Preparation of functionalized dialkylzincs via a boron-zinc exchange. Reactivity and catalytic asymmetric addition to aldehydes

Article abstract of DOI:10.1021/jo961129n

The hydroboration of olefins with Et₂BH provides diethyl(alkyl)boranes 2 which readily undergo a boron - zinc exchange with Et₂Zn providing a range of polyfunctional primary, secondary, and benzylic diorganozincs. The resulting diorganozincs 3 have been reacted with various electrophiles (allylic halides, acid chlorides, alkylidenemalonates, ethyl propiolate, nitroolefins) in the presence of CuCN·2LiCl with excellent yields. With secondary dialkylzincs prepared from diastereomerically pure diethyl(alkyl)boranes, the boron-zinc exchange occurs with loss of stereochemistry. The asymmetric addition of 3 to aldehydes in the presence of the chiral catalyst 55 furnishes optically active polyfunctional secondary alcohols (50 to over 96% ee).

Full text of DOI:10.1021/jo961129n

J . Org. Chem. 1996, 61, 8229-8243
8229
P r ep a r a tion of F u n ction a lized Dia lk ylzin cs via a Bor on -Zin c
Exch a n ge. Rea ctivity a n d Ca ta lytic Asym m etr ic Ad d ition to
Ald eh yd es
Falk Langer, Lothar Schwink, Arokiasamy Devasagayaraj, Pierre-Yves Chavant, and
Paul Knochel*
Fachbereich Chemie der Philipps-Universit a¨ t Marburg, D-35032 Marburg, Germany
Received J une 13, 1996X
The hydroboration of olefins with Et
boron-zinc exchange with Et Zn providing a range of polyfunctional primary, secondary, and
benzylic diorganozincs. The resulting diorganozincs 3 have been reacted with various electrophiles
allylic halides, acid chlorides, alkylidenemalonates, ethyl propiolate, nitroolefins) in the presence
2
BH provides diethyl(alkyl)boranes 2 which readily undergo a
2
(
of CuCN‚2LiCl with excellent yields. With secondary dialkylzincs prepared from diastereomerically
pure diethyl(alkyl)boranes, the boron-zinc exchange occurs with loss of stereochemistry. The
asymmetric addition of 3 to aldehydes in the presence of the chiral catalyst 55 furnishes optically
active polyfunctional secondary alcohols (50 to over 96% ee).
In tr od u ction
Sch em e 1
Organozinc halides (RZnX) are useful synthetic inter-
mediates, and their chemistry has been actively inves-
1
tigated in the recent years. They tolerate a broad range
of functionalities and react in the presence of a copper
salt like CuCN‚2LiCl2 with various electrophiles in
excellent yields. They are readily prepared by the direct
insertion of zinc dust into primary or secondary alkyl
iodides.1 For the less reactive alkyl, alkenyl, or aryl
bromides, the insertion is best performed using Rieke-
,3
produce diethylzinc.9 The reaction has also been used
successfully for the preparation of benzylic and allylic
diorganozincs.10 Alkenyl zinc reagents prepared by this
method have been used for the enantioselective prepara-
tion of allylic alcohols.11 An elegant asymmetric synthe-
sis of (-)-muscone has been reported using an intramo-
lecular version of this reaction.12 Our synthetic approach
allows the preparation of functionalized dialkylzincs
starting from olefins avoiding the use of expensive alkyl
iodides as intermediates. Herein we wish to report the
scope and limitations of the boron-zinc exchange reac-
zinc.4 Diorganozincs (R
2
Zn) compared to organozinc
halides (RZnX) are less readily available. However, they
display a higher reactivity toward many electrophiles and
are well suited for applications in asymmetric synthesis.5
We have previously reported that functionalized diorg-
anozincs can be prepared by an iodine-zinc exchange
reaction.1
,5a
This method requires heating of the primary
6
alkyl iodide 1 with Et
strong contrast, we found that primary diethyl(alkyl)-
boranes 2 react within minutes at 0 °C with Et Zn
providing polyfunctional dialkylzincs 3 in over 90% yield
2
Zn at 50 °C for several hours. In
2
Scheme 1).7 The organoboranes 2 are readily obtained
tion using diethyl(alkyl)boranes and Et Zn and demon-
(
2
BH (5).8
strate the utility of these reagents for the catalytic
asymmetric addition to aldehydes.
by hydroboration of olefins of type 4 with Et
2
The first literature report of a boron-zinc exchange
was the reaction of dimethylzinc with triethylborane to
Resu lts a n d Discu ssion
X
Abstract published in Advance ACS Abstracts, October 15, 1996.
(
1) (a) Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93, 2117. (b)
Knochel, P. Synlett 1995, 393. (c) Knochel, P. Chemtracts-Org. Chem.
995, 8, 205.
2) (a) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J . J . Org.
The hydroboration of terminal olefins is conveniently
performed with Et
is readily prepared by mixing BH
ratio 1:2.13 Diethylborane (5) containing ca. 0.3 equiv of
Me S is stable for several months at 4 °C without
2
decomposition. The hydroboration of olefins 4 with Et -
2
BH (5), a hydroborating agent which
1
3
‚Me S and Et B in the
2
3
(
Chem. 1988, 53, 2390. (b) Knochel, P.; Rozema, M. J .; Tucker, C. E.;
Retherford, C.; Furlong, M.; AchyuthaRao, S. Pure Appl. Chem. 1992,
4, 361.
2
6
(
(
3) Gaudemar, M. Bull. Soc. Chim. Fr. 1962, 974.
4) (a) Rieke, R. D. Science 1989, 246, 1260. (b) Zhu, L.; Wehmeyer,
R. M.; Rieke, R. D. J . Org. Chem. 1991, 56, 1445.
5) (a) Rozema, M. J .; AchyuthaRao, S.; Knochel, P. J . Org. Chem.
992, 57, 1956. (b) Knochel, P.; Vettel, S.; Eisenberg, C. Appl.
Organomet. Chem. 1995, 9, 175. (c) Devasagayaraj, A.; Schwink, L.;
Knochel, P. J . Org. Chem. 1995, 60, 3311.
(
(9) Zakharkin, L. I.; Okhlobystin, O. Y. Z. Obsc. Khim. 1960, 30,
2134 (in English, 1960, 2109), Chem. Abstr. 1961, 55, 9319a.
(10) Thiele, K.-H.; Engelhardt, G.; K o¨ hler, J .; Arnstedt, M. J .
Organomet. Chem. 1967, 9, 385.
1
(
6) Rozema, M. J .; Eisenberg, C.; L u¨ tjens, H., Ostwald, R.; Belyk,
K.; Knochel, P. Tetrahedron Lett. 1993, 34, 3115.
7) (a) Langer, F.; Waas, J .; Knochel, P. Tetrahedron Lett. 1993, 34,
261. (b) Langer, F.; Devasagayaraj, A.; Chavant, P.-Y.; Knochel, P.
Synlett 1994, 410.
8) K o¨ ster, R.; Griasnow, G.; Larbig, W.; Binger, P. Liebigs Ann.
Chem. 1964, 672, 1.
(11) (a) Oppolzer, W.; Radinov, R. N. Helv. Chim. Acta 1992, 75,
170. (b) Srebnik, M. Tetrahedron Lett. 1991, 32, 2449. (c) Oppolzer,
W.; Radinov, R. N. Tetrahedron Lett. 1988, 29, 5645.
(12) (a) Oppolzer, W.; Radinov, R. N. J . Am. Chem. Soc. 1993, 115,
1593. (b) Oppolzer, W.; Radinov, R. N.; de Brabander, J . Tetrahedron
Lett. 1995, 36, 2607.
(
5
(
(13) K o¨ ster, R.; Binger, P. Inorg. Synth. 1974, 15, 141.
S0022-3263(96)01129-2 CCC: $12.00 © 1996 American Chemical Society

8
230 J . Org. Chem., Vol. 61, No. 23, 1996
Langer et al.
Sch em e 2
Sch em e 3
BH (5) displays regioselectivity comparable to disiamyl-
1
4
borane or thexylborane and is complete within a few
Sch em e 4
minutes at rt affording diethyl(alkyl)boranes 2 in 80-
9
5% yield (Scheme 1). The reaction of the organoboranes
2
2
with Et Zn (2 equiv) at 0 °C proceeds well in hexane,
ether, dibutyl ether, or in the absence of a solvent. It is
complete within 0.5 h with all primary diethyl(alkyl)-
boranes 2 but requires longer reaction times with second-
2
ary diethyl(alkyl)boranes. Et Zn is especially well suited
for performing the boron-zinc exchange because of the
high reactivity and high energy of its carbon-zinc bond.
The reaction of diethyl(octyl)borane with Et Zn (2 equiv)
2
produces at 0 °C within 3 min ca. 80% of ethyl(octyl)zinc
as shown by iodolysis experiments. By pumping off the
3
formed Et B the equilibrium is further shifted to the right
affording the desired dioctylzinc in high yield (>95%).
In the case of cyclohexyldiethylborane (6), the boron-
zinc exchange is complete after 3 h at 0 °C affording
dicyclohexylzinc (6a ) in over 90% yield. Also diethyl(1,2-
diphenylethyl)borane (7) is quantitatively converted to
the corresponding zinc reagent 8 within 3 h at rt. In
contrast secondary diethyl(alkyl)boranes bearing bulky
substituents in the R-position like the organoborane 9
indicated by NMR spectroscopy. Thus, under the reac-
tion conditions used, the boron-zinc exchange reaction
occurs with loss of stereochemistry.15
react at slower rates with Et
2
Zn furnishing the corre-
sponding dialkylzinc only after 40 h reaction time at rt.
