . Org. Chem. 1985,
50, 3115-3121.
For the determination of the structure of the major
isomer of 8, we attempted to synthesize a crystalline
amide via reaction of 8c with p-nitrobenzenesulfonyl
chloride or p-nitrobenzoyl chloride. This very sterically
demanding amine did not react under these reaction
conditions (Scheme 7). However, double deprotection of
the silyl groups in 8c by TBAF, followed by reaction with
(18) (a) Kobayashi, Y.; Takemoto, Y.; Kajimo, T.; Harada, H.; Ito,
Y.; Terashima, S. Tetrahedron 1992, 48, 1853-1868. (b) Midland, M.
M.; Koops, R. J . Org. Chem. 1992, 57, 1158-1161. (c) Annunziata, R.;
Benaglia, M.; Cinquini, M.; Cozzi, F.; Ponzini, F. J . Org. Chem. 1993,
58, 4746-4748.

6556 J . Org. Chem., Vol. 65, No. 20, 2000
Poisson and Normant
Sch em e 8
Sch em e 9
Sch em e 12a
a
Key: (i) HF(NEt3)3, CH3CN; (ii) disphosgene, NEt3, CH2Cl2,
30%.
Sch em e 10
relationships stepwise. We first checked that the Felkin
attack (A, Scheme 10) is still valid by conversion of 11f
to the oxazolidinone 13. Ha and Hb in 13 display a strong
NOE (16%), confirming the cis stereochemistry of the
oxazolidinone 13 (Scheme 12) and therefore the anti
relationship between the oxygen and the nitrogen in 8f.
In a second step, 8f was twice desilylated to 12f, semi-
hydrogenated to 14, and submitted to iodoetherification,
giving a major diastereomer 15. The known relative
configurations of Ha, Hb allowed the confirmation of the
cis relationship of Hb and Hc (NOE of 6% and 11%) in
15, thus securing the anti/anti configuration of 8f (Scheme
13).
Sch em e 11
To broaden the scope of this easy access to R-substi-
tuted vicinal amino alcohols, we tried the use of silylated
imines, to obtain free primary amines.
These silylamines are easily prepared19 but are not
very stable.16 They have been previously reacted, with
low yield, with the Grignard reagent analogous to 2a .16
Under our reaction conditions, 2b reacted with imine 16
giving a single diastereomer 17 in good yield, which was
subsequently benzylated to give a product analogous to
8f (Scheme 14).
p-nitrobenzoyl chloride on 9, furnished the crystalline
ester 10 whose single-crystal X-ray pattern showed an
anti-anti relationship of the substituents (Scheme 9).
Such stereochemistry corresponds to a Felkin-Anh
attack on the imine center, (see A in Scheme 10) by an
allenyl reagent such that interactions between Pr (in 2b)
and PhCHOTBDMS (in 7c) are minimized. Such modes
of attack have been proposed by Zweifel1 for aldehydes
and by Gaudemar15 and Yamamoto14 for imines (see B
in Scheme 10).
The same diastereoisomer is formed for 8d (MOM
protection), as shown by removal of the MOM moiety and
the TMS group leading to 9 (Scheme 11).
In the lactic series, the alcohol 11f derived from 8f gave
no satisfactory crystalline ester when submitted to the
same derivatization. We decided to ensure both relative
Con clu sion
In summary, the addition of allenylzinc bromides to
R-silyloxyaldehydes proceeds with low to moderate dia-
stereoselectivity. Changing the bromide ligand of zinc for
(19) (a) Hart, D. J .; Kanai, K.; Thomas, D. G.; Yang, T. K. J . Org.
Chem. 1983, 48, 283-294. (b) Ha, D. C.; Hart, D. J .; Yang, T. K. J .
Am. Chem. Soc. 1984, 106, 4819-4848. (c) Colvin, E. W.; MacGarry,
D. G. Chem. Commun. 1985, 539-540. (d) Cainelli, G.; Giacomini, D.;
Panunzio, M.; Martelli, G.; Spunta, G. Tetrahedron Lett. 1987, 28,
5369-5372.

Synthesis of Amino Alcohols from Imines
J . Org. Chem., Vol. 65, No. 20, 2000 6557
Sch em e 13a
a
Key: (i) TBAF (1 M/THF); (ii) H2, Pd Lindlar, quinoline, AcOEt; (iii) I2, CH3CN, NaHCO3.
organic layers were washed with brine and dried over MgSO4.
Sch em e 14
The volatiles were removed under reduced pressure and the
residue purified (unless otherwise specified) by flash chroma-
tography on silica gel (eluent pentane/ether, 95/5) to yield 5.
