Nickel-catalyzed preparations of functionalized organozincs

Article abstract of DOI:10.1021/jo960808v

The reaction of primary alkyl bromides or chlorides with diethylzinc in the presence of Ni(acac)₂ (5 mol %) furnishes the corresponding alkylzinc halides (X = Br, Cl) via a halogen-zinc exchange reaction. The treatment of terminal alkenes with diethylzinc (neat, 25-60°C) in the presence of Ni(acac)₂ as a catalyst (1-5 mol %) and 1,5-cyclooctadiene (COD) affords the corresponding dialkylzincs via a hydrozincation reaction. Whereas the conversion for simple alkenes bearing a remote functionality reaches 40 to 63%, the hydrozincation of allylic, homoallylic alcohols and allylic amines proceeds very efficiently (85-95% conversion). All the zinc organometallics obtained react with various electrophiles (allylic halides, enones, acid chlorides, alkynyl halides, ethyl propiolate) after transmetalation with CuCN·2LiCl. In the presence of the chiral catalyst 12, the dialkylzincs prepared add to aldehydes with high enantioselectivity.

Full text of DOI:10.1021/jo960808v

J . Org. Chem. 1996, 61, 7473-7481
7473
Nick el-Ca ta lyzed P r ep a r a tion s of F u n ction a lized Or ga n ozin cs
Stephan Vettel, Andrea Vaupel, and Paul Knochel*
Fachbereich Chemie der Philipps-Universit a¨ t Marburg, D-35032 Marburg, Germany
Received May 3, 1996X
2
The reaction of primary alkyl bromides or chlorides with diethylzinc in the presence of Ni(acac) (5
mol %) furnishes the corresponding alkylzinc halides (X ) Br, Cl) via a halogen-zinc exchange
reaction. The treatment of terminal alkenes with diethylzinc (neat, 25-60 °C) in the presence of
Ni(acac) as a catalyst (1-5 mol %) and 1,5-cyclooctadiene (COD) affords the corresponding
2
dialkylzincs via a hydrozincation reaction. Whereas the conversion for simple alkenes bearing a
remote functionality reaches 40 to 63%, the hydrozincation of allylic, homoallylic alcohols and allylic
amines proceeds very efficiently (85-95% conversion). All the zinc organometallics obtained react
with various electrophiles (allylic halides, enones, acid chlorides, alkynyl halides, ethyl propiolate)
after transmetalation with CuCN‚2LiCl. In the presence of the chiral catalyst 12, the dialkylzincs
prepared add to aldehydes with high enantioselectivity.
Organozincs are an important class of organometallics
for organic synthesis1 and organometallic synthesis.2
Diorganozincs have also found extensive applications in
Sch em e 1
3
asymmetric synthesis, since they add to aldehydes in
the presence of a chiral catalyst with high enantioselec-
tivity.3 They can be prepared by transmetalation from
organomagnesium4k or zirconocene reagents, by an
,4
5
iodine-zinc exchange,4 or by a boron-zinc exchange.
a
6
This last method is the most general and most versatile
Scheme 1). Recently, we have shown that the presence
of transition metal salts strongly accelerates the iodine-
(
Sch em e 2
*
To whom correspondence should be addressed. E-mail: Knochel@
ps1515.chemie.uni-marburg.de.
X
Abstract published in Advance ACS Abstracts, September 15, 1996.
(
1) (a) Knochel, P.; Singer, R. Chem. Rev. 1993, 2117. (b) Knochel,
P. Synlett 1995, 393.
2) (a) Stadtm u¨ ller, H.; Knochel, P. Organometallics 1995, 14, 3163.
b) D o¨ tz, K. H.; Christoffers, C.; Knochel, P. J . Organomet. Chem. 1995,
(
(
4
1
89, C84. (c) Schwink, L.; Vettel, S.; Knochel, P. Organometallics 1995,
4, 5000.
(3) (a) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833. (b) Noyori, T.;
Kitamura, M. Angew. Chem 1991, 103, 34; Angew. Chem., Int. Ed.
Engl. 1991, 30, 49. (c) Knochel, P.; Vettel, S.; Eisenberg, C. Appl.
Organomet. Chem. 1995, 9, 175.
zinc exchange and modifies even the nature of organo-
metallic produced.7
(
4) (a) Rozema, M. J .; AchyuthaRao, S.; Knochel, P. J . Org. Chem.
-10
1
1
992, 57, 1956. (b) Brieden, W.; Ostwald, R.; Knochel, P. Angew. Chem
993, 105, 629; Angew. Chem., Int. Ed. Engl. 1993, 32, 582. (c) Knochel,
Thus, the copper(I)-catalyzed iodine-zinc exchange
P.; Brieden,W.; Eisenberg, C.; Rozema, M. J . Tetrahedron Lett. 1993,
7
reaction provides diorganozincs, whereas a palladium-
3
1
3
4, 5881. (d) Nowotny, S.; Vettel, S.; Knochel, P. Tetrahedron Lett.
994, 35, 4539. (e) Eisenberg, C.; Knochel, P. J . Org. Chem. 1994, 59,
760. (f) Vettel, S.; Knochel, P. Tetrahedron Lett. 1994, 35, 5849. (g)
8
9
(II)- or manganese(II) -catalyzed iodine- or bromine-
zinc exchange leads to organozinc halides. Also, nickel-
Ostwald, R.; Chavant, P.-Y.; Stadtm u¨ ller, H.; Knochel, P. J . Org. Chem.
(
II) has proven to be an excellent catalyst for the iodine-
1
3
994, 59, 4143. (h) Schwink, L.; Knochel, P. Tetrahedron Lett. 1994,
5, 9007. (i) L u¨ tjens, H.; Nowotny, S.; Knochel, P. Tetrahedron:
10
and bromine-zinc exchange. Herein we show that this
high catalytic activity allows the conversion of primary
alkyl bromides of type 1 and primary alkyl chlorides of
type 2 to the corresponding alkylzinc halides 3. The
nickel catalysis also allows a formal hydrozincation of
terminal alkenes 4, providing in this case dialkylzincs 5
(Scheme 2).11 Herein, we describe the scope and limita-
tions of these new preparations of functionalized zinc
organometallics as well as some applications in asym-
metric synthesis.
Asymmetry 1995, 6, 2675. (j) Seebach, D.; Behrendt, L.; Felix, D.
Angew. Chem. 1991, 103, 991; Angew. Chem., Int. Ed. Engl. 1991, 30,
1
4
5
1
1
008. (k) Bussche-H u¨ nnefeld, J . L. v. d.; Seebach, D. Tetrahedron 1992,
8, 5719. (l) Oppolzer, W.; Radinov, R. N. Tetrahedron Lett. 1991, 32,
777. (m) Oppolzer, W.; Radinov, R. N. Helv. Chim. Acta 1992, 75,
70. (n) Oppolzer, W.; Radinov, R. N. J . Am. Chem. Soc. 1993, 115,
593.
(5) Wipf, P.; Xu, W. Tetrahedron Lett. 1994, 35 , 5197.
(
6) (a) Langer, F.; Waas, J . R.; Knochel, P. Tetrahedron Lett. 1993,
3
4, 5261. (b) Langer, F.; Devasagayaraj, A.; Chavant, P.-Y.; Knochel,
P. Synlett 1994, 410.
7) Rozema, M. J .; Eisenberg, C.; L u¨ tjens, H.; Ostwald, R.; Belyk,
K.; Knochel, P. Tetrahedron Lett. 1993, 34, 3115.
8) (a) Stadtm u¨ ller, H.; Lentz, R.; D o¨ rner, W.; St u¨ demann, T.;
(
Our first observations have shown that primary alkyl
(
Tucker, C. E.; Knochel, P. J . Am. Chem. Soc. 1993, 115, 7027. (b)
Stadtm u¨ ller, H.; Tucker, C. E.; Vaupel, A.; Knochel, P. Tetrahedron
Lett. 1993, 34, 7911.
bromides and chlorides (FG-RCH
2 2 2
CH X) react with Et -
Zn in the presence of Ni(acac) (5 mol %) without solvent
2
furnishing the corresponding alkylzinc halides in ca. 70-
80% yield. The reaction is accompanied by ca. 10% of
(
9) Klement, I.; Chau, K.; Cahiez, G.; Knochel, P. Tetrahedron Lett.
994, 35, 1177.
10) (a) Vaupel, A.; Knochel, P. Tetrahedron Lett. 1994, 35, 8349.
b) Vaupel, A.; Knochel, P. Tetrahedron Lett. 1995, 36, 231.
11) Vettel, S.; Vaupel, A.; Knochel, P. Tetrahedron Lett. 1995, 36,
023.
1
(
the protonated product FG-RCH
the elimination product FG-RCHdCH
nature of the nickel catalyst shows that a range of nickel-
2
CH
3
and ca. 10% of
(
2
. Variation of the
(
1
S0022-3263(96)00808-0 CCC: $12.00 © 1996 American Chemical Society

7
474 J . Org. Chem., Vol. 61, No. 21, 1996
Vettel et al.
Sch em e 3
Ta ble 1. P r od u cts 6b-j Obta in ed by th e Ha logen -Zin c
Exch a n ge Rea ction (X ) Br or Cl) Usin g Et2Zn a n d
Ni(a ca c)2 (5 m ol %), F ollow ed by Tr a n sm eta la tion w ith
Cu CN‚2LiCl a n d Su bsequ en t Rea ction w ith a n
Electr op h ile (0.7 equ iv Ba sed on Ha loa lk a n e)
(
II) complexes (e.g., NiCl
2
, NiCl
2
(PPh
3
)
2
, NiCl
2
3
‚4PPh , Ni-
1
2
(mesal)
2
) are appropriate catalysts. However, the best
conditions for performing a zinc-halogen exchange con-
sist of treating neat a primary alkyl bromide with Ni-
(
acac)
conversion to the corresponding zinc reagent is complete
within a few hours (1.5-2 h). With less Et Zn, more
protonated and elimination product was formed.
2 2
(5 mol %) and Et Zn (2 equiv) at 55 °C. The
2
A
possible catalytic cycle is shown in Scheme 3. Under the
reductive conditions, Ni(0) is formed catalytically from
Ni(acac) and Et Zn. This nickel(0) species undergoes an
2 2
insertion reaction into the alkyl halide. The alkyl group
is transmetalated to zinc, and the resulting diethyl nickel
complex is reduced to Ni(0) with the concomitant forma-
tion of ethylene and ethane (Scheme 3).
By using an alkyl chloride as substrate, longer reaction
times are required. Thus, n-octyl chloride (2a ) is con-
verted to octylzinc chloride after a reaction time of 72 h
at 60 °C (95% conversion). The presence of a functional
group further reduces the reaction rate, and the chloro-
triflamide 2b leads to the corresponding zinc reagent 3a
after 14 d at 60 °C. After transmetalation with CuCN‚-
a
Isolated yield of analytically pure products based on electro-
phile. b Yield obtained using 1-chlorooctane 2a . c 0.5 equiv of
electrophile. d 4 equiv of electrophile, yield based on bromoalkane.
2
LiCl13 to the copper-zinc species, an excess of allyl
bromide was added, leading to the desired product 6a in
3% isolated yield (eq 1). This procedure is general, and
ibility of the reactions. Furthermore, a higher stability
of the nickel catalytic system is achieved in this way. The
performance of the reaction in a solvent like toluene leads
to polymerization; with THF no reaction was observed.