The reaction tolerates a range of functional groups like
an ester, nitrile, boronic ester, halide (Cl, Br, or I),
acrylate, phthalimide and functionalities bearing a rela-
tively acidic proton like a nitroalkane, alkylmalonate, or
trifluoroacetamide. Thus, the olefins 15-17 each bearing
an acidic proton16 undergo, after hydroboration, a smooth
boron-zinc exchange reaction. In the presence of a
catalytic amount of CuCN and an excess of allylating
agent, the intermediate zinc reagents are allylated lead-
ing to the products 18-20 in high overall yields, showing
that diorganozincs bearing an acidic proton at the R-posi-
tion of a malonate or nitro group or bearing a trifluoro-
acetamide function are viable intermediates (Scheme 4).
The boron-zinc exchange is considerably faster than
the iodine-zinc exchange reaction. Thus the diethyl-
(iodoalkyl)borane 2a prepared from 6-iodo-1-hexene can
either undergo an iodine-zinc or a boron-zinc exchange.
Only the latter exchange reaction provides the zinc
reagent 3a . The expected products 21-23 are obtained
after transmetalation with CuCN‚2LiCl and respective
This reaction requires a large excess of Et
Scheme 2).
2
Zn (6 equiv;
The resulting zinc reagent 10 is obtained as a 3:1
mixture of diastereoisomers as indicated by the stereo-
chemistry of the allylated product 11. In order to
determine if the loss of stereochemistry is due to the
drastic reaction conditions required for the preparation
of 10 or is an intrinsic characteristic of the boron-zinc
exchange, we have submitted the primary boranes 12a
2
and 12b to the reaction with Et Zn (Scheme 3). The
diethyl(alkyl)boranes 12a and 12b were prepared by the
diastereoselective hydroboration of the deuterated sty-
renes 13a and 13b. The treatment of 12a and 12b with
2
Et Zn provides the zinc reagents 12c and 12d (0 °C, 0.5
1
2
h) which H and D NMR spectra clearly indicate the
formation of a 1:1 mixture of diastereoisomeric organo-
metallics. This result was confirmed by the trapping of
the zinc reagents with benzoyl chloride after transmeta-
lation with CuCN‚2LiCl providing the ketone 14 in 94%
yield. The incorporation of deuterium was close to 100%,
but a 1:1 mixture of diastereoisomers was obtained as
(15) (a) Duddu, R.; Eckhardt, M.; Furlong, M.; Knoess, H. P.; Berger,
S.; Knochel, P. Tetrahedron 1994, 50, 2415. (b) Wang, F.; Tang, J .;
Labaudiniere, L.; Marek, I.; Normant, J . F. Synlett 1995, 723.
(16) Knoess, H. P.; Furlong, M. T.; Rozema, M. J .; Knochel, P. J .
Org. Chem. 1991, 56, 5974.
(
14) Brown, H. C. Organic Synthesis via Boranes; Wiley: New York,
1
975.

Functionalized Dialkylzincs via a Boron-Zinc Exchange
J . Org. Chem., Vol. 61, No. 23, 1996 8231
Sch em e 5
electrophiles like ethyl R-(bromomethyl)acrylate or di-
ethyl benzylidenemalonate the desired coupling products
4
2 and 43 are obtained respectively in 77% and 71%
overall yield. A chiral olefin like (-)-â-pinene (44) is
readily converted into chiral dimyrtanylzinc (45) via the
intermediate diethyl(myrtanyl)borane (46). In the pres-
ence of CuCN‚2LiCl, it reacts with benzoyl chloride or
ethyl R-(bromomethyl)acrylate furnishing the chiral ad-
ducts 47 and 48 in 85 and 82% overall yield (Scheme 7).
Besides primary dialkylzincs, secondary alkyl and
benzylic diorganozincs can be prepared and reacted with
electrophiles in the presence of a copper(I) catalyst.
Steric hindrance slows down the boron-zinc exchange
reaction and limits the application of this reaction to
sterically noncrowded secondary alkylboranes. However,
a number of secondary dialkylzincs have been prepared
and reacted with electrophiles to provide products 49-
5
4 (Table 2). As mentioned above, secondary diorg-
anozincs are prepared from the corresponding boranes
with loss of stereochemistry, resulting in the formation
of diastereomeric mixtures of products after transmeta-
lation and quenching with an electrophile.
1
7
reaction with ethyl R-(bromomethyl)acrylate, ethyl pro-
The boron-zinc exchange provides an efficient entry
to diorganozincs. The enantioselective addition of these
organometallics to aldehydes will be examined next. The
addition of diethylzinc to aldehydes in the presence of a
chiral catalyst has been intensively investigated over the
last 10 years.19 We have already shown that higher
dialkylzincs, as well as functionalized diorganozincs
piolate, and nitrostyrene18 (Scheme 5).
Polyfunctional dialkylzincs derived from alkaloids can
also be prepared and give access to various derivatives
of biologically active molecules having therefore a poten-
tial pharmaceutical interest. The hydroboration of (-)-
cinchonidine acetate (24) with diethylborane (5) furnishes
in quantitative yield the corresponding organoborane
which smoothly undergoes a boron-zinc exchange by
producing after evapora-
Zn the expected
diorganozinc reagent as an orange foam. It was quan-
titatively allylated with an excess of allyl bromide in the
presence of CuCN‚2LiCl (10 mol %) leading to the product
5
prepared via an iodine-zinc exchange, can be added
with high enantioselectivity to aldehydes in the presence
treatment with Et
2
Zn in CH
2
Cl
2
of (1R,2R)-1,2-bis(trifluoromethanesulfonamido)cyclo-
tion of the solvent and the excess of Et
2
hexane20 (55) as catalyst and Ti(Oi-Pr)
as cocatalyst.
21
4
The use of olefins as starting materials for asymmetric
catalysis is of special interest since it constitutes a high
value adding process and has considerable synthetic
potential. Olefins are usually cheap and environmentally
friendly substrates, so these transformations are also of
industrial relevance (Scheme 8).
2
5 (eq 1).
Thus, a one-pot procedure allowing the conversion of
olefins 4 to chiral polyfunctional alcohols 56 would be of
great interest. Herein, we report our results demon-
strating that this approach provides a predictable method
for the asymmetric synthesis of a variety of optically
active secondary alcohols.22 A range of dialkylzincs
prepared via the boron-zinc exchange reaction can be
added to various aliphatic, unsaturated, or aromatic
Besides allylic halides (entries 1, 11 of Table 1), a
variety of electrophiles like an alkylidenemalonate (en-
tries 4, 8, 13), acid chlorides (entries 5, 6, 9, 10), 3-iodo-
aldehydes using 55 (8 mol %) as catalyst and Ti(Oi-Pr)
4
(2 equiv) as cocatalyst.22 Various dialkylzincs have been
used directly after pumping off the excess diethylzinc and
triethylborane formed during their preparation. The zinc
reagent was added to a solution of the preformed catalyst
2
7
-cyclohexenone (entries 2, 3), and nitrostyrene (entries
, 12) react with dialkylzincs prepared via the boron-
zinc exchange and subsequent transmetalation with
CuCN‚2LiCl providing the polyfunctional products 26-
1
3
8. A remarkable chemoselectivity is observed in these
(19) (a) For excellent reviews, see: Soai, K.; Niwa, S. Chem. Rev.
1
992, 92, 833. (b) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed.
Engl. 1991, 30, 49.
20) (a) Galsbol, F.; Steenbol, P.; Sondergaard-Sorensen, B. Acta
reactions and many polyfunctional molecules become
available with this reaction sequence. Especially impres-
sive is the behavior of the unsaturated organoborane 39
obtained by the selective hydroboration of the dienic ester
0. After a boron-zinc exchange, the diorganozinc 41
bearing a sensitive acrylate functionality is obtained
(
Chem. Scand. 1972, 26, 3605. (b) Larrow, J . F.; J acobsen, E. N.; Gao,
Y.; Hong, Y.; Nie, X.; Zepp, C. M. J . Org. Chem. 1994, 59, 1939.
(21) (a) Takahashi, H.; Kawakita, T.; Ohno, M.; Yoshioka, M.;
4
Kobayashi, S. Tetrahedron 1992, 48, 5691. For other titanium-mediated
asymmetric additions to aldehydes, see: (b) Schmidt, B.; Seebach, D.
Angew. Chem., Int. Ed. Engl. 1991, 30, 99. (c) Seebach, D.; Behrendt,
L.; Felix, D. Angew. Chem., Int. Ed. Engl. 1991, 30, 1008. (d) Schmidt,
B.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1991, 30, 1321. (e) v. d.
Bussche-H u¨ nnefeld, J . L.; Seebach, D. Tetrahedron 1992, 48, 5719. (f)
Seebach, D.; Plattner, D. A.; Beck, A. K.; Wang, Y. M.; Hunziker, D.;
Petter, W. Helv. Chim. Acta 1992, 75, 2171. (g) Seebach, D.; Beck, A.