4-Hyd r oxy-3-m eth yl-5-p h en yl-5-tr iisop r op ylsilyloxy-1-
(tr im eth ylsilyl)p en t-1-yn e (5a ). General procedure A was
applied to 4a (585 mg, 2 mmol) and 2a (2 mmol). 5a (753 mg,
90%) was obtained as a colorless oil, consisting of a mixture
of two diastereomers (de ) 7%). Min or d ia ster eom er : IR
1
(neat) ν cm-1 3500, 2170; H NMR (400 MHz, CDCl3) δ 0.21
(9H, s), 0.98-1.22 (21H, m), 1.23 (3H, d, J ) 7.2 Hz), 2.24
(1H, ddd, J ) 0.9, 2.2, 7.1 Hz), 3.03 (1H, dd, J ) 1.0, 1.8 Hz),
3.46 (1H, app dt, J ) 2.2, 8.6 Hz), 4.94 (1H, d, J ) 8.5 Hz),
7.28-7.43 (5H, m); 13C NMR (100 MHz, CDCl3) δ 0.0, 13.9,
17.6 17.8, 18.0, 28.2, 77.9, 79.7, 86.8, 107.0, 127.0, 127.9, 128.0,
141.0. Ma jor d ia ster eom er : IR (neat) ν cm-1 3580, 2170; 1H
NMR (400 MHz, CDCl3) δ 0.20 (9H, s), 0.95-1.03 (21H, m),
1.28 (1H, d, J ) 7.2 Hz), 1.76 (1H, br d, J ) 6.8 Hz), 3.12 (1H,
dq, J ) 3.1, 7.1 Hz), 3.48 (1H, m), 4.74 (1H, d, J ) 7.4 Hz),
7.28-7.40 (5H, m); 13C NMR (100 MHz, CDCl3) δ 0.0, 12.3,
17.8, 17.9, 18.1, 29.7, 76.9, 78.4, 87.7, 107.0, 127.6, 127.8, 127.9,
141.8; MS (CI) 436 (M + NH4+), 419 (MH+), 262 (MH+ - TIPS),
245 (MH+ - TIPSOH). Anal. Calcd for C24H42O2Si2: C, 68.84;
H, 10.11. Found: C, 68.74; H, 10.26.
5-ter t-Bu t yld im et h ylsilyloxy-4-h yd r oxy-3-m et h yl-5-
p h en yl-1-(tr im eth ylsilyl)p en t-1-yn e (5b). General proce-
dure A was applied to 4b (500 mg, 2 mmol) and allenylzinc
2a (2 mmol). 5b was obtained as a crude mixture of diatere-
omers (5:3:1). Due to the poor diastereoselectivity, no further
purification of this product was realized.
5-ter t-Bu t yld ip h en ylsilyloxy-4-h yd r oxy-3-m et h yl-5-
p h en yl-1-(tr im eth ylsilyl)p en t-1-yn e (5c). General proce-
dure A was applied to 4c (750 mg, 2 mmol) and allenylzinc 2a
(2 mmol). The title compound (511 mg, 51%) was obtained as
a colorless oil consisting in a mixture of diastereomers (de )
17%). Ma jor d ia ter eom er : IR (neat) ν cm-1 3580, 2250, 2170;
1H NMR (400 MHz, CDCl3) δ 0.15 (9H, s), 1.13 (9H, s), 1.20
(1H, d, J ) 7.0 Hz), 2.25 (1H, dq, J ) 2.4, 7.0 Hz), 2.68 (1H, d,
J ) 4.2), 3.62 (1H, ddd, J ) 2.6, 4.2, 8.2 Hz), 4.89 (1H, d, J )
8.2 Hz), 7.24-7.73 (15H, m); 13C NMR (100 MHz, CDCl3) δ
0.0, 18.1, 19.3, 26.9, 28.6, 78.5, 79.0, 87.0, 106.6, 127.1, 127.2,
127.5, 127.8, 129.4, 129.5, 131.0, 131.2, 135.6, 135.7; 140.3.
Min or d ia ster eom er : IR (neat) ν cm-1 3560, 2060, 2165; 1H
NMR (400 MHz, CDCl3) δ 0.22 (9H, s), 1.13 (9H, s), 1.27 (3H,
d, J ) 7.1 Hz), 1.93 (1H, d, J ) 7.4 Hz), 3.08 (1H, dq, J ) 3.6,
7.1 Hz), 3.68 (1H, app. dt, J ) 3.6, 7.0 Hz), 4.77 1H, d, J ) 6.8
Hz), 7.20-7.71 (15H, m); 13C NMR (100 MHz, CDCl3) δ 0.0,
18.2, 19.4, 26.9, 28.5, 77.6, 77.7, 87.6, 106.8, 127.0, 127.3, 127.4,
127.7, 129.2; 129.3, 131.4, 131.5, 135.5, 137.7, 140.4; MS (CI)
518 (M + NH4+), 501 (MH+), 423, 392, 262 (MH+ - TBDPS),
245 (MH+ - TBDPSOH). Anal. Calcd for C31H40O2Si2: C,
74.34; H, 8.05. Found: C, 74.28; H, 8.14.
other halides, alkoxides, amides, showed that these
substituents have an influence on the diastereoselectivity
which, however, never exceeded 40% de. On the contrary,
R-benzyloxy or R-silyloxy imines, either benzylated or
silylated at nitrogen, undergo a highly diastereoselective
addition of substituted allenylzinc reagents to give
R-ethynyl vicinal amino alcohols of anti/anti type. Fur-
ther insight to this reaction is undertaken as well as the
study of the configurational stability of zinc derivatives
2a and 2b by means of the “Hoffmann test” which will
be reported in due course.
Exp er im en ta l Section
The 1:2 solution of NH4OH/NH4Cl is prepared by mixing
two volumes of a saturated aqueous solution of NH4Cl and one
volume of a 30% aqueous solution of ammonia.