In DMF the same conversion as without solvent is
observed; however, more protonated product is formed.
This hydrozincation16 allows an expeditive functional-
7
2
ization of unactivated double bonds. Ni(acac) (1 mol %)
in the presence of COD proved again to be the best
catalytic system. Contrary to the halogen-zinc ex-
change, this reaction reaches maximum conversions
between 40 and 63% with simple terminal alkenes. No
reaction was observed with internal olefins. Function-
alized alkenes bearing a remote functional group like an
ester (4b) or a triflamide (6a ) display a similar behavior
affording the corresponding diorganozinc (50-60 °C, 3
h). All these diorganozincs can be trapped after trans-
metalation using CuCN‚2LiCl with various electrophiles
leading to the products 6c,d ,f and 7a -f (Table 2).
Satisfactory yields can be reached by adding ca. 0.35-
0.55 equiv of the electrophile based on the starting alkene
taken as one equivalent. The mechanism of the reaction
may be analogous to the nickel-catalyzed hydromagne-
sation reported by Felkin and Marko,17 although the
presence of COD may lead to more complex reaction
various alkylzinc bromides or chlorides prepared in this
way were reacted with electrophiles (iodine, ethyl (2-
bromomethyl)acrylate,14 ethyl propiolate, benzoyl chlo-
ride, diethyl benzylidenemalonate, benzylideneacetone,
nitrostyrene) to furnish the expected products 6b-j in
satisfactory yields (Table 1). At the high reaction tem-
peratures required for this insertion reaction no alkyl
coupling was observed.15
After some experimentation, we found that terminal
olefins of type 4 are converted to diorganozincs of type 5
with diethylzinc in the presence of a catalytic amount of
Ni(acac)
catalytic with respect to Ni(II) if halogen-free nickel salts
are used like Ni(acac) or Ni(mesal) . Not only Ni(II) can
be used, but in situ generated Ni(0)-complexes (Ni-
acac) also give similar
2
(1-5 mol %) (Scheme 2). The reaction is only
2
2
(
2
-i-Bu
2
AlH-COD) or Ni(COD)
2
results. The addition of 1,5-cyclooctadiene (COD; 1-2
mol %) has a positive effect leading to a better reproduc-
(16) For other hydrozincation reactions see: (a) Dzhemilev, U. M.;
Vostrikova, O. S.; Sultanov, R. M. Izv. Akad. Nauk SSSR, Ser. Khim.
1
983, 5, 1195. Dzhemilev, U. M.; Vostrikova, O. S.; Tolsstikov, G. A.
(
12) mesal ) N-methylsalicylaldimino. (a) Klemm, W.; Raddatz, K.-
J . Organomet. Chem. 1986, 304, 17. (c) Gao, Y.; Urabe, H.; Sato, F. J .
Org. Chem. 1994, 59, 5521. (d) Gao, Y.; Harada, K.; Hata, T.; Urabe,
H.; Sato, F. J . Org. Chem. 1995, 60, 290.
H. Z. Anorg. Allgem. Chem. 1942, 250, 207. (b) Lardicci, L.; Giacomelli,
G. P.; Salvadori, P.; Pino, P. J . Am. Chem. Soc. 1971, 93, 5794.
(
13) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J . J . Org. Chem.
(17) (a) Felkin, H.; Swierczewski, G. Tetrahedron 1975, 31, 2735.
(b) Chuit, C.; Felkin, H.; Frajerman, C.; Roussi, G.; Swierczewski, G.
J . Chem. Soc., Chem. Commun. 1968, 1604. (c) Farady, L.; Bencze, L.;
Marko, L. J . Organomet. Chem. 1967, 10, 505. (d) Farady, L.; Marko,
L. J . Organomet. Chem. 1971, 28, 159.
1
988, 53, 2390.
(
14) Villieras, J .; Rambaud, M. Synthesis 1982, 924.
(15) Devasagayaraj, A.; St u¨ demann, T.; Knochel, P. Angew. Chem.
1
995, 107, 2952; Angew. Chem., Int. Ed. Engl. 1995, 34, 2723.

Ni-Catalyzed Preparations of Functionalized Organozincs
J . Org. Chem., Vol. 61, No. 21, 1996 7475
Ta ble 2. P r od u cts 6c,d ,f a n d 7a -f Obta in ed by th e
Hyd r ozin ca tion of Ter m in a l Alk en es 4 w ith Et2Zn in th e
P r esen ce of Ni(a ca c)2, F ollow ed by Tr a n sm eta la tion w ith
Cu CN‚2LiCl a n d Su bsequ en t Rea ction w ith a n
Electr op h ile (0.9 equ iv of Electr op h ile Ba sed on Rest R
of th e Zin c Com p ou n d )
Ta ble 3. P r od u cts 17a -l Obta in ed by th e
Hyd r ozin ca tion of Allylic a n d Hom oa llylic Alcoh ols
14a -f w ith Et2Zn in th e P r esen ce of Ni(a ca c)2, F ollow ed
by Tr a n sm eta la tion w ith Cu CN‚2LiCl a n d Su bsequ en t
Rea ction w ith a n Electr op h ile
a
Isolated yield of analytically pure products based on electro-
phile. b 1.2 equiv of electrophile, yield based on zinc compound. 2
equiv of TMSCl, 0.7 equiv of electrophile based on rest R of the
zinc compound.
c
pathways.18 Thus, the reaction of Et
Zn with Ni(acac)
2 2
may provide an ethylnickel(II) complex 8 that gives, after
â-hydride elimination, the nickel(II) hydride 9. A ligand
exchange from ethylene to the alkene 4 furnishes the
nickel-olefin complex 10, which undergoes an insertion
reaction (hydronickelation)19 to give the alkylnickel(II)
a
Isolated yield of analytically pure products based on alkene.
b
No TMSCl was added. c The TMS group of 17e has been removed
by treatment with Bu4NF in THF.
cyclohexane (12)21 (5-8 mol %) and Ti(Oi-Pr)
equiv) in toluene affording functionalized secondary
alcohols 13a -c in 89-95% ee (Scheme 5).
(1.25-2
4
2
complex 11. A transmetalation of 11 with Et Zn trans-
fers the hydrometalated alkene fragment from nickel to
zinc, affording the dialkylzinc 5 (Scheme 4).20
As noticed by Felkin17 and others, the hydrometala-
tion of allylic and homoallylic alcohols is easier than the
hydrometalation of unfunctionalized alkenes. We have
used a range of allylic and homoallylic alcohols as
substrates for the hydrozincation procedure and were
pleased to find that a good conversion was obtained in
these reactions. The treatment of allylic or homallylic
22
The moderate conversion for simple terminal alkenes
may be explained by the reversibility of the hydrometa-
lation reaction. Thus, heating of pure dioctylzinc pre-
pared by boron-zinc exchange with a catalytic amount
2
of Ni(acac) (5 mol %) and COD (10 mol %) for 3 h at 50
°
C affords 5% of 1-octene as shown by GC analysis. The
diorganozincs prepared by hydrozincation enantioselec-
tively add to aldehydes in the presence of catalytic
amounts of (R,R)-1,2-bis(trifluoromethanesulfonamido)-
alcohols of type 14 with Et
mol %) in the presence of Ni(acac)
at 40 °C furnishes the hydrozincated products 15 with a
conversion greater than 85%. Attempts to use the zinc
reagents 15 for quenching experiments were disappoint-
ing due to their too low reactivity resulting from the
2
Zn (3 equiv) and COD (10
(5 mol %) for 4-6 h
2
(
18) Keim, W.; Behr, A.; Kraus, G. J . Organomet. Chem. 1983, 251,
77.
19) (a) Sato, Y.; Takimoto, M.; Hayashi, K.; Katsuhara, T.; Takagi,
3
(
K.; Mori, M. J . Am. Chem. Soc. 1994, 116, 9771. (b) Sato, Y.; Takimoto,
M.; Mori, M. Tetrahedron Lett. 1996, 37, 887.
(
20) For an alternative mechanism involving Ni(0) see: Eisch, J .
J .; Sexsmith, S. R.; Fichter, K. C. J . Organomet. Chem. 1990, 382, 273.
21) (a) Yoshioka, M.; Kawakita, T.; Ohno, M. Tetrahedron Lett.
989, 30, 1657. (b) Takahashi, H.; Kawakita, T.; Yoshioka, M.;
(22) (a) Eisch, J . J .; Galle, J . E. J . Organomet. Chem. 1978, 160,
C8. (b) Hoveyda, A. H.; Xu, Z. J . Am. Chem. Soc. 1991, 113, 5079. (c)
Hoveyda, A. H.; Xu, Z.; Morken, J . P.; Houri, A. F. J . Am. Chem. Soc.
1991, 113, 8950. (d) Hoveyda, A. H.; Morken, J . P.; Houri, A. F.; Xu,
Z. J . Am. Chem. Soc. 1992, 114, 6692. (e) Houri, A. F.; Didiuk, M. T.;
Xu, Z.; Horan, N. R.; Hoveyda, A. H. J . Am. Chem. Soc. 1993, 115,
6614.
(
1
Kobayashi, S.; Ohno, M. Tetrahedron Lett. 1989, 30, 7095. (c) Taka-
hashi, H.; Kawakita, T.; Ohno, M.; Yoshioka, M.; Kobayashi, S.
Tetrahedron 1992, 48, 5691.

7
476 J . Org. Chem., Vol. 61, No. 21, 1996
Vettel et al.
Sch em e 4
Sch em e 5
Sch em e 6
Sch em e 7
chelation of zinc with oxygen.23 In order to increase this
reactivity TMSCl (2.0 equiv) was added. The high
affinity of silicon for oxygen should result in the opening
of the zinc metalacycle 15 and affords the alkylzinc
chloride 16 in which the alcoholate function has been
protected as a TMS-ether (Scheme 6). After addition of
CuCN‚2LiCl and an electrophile such as allylic bromide,
diethyl benzylidenemalonate, iodine, acid chlorides, or an
alkynyl bromide,24 the expected products 17a -l were
obtained in 61-76% isolated yields (Table 3). The
hydrozincation of allylic amine derivatives was also
investigated. The most reactive amine, N-allylmorpho-
line 18a , undergoes a quantitative hydrozincation within
sulting amino-substituted zinc-copper organometallics
react with several electrophiles (alkynyl bromide, allylic
halide, ethyl propiolate, and diethyl benzylidenema-
lonate) to yield polyfunctional amines 19a -h in 62-76%
overall yield (eq 2 and Table 4).
1
h at rt. Depending on the steric hindrance at nitrogen,
a rate decrease was observed (Scheme 7).
Unfortunately, the introduction of a substitution at
position 2 hampers the hydrozincation (18e in Scheme
In summary, we have reported several new nickel-
catalyzed preparations of functionalized dialkylzincs.
Whereas the nickel-catalyzed bromine- and chlorine-
zinc exchange reaction provides alkylzinc halides, the
hydrozincation of alkenes furnishes dialkylzincs that can
be added with excellent enantioselectivity to aldehydes.
The conversion of the hydrozincation is independent of
7
). After a transmetalation with CuCN‚2LiCl, the re-
(
(
23) Klumpp, G. W. Red. Trav. Chim. Pays-Bas 1986, 105, 1.