K.; Schmidt, B.; Wang, Y. M. Tetrahedron 1994, 50, 4363. (h) Weber,
B.; Seebach, D. Tetrahedron 1994, 50, 7473.
(
Scheme 6).
After transmetalation with CuCN‚2LiCl, a copper
reagent is formed. It shows no tendency to polymerize
under our reaction conditions. After the addition of
(
17) Villieras, J .; Rambaud, M. Synthesis 1982, 924.
(18) J ubert, C.; Knochel, P. J . Org. Chem. 1992, 57, 5431.
(22) Schwink, L.; Knochel, P. Tetrahedron Lett. 1994, 35, 9007.

8
232 J . Org. Chem., Vol. 61, No. 23, 1996
Langer et al.
Ta ble 1. P olyfu n ction a l P r od u cts 26-38 Obta in ed fr om Olefin s 4a -h by Su ccessive Hyd r obor a tion , Bor on -Zin c
Exch a n ge, Tr a n sm eta la tion w ith Cu CN‚2LiCl a n d Rea ction w ith a n Electr op h ile
consisting of 55 and Ti(Oi-Pr)
4
at -60 °C followed by the
of Table 3). Better results are obtained by performing
these reactions in ether (entry 4). The addition of
dimyrtanylzinc (45) to aldehydes is complicated by a
â-hydride transfer resulting in the reduction of the
aldehyde and low yields (17%) of the addition product
(56f). Nevertheless, the ligand-controlled diastereose-
lectivity of the addition is excellent (>96% de; entry 6).
addition of the aldehyde at -20 °C. The reaction mixture
was generally stirred for 5-10 h at this temperature,
providing the chiral alcohols 56 in 11-88% yield and with
5
0 to over 96% ee. Remarkably, a range of functionalities
are tolerated in this reaction (Table 3). The addition of
long chain dialkylzincs proceeds well although poor
solubility of the dialkylzinc in toluene leads in some cases
to moderate yields and enantioselectivities (entries 1-5
The more reactive secondary dialkylzincs like (c-Hex)
2
Zn
(6a ) furnish alcohols with lower enantioselectivity (entry

Functionalized Dialkylzincs via a Boron-Zinc Exchange
J . Org. Chem., Vol. 61, No. 23, 1996 8233
Sch em e 6
Ta ble 2. P olyfu n ction a l P r od u cts 49-54 Obta in ed by
th e Rea ction of Secon d a r y Dia lk ylzin cs w ith
Electr op h iles in th e P r esen ce of Cu CN‚2LiCl
Sch em e 7
7
). An alcohol function protected as the corresponding
pivalic ester can be present in dialkylzincs without
significant loss of enantiomeric excess, even if the piv-
aloxy group is relatively close (γ-position) to the carbon-
zinc bond (entries 8-12). Interestingly, an ethyl acrylate
function does not disturb the course of the asymmetric
addition and highly functionalized molecules like 56m -o
can be prepared in 80-95% ee and satisfactory yields
Sch em e 8
(69-72%). The use of silyl protecting groups is more
problematic and whereas a TMS-group is not suited, the
more bulky TIPS-group23 gives better results and a
TBDMS protected alcohol separated by four carbon atoms
from the zinc adds highly selectively to unsaturated
aldehydes (entries 16-18). Iodine or bromine substituted
dialkylzincs add smoothly to aldehydes and afford the
corresponding alcohols in good enantiomeric excess (60-
property (if enantiomerically enriched) of crystallizing in
double layers forming small lipophilic tubes.24 Thus, the
oxidation of eicosanol (58) with PCC on SiO
C to rt) provides the aldehyde 59 in 94% yield. The
treatment of 59 with bis(5-bromopentyl)zinc in the pres-
ence of the chiral catalyst 55 (8 mol %) and Ti(Oi-Pr) in
2 2 2
(CH Cl , 0
9
0% ee; entries 19-23). Although, most diorganozincs
2
5
°
can be handled without special precautions, it is recom-
mended to use a protecting shield and a reaction tem-
perature below 10 °C for reactions involving (Br(CH ) ) -
2 5 2
Zn since an explosive decomposition of this specific
reagent has been observed twice during its preparation.
As an application of this methodology, we have per-
4
ether (0 °C, 10 h) affords the bromo alcohol 60 in 69%
1
yield and 92% ee as determined by H NMR analysis of
the O-acetylmandelate using (S)-(+)-O-acetylmandelic
2
6
2
acid for derivatization. Coupling of 60 with Bu Cu(CN)-
formed a short synthesis of ginnol 57 ((S)-10-nona-
Li227 (5 equiv, -60 °C to 0 °C, 1 h) provides 57 in 95%
cosanol)24 in three steps starting from commercially
available material (61% overall yield and 92% ee). Ginnol
is found in several plants and possess the interesting
(
25) (a) Corey, E. J .; Suggs, J . W. Tetrahedron Lett. 1975, 2647. (b)
Piancatelli, G.; Scettri, A.; D’Auria, M. Synthesis 1982, 245.
26) Parker, D. J . Chem. Soc., Perkin Trans. 2 1983, 83.
(
(
23) R u¨ cker, C. Chem. Rev. 1995, 95, 1009.
(27) (a) Lipshutz, B. H. Synthesis 1987, 325. (b) Lipshutz, B. H.
Synlett 1990, 119. (c) Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J . A.
Tetrahedron 1984, 40, 5005.
(24) Furhop, J .-H.; Bedurke, T.; Hahn, A.; Grund, S.; Gatzmann,
J .; Riederer, M. Angew. Chem., Int. Ed. Engl. 1994, 33, 350.

8
234 J . Org. Chem., Vol. 61, No. 23, 1996
Langer et al.
Ta ble 3: P olyfu n ction a l Secon d a r y Alk oh ols 56a -w Obta in ed by a On e-P ot Hyd r obor a tion , Bor on -Zin c Exch a n ge a n d
Asym m etr ic Ad d ition to th e Ald eh yd es 57

Functionalized Dialkylzincs via a Boron-Zinc Exchange
J . Org. Chem., Vol. 61, No. 23, 1996 8235
Ta ble 3 (Con tin u ed )
Sch em e 9
GC or TLC analysis. The precipitate formed was removed by
filtration and the solvents were evaporated. The crude residue
was directly analyzed by H NMR spectroscopy.
1
St a r t in g Ma t er ia ls. Pyridinium chlorochromate (PCC),
copper cyanide, (-)-â-pinene, ethyl propiolate, nitrostyrene,
(-)-cinchonidine, diethyl benzylidenemalonate, benzoyl chlo-
ride, allyl bromide, titanium tetraisopropoxide, and diethyl
allylmalonate (16) were purchased and directly used or in some
cases after distillation. Lithium chloride was dried 1 h at 140
°
C under vacuum (0.1 mmHg). Ethyl R-(bromomethyl)acry-
1
7
2
8
late, 3-iodo-2-cyclohexen-1-one, (1R,2R)-1,2-bis(trifluo-
2
0
romethanesulfonamido)cyclohexane 25, triisopropylsilyl chlo-
ride,29 titanium tetra-tert-butoxide, (Z)- and (E)-2-deuterio-
30
1
-ethyl-1-phenylethylene 13a and 13b,31 pinacol 4-pen-
3
2
33
tenylboronate (4b), 6-nitro-1-hexene (15), 3-pivaloxy-1-
propene,34 4-pivaloxy-1-butene, 5-pivaloxy-1-pentene (4c),
34
34
3
4
35
6
-pivaloxy-1-hexene, allyl benzoate (4d ), 5-bromo-1-pen-
3
6
36
37
tene, 6-bromo-1-hexene (4e), 6-cyano-1-hexene (4f), N-(5-
hexenyl)phthalimide (4g), 4-methyl-4-nitro-1-pentene (4h ),
4
pene, 4-(tert-butyldimethylsiloxy)-1-butene, 6-iodo-1-hex-
ene,41 and (-)-cinchonidine acetate (24) were prepared
according to literature procedures.
yield (Scheme 9). Although the direct addition of di-
nonylzinc to 59 proceeds well, it was not possible to
determine the optical purity of the resulting product 57
by standard methods due to the similarity of the alkyl
substituents attached to the chiral center.
In summary, we have described a general preparation
of functionalized dialkylzincs starting from olefins using
a hydroboration followed by a boron-zinc exchange
mediated by diethylzinc. The method can be applied to
prepare primary and secondary dialkylzincs as well as
benzylic zinc reagents. The synthetic utility of these
organometallics after transmetalation with CuCN‚2LiCl
has been demonstrated. Furthermore the addition of
these diorganozincs to aldehydes in the presence of the
38
39
40
-triisopropylsiloxycyclopentene, 3-(triisopropylsiloxy)-1-pro-
4
0
40
42
P r ep a r a tion of Dieth ylbor a n e (5). A solution of dieth-
ylborane (5) was prepared by mixing triethylborane (30.3 g,
(28) Piers, E.; Nagakura, I. Synth. Commun. 1975, 5, 193.
(29) (a) Cunico, R. F.; Bedell, L. J . Org. Chem. 1980, 45, 4797. (b)
Cunico, R. F.; Dexheimer, E. M. Synth. React. Inorg. Met.-Org. Chem.
1974, 4, 23. (c) Colvin, E. W. Silicon Reagents in Organic Synthesis;
Academic Press: London, 1988; p 120.