Gen er a l P r oced u r e for th e F or m a tion of th e In ter m e-
d ia te Allen ylzin c: Allen ylzin c Rea gen t 2a . s-BuLi (1.3
M/hexane, 1.7 mL, 2.2 mmol) was added dropwise to a solution
of 1-(trimethylsilyl)but-1-yne (252 mg, 2.0 mmol) in dry THF
(10 mL) at -40 °C under a nitrogen atmosphere. The reaction
mixture was stirred for 1 h at 0 °C and cooled to -20 °C. ZnBr2
(1M/THF, 2.2 mL, 2.2 mmol) was then added dropwise leading
to a colorless solution of 2a .
Allen ylzin c Rea gen t 2b. Prepared according to the general
procedure, using 1-(trimethylsilyl)hex-1-yne (308 mg, 2 mmol).
Ald eh yd es 4a -f. Aldehydes, derived from either ethyl
lactate or ethyl mandelate, were prepared by protection of the
free alcohol by standard methods, followed by a controlled (-78
°C) DIBALH reduction of the ester function. All data were in
accord with literature reports.12a-f
Gen er a l P r oced u r e A: Ad d ition of Allen ylzin c Re-
a gen ts 2 to r-Ch ir a l Ald eh yd es 4. A solution of aldehyde 4
(2 mmol) in THF (5 mL) was added dropwise to the allenylzinc
reagent 2 (2 mmol) at -50 °C (unless otherwise specified)
under a nitrogen atmosphere. The reaction mixture was stirred
for 1 h at -50 °C and allowed to warm to 0 °C. It was
subsequently quenched by addition of a 1:2 solution of NH4-
OH/NH4Cl (10 mL) and stirred for 30 min at room tempera-
ture. Water (10 mL) and ether (10 mL) were added, followed
by a vigorous stirring. The layers were separated and the
aqueous phase extracted twice with ether. The combined
4-Hyd r oxy-5-p h en yl-3-n -p r op yl-5-tr iisop r op ylsilyloxy-
1-(tr im eth ylsilyl)p en t-1-yn e (5d ). General procedure A was
applied to 4b (500 mg, 2 mmol) and allenylzinc 2b (2 mmol)
with an addition temperature of the aldehyde of -70 °C. 5d
m a jor (320 mg, 40%) and 5d m in or (200 mg, 25%) were
obtained as a colorless oils (de ) 20%). Ma jor d ia ster e-

6558 J . Org. Chem., Vol. 65, No. 20, 2000
Poisson and Normant
om er : IR (neat) ν cm-1 3500, 2180; 1H NMR (400 MHz, CDCl3)
δ 0.15 (3H, s), 0.13 (3H, s), 0.27 (9H, s), 1.00 (3H, t, J ) 6.8
Hz), 1.40-1.80 (5H, m), 3.13 (1H, ddd, J ) 2.0, 5.6, 9.2 Hz),
3.50 (1H, app dt, J ) 2.0, 8.0 Hz), 4.64 (1H, d, J ) 8.0 Hz),
7.32-7.47 (5H, m); 13C NMR (100 MHz, CDCl3) δ -5.3-4.8,
0.0, 13.4, 17.8, 20.4, 25.5, 33.9, 34.9, 76.6, 76.7, 88.4, 105.9,
127.1, 127.5, 127.9, 142.1. Min or d ia ster eom er : 1H NMR
(400 MHz, CDCl3) δ 0.11 (3H, s), 0.20 (3H, s), 0.21 (9h, s),
0.80-1.00 (12H, m), 1.30-1.70 (4H, m), 2.31 (1H, m), 3.51 (1H,
dd, J ) 2.4 and 7.2 Hz), 4.74 (1H, d, J ) 7.6 Hz), 7.32-7.53
s), 0.91 (3H, t, ) 7.2 Hz), 1.08 (9H, s), 1.20-1.70 (4H, m), 5.57
(1H, m), 2.63 (1H, m), 3.68 (1H, d, J ) 13.6 Hz), 3.84 (1H, d,
J ) 13.6 Hz), 5.01 (1H, d, J ) 5.6 Hz), 7.09-7.68 (20H, m).
Ma jor d ia ster eom er : 1H NMR (400 MHz, CDCl3) δ 0.13 (9H,
s), 0.86 (3H, t, J ) 7.2 Hz), 1.08 (9H, s), 1.20-1.70 (4H, m),
2.75 (1H, dd, J ) 3.62, 6.4 Hz), 3.00 (1H, ddd, J ) 3.2, 5.2, 8.8
Hz), 3.39 (1H, d, J ) 13.2 Hz), 3.50 (1H, d, J ) 13.2 Hz), 4.83
(1H, d, 6.4 Hz), 7.09-7.68 (20H, m); 13C NMR (CDCl3) δ 0.3,
13.8, 19.5, 20.7, 26.9, 27.1, 35.1, 35.7, 53.1, 65.5, 78.4, 87.4,
108.2, 127.1, 127.3, 127.5, 127.9, 128.0, 133.7, 133.9, 135.9,
(5H, m); MS (CI) 422 (M + NH4+), 405 (MH+), 290 (MH+
-
141.2, 142.2; MS (CI) 618 (MH+). Anal. Calcd for C40H51
-
TBDMS), 273 (MH+ - TBDMSOH). Anal. Calcd for C23H40O2-
Si2: C, 68.25; H, 9.96. Found: C, 68.14, H, 10.14.
NOSi2: C, 77.74; H, 8.32; N, 2.27. Found: C, 77.80; H, 8.48;
N, 2.20.