24) Yeh, M. C. P.; Knochel, P. Tetrahedron Lett. 1989, 30, 4799.

Ni-Catalyzed Preparations of Functionalized Organozincs
J . Org. Chem., Vol. 61, No. 21, 1996 7477
N-allyl-N,N-diphenylamine (18d ),29 1-bromo-1-butyne, 1-bro-
mo-1-octyne,32 and 1-bromo-2-phenylacetylene. The prepara-
tion of 3-butenyl pivalate (4b), 5-[(triisopropylsilyl)oxy]-1-
penten-3-ol (14d ), 4-hydroxy-5-hexenyl pivalate (14e), and (N-
benzyl-N-allyl)-4-aminobutyl pivalate (18e) is described in the
supporting information.
31
Ta ble 4. P r od u cts 19a -h Obta in ed by th e
Hyd r ozin ca tion of Allylic Am in es 18a -e w ith Et2Zn in
th e P r esen ce of Ni(a ca c)2, F ollow ed by Tr a n sm eta la tion
w ith Cu CN‚2LiCl a n d Su bsequ en t Rea ction w ith a n
Electr op h ile
33
P r ep a r a tion of P r od u cts 6a -j fr om Ha loa lk a n es 1-2.
Typ ica l P r oced u r e for th e P r ep a r a tion of Alk ylzin c
Ha lid es 3 a n d Th eir Rea ction w ith Electr op h iles. A 50
mL two-necked flask equipped with an argon inlet, a magnetic
stirring bar, and a septum cap was charged with Ni(acac)
mg, 0.20 mmol, 5 mol %) followed by 1-bromoalkane (4.00
mmol). The mixture was cooled to 0 °C, and Et Zn (0.82 mL,
.0 mmol, 2 equiv) was added dropwise. After completion of
2
(51
2
8
the addition, the cooling bath was removed and the reaction
mixture was stirred in a preheated oil bath at 55 °C for 2 h.
Ca u tion : Large amounts of gas are produced in the reaction
especially for large scale reactions! The excess of Et
2
Zn was
distilled off in vacuo. The black residue was dissolved in THF
(2 mL) and cooled to -60 °C, and a solution of CuCN‚2LiCl
(CuCN: 322 mg, 3.6 mmol; LiCl: 305 mg, 7.2 mmol) in THF
(4 mL) was added. The electrophile (2.80 mmol, 0.7 equiv)
was added, and the reaction mixture was warmed to the
temperature described. It was diluted with ether (20 mL) and
was quenched by addition of a saturated aqueous NH
solution (30 mL). The aqueous layer was extracted with ether
3 × 20 mL). The combined organic layer was washed with
brine (20 mL), dried (MgSO ), and filtered. The solvent was
4
Cl
(
4
evaporated, and the residual oil was purified by flash chro-
matography (hexanes/ether 9:1) to afford the product.
Typ ica l P r oced u r e for th e Allyla tion of Alk ylzin c
Ha lid es 3. (N-Ben zyltr iflu or om eth a n esu lfon a m id o)h ex-
5
-en e (6a ). The zinc compound was prepared as described
above. It was dissolved in THF, and a solution of CuCN‚2LiCl
10 mol %) in THF was added at -60 °C. Allyl bromide (3.2
equiv) was added, and the reaction mixture was warmed to 0
C overnight. After usual workup, the residual oil was purified
(
°
a
Isolated yield of analytically pure products based on alkene.
by flash chromatography (hexanes/ether 9:1) to afford the
product 6a (73% yield) as a colorless liquid. IR (neat): 2940
the excess of Et
2
Zn but strongly depends on the nature
1
(
3
m), 1390 (s), 1230 (s), 1195 (s), 1140 (s). H-NMR (CDCl ,
of the alkene. Conversions of alkenes bearing a remote
functionality reach 40-63%, whereas with allylic and
homoallylic alcohols as well as tertiary allylic amines
conversions of the hydrozincation lay between 85-95%.
Although less general and practical than the boron-zinc
exchange reaction for the preparation of functionalized
dialkylzincs, this method provides an efficient one-step
preparation of functionalized organozincs bearing a hy-
droxy or amino function in the allylic position starting
from alkenes.
300 MHz): δ 7.42-7.33 (m, 5H), 5.69 (ddt, J ) 6.7, 10.6, 16.8
Hz, 1H), 4.99-4.86 (m, 2H), 4.52 (br, 2H), 3.28 (t, J ) 7.8 Hz,
1
3
2
H), 1.96 (m, 2 H), 1.57-1.41 (m, 2H), 1.28 (m, 2H). C-NMR
(CDCl
3
, 75 MHz): δ 137.7, 134.5, 128.9, 128.5, 128.4, 120.2
(
3
(
q, J CF ) 321 Hz), 115.0, 52.0, 48.0, 32.9, 27.1, 25.5. MS (EI):
+
21 (M , 23), 91 (100). Anal. Calcd for C14
321.364): C, 52.33; H, 5.65; N, 4.36. Found: C, 52.38; H, 5.55;
N, 4.40.
18 3 2
H F NO S
1
-Iod oocta n e (6b). The octyl zinc iodide was prepared as
above from 1-bromooctane (579 mg, 3.00 mmol). It was
dissolved in THF (3 mL) and cooled to -70 °C and a solution
of iodine (1.14 g, 4.5 mmol) in THF (5 mL) added. The reaction
mixture was warmed to -10 °C within 1 h. It was diluted
with ether (30 mL) and quenched with water (20 mL) and
Exp er im en ta l Section
aqueous saturated NaS
with ether (2 × 20 mL). The combined organic layer was
washed with brine (20 mL), dried (MgSO ), and filtered. The
2 3
O . The aqueous layer was extracted
Gen er a l Con sid er a tion s. Unless otherwise indicated, all
reactions were carried out under argon. Solvents (THF,
toluene) were dried and freshly distilled over sodium/ben-
zophenone. Reactions were monitored by gas-liquid-phase
chromatography (GC) or thin-layer chromatography (TLC)
analysis of hydrolyzed aliquots.
4
solvent was evaporated, and the residual oil was purified by
flash chromatography (hexanes) to afford the product 6b (488
1
mg, 2.03 mmol, 68% yield) as a colorless liquid. H-NMR
(CDCl
7.1 Hz, 2H), 1.47-1.17 (m, 10H), 0.85 (t, J ) 6.5 Hz, 3H). C-
NMR (CDCl , 50 MHz): δ 33.5, 31.7, 30.4, 29.0, 28.4, 22.6,
3
, 200 MHz): δ 3.15 (t, J ) 7.0 Hz, 2H), 1.79 (quint, J )
13
Sta r tin g Ma ter ia ls. The following starting materials were
prepared according to literature procedures: ethyl (2-bromo-
3
1
4
methyl)acrylate, 3-(N-benzyl-N-(trifluoromethyl)sulfonami-
14.0, 7.1 (identical with commercially available material from
Aldrich).
4
g
25
do)propyl chloride (2b), 4-methyl-1-penten-3-ol (14a ), 1-non-
2
6
26
en-3-ol (14b), 1-ethenyl-1-cyclohexanol (14c), 1-phenyl-3-
Eth yl 2-Non yla cr yla te (6c). (a) Ethyl (2-bromomethyl)-
2
7
28
14
buten-1-ol (14f), N-allylmorpholine (18a ), N-allyl-N-methyl-
acrylate (0.7 equiv) was used as electrophile; reaction con-
2
9
30
N-phenylamine (18b), N-allyl-N,N-dibenzylamine (18c),
ditions: -60 to 0 °C 2 h, 2 h at 0 °C; hexanes/ether 9:1, 79%
yield, yellowish oil. IR (neat): 2925 (s), 2860 (s), 1720 (s), 1180
1
(
s), 1150 (s). H-NMR (CDCl
3
, 300 MHz): δ 6.09 (d, J ) 1.3
(
25) Midland, M. M.; Koops, R. W. J . Org. Chem. 1990, 55, 5058.
(26) Smith, J . G.; Drozda, S. E., Petraglia, S. P.; Quinn, N. R.; Rice,
Hz, 1H), 5.47 (dt, J ) 1.3, 1.3 Hz, 1H), 4.18 (q, J ) 7.1 Hz,
2H), 2.26 (dd, J ) 7.1, 7.6 Hz, 2H), 1.43 (m, 2H), 1.30-1.24
E. M.; Taylor, B. S.; Viswanathan, M. J . Org. Chem. 1984, 49, 4112.
(
(
27) Smith, G. G.; Voorhees, K. J . J . Org. Chem. 1970, 35, 2182.
28) Bergbreiter, D. E.; Chen, B.; Lynch, T. J . J . Org. Chem. 1983,
4
5
8, 4179.
(31) Brandsma, L.; Verkruijsse, H. D. Synthesis 1990, 985.
(32) Correia, J . J . Org. Chem. 1992, 57, 4555.
(33) Vogel, A. Textbook of Practical Organic Chemistry; 4th ed.;
Longman: London, 1981; p 352.
(
(
29) Barnah, J . B.; Samuelson, A. G. Tetrahedron 1991, 45, 9449.
30) Garro-Helion, F.; Merzouk, A.; Guib e´ , F. J . Org. Chem. 1993,
8, 6109.

7
478 J . Org. Chem., Vol. 61, No. 21, 1996
Vettel et al.
(
m, 12H), 1.27 (t, J ) 7.2 Hz, 3H), 0.85 (t, J ) 6.7 Hz, 3H).
(69), 81 (100). Anal. Calcd for C12
H, 8.83. Found: C, 62.85; H, 9.02.
H
20
O
4
(228.288): C, 63.14;
1
3
C-NMR (CDCl , 75 MHz): δ 167.3, 141.2, 124.0, 60.4, 31.86,
3
3
2
1.84, 29.5, 29.4, 29.3, 29.2, 28.4, 22.6, 14.2, 14.0. MS (EI):
Eth yl 6-Nitr o-5-p h en ylh exa n oa te (6i). Nitrostyrene (0.5
equiv) was used as electrophile; reaction conditions: -40 to
-5 °C, overnight; hexanes/ether 20:1-9:1, 51% yield, yellowish
+
26 (M , 3), 115 (100), 55 (71), 43 (74), 41 (71). Anal. Calcd
for C14
H, 11.82.
b) The procedure described for the preparation of 6c was
followed with 1-chlorooctane 2a (60 °C, 3 d). Ethyl (2-
bromomethyl)acrylate (0.7 equiv) was used as electrophile;
reaction conditions: -40 to 0 °C, overnight; hexanes/ether 9:1,
5
26 2
H O (226.360): C, 74.29; H, 11.58. Found: C, 74.34;
oil. IR (neat): 1720 (s), 1545 (s), 1375 (s), 1200 (s), 700 (s).
1
(
3
H-NMR (CDCl , 300 MHz): δ 7.31-7.21 (m, 3H), 7.16-7.10
(m, 2H), 4.50 (dd, J ) 2.6, 7.6 Hz, 2H), 4.04 (q, J ) 7.1 Hz,
2H), 3.40 (m, 1H), 2.21 (m, 2H), 1.72-1.64 (m, 2H), 1.52-1.41
(m, 2H), 1.17 (t, J ) 7.1 Hz, 3H). C-NMR (CDCl , 75 MHz):
3
1
4
1
3
6% yield, yellowish oil.