(30) (a) Bradley, D. C.; Thomas, I. M. J . Chem. Soc. 1959, 3404. (b)
Rust, J . B.; Takimoto, H. H.; Denault, G. C. J . Org. Chem. 1960, 25,
2040. (c) Nowotny, S.; Vettel, S.; Knochel, P. Tetrahedron Lett. 1994,
3
5, 4539.
chiral catalyst 55 and Ti(Oi-Pr)
4
proceeds with high
(31) (a) Achyutha Rao, S.; Knochel, P. J . Am. Chem. Soc. 1991, 113,
enantioselectivity giving a unique access to polyfunctional
secondary alcohols with often excellent optical purity (50
to over 96% ee).
5
735. (b) Chou, S.-S. P.; Kuo, H.-L.; Wang, C.-Y.; Tsai, C.-Y.; Sun, C.-
M. J . Org. Chem. 1989, 54, 868. (c) Shibata, K.; Aida, T.; Inoue, S.
Tetrahedron Lett. 1992, 33, 1077.
(
32) Tucker, C. E.; Davidson, J .; Knochel, P. J . Org. Chem. 1992,
7, 3482.
33) Andersen, S. H.; Das, N. B.; J oergensen, R. D.; Kjeldsen, G.;
5
(
Exp er im en ta l Section
Knudsen, J . S.; Subhash, S. C.; Torssell, K. B. G. Acta Chem. Scand.
Ser. B 1982, 36, 1.
Gen er a l Con sid er a tion s. Unless otherwise indicated all
reactions were carried out under argon. Solvents (THF, ether,
toluene) were dried and freshly distilled over sodium/ben-
zophenone. Reactions were monitored by gas chromatography
(
34) (a) Gaylord, N. G.; Eirich, F. R. J . Am. Chem. Soc. 1952, 74,
3
34. (b) Zamarlik, M. H. C. R. Acad. Sci. (C) 1970, 271, 1138.
(
(
35) Deming, T. J .; Novak, B. M. J . Am. Chem. Soc. 1993, 115, 9101.
36) Antczak, K.; Kingston, J . F.; Alward, S. J .; Fallis, A. G. Can. J .
(GC) or thin-layer chromatography (TLC) analysis of hydro-
Chem. 1984, 62, 829.
(37) Lipshutz, B. H.; Parker, D. A.; Nguyen, S. L.; McCarthy, K. E.;
Barton, J . C.; Whitney, S. E.; Kotsuni, H. Tetrahedron 1986, 42, 2873.
lyzed aliquots. For handling Et Zn, Et B and Et BH, a
2
3
2
laboratory coat, leather gloves, and a helmet with a face
protection shield were worn due to the pyrophoric nature of
these reagents. Any contact of them with air or moisture was
(
38) Barlin, G. B.; Ireland, S. J .; J iravinyu, C.; Nguyen, T. M. T.;
Kotecka, B.; Rieckmann, K. H. Aust. J . Chem. 1993, 46, 1695.
39) (a) Aleksandrowicz, P.; Piotrowska, H.; Sas, W. Tetrahedron
(
carefully avoided. Small amounts of Et
2
Zn or volatile boranes
1982, 38, 1321. (b) Ono, N.; Zinsmeister, K.; Kaji, A. Bull. Chem. Soc.
J pn. 1985, 58, 1069.
that have been distilled from reaction mixtures were collected
in a cold trap and decomposed by diluting with hexanes and
dropwise addition of 2-propanol.
(
40) (a) Pirrung, M. C.; Webster, N. J . G. J . Org. Chem. 1987, 52,
3
6
603. (b) Corey, E. J .; Venkateswarlu, A. J . Am. Chem. Soc. 1972, 94,
190.
Derivatization of the secondary alcohols 56 with (S)-O-
acetylmandelic acid was performed according to Parker’s
(
41) Ashby, M. T.; Enemark, J . M.; Lichtenberger, D. L. Inorg. Chem.
1
988, 27, 191.
2
6
method. Completion of the esterification was monitored by
(42) Pettit, G. R.; Gupta, S. K. J . Chem. Soc., C 1986, 1208.

8
236 J . Org. Chem., Vol. 61, No. 23, 1996
Langer et al.
3
10 mmol) and borane-dimethyl sulfide complex (11.4 g, 150
(CDCl
3
, 77 MHz): 1.52 (m). 13C NMR (CDCl
3
, 50 MHz): δ
mmol) at 0 °C. The reaction mixture was ready to use after 5
min of stirring. Diethylborane prepared under these condi-
tions contains ca. 0.3 equiv of dimethyl sulfide and is stable
at 4 °C (refrigerator) for several months.
Cycloh exyld ieth ylbor a n e (6). The hydroboration was
performed by mixing cyclohexene (4.52 g, 55 mmol) and
diethylborane freshly prepared as described above (8.70 g, 50
mmol). After 2 h of stirring at rt, the solvent was carefully
distilled off (760 mmHg, rt to 60 °C) affording a crude product
147.7 (t, J ) 6.5 Hz), 128.1, 127.3, 125.6, 44.0, 35.9 (br), 33.0,
12.3.
Bis(1-deu ter io-2-ph en ylbu tyl)zin c (12c an d 12d). Prepa-
ration according to the typical procedure A (see below) using
either the organoborane 12a (0.97 g, 4.78 mmol) or 12b (1.00
g, 2.42 mmol) and diethylzinc (1.18 g, 9.55 mmol and 1.49 g,
12.1 mmol) yielding 12c (0.79 g, 99%) and 12d (1.18 g, 98%)
1
13
as a 1:1 mixture of diastereoisomers. The H and C NMR
spectra of both 12c and 12d are identical. 1H NMR (CDCl
,
3
(6) which was used directly (6.69 g, 88% yield). Distillation
200 MHz): δ 7.64 (m, 4H), 7.47 (m, 6H), 3.01 (q, J ) 6.8 Hz,
of this crude reaction mixture led to extensive disproportion-
ation affording mixtures of 6 (bp 39 °C/0.2 mmHg), dicyclo-
hexylethylborane, and tricyclohexylborane. This behavior is
typical for all secondary organoboranes prepared.
Dieth yl(1,2-d ip h en yleth yl)bor a n e (7). A mixture of
stilbene (2.82 g, 15.6 mmol) and diethylborane (2.86 g, 15.6
mmol) was stirred at rt for 5 h. The solvent was evaporated
2H), 1.87 (m, 4H), 1.14 (t, J ) 7.2 Hz, 6H), 0.80 (d, J ) 8.0
2
Hz, 1H), 0.70 (d, J ) 10.0 Hz, 1H).1 D NMR (CDCl
3
, 77
3
MHz): δ 0.80 (s, 1D), 0.70 (s, 1D).
C NMR (CDCl
3
, 125
MHz): δ 151.2, 128.6, 128.5, 125.5, 45.5, 34.0, 26.0 (t, J ) 18.6
Hz), 12.8.
(
1-Deu ter io-2-p h en ylbu tyl)p h en yl Keton e (14a a n d
1
4b). Preparation according to the typical procedure A (see
below) using the organozinc 12c or 12d (0.66 g, 2.0 mmol) and
benzoyl chloride (0.56 g, 4.0 mmol). Reaction conditions: -20
°C, 10 h. Yield of 14a and 14b (1:1 mixture of diastereoiso-
mers): 0.90 g, 94%. IR (neat): 1680 (vs), 1450 (s), 1275 (m),
755 (s), 700 (s), 685 (s), 555 (m) cm
MHz): δ 7.93 (d, J ) 9.0 Hz, 2H), 7.55 (t, J ) 7.4 Hz, 1H),
(0.1 mmHg, rt, 3 h) affording crude 7 (3.10 g, 79% yield) which
1
was directly used for the next step. The crude H NMR and
1
3
C NMR spectra of 7 clearly show that also bis- and tris(1,2-
diphenylethyl)borane derivatives have been formed (ca. 50%).
-
1
1
1
.
3
H NMR (CDCl , 500
H NMR (200 MHz, CDCl
H), 3.05 (m, 2H), 1.45 (m, 4H), 0.95 (m, 6H). C NMR (50
MHz, CDCl ): δ 141.5, 141.3, 141.2, 140.4, 128.7, 128.6, 128.5,
28.4, 128.3, 128.2, 128.1, 127.9, 46.6 (br), 36.8, 17.3 (br), 8.5,
.1.
Dieth yl(tr a n s-2-p h en ylcycloh exyl)bor a n e (9). A mix-
3
): δ 7.60-6.90 (m, 10H), 3.30 (m,
13
1
7
.45 (t, J ) 7.5 Hz, 2H), 7.36-7,20 (m, 5H), 3.30 (m, 2H), 1.84
2
3
(
m, 1H), 1.69 (m, 1H), 0.86 (t, J ) 7.4 Hz, 3H). D NMR
1
8
13
(
CDCl
3
, 77 MHz): 3.40-3.20 (m, 1D).
): δ 199.1, 144.5, 137.1, 132.8, 128.4, 128.3, 128.1, 127.5,
26.2, 45.1 (t, J ) 19.1 Hz), 42.9, 29.1 (d, J ) 2.5 Hz), 12.0.
MS (EI): 239 (14), 210 (44), 118 (100), 105 (99), 77 (100). Anal.
Calcd for C17 17DO: C, 85.31; H, 7.16. Found: C, 85.25; H,
.36.