5-ter t-Bu tyld ip h en ylsilyloxy-4-h yd r oxy-5-p h en yl-3-n -
p r op yl-1-(tr im eth ylsilyl)p en t-1-yn e (5e). General proce-
dure A was applied to 4c (750 mg, 2 mmol) and 2b (2 mmol),
with an addition temperature of the aldehyde of -70 °C. 5e
was obtained as a crude mixture of diastereomer (3:1).
(4,5-cis)-5-P h en yl-4-(3-(1-(tr im eth ylsilyl)h ex-1-yn oyl))-
1,2-d ioxola n -2-on e (6-cis). TBAF (1 M in THF) was added
dropwise to a THF solution of 5d m a jor (100 mg, 0.2 mmol).
After completion, the reaction was diluted with water and the
aqueous phase extracted twice with ether. The combined
organic phases were dried over MgSO4 and the volatiles
removed under reduced pressure. CH2Cl2 (5 mL) and NEt2-Pr
(1.2 equiv) were added to the residue. This solution was
subsequently treated with diphosgene (1.1 equiv) at 0 °C. The
reaction was monitored by TLC. After completion, the reaction
was diluted with water (5 mL) and the aqueous phase
extracted twice with ether. The combined organic phases were
dried over MgSO4 and the volatiles removed under reduced
pressure. The residue was purified by flash chromatography
on silica gel (eluent pentane/ether, 70/30) to yield 6-cis (31
mg, 51%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 0.79
(1H, t, J ) 7.2 Hz), 1.23-1.61 (4H, m), 2.17 (2H, m), 4.80 (1H,
d, J ) 3.3, 7.8 Hz), 5.83 (1H, d, J ) 7.8 Hz), 7.40-7.47 (5H,
m); 13C NMR (100 MHz, CDCl3) δ 13.5, 19.9, 32.7, 34.2, 73.7,
80.4, 80.8, 81.5, 126.6, 128.8, 129.4, 132.2, 154.5.
4-N-Ben zyla m in o-5-p h en yl-3-n -p r op yl-5-tr iisop r op yl-
silyloxy-1-(tr im eth ylsilyl)p en t-1-yn e (8b). General proce-
dure B was applied to 7b (149 mg, 0.39 mmol) and 2b (0.39
mmol). 8b (145 mg, 70%) was obtained as a colorless oil as a
single diastereomer: 1H NMR (400 MHz, CDCl3) δ 0.16 (9H,
s), 0.96 (3H, t, J ) 7.1 Hz), 1.00 (21H, m), 1.10-1.70 (4H, m),
2.65 (1H, dd, J ) 2.9, 7.7 Hz), 3.12 (1H, ddd, J ) 2.9, 5.5, 8.7
Hz), 3.22 (1H, d, J ) 12.9 Hz), 3.38 (1H, d, J ) 12.9 Hz), 4.78
(1H, d, J ) 7.7 Hz), 7.03-7.47 (5H, m); 13C NMR (100 MHz,
CDCl3) δ 0.2, 12.6, 13.8, 18.0, 18.1, 20.9, 35.2, 53.4, 66.3, 77.8,
87.5, 108.3, 126.5, 127.3, 127.7, 127.9, 128.0, 128.2, 141.2,
143.9.
4-N-Ben zyla m in o-5-ter t-bu tyld im eth ylsilyloxy-5-p h en -
yl-3-n -p r op yl-1-(tr im eth ylsilyl)p en t-1-yn e (8c). General
procedure B was applied to 7c (509 mg, 1.5 mmol) and 2b (1.5
mmol). 8c (564 mg, 76%) was obtained as a colorless oil
consisting of a single diastereomer: 1H NMR (400 MHz,
CDCl3) δ -0.21 (3H, s), 0.09 (3H, s), 0.89 (9H, s), 0.91 (3H, t,
J ) 4.8 Hz), 1.37-1.43 (3H, m), 1.60-1.80 (1H, m), 2.59 (1H,
dd, J ) 2.8, 8.4 Hz), 3.10-3.17 (3H, m), 3.29 (1H, d, J ) 12.8
Hz), 4.61 (1H, d, J ) 8.4 Hz), 7.16-7.41 (10H, m); 13C NMR
(100 MHz, CDCl3) δ -5.0, -4.4, 0.3, 13.7, 16.1, 20.8, 25.8, 35.0,
53.1, 65.7, 77.0, 87.5, 108.3, 126.5, 127.2, 127.7, 127.8, 127.9,
128.2, 141.1, 144.0; MS (CI) 494 (MH+), 354. Anal. Calcd for
C
30H47NOSi2: C, 72.96; H, 9.59; N, 2.84. Found: C, 72.65; H,
(4,5-tr a n s)-5-P h en yl-4-(3-(1-(tr im eth ylsilyl)h ex-1-yn oyl))-
1,2-d ioxola n -2-on e (6-tr a n s). The same procedure was ap-
plied to 5d m in or (50 mg, 0.12 mmol) to yield 6-tr a n s (15
mg, 61%): 1H NMR (400 MHz, CDCl3) δ 0.94 (3H, t, J ) 7.2
Hz), 1.46-1.76 (4H, m), 2.30 (1H, d, J ) 2.5 Hz), 2.75-2.79
(1H, m), 4.52 (1H, dd, J ) 2.9, 6.3 Hz), 5.58 (1H, d, J ) 6.3
Hz), 7.37-7.46 (5H, m); 13C NMR (100 MHz, CDCl3) δ 13.7,
20.5, 29.8, 32.6, 35.3, 73.8, 80.0, 81.0, 84.3, 125.9, 129.4, 129.8,
136.4, 154.3.