δ 172.8, 138.9, 128.9, 127.6, 127.4, 80.6, 60.2, 44.0, 33.6, 32.2,
2.2, 14.1. MS (EI): 218 (25), 131 (100), 91 (76). Anal. Calcd
for C14 (265.309): C, 63.38; H, 7.22; N, 5.28. Found:
2
(
E)-Eth yl Un d ec-2-en oa te (6d ). Ethyl propiolate (0.7
H
19NO
4
equiv) was used as electrophile; reaction conditions: 0 °C, 3.5
h; hexanes/ether 9:1, 64% yield, yellowish liquid. IR (neat):
2
MHz): δ 6.93 (dt, J ) 15.6, 7.0 Hz, 1H), 5.77 (dt, J ) 15.6, 1.6
Hz, 1H), 4.15 (q, J ) 7.2 Hz, 2H), 2.16 (ddt, J ) 7.4, 7.1, 1.5
Hz, 2H), 1.42 (quint, J ) 7.1 Hz, 2H), 1.30-1.23 (m, 10H),
1
(
C, 63.11; H, 7.31; N, 5.42.
1
Eth yl Hep t-6-en oa te (6j). Allyl bromide (4 equiv) was
used as electrophile (see 6a ); reaction conditions: -60 to 0
920 (s), 1720 (s), 1265 (m), 980 (w). H-NMR (CDCl
3
, 300
°
C, overnight; Kugelrohr distillation, 65% yield, colorless
liquid. IR (neat): 2940 (m), 1730 (s), 1260 (s), 1170 (m), 905
1
1
3
(m). H-NMR (CDCl
6
3
, 300 MHz): δ 5.73 (ddt, J ) 17.0, 10.3,
.25 (t, J ) 7.1 Hz, 3H), 0.85 (t, J ) 6.7 Hz, 3H). C-NMR
.7 Hz, 1H), 4.98-4.87 (m, 2H), 4.06 (q, J ) 7.2 Hz, 2H), 2.24
CDCl , 75 MHz): δ 166.7, 149.3, 121.2, 60.0, 32.1, 31.8, 29.3,
3
+
(t, J ) 7.5 Hz, 2H), 2.01 (m, 2H), 1.58 (m, 2H), 1.36 (m, 2H),
2
9.13, 29.10, 28.0, 22.6, 14.2, 14.0. MS (EI): 212 (M , 1), 101
1
3
1
1
(
.19 (t, J ) 7.2 Hz, 3H). C-NMR (CDCl
3
, 75 MHz): δ 173.5,
(
(
95), 73 (75), 55 (100), 43 (94). Anal. Calcd for C13
212.333): C, 73.54; H, 11.39. Found: C, 73.34; H, 11.10.
Octyl P h en yl Keton e (6e). Benzoyl chloride (0.7 equiv)
24 2
H O
38.3, 114.5, 60.0, 34.1, 33.2, 28.3, 24.3, 14.1. MS (EI): 156
+
M , 3), 88 (100), 55 (82), 41 (90). Anal. Calcd for C
156.225): C, 69.19; H, 10.32. Found: C, 68.95; H, 10.64.
P r ep a r a tion of P r od u cts 7a -i fr om Ter m in a l Alk en es
4. Typ ica l P r oced u r e for th e Hyd r ozin ca tion of Alk en es
a n d Th eir Rea ction w ith Electr op h iles. Eth yl 2-Non yl-
9 16 2
H O
(
was used as electrophile; reaction conditions: -60 to -10 °C,
overnight; hexanes/ether 20:1-10:1, 54% yield, colorless liquid.
1
IR (neat): 2920 (s), 1685 (s), 750 (m), 690 (m). H-NMR
4
(
CDCl
3
, 200 MHz): δ 7.97-7.92 (m, 2H), 7.53-7.43 (m, 3H),
a cr yla te (6c). A 50 mL two-necked flask equipped with an
argon inlet, a magnetic stirring bar, and a septum cap was
2
1
5
2
1
1
.94 (dd, J ) 7.2, 7.6 Hz, 2H), 1.72 (quint, J ) 7.0 Hz, 2H),
1
3
3
.38-1.17 (m, 10H), 0.87 (t, J ) 6.5 Hz, 3H). C-NMR (CDCl ,
charged with Ni(acac)
(22 mg, 0.20 mmol, 2 mol %), followed by the alkene 4a (1.12
g, 10.0 mmol). The mixture was cooled to 0 °C, and Et Zn
0.61 mL, 6.0 mmol, 0.6 equiv) was dropwise added. The
2
(26 mg, 0.10 mmol, 1 mol %) and COD
0 MHz): δ 200.4, 137.0, 132.8, 128.5, 128.0, 38.5, 31.8, 29.4,
+
9.3, 29.1, 24.3, 22.6, 14.0. MS (EI): 218 (M , 4), 120 (94),
2
05 (100). Anal. Calcd for C15
0.16. Found: C, 82.35; H, 10.05.
Eth yl 2-Ca r beth oxy-3-p h en ylu n d eca n oa te (6f). (a) Di-
H22O (218.340): C, 82.52; H,
(
cooling bath was removed, and the reaction mixture was
stirred in a preheated oil bath at 50-60 °C for 3 h. Ca u tion :
Large amounts of gas are produced in the reaction especially
for large scale reactions! The conversion was checked by
iodolysis of an aliquot of the reaction mixture (40-45%). The
ethyl benzylidenemalonate (0.7 equiv) was as electrophile;
reaction conditions: -60 to 0 °C, overnight; hexanes/ether 9:1,
6
(
7
5% yield, colorless oil. IR (neat): 2925 (s), 1670 (m), 1255
1
s), 1185 (m), 755 (s), 700 (s). H-NMR (CDCl
3
, 300 MHz): δ
2
excess of Et Zn and unreacted olefin was distilled off in vacuo,
.21-7.17 (m, 2H), 7.13-7.08 (m, 3H), 4.16 (q, J ) 7.1 Hz, 2
yielding dioctylzinc (2.25 mmol). The black residue was
dissolved in THF (3 mL) and added to a cooled solution of
CuCN‚2LiCl (CuCN: 403 mg, 4.50 mmol; LiCl: 382 mg, 9.00
mmol) in THF (4 mL) at -60 °C. The mixture was stirred for
H), 3.79 (q, J ) 7.1 Hz, 2H), 3.55 (d, J ) 10.8 Hz, 1H), 3.28,
dt, J ) 10.8, 4.0 Hz, 1H), 1.65-1.52 (m, 2H), 1.21 (t, J ) 7.1
Hz, 3H), 1.24-1.05 (m, 12H), 0.84 (t, J ) 7.1 Hz, 3H), 0.77 (t,
(
1
3
J ) 6.8 Hz, 3H). C-NMR (CDCl
1
3
, 75 MHz): δ 168.4, 167.8,
1
0 min at rt and cooled back to -60 °C. Ethyl (2-bromo-
41.0, 128.3, 128.1, 126.7, 61.3, 60.9, 58.9, 45.6, 33.9, 31.7, 29.2
14
methyl)acrylate (773 mg, 4.00 mmol, 0.9 equiv) was added,
and the reaction mixture was warmed to -10 °C overnight. It
was diluted with ether (30 mL) and quenched by addition of a
+
(
2 C), 29.1, 26.9, 22.5, 14.0, 13.9, 13.6. MS (EI): 362 (M , 8),
02 (51), 190 (55), 91 (100). Anal. Calcd for C22
362.510): C, 72.89; H, 9.45. Found: C, 73.08; H, 9.40.
b) The procedure described for the preparation of 6c was
followed with 1-chlorooctane 2a . Diethyl benzylidenemalonate
2
(
34 4
H O
saturated aqueous NH
was extracted with ether (3 × 50 mL). The combined organic
layer was washed with brine (50 mL), dried (MgSO ), and
4
Cl solution (50 mL). The aqueous layer
(
4
(
0.5 equiv) was used as electrophile; reaction conditions: -40
filtered. The solvent was evaporated, and the residual oil was
purified by flash chromatography (hexanes/ether 9:1) to afford
the product 6c (665 mg, 2.94 mmol, 74% yield) as a yellowish
oil (see above for the spectral data).
(E)-Eth yl Un d ec-2-en oa te (6d ). Ethyl propiolate (0.9
equiv) was used as electrophile; reaction conditions: -60 to
-5 °C, overnight; hexanes/ether 9:1, 60% yield, yellowish oil
(see above for the spectral data).
to -5 °C, overnight; hexanes/ether 9:1, 68% yield, colorless
oil.
4
-P h en yld od eca n -2-on e (6g). Benzylideneacetone (0.5
equiv) was used as electrophile; reaction conditions: -60 to 0
C, overnight; hexanes/ether 9:1, 71% yield, colorless oil. IR
°
1
3
(neat): 2925 (s), 1705 (s), 1360 (s), 700 (s). H-NMR (CDCl ,
3
3
(
00 MHz): δ 7.30-7.25 (m, 2H), 7.19-7.15 (m, 3H), 3.18-
.07 (m, 1H), 2.71 (d, J ) 7.4 Hz, 2H), 1.99 (s, 3H), 1.69-1.51
Eth yl 2-Ca r beth oxy-3-p h en ylu n d eca n oa te (6f). Diethyl
benzylidenemalonate (0.9 equiv) was used as electrophile;
reaction conditions: -60 to 0 °C, overnight; hexanes/ether 9:1,
72% yield, colorless oil (see above for the spectral data).
Eth yl 2-(5-P iva loxyp en tyl)a cr yla te (7a ). The hydrozin-
cation procedure described for the preparation of 6c was
followed with alkene 4b (45% conversion), yielding bis(4-
pivaloxybutyl)zinc (1.13 mmol). Ethyl (2-bromomethyl)acry-
1
3
m, 2H), 1.35-1.01 (m, 12H), 0.89 (t, J ) 6.6 Hz, 3H). C-
NMR (CDCl
5
3
, 75 MHz): δ 207.4, 144.5, 128.3, 127.3, 126.4,
0.7, 41.2, 36.3, 31.7, 30.3, 29.4, 29.3, 29.1, 27.2, 22.5, 13.9.
+
MS (EI): 260 (M , 2), 202 (64), 147 (75), 91 (57), 43 (100). Anal.
Calcd for C18 28O (260.421): C, 83.02; H, 10.84. Found: C,
2.90, H, 10.95.
H
8
Eth yl 6-Ca r beth oxyh ep t-6-en oa te (6h ). Ethyl (2-bro-
momethyl)acrylate1 (0.7 equiv) was used as electrophile;
3
late (0.9 equiv) was used as electrophile; reaction condi-
14
reaction conditions: -40 to 0 °C, overnight; hexanes/ether 20:
tions: -60 to -10 °C, overnight; hexanes/ether 9:1, 90% yield,
1
1
-9:1, 62% yield, colorless liquid. IR (neat): 2940 (m), 1720
colorless oil. IR (neat): 2940 (m), 1720 (s), 1160 (s). H-NMR
1
(
s), 1630 (m), 1300 (br), 810 (m). H-NMR (CDCl
3
, 300 MHz):
(CDCl
3
, 200 MHz): δ 6.08 (s, 1H), 5.46 (s, 1H), 4.15 (q, J )
δ 6.07 (d, J ) 1.4 Hz, 1H), 5.46 (dt, J ) 1.4, 1.4 Hz, 1H), 4.13
7.1 Hz, 2H), 4.00 (t, J ) 6.5 Hz, 2H), 2.26 (t, J ) 7.2 Hz, 2H),
1
3
(
q, J ) 7.2 Hz, 2H), 4.06 (q, J ) 7.2 Hz, 2H), 2.25 (m, 2H),
1.60-1.28 (m, 6H), 1.25 (t, J ) 7.1 Hz, 3H), 1.14 (s, 9 H). C-
NMR (CDCl , 50 MHz): δ 178.5, 167.1, 140.7, 124.3, 64.1, 60.5,
38.6, 31.6, 28.3, 27.9, 27.1, 25.4, 14.1. MS (EI): 168 (24), 95
(44), 57 (100). Anal. Calcd for C15 (270.369): C, 66.64;
H, 9.69. Found: C, 66.36; H, 9.98.