C NMR (50 MHz,
CDCl
1
3
ture of 1-phenylcyclohexene (7.91 g, 50 mmol) and diethylbo-
rane (6.73 g, 50 mmol) was stirred at 50 °C for 3 days affording
the organoborane 9 (9.30 g, 96% yield) which was directly used
without further purification for the next step. The H NMR
and C NMR spectra of 9 show that a bis(diorgano)ethylbo-
rane has also been formed. H NMR (CDCl
7
0
δ 148.9, 148.6, 148.4, 128.2, 127.3, 127.0, 125.6, 125.4, 46.3,
4
2
H
7
1
Typ ica l P r oced u r e A for th e Bor on -Zin c Exch a n ge
a n d Cop p er (I)-Med ia t ed R ea ct ion w it h a n E lect r o-
p h ile: P r ep a r a tion of Dieth yl 6-Ca r beth oxy-1-p h en yl-
1
3
1
3
, 200 MHz): δ
.30 (m, 5H), 2.95-2.55 (m, 1H), 2.15-1.80 (m, 4H), 1.70-
6
-h ep ten ylm a lon a te (43) (Sch em e VI). Ethyl 3-buteny-
lacrylate (40) (1.85 g, 12.0 mmol) was cooled to 0 °C, and Et BH
12.0 mmol, 1 equiv; prepared from BH ‚Me S (3.80 g, 50
mmol), BEt (9.80 g, 100 mmol), and Et O (14.8 g)) was slowly
1
3
3
.90 (m, 14H), 0.60-0.35 (m, 1H). C NMR (50 MHz, CDCl ):
2
(
3
2
6.2, 46.1, 41.2 (br), 37.3, 36.6, 36.5, 27.4, 27.3, 27.2, 26.9, 26.8,
6.4, 26.1, 25.0, 18.5 (br), 17.8 (br), 17.3 (br), 8.5, 8.0.
E t h yl 2-[(tr a n s-2-P h en ylcycloh exyl)m et h yl]a cr yla t e
3
2
added via syringe. After 3 h at rt, the solvents were removed
under vacuum (0.1 mmHg, 0 °C, 0.5 h) affording the expected
(
11). Preparation according to the typical procedure A (see
diethyl(alkyl)borane (2.30 g, 86% yield) having ca. 95% purity
below) using the organoborane 9 (1.93 g, 10.0 mmol) and ethyl
R-(bromomethyl)acrylate
conditions: rt, 40 h (B/Zn-exchange) and -20 °C, 1 h (reaction
with electrophile). Yield of 11: 2.06 g, 84% (3:1 mixture of
diastereoisomers). IR (neat): 2920 (s), 1715 (s), 1445 (s), 1030
as shown by 1H and 13C NMR analysis. The organoborane
1
7
(1.74 g, 9.0 mmol). Reaction
(
1.01 g, 4.5 mmol) was transferred to a 50 mL Schlenk-flask
and cooled to 0 °C, and Et Zn (9.0 mmol, 0.92 mL, 2 equiv)
was added. After 0.5 h at 0 °C, the excess of Et Zn and formed
Et B were pumped off (0.1 mmHg, 0 °C, 3 h). The resulting
2
2
3
-
1
1
(
(
(
s), 755 (s), 700 (s) cm
m, 5H), 5.97 (m, 1H), 5.24 (m, 0.75H), 5.19 (s, 0.25H), 4.03
sext, J ) 7.2Hz, 2H), 2.30-2.20 (m, 2H), 1.90-1.55 (m, 6H),
.
3
H NMR (CDCl , 200 MHz): δ 7.12
oil was diluted with THF (3 mL) and cooled to -80 °C, and a
THF solution (4.5 mL) of CuCN‚2LiCl (prepared from CuCN
(0.40 g, 4.5 mmol) and LiCl (0.38 g, 9.0 mmol)) was added.
1
.45-1.10 (m, 3H), 1.15 (t, J ) 7.2 Hz, 2.25H), 1.07 (t, J ) 7.2
The reaction mixture was warmed to 0 °C and immediately
13
Hz, 0.75H), 0.82 (q, J ) 10.5 Hz, 1H). C NMR (50 MHz,
CDCl ): δ 167.1, 146.0, 145.1, 140.1, 139.4, 128.2, 127.9, 127.6,
25.9, 125.7, 125.6, 125.4, 60.3, 51.4, 46.0, 40.8, 38.9, 37.4, 36.2,
1.7, 28.5, 28.1, 26.8, 26.3, 26.2, 25.2, 20.2, 14.1, 14.0. MS
cooled back to -80 °C. Diethyl benzylidenemalonate (1.00 g,
3
4
.05 mmol, 0.9 equiv) was added, and the reaction mixture
1
3
was allowed to warm to rt. After 2 h, the conversion was
complete as shown by GC analysis of a reaction aliquot. The
reaction mixture was quenched with a saturated aqueous NH -
4
(
EI): 273 (4), 158 (38), 114 (28), 104 (26), 91 (100). Anal.
Calcd for C18 24O: C, 79.37; H, 8.88. Found: C, 79.08; H, 8.90.
1R*,2S*)-(1-Deu t er io-2-p h en ylb u t yl)d iet h ylb or a n e
12a ). A mixture of the styrene derivative 13a (0.89 g, 6.7
H
Cl solution (50 mL) and diluted with ether (100 mL). The
(
aqueous phase was extracted with ether (2 × 50 mL). The
(
combined organic phase was dried (MgSO ), evaporating of the
4
mmol) and diethylborane (0.98 g, 6.7 mmol) was stirred at rt
for 3 h affording the borane derivative 12a (1.12 g, 82% yield).
The crude 12a was used directly for the next step (boron-
zinc exchange). H NMR (CDCl
3
2
1
1
1
solvents afforded a crude oil which was purified by chroma-
tography (hexanes/ether 9:1), and pure 43 (1.36 g, 82%; overall
yield: 71%, based on the olefin 40) was obtained.
N-(5-Hexen yl)tr iflu or oa ceta m id e (17). To a suspension
of oil-free NaH (6.00 g, 250 mmol, 2 equiv) in DMF (50 mL)
was slowly added trifluoroacetamide (25.4 g, 225 mmol, 1.8
1
3
, 200 MHz): δ 7.33 (m, 5H),
.04 (quin, J ) 7.2 Hz, 1H), 1.80-1.50 (m, 3H), 1.40-1.25 (m,
2
H), 1.10-0.80 (m, 10H). D NMR (CDCl
3
, 77 MHz): 1.77 (m,
1
3
D). C NMR (50 MHz, CDCl
3
): δ 148.0 (t, J ) 6.8 Hz), 128.1,
equiv) in DMF (15 mL) leading to a vigorous evolution of H
After 0.5 h of stirring, the reaction mixture was treated with
-bromo-1-hexene (20.4 g, 125 mmol, 1 equiv) and the reaction
2
.
27.3, 125.5, 43.9 (d, J ) 4.0 Hz), 34.2 (br), 33.1, 20.0 (br),
1.5 (d, J ) 3.0 Hz), 8.2.
6
Tr is((1R*,2R*)-(1-deu ter io-2-ph en ylbu tyl))bor an e (12b).
mixture was heated to 80 °C for 10 h. The resulting precipitate
was filtered, the solvent was evaporated under reduced pres-
sure, and the residue was purified by distillation (bp 52-55
°C, 0.2 mmHg) affording the amide 17 as a colorless oil (12.2
g, 50% yield). IR (neat): 3310 (vs), 2940 (s), 1705 (vs), 1185
A mixture of the styrene derivative 13b (1.10 g, 8.2 mmol) and
diethylborane (1.21 g, 8.2 mmol) was stirred at rt for 3 h
affording after removing of all volatiles in high vacuum the
borane derivative 12b (1.02 g, 90% yield). The crude 12b was
1
-1
1
used directly for the next step (boron-zinc-exchange).
NMR (CDCl
Hz, 3H), 1.55-0.85 (m, 9H), 0.80-0.80 (m, 9H). D NMR
H
3
(vs), 914 (s) cm . H NMR (200 MHz, CDCl ): δ 7.10 (s, 1H),
3
, 200 MHz): δ 7.03 (m, 15H), 2.74 (quin, J ) 7.2
5.70 (m, 1H), 4.90 (m, 2H), 3.27 (q, J ) 6.7 Hz, 2H), 2.01 (q, J
2
13
) 6.9 Hz, 2H), 1.53 (m, 2H), 1.35 (m, 2H). C NMR (50 MHz,

Functionalized Dialkylzincs via a Boron-Zinc Exchange
J . Org. Chem., Vol. 61, No. 23, 1996 8237
CDCl
15.2, 40.1, 33.3, 28.4, 26.0. MS (EI): 195 (1), 126 (38), 82
100), 67 (54), 54 (36), 41 (18). Anal. Calcd for C NO:
C, 49.23; H, 6.20; N, 7.18. Found: C, 48.94; H, 6.18; N, 7.19.
An a lytica l Da ta of P r od u cts 18-23 P r ep a r ed Accor d -
in g to th e Typ ica l P r oced u r e A. 9-Nitr o-1-n on en e (18).