Im in es (7a -f). Imines were prepared, according to known
procedures,13 by slow addition of the amine to a cold solution
(0 °C) of the aldehyde in toluene in the presence of anhydrous
MgSO4. The reaction mixture was then diluted with ether and
washed with a cold dilute aqueous solution of NH4Cl. The
organic phase was dried over MgSO4 and the volatiles removed
under reduced pressure. They were used without further
purification.
Gen er a l P r oced u r e B: Ad d ition of Allen ylzin cs 2 to
r-Ch ir a l Im in es 7. A solution of imine 7 (2 mmol) in THF (5
mL) was added dropwise, over 10 min, to the allenylzinc 2 (2
mmol) at -70 °C (unless otherwise specified), under a nitrogen
atmosphere. The reaction mixture was further stirred for 1 h
at -70 °C, slowly allowed to warm to 0 °C, and subsequently
quenched by addition of 10 mL of a 1:2 solution of NH4OH/
NH4Cl. After vigorous stirring, water (10 mL) and ether (10
mL) were added. The layers were separated, and the aqueous
phase was extracted twice with Et2O. The combined organic
layers were washed with brine and dried over MgSO4. The
volatiles were removed under reduced pressure, and the
residue was purified by flash chromatography on silica gel
(eluent pentane/ether 98:2) to yield 8.
4-N-Ben zyla m in o-5-ter t-bu tyld ip h en ylsilyloxy-5-p h en -
yl-3-n -p r op yl-1-(tr im eth ylsilyl)p en t-1-yn e (8a ). General
procedure B was applied to 7a (695 mg, 2 mmol) and 2b (2
mmol). 8a (820 mg, 90%) was obtained as a colorless oil
consisting of a mixture of two diastereomers (de ) 86%).
Min or d ia ster eom er : 1H NMR (100 MHz, CDCl3) δ 0.00 (9H,
9.79; N, 2.80.
4-N-Ben zyla m in o-5-m eth oxym eth yloxy-5-p h en yl-3-n -
p r op yl-1-(tr im eth ylsilyl)p en t-1-yn e (8d ). General proce-
dure B was applied to 7d (808 mg, 3 mmol) and 2b (3 mmol)
with an addition temperature of the imine of -60 °C. 8d (1.0
g, 80%) was obtained as a colorless oil consisting in a single
diastereomer: 1H NMR (400 MHz, CDCl3) δ 0.21 (9H, s), 0.95
(3H, t, J ) 7.1 Hz), 1.30-1.60 (3H, m), 1.70-1.85 (1H, m),
2.78 (1H, dd, J ) 2.9, 8.7 Hz), 3.17 (1H, app sext, J ) 2.6 Hz),
3.27 (1H, d, J ) 12.8 Hz), 3.42-3.39 (4H, m), 4.58 (2H, ab
syst, J ) 1.5, 6.6 Hz), 4.70 (1H, d, J ) 8.7 Hz), 7.01-7.46 (10H,
m); 13C NMR (100 MHz, CDCl3) δ 0.0, 13.7, 20.7, 34.8, 35.1,
52.8, 55.6, 63.7, 79.5, 83.3, 93.8, 107.7, 126.3, 127.7, 127.89,
127.94, 128.1, 140.3, 140.6; MS (CI) 424 (MH+). Anal. Calcd
for C26H37NO2Si: C, 73.71; H, 8.80; N, 3.31. Found: C, 73.63;
H, 8.97; N, 3.15.
4-N-Ben zyla m in o-5-ben zyloxy-3-n -p r op yl-1-(tr im eth yl-
silyl)h ex-1-yn e (8e). General procedure B was applied to 7e
(615 mg, 2.43 mmol) and 2b (2.43 mmol). 8e (724 mg, 74%)
was obtained as a colorless oil consisting of a single diastere-
1
omer. H NMR (400 MHz, CDCl3) δ 0.00 (9H, s), 0.78 53H, t,
J ) 7.2 Hz), 1.17 (3H, d, J ) 6.4 Hz), 1.20-1.55 (4H, m), 2.43
(1H, dd, J ) 3.6, 7.2 Hz), 2.85 (1H, m), 3.46 (1H, dq, J ) 6.4,
7.2 Hz), 4.33 (1H, d, J ) 11.4 Hz), 4.45 (1H, d, J ) 11.4 Hz),
7.00-7.25 (10H, m); 13C NMR (100 MHz, CDCl3) δ 0.6, 14.3,
17.0, 21.4, 35.7, 36.0, 54.2, 63.9, 71.8, 78.1, 87.8, 108.7, 127.1,
127.8, 128.1, 128.6, 128.7, 139.2, 141.5; MS (CI) 408 (MH+).
Anal. Calcd for C26H37NOSi: C, 76.60; H, 9.15; N, 3.44.
Found: C, 76.42; H, 9.32; N, 3.34.