2
1
.25 (t, J ) 7.3 Hz, 2H), 1.59 (quint, J ) 7.5 Hz, 2H), 1.53-
.39 (m, 2H), 1.23 (t, J ) 7.2 Hz, 3H), 1.18 (t, J ) 7.2 Hz, 3H).
3
1
3
C-NMR (CDCl
3
, 75 MHz): δ 173.2, 166.8, 140.4, 124.2, 60.3,
26 4
H O
5
9.9, 33.8, 31.3, 27.7, 24.3, 14.0, 13.9. MS (EI): 183 (64), 154

Ni-Catalyzed Preparations of Functionalized Organozincs
,6-Hep ta d ien yl p iva la te (7b). Propargyl bromide (1.2
J . Org. Chem., Vol. 61, No. 21, 1996 7479
5
4.45 (bs, 2H), 3.18 (t, J ) 7.8 Hz, 2H), 2.44-2.14 (m, 3H), 2.13-
1
3
equiv, 80% in toluene) as electrophile; reaction conditions: -60
3
0.94 (m, 16H). C-NMR (CDCl , 50 MHz): δ 212.0, 134.4,
to -10 °C, overnight; hexanes/ether 20:1-9:1, 68% yield,
128.8, 128.5, 128.3, 120.1 (q, J C-F ) 322 Hz), 51.9, 48.1, 41.4,
colorless liquid. IR (neat): 3000 (m), 1955 (m), 1710 (s), 1150
38.9, 36.3, 31.2, 28.9, 27.6, 26.3, 26.1, 25.2. MS (EI): 286 (64),
1
(
3
s). H-NMR (CDCl
3
, 200 MHz): δ 5.05 (m, 1H), 4.64 (dd, J )
28 3 3
91 (100). Anal. Calcd for C20H F NO S (419.509): C, 57.26;
H, 6.73 ; N, 3.34. Found: C, 56.99; H, 6.44; N, 3.53.
.2, 3.2 Hz, 1H), 4.61 (dd, J ) 3.2, 3.2 Hz, 1H), 4.02 (t, J ) 6.6
Hz, 2H), 2.00 (m, 2H), 1.60 (m, 2H), 1.37 (m, 2H), 1.16 (s, 9H).
Typ ica l P r oced u r e for th e P r ep a r a tion of Ch ir a l
Alcoh ols 13a -c. (S)-(-)-1-P h en yl-1-n on a n ol (13a ). The
procedure described for the preparation of 7a was followed
with alkene 4a , yielding dioctylzinc (4.2 mmol) that was
diluted with toluene (3 mL). In a 50 mL two-necked flask
equipped with an argon inlet, a magnetic stirring bar, and a
septum cap a mixture of (R,R)-1,2-bis(trifluoromethanesulfona-
mido)cyclohexane (12) (32 mg, 0.083 mmol, 5 mol %) and Ti-
1
3
C-NMR (CDCl
8.6, 28.0, 27.7, 27.1, 25.3. MS (EI): 103 (12), 79 (62), 57 (100).
Anal. Calcd for C12 (196.290): C, 77.43; H, 10.27.
Found: C, 74.23; H, 10.39.
-(4-P iva loxybu tyl)cycloh exa n on e (7c). The hydrozin-
3
, 50 MHz): δ 208.5, 178.5, 89.5, 74.8, 64.1,
3
20 2
H O
3
cation procedure described for the preparation of 6c was
followed with alkene 4b, yielding bis(4-pivaloxybutyl)zinc (1.85
mmol). The black residue was dissolved in THF (4 mL) and
cooled to -60 °C, and a solution of CuCN‚2LiCl (CuCN: 331
mg, 3.70 mmol; LiCl: 315 mg, 7.40 mmol) in THF (4 mL) was
added. The mixture was stirred for 10 min at rt and cooled
back to -60 °C. After 10 min, TMSCl (804 mg, 7.40 mmol, 2
equiv) was added, and after further 10 min cyclohexenone (250
mg, 2.60 mmol, 0.7 equiv) was added dropwise. The reaction
mixture was warmed to -10 °C overnight and worked up as
usual. The solvent was removed in vacuo, and the residue
was diluted with THF (50 mL). Aqueous HCl (10%, 5 mL)
was slowly added, and the reaction mixture was stirred for
4
(Oi-Pr) (1.0 mL, 3.4 mmol, 2 equiv) in toluene (1.5 mL) was
heated to 50 °C for 30 min. The resulting clear solution was
cooled to -50 °C, and dioctylzinc in toluene was slowly added.
After 45 min, benzaldehyde (193 mg, 1.82 mmol) was added
and the reaction mixture was allowed to warm to -20 °C
overnight. It was diluted with ether (20 mL) and quenched
4
with saturated aqueous NH Cl. Aqueous HCl (10%) was added
until a clear solution resulted. The aqueous layer was
extracted with ether (3 × 10 mL) and treated with 2 N NaOH
(20 mL) to remove the catalyst. The combined organic layer
was dried (MgSO ) and concentrated. The resulting residue
4
was purified by flash chromatography (hexanes/ether 4:1) to
3
0 min at rt. It was diluted with ether (30 mL) and neutral-
ized with 2 N NaOH (20 mL). The aqueous layer was
extracted twice with ether (20 mL) and washed with brine (20
afford the product 13a (247 mg, 1.12 mmol, 62% yield, 90%
ee) as a colorless oil. [R]25
) -23.8 (c ) 2.5, CHCl
). IR
D
3
1
mL). The combined organic layer was dried (MgSO
4
) and
(neat): 3350 (br), 2920 (s), 2860 (s), 1030 (m). H-NMR (CDCl ,
3
filtered, and the solvent was evaporated. The residual oil was
purified by flash chromatography (hexanes/ether 9:1 to 4:1)
to afford the product 7c (458 mg, 1.80 mmol, 69% yield) as a
300 MHz): δ 7.33-7.24 (m, 5H), 4.60 (t, J ) 6.0 Hz, 1H), 2.29
(bs, 1H), 1.83-1.63 (m, 2H), 1.42-1.19 (m, 16H), 0.89 (t, J )
6.6 Hz, 3H). 13C-NMR (CDCl
, 75 MHz): δ 145.0, 128.3, 127.3,
3
colorless liquid. IR (neat): 2930 (m), 1725 (s), 1715 (s), 1155
125.9, 74.6, 39.0, 31.9, 29.5 (2 C), 29.3, 25.8, 22.6, 14.0. MS
1
+
(
2
(
4
s). H-NMR (CDCl
3
, 200 MHz): δ 3.96 (t, J ) 6.4 Hz, 2H),
(EI): 220 (M , 1), 107 (100). Anal. Calcd for C15
24
H O
.40-2.10 (m, 3H), 2.09-1.40 (m, 7H), 1.38-1.20 (m, 5H), 1.10
(220.356): C, 81.76; H, 10.98. Found: C, 81.68; H, 11.15.
13
1
s, 9H). C-NMR (CDCl
1.3, 38.7, 38.5, 35.9, 31.0, 28.4, 27.0, 25.0, 22.8. MS (EI): 152
17), 97 (93), 57 (100). Anal. Calcd for C15 (254.370) :
C, 70.83; H, 10.30. Found: C, 70.64; H, 10.52.
3
, 50 MHz): δ 211.5, 178.3, 63.9, 47.9,
The enantiomeric excess was determined in H-NMR of the
corresponding (S)-O-acetyl mandelate.34
(
H
26
O
3
(E)-(S)-(+)-1-P h en ylu n d ec-1-en -3-ol (13b). The reaction
was run as above with catalyst 12 (8 mol %), Ti(Oi-Pr) (1.25
4
E t h yl 2-Ca r b et h oxy-3-p h en yl-7-p iva loxyh ep t a n oa t e
7d ). Diethyl benzylidenemalonate (0.9 equiv) was used as
equiv), and cinnamaldehyde; -45 °C stirred overnight; hex-
25
(
anes/ether 4:1-1:1, 76% yield, 89% ee, colorless oil. [R]
+3.9 (c ) 2.0, CHCl ). IR (neat): 3340 (br), 2920 (s), 745 (m),
695 (m). H-NMR (CDCl , 300 MHz): δ 7.23 (m, 5H), 6.42 (d,
D
)
electrophile; reaction conditions: -60 to 0 °C, overnight;
3
1
hexanes/ether 4:1-1:1, 87% yield, yellowish oil. IR (neat):
3
1
J ) 15.9 Hz, 1H), 6.13 (dd, J ) 6.8, 15.9 Hz, 1H), 4.11 (m,
2
3
950 (m), 1750 (s), 1730 (s), 1260 (s). H-NMR (CDCl , 300
MHz): δ 7.23-7.11 (m, 5H), 4.18 (q, J ) 7.2 Hz, 2H), 3.87 (t,
1H), 2.41 (bs, 1H), 1.54-1.38 (m, 2H), 1.37-1.10 (m, 12H), 0.79
(t, J ) 6.4 Hz, 3H). 13C-NMR (CDCl
, 50 MHz): δ 136.7, 132.6,
J ) 6.4 Hz, 2H), 3.81 (q, J ) 7.2 Hz, 2H), 3.57 (q, J ) 11.0 Hz,
3
1
(
)
1
3
1
:
H), 3.30 (dt, J ) 3.6, 10.7 Hz, 1H), 1.65-1.39 (m, 4H), 1.23
129.9, 128.4, 127.4, 126.3, 72.9, 37.3, 31.8, 29.52, 29.48, 29.2,
+
t, J ) 7.2 Hz, 3H), 1.12-1.03 (m, 2H), 1.05 (s, 9H), 0.86 (t, J
25.4, 22.6, 14.0. MS (EI): 246 (M , 4), 228 (22), 133 (100), 91
1
3
(56). Anal. Calcd for C H26O (246.394): C, 82.87; H, 10.64.
7.2 Hz, 3H). C-NMR (CDCl
3
, 50 MHz): δ 178.3, 168.3,
17
67.6, 140.4, 128.2, 128.1, 126.8, 63.7, 61.4, 60.9, 58.6, 45.3,
8.5, 33.3, 28.1, 27.0, 23.2, 14.0, 13.5. MS (EI): 406 (M , 6),
Found: C, 82.61; H, 10.55.
+
1
The enantiomeric excess was determined in H-NMR of the
corresponding (S)-O-acetyl mandelate.34
61 (30), 144 (100), 57 (78). Anal. Calcd for C23
C, 67.96; H, 8.43. Found: C, 67.72; H, 8.61.