Overall yield (1.07 g, 82%) based on 6-nitro-1-hexene (0.98 g,
3
): δ 157.7 (q, J ) 37 Hz), 138.2, 116.1 (q, J ) 288 Hz),
J ) 7.6 Hz, 1H), 3.24 (t, J ) 6.0 Hz, 2H), 1.80 (m, 4H), 1.39
1
3
1
(
3
(m, 6H). C NMR (75 MHz, CDCl ): δ 139.5, 128.9, 127.6,
8
H
12
F
3
127.5, 80.9, 44.3, 33.3, 32.8, 30.2, 28.2, 26.7, 7.5. MS (EI): 361
(1), 314 (8), 118 (100), 104 (30), 91 (93), 55 (20). Anal. Calcd
for C14H20INO : C, 46.88; H, 5.58; N, 3.88. Found: C, 46.35;
2
H, 5.57; N, 3.93.
P r ep a r a tion of (-)-Cin ch on id in e Aceta te (24).42 (-)-
7
.6 mmol) and allyl bromide (6 g, 50 mmol). Reaction
conditions: 0 °C, 1 h. Purification by flash chromatography
hexanes/ether ) 9:1). IR (neat): 3080 (s), 2930 (vs), 1640 (s),
Cinchonidine (5.89 g, 20 mmol, 1 equiv) and Et
mmol, 1.5 equiv) in CH Cl
2 2
3
N (3.04 g, 30
(150 mL) were cooled to 0 °C.
Acetyl chloride (2.09 g, 27 mmol, 1.3 equiv) in CH Cl (10 mL)
(
1
2
2
555 (vs), 910 (m) cm-1
.
1
H NMR (200 MHz, CDCl
): δ 5.72
3
was added within 3 h to give a clear yellow solution. After 8
h at rt, the reaction mixture was worked up as usual affording
after evaporation of the solvent a pure material which was
(
m, 1H), 4.89 (m, 2H), 4.30 (t, J ) 7.1 Hz, 2H), 1.95 (m, 4H),
1
3
1
.27 (m, 8H). C NMR (50 MHz, CDCl
3.5, 28.5, 27.2, 26.0. MS (EI): 81 (29), 69 (30), 55 (100), 41
: C; 63.13; H, 10.01; N, 8.18.
Found: C, 63.28; H, 9.93; N, 8.29.
3
): δ (138.7, 114.1, 75.5,
1
3
(
directly used for the next step (5.99 g, 89% yield). H NMR
67). Anal. Calcd for C
9
H
17NO
2
3
(200 MHz, CDCl ): δ 8.78 (d, J ) 4.6 Hz, 1H), 8.14 (d, J ) 9.3
Hz, 1H), 8.03 (d, J ) 9.3 Hz, 1H), 7.58 (t, J ) 8.3 Hz, 1H),
7.46 (t, J ) 8.4 Hz, 1H), 7.31 (d, J ) 4.5 Hz, 1H), 6.43 (d, J )
7.5 Hz, 1H), 5.71 (m, 1H), 4.89 (m, 2H), 4.26 (m, 1H), 2.90 (m,
2H), 2.49 (m, 2H), 2.15 (m, 1H), 1.97 (s, 3H), 1.85-1.30 (m,
4
3
Dieth yl 5-Hexen ylm a lon a te (19). Overall yield (1.09
g, 85%) based on diethyl allylmalonate (1.05 g, 5.26 mmol) and
allyl bromide (6 g, 50 mmol). Reaction conditions: 0 °C, 1 h.
Purification by flash chromatography (hexanes/ether ) 9:1).
IR (neat): 3080 (w), 2980 (m), 2935 (m), 1750 (vs), 1735 (vs),
1
5H). 13C NMR (50 MHz, CDCl
): δ 169.7, 149.7, 148.4, 145.1,
3
141.5, 130.2, 128.9, 126.5, 125.8, 123.2, 118.5, 114.2, 73.8, 59.4,
56.4, 42.1, 49.4, 27.5, 27.3, 24.3, 20.8.
150 (s), 910 (m) cm-1
.
1
3
H NMR (200 MHz, CDCl ): δ 5.70
(
m, 1H), 4.89 (m, 2H), 4.12 (q, J ) 7.1 Hz, 4H), 3.24 (t, J ) 7.5
Allyla tion of th e Cin ch on id in e Aceta te (24) via th e
Hydr obor ation /Bor on -Zin c Exch an ge Sequ en ce. P r epa-
r a tion of th e Allyla ted Cin ch on id in e 25. Diethylborane
(4 mmol) prepared by mixing borane-dimethyl sulfide complex
(Fluka; 101 mg, 1.33 mmol, 1 equiv) and triethylborane
(Aldrich, 261 mg, 2.66 mmol, 2 equiv) at rt was added at 0 °C
to a solution of 24 (1.35 g, 4 mmol) in ether (8 mL) and was
stirred at 40 °C for 12 h giving a white suspension. All the
solvents were pumped off at 40 °C, 0.2 mmHg during 6 h
yielding a diethylborane adduct as a white powder (1.63 g, 4
mmol). Diethylzinc (8 mmol, ca. 0.8 mL, 2 equiv) was added
at rt to a suspension of the intermediate diethylborane
derivative (1.63 g, 4 mmol, 1 equiv) in CH Cl (5 mL). After
Hz, 1H), 1.98 (q, J ) 7.0 Hz, 2H), 1.82 (q, J ) 7.4 Hz, 2H),
1
3
1
.28 (m, 4H), 1.19 (t, J ) 7.1 Hz, 6H). C NMR (50 MHz,
CDCl ): δ 169.7, 138.7, 114.8, 61.4, 52.2, 33.6, 28.8, 28.7, 26.9,
4.3. MS (EI): 196 (11), 173 (41), 160 (57), 80 (100), 55 (44).
N-(8-Non en yl)tr iflu or oa ceta m id e (20). Overall yield
3
1
(1.13 g, 94%) based on 17 (1.04 g, 5.32 mmol) and allyl bromide
(6 g, 50 mmol). Reaction conditions: 0 °C, 1 h. Purification
by flash chromatography (hexanes/ether ) 9:1). IR (neat):
-
1
3
305 (s), 2940 (vs), 1705 (vs), 1561 (s), 1185 (vs), 910 (m) cm .
1
H NMR (300 MHz, CDCl
(
1
CDCl
1
(
3
): δ 7.10 (s, 1H), 5.71 (m, 1H), 4.88
m, 2H), 3.25 (q, J ) 6.8 Hz, 2H), 1.96 (q, J ) 6.9 Hz, 2H),
.50 (quint, J ) 7.0 Hz, 2H), 1.24 (s, 8H). C NMR (75 MHz,
): δ 157.3 (q, J ) 37 Hz), 138.7, 115.8 (q, J ) 288 Hz),
14.0, 39.8, 33.5, 28.8, 28.7, 28.6, 28.5, 26.4. MS (EI): 124
56), 96 (19), 82 (51), 69 (43), 55 (100), 41 (48). Anal. Calcd
for C11 NO: C, 55.69; H, 7.65; N, 5.90. Found: C, 55.47;
1
3
2
2
3
10 min of stirring, the white suspension turned into a clear
orange solution. The solvent, the excess diethylzinc, and the
formed triethylborane were removed under vacuum at rt (0.2
mmHg, 2 h). The entire procedure (5 mL CH Cl , 1 mL Et -
18 3
H F
2
2
2
H, 7.66; N, 6.00.
Eth yl (7-Iod oh ep tyl)a cr yla te (21). Overall yield (1.09 g,
Zn, then pumping off) was repeated to insure complete
conversion to the diorganozinc compound. Traces of remaining
7
5%) based on 6-iodo-1-hexene (1.31 g, 6.25 mmol) and ethyl
Et Zn were removed by evaporating twice with toluene (5 mL)
2
1
7
R-(bromomethyl)acrylate (0.87 g, 4.50 mmol). Reaction
and finally with CH Cl (5 mL) at 40 °C (0.2 mmHg, 6 h) giving
2
2
conditions: -20 °C, 1 h. Purification by flash chromatography
an orange foam of the intermediate zinc reagent. A suspension
of copper(I) cyanide (36 mg, 0.4 mmol, 0.1 equiv), lithium
chloride (34 mg, 0.8 mmol, 0.2 equiv), allyl bromide (4.84 g,
40 mmol, 10 equiv), and THF (1 mL) was added at -80 °C to
a solution of the diorganozinc compound (2 mmol, 0.5 equiv)
in THF (8 mL). The cooling bath was removed, and the
reaction mixture was allowed to slowly warm to rt. After the
usual workup the solvents were evaporated and the remaining
volatile compounds were removed at 50 °C (0.2 mmHg, 3 h).
The crude product was purified by flash chromatography
(ether/THF ) 4:1) yielding the desired product 25 as a yellow
foam (1.44 g, 95%). IR (neat): (2925 (s), 1745 (s), 1230 (s),
(
hexanes/ether ) 19:1). IR (neat): 2930 (s), 2860 (m), 1720
1 1
-
(s), 1190 (m) cm
3
. H NMR (CDCl , 200 MHz): δ 6.01 (s, 1H),
5
2
1
.49 (s, 1H), 4.18 (q, J ) 7.1 Hz, 2H), 3.16 (t, J ) 7.3 Hz, 2H),
.27 (t, J ) 7.7 Hz, 2H), 1.79 (quin, J ) 7.3 Hz, 2H), 1.45-
1
3
.25 (m, 8H), 1.27 (t, J ) 8.1 Hz, 3H). C NMR (50 MHz,
CDCl
3.5, 6.5. MS (EI): 324 (1), 197 (21), 123 (100), 81 (61), 67
45), 55 (65). Anal. Calcd for C12 : C, 44.46; H, 6.53.