4-N -Be n zyla m in o-5-t er t -b u t yld im e t h ylsilyloxy-3-n -
p r op yl-1-(tr im eth ylsilyl)h ex-1-yn e (8f). General procedure
B was applied to 7f (438 mg, 1.58 mmol) and 2b (1.58 mmol).
8f (335 mg, 52%) was obtained as a colorless oil consisting of
a single diastereomer: 1H NMR (400 MHz, CDCl3) δ 0.12 (3H,
s), 0.13 (3H, s), 0.16 (9H, s), 0.91 (9H, s), 0.95 (3H, t, J ) 7.2
Hz), 1.29 (3H, d, J ) 6.0 Hz), 1.40-1.60 (4H, m), 2.38 (1H, dd,
J ) 3.2, 7.2 Hz), 2.98 (1H, ddd, J ) 3.6, 5.2, 8.8 Hz), 3.83 (1H,

Synthesis of Amino Alcohols from Imines
J . Org. Chem., Vol. 65, No. 20, 2000 6559
dt, J ) 6.0, 7.2 Hz), 3.92 (1H, d, J ) 12.8 Hz), 4.01 (1H, d, J
) 13.0 Hz), 7.27-7.41 (5H, m); 13C NMR (100 MHz, CDCl3) δ
-4.9, -4.2, 0.1, 13.8, 17.9, 20.8, 20.9, 25.9, 35.2, 35.3, 54.3,
65;8, 70.9, 87.3, 108.0, 126.7, 128.2, 141.2.
gel (eluent cyclohexane/EtOAc, 98/2) to yield 13 (100 mg, 30%)
as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 0.18 (9H, s),
0.9 (3H, t, J ) 7.4 Hz), 1.15-1.35 (3H, m), 1.56 (1H, d, J )
6.8 Hz), 1.55-1.70 (1H, m), 2.64 (1H, ddd, J ) 2.9, 4.1, 7.3
Hz), 3.58 (1H, dd, J ) 2.8, 7.6 Hz), 4.16 (1H, d, J ) 15.6 Hz),
4.66 (1H, app quint, J ) 6.7 Hz), 5.02 (1H, d, J ) 15.6 Hz),
7.26-7.40 (5H, m); 13C NMR (100 MHz, CDCl3) δ 0.2, 14.0,
15.7, 21.6, 33.5, 34.4, 47.3, 59.9, 78.0, 90.2, 105.3, 128.2, 128.2,
129.2, 136.6, 158.9; MS (CI) 361 (M + NH4+), 344 (MH+). Anal.
Calcd for C20H29NO2Si: C, 69.92; H, 8.51; N, 4.08. Found: C,
70.11; H, 9.03; N, 3.88.
4-N-Ben zyla m in o-5-ter t-bu tyld im eth ylsilyloxy-3-m eth -
yl-1-(tr im eth ylsilyl)h ex-1-yn e (8g). General procedure B
was applied to 7f (555 mg, 2.1 mmol) and 2a (2.1 mmol). 8f
(309 mg, 61%) was obtained as a colorless oil consisting of a
single diastereomer: 1H NMR (400 MHz, CDCl3) δ 0.10 (3H,
s), 0.11 (3H, s), 0.15 (9H, s), 0.91 (9H, s), 1.25 (3H, d, J ) 6.0
Hz), 1.26 (3H, d, J ) 7.2 Hz), 2.36 (1H, dd, J ) 4.0, 6.8 Hz),
3.02 (1H, dq, J ) 4.0, 7.2 Hz), 3.82 51H, app. qt, J ) 6.0 Hz),
3.93 (1H, d, J ) 13.0 Hz), 4.00 (1H, d, J ) 13.0 Hz), 7.25-
7.40 (5H, m); 13C NMR (100 MHz, CDCl3) δ -5.0, -4.4, 0.0,
17.9, 19.1, 20.3, 25.7, 29.4, 54.3, 67.1, 70.7, 86.2, 109.1, 126.6,
4-N-Ben zyla m in o-5-h yd r oxy-3-n -p r op yl-h ex-1-en e (14).
TBAF (2 mL, 2 mmol, 1 M/THF) was added at room temper-
ature to a solution of 8f (209 mg, 0.48 mmol) in THF (5 mL).
The reaction mixture was stirred at room temperature for 5
h, and the volatiles were removed under reduced pressure. The
residue was purified by flash chromatography on silica gel
(eluent cyclohexane/EtOAc, 4/1) to yield 12f (103 mg, 94%) as
a colorless oil: 1H NMR (400 MHz, CDCl3) δ 0.94 (3H, t, J )
7.2 Hz), 1.21 (3H, d, J ) 6.5 Hz), 1.30-1.75 (4H, m), 2.17 (1H,
d, J ) 2.5 Hz), 2.55 (1H, dd, J ) 3.7, 5.0 Hz), 2.68 (1H, m),
3.86 (2H, m), 4.02 (1H, d, J ) 12.9 Hz), 7.26-7.39 (5H, m);
13C NMR (100 MHz, CDCl3) δ 13.7, 19.0, 20.6, 33.3, 35.9, 53.3,
63.5, 68.1, 71.9, 85.0, 127.1, 128.2, 128.4, 140.5. Amino alcohol
12f (103 mg, 0.42 mmol) in EtOAc (5 mL) was hydrogenated
under 1 atm of H2 in the presence of quinoline (12 µL, 0.1
mmol) and Lindlar catalyst (5 mg, 0.05 mmol). The reaction
was followed on TLC. After complete consumption of the
starting material, the reaction mixture was filtered, and
concentrated under reduced pressure. The residue was purified
by flash chromatography on silica gel (eluent cyclohexane/
EtOAc, 4/1) to yield 14 in quantitative yield: 1H NMR (400
MHz, CDCl3) δ 0.89 (3H, m), 1.15 (3H, d, J ) 6.4 Hz), 1.16-
1.44 (4H, m), 2.19 (1H, m), 2.54 (1H, dd, J ) 4.3, 6.6 Hz), 3.03
(1H, br. d, J ) 6.6 Hz), 3.75 (1H, d, J ) 12.6 Hz), 3.88 (2H,
m), 5.08 (1H, dd, J ) 1.9, 16.7 Hz), 5.14 (1H, dd, J ) 1.9, 10.2
Hz), 5.82 (1H, ddd, J ) 9.4, 10.2, 17.0 Hz), 7.35 (5H, m); 13C
NMR (100 MHz, CDCl3) δ 14.3, 18.5, 22.5, 34.1, 46.5, 54.3,
64.8, 66.9, 116.6, 127.4, 218.6, 128.7, 140.7, 140.9.