E t h yl 2-[7-(N-Ben zylt r iflu or om et h a n esu lfon a m id o)-
34 6
H O (406.501)
(S)-(+)-5-Hyd r oxy-8-[(tr iisop r op ylsilyl)oxy]octyl P iv-
a la te (13c). The reaction was run as above with catalyst 12
(
4
8 mol %) and Ti(Oi-Pr)
-[(Triisopropylsilyl)oxy]butanal4f was added at -50 °C and
allowed to warm to -10 °C overnight; hexanes/ether 4:1-1:1,
8% yield, 95% ee, colorless oil. [R]25
) +0.8 (c ) 15.7, C ).
IR (neat): 3450 (br), 2865 (s), 1725 (s), 1290 (s), 765 (s). H-
NMR (CDCl , 300 MHz): δ 4.01 (t, J ) 6.5 Hz, 2H), 3.70 (t, J
5.5 Hz, 2H), 3.58 (m, 1H), 2.75 (d, J ) 4.0 Hz, 1H), 1.68-
4
(2 equiv) in toluene (2 mL).
h ep tyl]a cr yla te (7e). The hydrozincation procedure de-
scribed for the preparation of 6c was followed with alkene 6a
63% conversion), yielding bis[6-(N-benzyltrifluormethane-
(
6
D
6 6
H
sulfonamido)hexyl]zinc (1.85 mmol). Ethyl (2-bromomethyl)-
1
1
4
acrylate (251 mg, 1.30 mmol, 0.7 equiv) was used as
electrophile; reaction conditions: -60 to -30 °C, overnight;
hexanes/ether 20:1-9:1, 82% yield, colorless oil. IR (neat):
3
)
1
1.56 (m, 5H), 1.50-1.36 (m, 5H), 1.15 (s, 9H), 1.11-0.96 (m,
2
930 (m), 1710 (s), 1395 (s), 1225 (s), 1195 (s), 1145 (s). H-
NMR (CDCl , 200 MHz): δ 7.35 (m, 5H), 6.11 (d, J ) 1.0 Hz,
H), 5.47 (d, J ) 1.0 Hz, 1H), 4.50 (bs, 2H), 4.18 (q, J ) 7.2
Hz, 2H), 3.23 (t, J ) 7.8 Hz, 2H), 2.24 (t, J ) 8.4 Hz, 2H),
1
3
2
3
1H). C-NMR (CDCl
8.6, 36.9, 34.8, 29.2, 28.6, 27.1, 22.1, 17.9, 11.9. MS (EI): 359
Si
3
, 75 MHz): δ 178.5, 71.1, 64.3, 63.7,
3
1
(
6), 215 (44), 109 (80), 57 (100). Anal Calcd for C22
46 4
H O
1
3
(402.692) C, 65.62; H, 11.51. Found: C, 65.59; H, 11.43.
1
5
1
2
3
.72-1.10 (m, 10H), 1.32 (t, J ) 7.2 Hz, 3H). C-NMR (CDCl ,
1
The enantiomeric excess was determined in H-NMR of the
corresponding (S)-O-acetyl mandelate.34
0 MHz): δ 167.2, 140.9, 134.4, 128.9, 128.5, 128.3, 124.1,
20.1 (q, J CF ) 322 Hz), 60.5, 51.9, 48.1, 31.7, 29.7, 28.7, 28.1,
7.6, 26.2, 14.1. MS (EI): 390 (2), 302 (47), 91 (100). Anal.
P r ep a r a tion of P r od u cts 17a -l fr om Allylic a n d Ho-
m oa llylic Alcoh ols 14a -f. Typ ica l P r oced u r e for th e
Hyd r ozin ca tion of Allylic a n d Hom oa llylic Alcoh ols
Calcd for C20
Found: C, 55.0; H, 6.65; N, 3.38.
-[6-(N-Ben zylt r iflu or om et h a n esu lfon a m id o)h exyl]-
28 3 4
H F NO S (435.508): C, 55.16; H, 6.48; N, 3.22.
1
4a -f. Eth yl 2-(4-Hyd r oxy-5-m eth ylh exyl)a cr yla te (17a ).
3
A 25 mL three-necked flask equipped with an argon inlet, a
magnetic stirring bar, an internal thermometer, and a septum
cycloh exa n on e (7f). Cyclohexenone (0.7 equiv; TMSCl, 2
equiv) as electrophile (see preparation of 7c); reaction condi-
tions: -60 °C to rt, overnight; hexanes/ether 9:1-4:1, 52%
cap was charged with Ni(acac)
2
(66 mg, 0.25 mmol, 5 mol %)
yield, colorless oil. IR (neat): 2930 (m), 1705 (m), 1395 (s),
1
1
225 (s), 1195 (s). H-NMR (CDCl
3
, 200 MHz): δ 7.29 (m, 5H),
(34) Parker, D. J . Chem. Soc., Perkin Trans. 2 1983, 83.

7
480 J . Org. Chem., Vol. 61, No. 21, 1996
Vettel et al.
and COD (54 mg, 0.5 mmol, 10%), followed by the allylic
(26), 189 (100), 147 (54), 69 (21). Anal. Calcd for C20
(350.41): C, 68.57; H, 8.57. Found: C, 68.53; H, 8.30.
30 5
H O
alcohol 14a (0.5 g, 5.0 mmol). The mixture was cooled to -78
°
C, and Et
2
Zn (1.5 mL, 15.0 mmol, 3 equiv) was added
1-P h en yl-1-u n d ecyn -5-ol (17f). 1-Bromo-2-phenylacety-
lene (2 equiv) as electrophile; reaction conditions: -53 °C, 2
d; hexanes/ether 9:1-4:1, 71% yield, colorless oil. IR (neat):
dropwise. After completion of the addition, the cooling bath
was removed and the reaction mixture was warmed gradually
to 40 °C. It was stirred at this temperature for 5 h, and the
1
3350 (vs, br), 2910 (vs), 2850 (s), 1600 (m). H-NMR (CDCl
3
,
excess Et
2
Zn was distilled off in vacuo. THF (5 mL) was added
300 MHz): δ 7.40 (m, 5H), 3.76 (m, 1H), 2.54 (t, J ) 7.2 Hz,
to the reaction mixture and was distilled off again. This
procedure was repeated twice. The black residue was dis-
solved in THF (5 mL) and cooled to -78 °C. At this temper-
ature, TMSCl (1.2 mL, 10.0 mmol) was added, and the reaction
mixture was allowed to warm to rt within 12 h. It was cooled
back to -78 °C, and a solution of CuCN‚2LiCl (CuCN: 0.45 g,
2H), 2.02 (s, br, 1H), 1.68 (m, 2H), 1.49 (m, 2H), 1.29 (m, 2H),
1
3
0.91 (t, J ) 6.4 Hz, 3H). C-NMR (CDCl , 75 MHz): δ 131.6,
3
128.3, 127.7, 123.9, 89.9, 81.1, 71.1, 37.5, 36.1, 31.9, 29.4, 25.7,
22.7, 16.1, 14.2. MS (EI): 159 (100), 128 (41), 91 (15), 43 (19).
Anal. Calcd for C H24O (244.35): C, 83.56; H, 9.89. Found:
1
7
C, 83.65; H, 10.02.
5
.0 mmol; LiCl: 0.42 g, 10.0 mmol) in THF (8 mL) was added.
1-Hexyl-4-oxo-4-p h en ylbu tyl Ben zoa te (17g). The in-
termediate zinc alcoholate was not protected with TMSCl, and
after transmetalation with CuCN‚2LiCl, benzoyl chloride (2.4
equiv) as electrophile was added. Reaction conditions: -78
to -5 °C, 24 h; hexanes/ether 9:1-4:1, 65% yield, colorless oil.
The mixture was stirred for 5 min at 0 °C and was cooled back
1
4
to -78 °C. Ethyl (2-bromomethyl)acrylate (0.98 g, 5.0 mmol,
.0 equiv) was added, and the reaction mixture was warmed
to 0 °C within 1 h. It was diluted with ether (30 mL) and
quenched by addition of a saturated aqueous NH Cl solution
50 mL). Precipitated copper salts were dissolved by addition
1
1
4
IR (neat): 2920 (m), 1712 (s), 1690 (s), 1290 (vs). H-NMR
(
(CDCl , 300 MHz): δ 8.02 (d, J ) 7.2 Hz, 2H), 7.99 (d, J ) 7.1
3
of small portions of aqueous NH
3
solution. The aqueous layer
Hz, 2H), 7.39 (m, 6H), 5.24 (m, 1H), 3.07 (t, J ) 7.5 Hz, 2H),
was separated and extracted with ether (3 × 50 mL). The
2.14 (m, 2H), 1.72 (m, 2H), 1.33 (m, 8H), 0.85 (t, J ) 6.8 Hz,
1
3
combined organic layer was dried (MgSO ) and filtered, and
4
3H). C-NMR (CDCl , 75 MHz): δ 199.4, 166.4 136.9, 133.0,
3
the solvent was evaporated. The residual oil was purified by
flash chromatography (hexanes/ether 9:1) to afford the product
132.9, 130.6, 129.6, 128.6, 128.4, 74.6, 34.7, 31.8, 29.3, 28.8,
25.4, 22.6, 14.3. MS (EI): 248 (6), 247 (36), 105 (100), 77 (20).
Anal. Calcd for C H O (352.42): C, 78.39; H, 8.00. Found:
1
7a (0.74 g, 3.14 mmol, 63% yield) as a colorless oil. IR
2
3
28
3
1
(
(
7
2
neat): 3410 (s, br), 2920 (vs), 1720 (vs), 1620 (m). H-NMR
CDCl , 300 MHz): δ 6.07 (s, 1H), 5.46 (s, 1H), 4.13 (q, J )
.2 Hz, 2H), 3.30 (bs, 1H), 2.26 (m, 2H), 1.72 (m, 1H), 1.56 (m,
H), 1.43 (m, 2H), 1.22 (t, J ) 7.2 Hz, 3H), 0.83 (d, J ) 6.8
C, 78.24; H, 7.94.
3
1
-(4-Car beth oxy-4-pen ten yl)cycloh exan -1-ol (17h ). Eth-
14
yl (2-bromomethyl)acrylate (1.2 equiv) as electrophile; reac-
tion conditions: -78 to 0 °C, 1 h; hexanes/ether 4:1, 66% yield,
1
3
Hz, 6H). C-NMR (CDCl
3
, 75 MHz): δ 167.2, 140.7, 124.3,
6.2, 60.4, 33.5, 31.6, 24.8, 18.7, 17.0, 14.1. MS (EI): 171 (26),
25 (100), 97 (41), 41 (28). Anal. Calcd for
colorless oil. IR (neat): 3440 (s, br), 2930 (vs), 2850 (s), 1715
7
1
1
(
5
1
vs), 1620 (m). H-NMR (CDCl
3
, 300 MHz): δ 6.00 (s, 1H),
12 22 3
C H O
.40 (s, 1H), 4.07 (q, J ) 7.2 Hz, 2H), 2.17 (t, J ) 7.6 Hz, 2H),
.35 (m, 15H), 1.16 (t, J ) 7.6 Hz, 3H). C-NMR (CDCl , 75
3
(214.24): C, 67.29; H, 10.28. Found: C, 67.20; H, 10.32.