Found: C, 44.51; H, 6.45.
E)-Eth yl 9-Iod o-2-n on en oa te (22). Overall yield (1.39
3
): δ 166.5, 140.2, 123.5, 59.8, 32.7, 31.1, 29.7, 28.2, 27.6,
1
(
H21IO
2
(
g, 79%) based on 6-iodo-1-hexene (1.47 g, 7 mmol) and ethyl
propiolate (0.56 g, 5.7 mmol). Reaction conditions: -50 °C to
-
1
1
1025 (s), 760 (s) cm
3
. H NMR (200 MHz, CDCl ): δ 8.80 (d,
-
40 °C, 10 h. Purification by flash chromatography (hexanes/
J ) 4.6 Hz, 1H), 16 (d, J ) 9.2 Hz, 1H), 8.04 (d, J ) 9.4 Hz,
1H), 7.61 (t, J ) 8.3 Hz, 1H), 7.49 (t, J ) 8.3 Hz, 1H), 7.31 (d,
J ) 4.5 Hz, 1H), 5.67 (m, 1H), 4.85 (m, 2H), 3.29 (m, 1H), 2.93
(m, 2H), 2.52 (m, 1H), 2.19 (m, 1H), 2.01 (s, 3H), 1.15-1.95
ether ) 9:1). IR (neat): 2930 (s), 1720 (s), 1660 (m), 1200 (s),
-
1
1
1
5
040 (m) cm
.76 (d, J ) 15.6 Hz, 1H), 4.13 (q, J ) 7.1 Hz, 2H), 3.13 (t, J
6.9 Hz, 2H), 2.15 (q, J ) 7.1 Hz, 2H), 1.76 (quint, J ) 6.7
.
3
H NMR (200 MHz, CDCl ): δ 6.89 (m, 1H),
1
3
)
3
(m, 13H). C NMR (50 MHz, CDCl ): δ 169.4, 149.5, 148.2,
1
3
Hz, 2H), 1.32 (m, 6H), 1.23 (t, J ) 6.2 Hz, 3H). C NMR (50
MHz, CDCl ): δ 165.1, 147.4, 120.0, 58.6, 31.8, 30.5, 28.7, 26.5,
6.3, 12.8, 5.6; MS (EI): 310 (10), 265 (23), 109 (100), 95 (22),
7 (25), 55 (30). Anal. Calcd for C11 : C, 42.60; H, 6.17.
145.0, 138.2, 130.0, 128.7, 126.4, 125.6, 123.0, 118.3, 114.1,
73.6, 59.0, 58.0, 42.0, 34.9, 33.9, 33.4, 27.9, 26.4, 25.2, 23.7,
20.6. MS (EI): 378 (13), 319 (43), 168 (100), 159 (18), 84 (22).
3
2
6
H
19IO
2
30 2 2
Anal. Calcd for C24H N O : C, 76.16; H, 7.99; N, 7.40.
Found: C, 42.86; H, 6.10.
Found: C, 75.80; H, 8.18; N, 7.41.
8
-Iod o-1-n itr o-2-p h en ylocta n e (23). Overall yield (1.69
P r od u cts 26-38 of Ta ble 1 P r ep a r ed Accor d in g to th e
Typ ica l P r oced u r e A. Ethyl 2-undecylacrylate (26). Overall
yield based on 1-decene: 1.02 g, 80% using 1-decene (0.70 g,
5.0 mmol) and ethyl R-(bromomethyl)acrylate17 (0.87 g, 4.5
mmol). Purification of 26 by flash chromatography (hexanes/
ether ) 19:1). IR (neat): 2930 (vs), 2860 (vs), 1720 (vs), 1465
g, 4.7 mmol, 82% yield) based on 6-iodo-1-hexene (1.47 g, 7
mmol) and nitrostyrene (0.85 g, 5.7 mmol). Reaction condi-
tions: -40 °C, 1 h; -10 °C, 8 h. Purification by flash
chromatography (hexanes/ether ) 9:1). IR (neat): 2930 (s),
1
1
550 (s), 1380 (m), 1200 (w), 700 (m) cm-1
.
H NMR (300 MHz,
-
1
1
CDCl
3
): δ 7.37 (m, 5H), 4.65 (d, J ) 8.0 Hz, 2H), 3.55 (quint,
(s), 1180 (s) cm
.
H NMR (300 MHz, CDCl ): δ 6.04 (s, 1H),
3
5
.42 (s, 1H), 4.13 (q, J ) 7.2 Hz, 2H), 2.22 (t, J ) 7.5 Hz, 2H),
13
(43) Salomon, R. G.; Coughlin, D. J .; Ghosh, S.; Zagorski, M. G. J .
1.40 (t, J ) 7.3 Hz, 2H), (m, 19H), 0.80 (t, J ) 6.6 Hz, 3H).
NMR (75 MHz, CDCl ): δ 167.2, 141.0, 123.8, 60.3, 32.5, 31.7,
C
Am. Chem. Soc. 1982, 104, 998.
3

8
238 J . Org. Chem., Vol. 61, No. 23, 1996
Langer et al.
2
9.5, 29.4, 29.3, 29.2, 29.0, 28.3, 22.5, 14.0, 13.9. MS (EI): 254
13C NMR (50 MHz, CDCl
45.2, 34.8, 33.7, 33.4, 29.3, 28.7, 27.6. MS (EI): 268 (1), 266
3
): δ 140.3, 129.8, 128.5, 128.4, 81.8,
(
18), 209 (22), 141 (14), 115 (100), 102 (93). Anal. Calcd for
: C, 75.54; H, 11.89. Found: C, 75.52; H, 12.04.
P in a col 5-(3-Oxocycloh exen yl)bor on a te (27). Overall
yield (1.31 g, 81%) based on pinacol 4-pentylboronate (4b) (1.22
C
16
H
30
O
2
(1), 118 (100), 104 (19), 91 (58). Anal. Calcd for C14
BrNO : C, 53.51; H, 6.42; N, 4.46. Found: C, 53.72; H, 6.46;
N, 4.55.
20
H -
2
2
8
g, 6.2 mmol) and 3-iodo-2-cyclohexen-1-one (1.23 g, 5.5 mmol).
Dieth yl (7-Cya n o-1-p h en ylh ep tyl)m a lon a te (33). Over-
all yield (1.76 g, 74%) based on 6-heptenenitrile (4f) (0.81 g,
Reaction conditions: -30 °C, 10 h. Purification by flash
chromatography (hexanes/ether ) 2:1). IR (neat): 2940 (s),
7
.40 mmol) and diethyl benzylidenemalonate (1.50 g, 6.06
660 (s), 1630 (m), 1370 (s), 1140 (s), 960 (m) cm-1
.
1
H NMR
1
mmol). Reaction conditions: rt, 10 h. Purification by flash
(
(
(
1
(
200 MHz, CDCl
quin, J ) 6.4 Hz, 2H), 1.45-1.09 (m, 6H), 1.09 (s, 12H), 0.65
t, J ) 7.0 Hz, 2H). 13C NMR (50 MHz, CDCl
): δ 199.7, 166.7,
25.6, 82.9, 38.0, 37.4, 31.9, 29.7, 26.7, 24.9, 23.8, 22.8, 11.0
br). MS (EI): 292 (5), 234 (8), 193 (35), 179 (21), 123 (45),
3
): δ 5.71 (s, 1H), 2.23-2.07 (m, 6H), 1.83
chromatography (hexanes/ether ) 4:1). IR (neat): 2930 (s),
-1
1
2
500 (w), 1690 (s), 1600 (s), 1530 (s) cm . H NMR (200 MHz,
3
CDCl
): δ 7.92 (m, 4H), 2.76 (t, J ) 7.1 Hz, 2H), 2.09 (t, J )
3
13
6
.9 Hz, 2H), 1.40 (sept, J ) 7.2 Hz, 4H), 1.90 (m, 4H).
C
NMR (50 MHz, CDCl
3
): δ 197.8, 149.4, 140.6, 128.3, 123.1,
1
6
10 (34), 82 (58), 55 (30), 40 (100). Calcd for C17
9.87; H, 10.00. Found: C, 69.61; H, 10.16.
3
H29BO : C,
1
19.1, 38.1, 27.7, 27.5, 24.4, 22.7, 16.3. MS (EI): 260 (1), 165
4
(78), 150 (100), 104 (33), 83 (21). Anal. Calcd for C21H29NO :
3
-(5-P iva loxyp en tyl)-2-cycloh exen -1-on e (28). Overall
C, 64.60; H, 6.20 N, 10.76. Found: C, 64.43; H, 6.40; N, 10.98.
N-(7-Oxo-7-ph en ylh eptyl)ph th alim ide (35). Overall yield
yield (1.31 g, 66%) based on 4-pentenyl pivalate (4c) (1.16 g,
6
2
8
.8 mmol) and 3-iodo-2-cyclohexen-1-one (1.23 g, 5.53 mmol).
(1.18 g, 3.5 mmol, 68%) based on benzoyl chloride (0.62 g, 4.4
Reaction conditions: -30 °C, 10 h. Purification by flash
mmol) and N-(5-hexenyl)phthalimide (4g) (1.32 g, 5.76 mmol).