4-N -Be n zyla m in o-2-iod om e t h yl-5-m e t h yl-3-n -p r op -
yltetr a h yd r ofu r a n (15). 14 (0.48 mmol) in solution in CH3-
CN (3 mL) was added dropwise to a CH3CN (5 mL) solution
of iodine (190 mg, 0.73 mmol) at -40 °C. The reaction mixture
was slowly allowed to warm to 0 °C. A saturated solution of
Na2SO3 (5 mL) was then added. The reaction mixture was
diluted with ether, the layers were separated, and the aqueous
phase was extracted twice with ether. The combined organic
phase was dried over MgSO4, and the volatiles were removed
under reduced pressure. The residue was purified by flash
chromatography on silica gel (eluent cyclohexane/EtOAc, 9/1)
to afford 15 (55 mg, 30%) as a colorless oil: 1H NMR (400 MHz,
CDCl3) δ 0.98 (3H, t, J ) 7.1 Hz), 1.15-1.45 (7H, m), 2.05 (1H,
app quint, J ) 7.4 Hz), 2.93 (1H, dd, J ) 5.4, 6.5 Hz), 3.24
(1H, dd, J ) 5.0, 10.5 Hz), 3.37 (1H, dd, J ) 4.7, 10.5 Hz),
3.67 (1H, app q, J ) 6.0 Hz), 3.71 (1H, d, J ) 13.1 Hz), 3.84
(1H, d, J ) 13.1 Hz), 3.96 (1H, app quint, J ) 6.0 Hz), 7.25-
7.40 (5H, m); 13C NMR (100 MHz, CDCl3) δ 11.9, 14.3, 20.7,
45.9, 52.3, 65.3, 79.2, 81.8, 127.1, 128.1, 128.4, 140.2.
128.1, 132.5, 141.1; MS (CI) 404 (MH+). Anal. Calcd for C23H41
-
NOSi2: C, 68.42; H, 10.24; N, 3.47. Found: C, 68.52, H, 10.33;
N, 3.30.
4-N-Ben zyla m in o-5-ter t-bu tyld im eth ylsilyloxy-3-m eth -
yl-5-p h en yl-1-(tr im eth ylsilyl)p en t-1-yn e (8h ). General pro-
cedure B was applied to 7c (679 mg, 2.0 mmol) and 2a (2.0
mmol). 8h (630 mg, 68%) was obtained as a colorless oil
consisting of a single diastereomer: 1H NMR (400 MHz,
CDCl3) δ -0.20 (3H, s), 0.10 (3H, s), 0.20 (9H, s), 0.89 (9H, s),
1.26 (3H, t, J ) 7.2 Hz), 2.55 (1H, dd, J ) 3.2, 8.4 Hz), 3.18
(1H, d, J ) 13.2 Hz), 3.22 (1H, dq, J ) 3.2, 7.2 Hz), 3.31 (1H,
d, J ) 13.2 Hz), 4.61 (1H, d, J ) 8.4 Hz), 7.03-7.42 (10H, m);
13C NMR (100 MHz, CDCl3) δ -5.0, -4.5, 0.3, 18.1, 25.8, 29.4,
53.4, 67.3, 77.7, 86.3, 109.2, 126.6, 127.8, 127.9, 128.0, 128.3,
141.0, 143.8; MS (CI) 466 ((MH+). Anal. Calcd for C28H43
-
NOSi2: C, 72.20; H, 9.30; N, 3.01. Found: C, 72.34; H, 9.14;
N, 3.01.
St r u ct u r e Det er m in a t ion . 4-N-Ben zyla m in o-5-p -n i-
tr oben zoyloxy-5-ph en yl-3-n -pr opyl-pen t-1-yn e (10). TBAF
(3 mL, 3 mmol, 1 M/THF) was added at room temperature to
a THF (2 mL) solution of 8c (645 mg, 1.3 mmol). The reaction
was followed by TLC. When no starting material was left (5
h), the volatiles were removed under reduced pressure to yield
9 as a crude material that was used as such. p-Nitrobenzoyl
chloride (291 mg, 1.6 mmol) was added to a solution of 9 and
DMAP (160 mg, 1.3 mmol) in dry CH2Cl2 (5 mL). The reaction
mixture was stirred at room temperature for 3 h. Water (3
mL) and ether (10 mL) were then added. The layers were
separated, and the aqueous one was extracted twice with ether.