13
2
-Meth yl-6-n on yn -3-ol (17b). 1-Bromo-1-butyne (1.3 equiv)
MHz): δ 167.3, 140.9, 124.3, 71.2, 60.6, 41.9, 37.7, 37.5, 32.2,
25.9, 22.3, 22.0, 21.8, 14.2. MS (EI): 197 (6), 142 (73), 99 (100),
81 (49). Anal. Calcd for C H O (240.30): C, 70.00; H, 10.05.
was used as electrophile; reaction conditions: -60 °C, 2 d;
hexanes/ether 9:1-4:1, 68% yield, colorless liquid. IR (neat):
1
4
24
3
1
3
3
(
0
7
450 (s, br), 2950 (vs), 2350 (w), 1720 (m). H-NMR (CDCl
3
,
Found: C, 70.01; H, 10.24.
00 MHz): δ 3.36 (m, 1H), 2.16 (m, 2H), 2.03 (m, 3H), 1.55
E t h yl 2-[4-H yd r oxy-6-[(t r iisop r op ylsilyl)oxy]h exyl]-
m, 3H), 1.52 (m, 2H), 1.42 (m, 1H), 0.99 (t, J ) 7.5 Hz, 3H),
a cr yla te (17i). Ethyl (2-bromomethyl)acrylate14 (1.5 equiv)
1
3
.68 (d, J ) 7.0 Hz, 6H). C-NMR (CDCl
3
, 75 MHz): δ 82.2,
was used as electrophile; reaction conditions: -78 to 0 °C, 1
9.0, 75.8, 33.6, 32.9, 18.4, 17.2, 15.5, 14.1, 12.2. MS (EI): 121
h; hexanes/ether 9:1, 62% yield, colorless oil. IR (neat): 3450
(
(
18), 111 (43), 55 (83), 41 (100). Anal. Calcd for C10
154.22): C, 77.87; H, 11.75. Found: C, 77.62; H, 11.88.
-Iod o-4-m eth ylp en ta n -3-ol (17c). The zinc reagent was
H
18
O
(m, br), 2910 (vs), 1715 (vs), 1295 (m), 1150 (vs).
1
H-NMR
(CDCl , 300 MHz): δ 6.06 (s, 1H), 5.45 (s, 1H), 4.13 (q, J )
3
1
7.1 Hz, 2H), 3.92 (m, 1H), 3.87 (m, 2H), 3.59 (s, 1H), 2.24 (m,
2H), 1.56 (m, 3H), 1.48 (m, 3H), 1.22 (t, J ) 7.1 Hz, 3H), 1.01
directly quenched by the addition of iodine (3 equiv) dissolved
1
3
in THF at -78 °C; hexanes/ether 19:1, 76% yield, yellow oil.
3
(s, 21H). C-NMR (CDCl , 75 MHz): δ 167.1, 140.7, 124.2,
1
IR (neat): 3350 (s, br), 2900 (s). H-NMR (CDCl
3
, 300 MHz):
71.9, 63.3, 60.4, 38.3, 36.9, 31.6, 24.2, 17.8, 14.0, 11.8. MS
(EI): 329 (4), 131 (69), 119 (100), 107 (96). Anal. Calcd for
δ 3.48 (m, 1H), 3.32 (m, 2H), 1.89 (m, 2H), 1.70 (m, 1H), 1.54
1
3
(
7
1
d, J ) 5.2 Hz, 1H), 0.92 (d, J ) 6.7 Hz, 6H). C-NMR (CDCl
3
+
,
20 46 4
C H O Si (344.44): C, 64.97; H, 10.82. Found: C, 64.88; H,
10.96.
5 MHz): δ 76.3, 37.7, 33.5, 18.6, 17.4, 4.2. MS (EI): 227 (M ,
3), 185 (38), 73 (100), 57 (40). Anal. Calcd for C
6
H
13IO
Eth yl 2-(4-Hyd r oxy-7-p iva loxyh ep tyl)a cr yla te (17j).
Ethyl (2-bromomethyl)acrylate14 (1.0 equiv) was used as
electrophile; reaction conditions: -78 to 0 °C, 1 h; hexanes/
(227.15): C, 31.72; H, 5.73. Found: C, 32.01; H, 5.65.
5
,5-Dim et h yl-1-isop r op yl-4-oxoh exyl P iva la t e (17d ).
The intermediate zinc alcoholate was not protected with
TMSCl, and after transmetalation with CuCN‚2LiCl, pivaloyl
chloride (2.4 equiv) was added as electrophile. Reaction con-
ditions: -78 to -5 °C, 2 d; hexanes/ether 9:1, 61% yield,
ether 4:1-1:1, 63% yield, colorless oil. IR (neat): 3450 (m,
1
br), 2950 (s), 1715 (vs), 1620 (m). H-NMR (CDCl
3
, 300
MHz): δ 6.07 (s, 1H), 5.47 (s, 1H), 4.10 (q, J ) 7.1 Hz, 2H),
4.00 (t, J ) 10.0 Hz, 2H), 3.57 (s, 1H), 2.24 (m, 2H), 1.97 (m,
colorless oil. IR (neat): 2940 (vs), 1715 (vs), 1705 (vs), 1283
1H), 1.68-1.43 (m, 8H), 1.37 (t, J ) 7.1 Hz, 3H), 1.12 (s, 9H).
1
13
(
s), 1160 (vs). H-NMR (CDCl
3
, 300 MHz): δ 4.63 (m, 1H),
3
C-NMR (CDCl , 75 MHz): δ 178.5, 167.2, 140.6, 124.4, 70.8,
2
9
2
.40 (m, 2H), 1.77 (m, 2H), 1.65 (m, 1H), 1.13 (s, 9H), 1.05 (s,
H), 0.83 (d, J ) 6.1 Hz, 6H). C-NMR (CDCl
15.1, 178.1, 77.3, 44.1, 39.0, 32.6, 31.8, 27.3, 26.5, 25.5. MS
64.3, 60.5, 38.6, 36.8, 33.6, 31.6, 27.1, 24.8, 24.4, 14.4. MS
(EI): 250 (5), 125 (40), 71 (81), 57 (100). Anal. Calcd for
1
3
3
, 75 MHz): δ
C
17
H
30
O
5
(314.33): C, 64.95; H, 9.61. Found: C, 64.88; H, 9.66.
(
(
EI): 185 (8), 129 (42), 57 (100). Anal. Calcd for C16
270.37): C, 71.11; H, 11.11. Found: C, 70.94; H, 11.20.
Eth yl 2-Ca r beth oxy-6-h yd r oxy-7-m eth yl-3-p h en yloc-
30 3
H O
4-Iod o-1-p h en ylbu ta n -1-ol (17k ). Iodine (3 equiv) was
used as electrophile; reaction conditions: -78 °C to rt, 1 h;
hexanes/ether 95:5, 70% yield, yellow oil. IR (neat): 3355 (s,
br), 2910 (s). 1H-NMR (CDCl
, 300 MHz): δ 7.32 (m, 5H), 4.64
13
ta n oa te (17e). Diethyl benzylidene malonate (1.0 equiv) was
used as electrophile; after usual workup the crude product was
dissolved in THF and treated with a 1 M solution of Bu
THF at 0 °C (3 h); hexanes/ether 1:1, 64% yield, yellow oil. IR
3
(t, J ) 6.5 Hz, 1H), 3.13 (m, 2H), 1.83 (m, 5H).
(CDCl , 75 MHz): δ 144.7, 129.0, 128.2, 126.3, 73.9, 40.1, 30.2,
7.4. MS (EI): 148 (100), 147 (97), 105 (95), 77 (26). Anal.
Calcd for C10 13IO (275.19): C, 43.64; H, 4.73. Found: C,
43.82; H, 4.64.
C-NMR
4
NF in
3
1
(neat): 3480 (s, br), 2970 (s), 1720 (vs). H-NMR (CDCl
3
, 300
H
MHz): δ 7.17 (m, 5H), 4.17 (q, J ) 6.5 Hz, 2H), 3.80 (m, 2H),
3
2
.56 (d, J ) 10.9 Hz, 1H), 3.31 (m, 2H), 1.74 (m, 1H), 1.55 (m,
H), 1.43 (m, 2H), 1.20 (t, J ) 7.2 Hz, 3H), 1.10 (m, 1H), 0.86
Eth yl 2-[5-P h en yl-5-[(tr im eth ylsilyl)oxy]p en tyl]a cr y-
la te (17l). Ethyl (2-bromomethyl)acrylate14 (1.1 equiv) was
used as electrophile; reaction conditions: -78 to 0 °C, 1 h;
(
m, 3H), 0.73 (t, J ) 6.8 Hz, 3H), 0.68 (t, J ) 6.8 Hz, 3H).
1
3
C-NMR (CDCl
3
, 75 MHz): δ 168.3, 167.4, 140.7, 128.2, 126.7,
hexanes/ether 9:1, 72% yield, colorless oil. IR (neat): 2920
1
7
6.5, 61.4, 58.7, 45.7, 33.4, 31.0, 30.4, 18.8, 13.9. MS (EI): 259
(s), 2880 (m), 1710 (vs), 1630 (m). H-NMR (CDCl
3
, 300

Ni-Catalyzed Preparations of Functionalized Organozincs
J . Org. Chem., Vol. 61, No. 21, 1996 7481
MHz): δ 7.26 (m, 5H), 6.11 (s, 1H), 5.43 (s, 1H), 4.58 (dd, J )
2H), 2.86 (s, 3H), 2.35 (m, 2H), 1.53 (m, 4H), 1.31 (t, J ) 7.8
1
3
7
.7 Hz, 5.0 Hz, 1H), 4.16 (q, J ) 7.1 Hz, 2H), 2.25 (t, J ) 6.9
3
Hz, 3H). C-NMR (CDCl , 75 MHz): δ 167.2, 149.4, 140.8,
Hz, 2H), 1.63 (m, 2H), 1.45 (m, 4H), 1.30 (t, J ) 7.1 Hz, 3H),
129.2, 124.6, 116.0, 112.2, 60.6, 52.6, 38.4, 31.9, 26.4, 26.1, 14.3.
1
3
+
0
1
0
.00 (s, 9H). C-NMR (CDCl
3
, 75 MHz): δ 167.1, 145.5, 140.9,
MS (EI): 261 (M , 12), 120 (100). Anal. Calcd for C16H23NO
2
28.1, 127.3, 125.7, 124.1, 74.8, 60.3, 40.4, 31.7, 28.3, 25.4, 14.1,
.0. MS (EI): 180 (21), 179 (100), 73 (47). Anal. Calcd for
(261.32): C, 73.53; H, 8.86; N, 5.36. Found: C, 73.26; H, 8.72;
N, 5.46.
C
19
H
30
O
3
Si (334.37): C, 68.26; H, 8.98. Found: C, 68.48; H,
(E)-E t h yl 6-(N,N-d ib en zyla m in o)h ex-2-en oa t e (19e).
Ethyl propiolate (1.0 equiv) was used as electrophile; reaction
conditions: -78 to -10 °C, 12 h; hexanes/ether 9:1, 65% yield),
9
.10.
P r ep a r a tion of P r od u cts 19a -h fr om Allylic Am in es
1
8a -d ,f. Typ ica l P r oced u r e for th e Hyd r ozin ca tion of
colorless oil. IR (neat): 2830 (m), 2700 (s), 1720 (vs), 1660
1
Allylic Am in es 18a-d,f. N-4-Un decyn ylm or ph olin e (19a).
A 25 mL three-necked flask equipped with an argon inlet, a
magnetic stirring bar, and an internal thermometer was
(s). H-NMR (CDCl
3
, 300 MHz): δ 7.32 (m, 10H), 6.87 (dt, J
) 15.2, 6.9 Hz, 1H), 5.96 (d, J ) 15.7 Hz, 1H), 4.13 (q, J ) 7.2
Hz, 2H), 3.51 (s, 4H), 2.39 (t, J ) 6.7 Hz, 2H), 2.12 (m, 2H),
1
3
charged with Ni(acac)
2
(66 mg, 0.25 mmol, 5 mol %), COD (54
1.61 (q, J ) 7.1 Hz, 2H), 1.28 (t, J ) 7.2 Hz, 3H). C-NMR
mg, 0.50 mmol, 10 mol %), and the amine 18a (636 mg, 5.0
mmol). The resulting green suspension was cooled to -78 °C,
and Et
(CDCl
60.0, 58.4, 52.7, 29.8, 25.6, 14.3. MS (EI): 337(M , 2), 210
(66), 91(100). Anal. Calcd for C22 (337.41): C, 78.31;
3
, 75 MHz): δ 166.5, 148.9, 138.1, 128.8, 127.1, 121.3,
+
2
Zn (1.0 mL, 10.0 mmol, 2 equiv) was added. After
H27NO
2
completion of the addition, the cooling bath was removed and
the reaction mixture was allowed to warm to rt and stirred
for 1 h. After complete conversion of the starting material,
H, 8.58; N, 4.15. Found: C, 78.07; H, 8.82; N, 4.09.
E t h yl 2-[4-(N,N-Dib en zyla m in o)b u t yl]a cr yla t e (19f).
Ethyl (2-bromomethyl)acrylate14 (1.2 equiv) was used as
electrophile; reaction conditions: -78 to 0 °C, 1 h; hexanes/
2
THF (5 mL) was added. The solvent and excess of Et Zn was
removed in vacuo. This procedure was repeated twice, and
the resulting pure zinc compound was redissolved in THF (2
mL). After the mixture was cooled to -60 °C a solution of
CuCN‚2LiCl (CuCN: 0.45 g, 5.0 mmol; LiCl: 0.42 g, 10 mmol)
in THF (5 mL) was added, and the reaction mixture was
warmed to 0 °C for 10 min. It was cooled again to -78 °C,
and 1-bromo-1-octyne (1.12 g, 6.0 mmol, 1.2 equiv) was added
as electrophile. The mixture was warmed to -60 °C and
stirred for 4 d. It was worked up as above and purified by
flash chromatography (hexanes/ether 2:1 to 100% ether) to
afford the product 19a (769 mg, 3.2 mmol, 64% yield) as a
ether 99:1-95:5, 66% yield, yellow oil. IR (neat): 2990 (vs),
1
2900 (s), 1720 (vs). H-NMR (CDCl
3
, 300MHz): δ 7.44 (m, 10
H), 6.17 (s, 1H), 5.49 (s, 1H), 4.23 (q, J ) 7.1 Hz, 2H), 3.61 (s,
4H), 2.49 (t, J ) 6.6 Hz, 2H), 2.28 (t, J ) 7.4 Hz, 2H), 1.54 (m,
1
3
4H), 1.33 (t, J ) 7.1 Hz, 3H). C-NMR (CDCl , 75 MHz): δ
3
167.2, 140.9, 139.9, 128.7, 128.1, 126.9, 124.2, 60.4, 58.3, 53.0,
31.6, 26.5, 25.8, 14.2. MS (EI): 210 (93), 91 (100). Anal. Calcd
for C23
2
H29NO (351.43): C, 78.60; H, 8.31; N, 3.98. Found:
C, 78.90; H, 8.50; N, 3.88.
Eth yl 2-[4-(N,N-Dip h en yla m in o)bu tyl]a cr yla te (19g).
Ethyl (2-bromomethyl)acrylate14 (1.0 equiv) was used as
electrophile; reaction conditions: -78 to 0 °C, 1 h, 62% yield,
colorless oil. IR (neat): 2930 (vs), 1710 (vs), 1595 (vs), 1505
colorless oil. IR (neat): 2920 (vs), 2880 (s), 2805 (m), 1460
1
(
m), 1105 (s). H-NMR (CDCl
3
, 300 MHz): δ 3.57 (m, 4H),
2
.29 (m, 6H), 2.02 (m, 4H), 1.53 (m, 2H), 1.29 (m, 8H), 0.74
(vs). 1H-NMR (CDCl
3
, 300 MHz): δ 7.25 (m, 4H), 6.97 (m, 6H),
1
3
(
m, 3H). C-NMR (CDCl
3.6, 31.2, 28.9, 28.3, 25.9, 22.4, 18.5, 16.5, 13.8. MS (EI): 180
9), 166 (52), 100 (100), 56 (10). Anal. Calcd for C15
237.39): C, 75.90; H, 11.46; N, 5.89. Found: C, 75.73; H,
3
, 75 MHz): δ 80.3, 79.3, 66.8, 57.8,
6.13 (s, 1H), 5.48 (s, 1H), 4.18 (q, J ) 7.1 Hz, 2H), 3.70 (t, J )
7.4 Hz, 2H), 2.32 (t, J ) 7.6 Hz, 2H), 1.71 (m, 2H), 1.56 (m,
5
1
3
(
(
H
27NO
2H), 1.29 (t, J ) 7.1 Hz, 3H). C-NMR (CDCl , 75 MHz): δ
3
167.3, 148.3, 140.9, 129.4, 124.7, 121.3, 121.1, 60.7, 52.3, 31.8,
27.3, 26.2, 14.4. MS (EI): 323 (M , 22), 183 (14), 182 (100).
+
1
1.44; N, 6.09.
N-(5,5-Dicar beth oxy-4-ph en ylpen tyl)m or ph olin e (19b).
2
Anal. Calcd for C21H25NO (323.38): C, 77.99; H, 7.78; N, 4.33.
Diethyl benzylidenemalonate (1.2 equiv) was used as electro-
Found: C, 78.12; H, 7.81; N, 4.33.
phile; reaction conditions: -78 to 0 °C, 2 d; hexanes/ether 2:1
Eth yl 2-[4-[N-Ben zyl-N-(4-p iva loxybu tyl)a m in o]bu tyl]-
a cr yla te (19h ). Ethyl (2-bromomethyl)acrylate1 (1.0 equiv)
was used as electrophile; reaction conditions: -78 to 0 °C, 1
4
to 100% ether, 68% yield, yellow oil. IR (neat): 3100 (vs), 1735
1
(
4
5
vs), 1450 (s). H-NMR (CDCl
3
, 300 MHz): δ 7.24 (m, 5H),
.20 (q, J ) 7.1 Hz, 2H), 3.82 (q, J ) 7.1 Hz, 2H), 3.60 (m,
h; hexanes/ether 4:1 to 100% ether, 62% yield, colorless oil.
1
H), 2.25 (m, 7H), 1.63 (m, 2H), 1.25 (t, J ) 7.1 Hz, 3H), 1.21
IR (neat): 2820 (s), 1710 (vs), 1185 (s). H-NMR (CDCl
3
, 300
1
3
(
m, 2H), 0.91 (t, J ) 7.1 Hz, 3H). C-NMR (CDCl
3
, 75 MHz):
MHz): δ 7.31 (m, 5H), 6.13 (s, 1H), 5.49 (s, 1H), 4.20 (q, J )
7.2 Hz, 2H), 4.04 (t, J ) 6.2 Hz, 2H,), 3.55 (s, 2H), 2.43 (m,
3H), 2.26 (m, 2H), 1.60 (m, 7H), 1.33 (t, J ) 7.1 Hz, 3H), 1.20
δ 168.3, 167.7, 140.6, 128.4, 128.2, 126.9, 66.8, 61.4, 60.9, 58.7,
+
5
3
8.5, 53.6, 45.5, 31.7, 23.9, 14.0, 13.6. MS (EI): 377 (M , 3),
04 (13), 100 (100), 42 (13). Anal. Calcd for C21
1
3
H
31NO
5
(s, 9H).
3
C-NMR (CDCl , 75 MHz): δ 178.5, 167.3, 141.0,
(
377.38): C, 66.83; H, 8.27; N, 3.71. Found: C, 66.61; H, 8.49;
N, 3.94.
N-(5-Ca r beth oxy-5-h exen yl)m or p h olin e (19c). Ethyl
140.1, 128.8, 128.3, 126.7, 124.3, 64.3, 60.5, 58.7, 53.6, 53.4,
38.7, 31.7, 27.2, 26.7, 26.6, 23.6, 14.2. MS (EI): 276 (42), 274
4
(31), 91 (100), 57 (18). Anal. Calcd for C21H37NO (367.47):
C, 68.63; H, 10.14; N, 3.81. Found: C, 68.55; H, 10.03; N, 3.91.
1
4
(
2-bromomethyl)acrylate (1.0 equiv) was used as electrophile;
reaction conditions: -78 to 0 °C, 1 h; hexanes/ ether 1:1 to
00% ether, 76% yield, yellow oil. IR (neat): 2915 (s), 2850
1
Ack n ow led gm en t. We thank the DFG (SFB 260)
and the Fonds der Chemischen Industrie for generous
financial support. We thank WITCO AG, BASF AG,
BAYER AG, Chemetall, Sipsy, and Chiroscience for the
generous gift of chemicals.
1
(s), 2800 (m), 1705 (vs). H-NMR (CDCl
3
, 300 MHz): δ 5.96
(
s, 1H), 5.34 (s, 1H), 4.01 (q, J ) 7.1 Hz, 2H), 3.52 (t, J ) 4.7
Hz, 4H), 2.24 (m, 4H), 2.14 (m, 4H), 1.32 (m, 4H), 1.16 (t, J )
1
3
7
6
4
.1 Hz, 3H). C-NMR (CDCl
6.8, 60.3, 58.6, 53.6, 31.6, 25.9, 21.1, 14.0. MS (EI): 241 (M ,
), 196 (5), 100 (100). Anal. Calcd for C13 (241.29):
3
, 75 MHz): δ 166.9, 140.6, 124.1,
+
H
23NO
3
Su p p or tin g In for m a tion Ava ila ble: Text giving experi-
mental procedures and analytical data for compounds 4b,
C, 64.71; H, 9.59; N, 5.80. Found: C, 64.69; H, 9.80; N, 5.90.
N-(5-Ca r b et h oxy-5-h exen yl)-N-m et h yla n ilin e (19d ).
1
4d ,e, 18e, 6, 7, 13, 17, and 19 (23 pages). This material is
1
4
Ethyl (2-bromomethyl)acrylate (1.0 equiv) was used as
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.
electrophile; reaction conditions: -78 to 0 °C, 1 h; hexanes/
ether 19:1-9:1, 74% yield, yellow oil. IR (neat): 2915 (s), 1705
1
(
(
1
vs), 1600 (s), 1500 (s). H-NMR (CDCl
3
, 300 MHz): δ 7.23
dd, J ) 8.1, 7.1 Hz, 2H), 6.69 (d, J ) 8.2 Hz, 3H), 6.16 (s,
H), 5.52 (s, 1H), 4.23 (q, J ) 7.1 Hz, 2H), 3.33 (t, J ) 6.9 Hz,
J O960808V