The combined organic phase was washed with brine and dried
over MgSO4. The volatiles were removed under reduced
pressure and the residue purified by flash chromatography on
silica gel (eluent cyclohexane/EtOAc, 9/1) to yield 10 (500 mg,
97%) as orange crystals. It was recrystallized from pentane/
ether (4/1) to obtain satisfactory monocrystals: mp ) 84 °C;
1H NMR (400 MHz, CDCl3) δ 0.86-0.96 (6H, m), 1.30-1.36
(3H, m), 1.45 (1H, m), 2.23 (1H, d, J ) 2.4 Hz), 2.84 (1H, m),
3.10 (1H, dd, J ) 2.2, 6.3 Hz), 3.77 (2H, s), 6.33 (1H, d, J )
6.3 Hz), 7.27-7.50 (10H, m), 8.33 (2H, d, J ) 8.9 Hz), 8.39
(2H, d, J ) 8.9 Hz); 13C NMR (100 MHz, CDCl3) δ 13.9, 19.9,
33.1, 35.6, 52.4, 62.6, 68.8, 77.8, 35.2, 123.8, 127.0, 127.1, 128.4,
128.5, 128.6, 128.8, 131.3, 135.8, 138.7, 140.3, 150.8, 164.0.
3-Ben zyl-4-(3-(1-(tr im eth ylsilyl)h ex-1-yn oyl))-5-m eth -
yl-2-oxa zolid in on e (13). HF(NEt3)3 (0.5 mL, 3 mmol) was
added dropwise to a solution of 8f (405 mg, 0.95 mmol) in CH3-
CN (5 mL). The reaction mixture was stirred for 1 h, and a
saturated solution of NaHCO3 (2 mL) was added. The organic
phase was extracted twice with ether and dried over MgSO4.
The volatiles were removed under reduced pressure to yield
11f, which was used without purification, and some fully
desilylated product. 11f was added to a solution of NEt3 (870
µL, 5.0 mmol) in CH2Cl2 (5 mL) at room temperature under
nitrogen. Diphosgene (181 µL, 1.5 mmol) was added dropwise
to this solution maintained at room temperature by means of
a water bath. After 30 min of stirring, the reaction was
quenched with water and diluted with ether (10 mL). The
layers were separated, and the aqueous phase was extracted
twice with ether. The combined organic phase was dried over
MgSO4. The volatiles were removed under reduced pressure,
and the residue was purified by flash chromatography on silica
4-Am in o-3-n -p r opyl-5-ter t-bu tyldim eth ylsilyloxy-1-(tr i-
m eth ylsilyl)h ex-1-yn e (17). LiHMDS (2.1 mL, 2.1 mmol, 1
M/THF) was added dropwise to a solution of 2-tert-butyldi-
methylsilyloxypropanal (377 mg, 2 mmol) in THF (10 mL) at
-60 °C under a nitrogen atmosphere. The reaction mixture
was allowed to warm to -40 °C and stirred for 40 min at this
temperature. It was subsequently cooled to -70 °C, and 2b
(2.2 mmol) was added dropwise. The reaction mixture was
stirred overnight as the temperature of the reaction raised to
-30 °C. The reaction was quenched by addition of 10 mL of a
1:2 solution of NH4OH/NH4Cl. After vigorous stirring, water
(10 mL) and ether (10 mL) were added. The layers were
separated, and the aqueous phase was extracted twice with
Et2O. The combined organic layers were washed with brine
and dried over MgSO4. The volatiles were removed under
reduced pressure, and the residue was purified by flash
chromatography on silica gel (eluent pentane/ether 9:1) to yield

6560 J . Org. Chem., Vol. 65, No. 20, 2000
Poisson and Normant
17 (102 mg, 60%) as a colorless oil: 1H NMR (400 MHz, CDCl3)
δ 0.09 (3H, s), 0.10 (3H, s), 0.16 (9H, s), 0.90 (9H, s), 0.93 (3H,
t, J ) 4.0 Hz), 1.23 (3H, d, J ) 6.0 Hz), 1.30-1.65 (4H, m),
2.40 (1H, dd, J ) 3.2, 8.0 Hz), 2.88 (1H, ddd, J ) 3.2, 5.2, 8.8
Hz), 3.66 (1H, dq, J ) 6.0, 8.0 Hz); 13C NMR (100 MHz, CDCl3)
δ -5.0, -4.3, 0.12, 13.7, 17.9, 20.3, 20.6, 25.8, 34.6, 35.0, 60.0,
J .F.P.) and Mrs. J . Vaissermann (UPMC) for X-ray
analysis of 10.
Su p p or tin g In for m a tion Ava ila ble: ORTEP diagram
and crystallographic table of 10. This material is available free
of charge via the Internet at http://pubs.acs.org.
70.8, 87.6, 107.3; MS (CI) 342 (MH+). Anal. Calcd for C18H39
-
NOSi2: C, 63.27; H, 11.50; N, 4.10. Found: C, 63.09; H, 11.61;
N, 3.98.
Ackn owledgm en t. We gratefullyacknowledge Rhoˆne-
Poulenc Rorer for financial support of this work (to
J O005509R