Reaction conditions: -10 °C, 10 h. Purification by crystal-
lization from EtOH (100 mL) yielding a white solid (mp 150
chromatography (hexanes/ether ) 9:1). IR (neat): 2940 (s),
720 (s), 1670 (s), 1480 (m), 1290 (s), 1160 (s) cm-1
.
1
H NMR
1
(200 MHz, CDCl
3
): δ 5.80 (s, 1H), 3.98 (t, J ) 6.5 Hz, 2H),
°
C). IR (neat): 2940 (s), 1705 (vs), 1674 (s), 1400 (s), 730 (s),
2
6
1
2
6
.32-2.12 (m, 6H), 1.91 (quin, J ) 7.0 Hz, 2H), 1.66-1.27 (m,
-1
1
7
7
2
29 (m) cm
.
3
H NMR (200 MHz, CDCl ): δ 7.80 (m, 2H),
1
3
H), 1.12 (s, 9H). C NMR (50 MHz, CDCl ): δ 198.8, 177.5,
3
.69 (m, 2H), 7.58 (m, 2H), 7.33 (m, 3H), 3.56 (t, J ) 7.2 Hz,
H), 2.84 (t, J ) 7.3 Hz, 2H), 1.59 (q, J ) 7.0 Hz, 4H), 1.29
65.2, 124.7, 63.0, 37.7, 36.9, 36.3, 28.6, 27.4, 26.2, 25.5, 24.6,
1.7. MS (EI): 266 (7), 181 (15), 123 (38), 110 (20), 82 (28),
13
3
(m, 4H). C NMR (50 MHz, CDCl ): δ 200.0, 168.2, 136.7,
9 (18), 57 (100), 41 (47). Anal. Calcd for C16
26 3
H O : C, 72.14;
1
2
7
33.7, 132.7, 131.9, 128.4, 127.8, 122.9, 38.2, 37.7, 28.9, 28.4,
6.5, 23.9. MS (EI): 335 (16), 216 (21), 160 (33), 105 (100),
7 (36). Anal. Calcd for C21H21NO : C, 75.20; H, 6.31; N, 4.18.
3
H, 9.84. Found: C, 71.97; H, 9.90.
Dieth yl [4-(Ben zoyloxy)-1-p h en ylbu tyl]m a lon a te (29).
Overall yield (0.90 g, 81%) based on allyl benzoate (4d ) (1.01
g, 6.25 mmol) and diethyl benzylidenemalonate (1.88 g, 3.50
mmol). Reaction conditions: 0 °C, 12 h. Purification by flash
chromatography (hexanes/ether ) 19:1). IR (neat): 1760 (s),
Found: C, 74.99; H, 6.41; N, 4.23.
N-(7-Ca r beth oxy-7-octen yl)p h th a lim id e (36). Overall
yield (1.47 g, 81%) based on N-(5-hexenyl)phthalimide (4g)
1
7
-1
1
(1.35 g, 5.88 mmol) and ethyl R-(bromomethyl)acrylate (0.87
g, 4.5 mmol). Reaction conditions: -20 °C, 1 h. Purification
by flash chromatography (hexanes/ether ) 4:1). IR (neat):
1
730 (s), 1260 (m), 1030 (m), 700 (m) cm
.
H NMR (200 MHz,
CDCl
3
): δ 7.97 (m, 2H), 7.55-7.30 (m, 3H), 7.25-7.08 (m, 5H),
4
1
1
0
1
6
.27 (t, J ) 6.4 Hz, 1H), 4.17 (q, J ) 7.1 Hz, 2H), 3.57 (d, J )
-
1 1
2
935 (s), 1775 (s), 1720 (s), 1395 (s), 1185 (s), 720 (s) cm . H
1.2 Hz, 1H), 3.19 (dt, J ) 11.2 Hz, J ) 3.8 Hz, 1H), 1.78-
NMR (200 MHz, CDCl ): δ 7.85 (m, 2H), 7.61 (m, 2H), 6.01
3
.42 (m, 4H), 1.22 (t, J ) 7.1 Hz, 3H), 0.86 (t, J ) 7.1 Hz, 3H),
1
3
(s, 1H), 5.40 (s, 1H), 4.10 (q, J ) 7.1 Hz, 2H), 3.57 (t, J ) 7.1
Hz, 2H), 2.18 (t, J ) 7.1 Hz, 2H), 1.57 (s, 2H), 1.24 (m, 11H).
.65 (t, J ) 7.3 Hz, 3H). C NMR (50 MHz, CDCl ): δ 169.5,
3
68.8, 141.6, 133.8, 130.4, 129.3, 129.2, 129.1, 127.7, 68.5, 62.4,
2.0, 59.6, 48.3, 29.6, 28.0, 26.7, 15.0, 14.6, 12.6. MS (EI): 278
1
3
C NMR (50 MHz, CDCl ): δ 168.1, 167.0, 140.7, 133.5, 131.9,
3
1
23.9, 122.8, 60.2, 37.7, 31.5, 28.8, 28.7, 28.3, 28.0, 26.5, 14.0.
MS (EI): 343 (3), 297 (17), 160 (100), 148 (20), 122 (28). Anal.
Calcd for C20 : C, 69.95; H, 7.34; N, 4.08. Found: C,
0.01; H, 7.34; N, 4.10.
,6-Din itr o-6-m eth yl-2-ph en ylh eptan e (37). Overall yield
0.83 g, 59%) based on 4-methyl-4-nitro-1-pentene (4h ) (0.72
(
13), 204 (74), 159 (32), 131 (41), 119 (60), 91 (100). Anal. Calcd
for C24 : C, 69.89; H, 6.84. Found: C, 69.58; H, 6.85.
-Cyclop r op yl-4-oxobu tyl Ben zoa te (30). Overall yield
1.00 g, 64%) based on allyl benzoate (4d ) (1.20 g, 7.40 mmol)
28 6
H O
H
25NO
4
4
7
(
1
and cyclopropylcarbonyl chloride (0.56 g, 5.40 mmol). Reaction
conditions: -10 °C, 10 h. Purification by flash chromatogra-
phy (hexanes/ether ) 9:1). IR (neat): 1720 (s), 1700 (s), 1280
(
g, 5.6 mmol) and nitrostyrene (0.56 g, 4 mmol). Reaction
conditions: -40 °C, 4 h, then 0 °C, 2 h. Purification by flash
chromatography (hexanes/ether ) 4:1). IR (neat): 3055 (w),
-1
1
(s), 1120 (m), 712 (s) cm
3
. H NMR (200 MHz, CDCl ): δ 7.98
(d, J ) 7.9 Hz, 2H), 7.52-7.35 (m, 3H), 4.29 (t, J ) 8.0 Hz,
3
029 (w), 2951 (m), 1603 (m), 1535 (vs), 1382 (m), 771 (s), 702
2
2
1
H), 2.69 (t, J ) 7.0, 2H), 2.25-1.80 (m, 3H), 1.03-0.75 (m,
13
-
1
1
(s) cm
7
1
NMR (75 MHz, CDCl
1
.
H NMR (300 MHz, CDCl ): δ 7.38-7.28 (m, 3H),
3
H). C NMR (50 MHz, CDCl
28.6, 127.4, 63.3, 62.5, 38.7, 27.8, 27.7, 22.0, 19.5, 9.8. MS
3
): δ 208.7, 165.5, 132.0, 129.3,
.20-7.17 (m, 2H), 4.54 (d, J ) 7.7 Hz, 2H), 3.50-3.40 (m,
13
H), 1.94-1.67 (m, 4H), 1.50 (s, 6H), 1.22-1.15 (m, 2H).
): δ 138.8, 129.1, 128.0, 127.9, 127.5,
27.2, 87.9, 80.8, 44.0, 40.3, 32.7, 25.8, 21.5. MS (EI): 280
C
(
EI): 232 (1), 110 (48), 105 (70), 69 (100), 41 (45). Anal. Calcd
for C14 : C, 72.39; H, 6.94. Found: C, 72.21; H, 6.70.
,12-Bis(ben zoyloxy)-4,9-d ioxod od eca n e (31). Overall
16 3
H O
3
1
+
(M , 2), 233 (3), 131 (39), 117 (50), 104 (44), 91 (100), 69 (75).
yield (0.65 g, 53%) based on allyl benzoate (4d ) (1.22 g, 7.40
mmol) and adipoyl chloride (0.44 g, 2.40 mmol). Reaction
conditions: -10 °C, 10 h. Purification by flash chromatogra-
phy (hexanes/ether ) 9:1). IR (neat): 2940 (m), 1710 (s), 1280
Anal. Calcd for C14 C, 59.98; H, 7.19; N, 9.99.
20 2 4
H N O :
Found: C, 60.16; H, 7.15; N, 10.08.
Dieth yl (5-Meth yl-5-n itr o-1-ph en ylh exyl)m alon ate (38).
Overall yield (1.16 g, 62%) based on 4-methyl-4-nitro-1-pentene
(4h ) (0.72 g, 5.6 mmol) and diethyl benzylidenemalonate (1.0
g, 4 mmol). Reaction conditions: -78 °C to -40 °C, 4 h, then
0 °C, 8 h. Purification by flash chromatography (hexanes/ethyl
acetate ) 4:1). IR (neat): 3064 (w), 3031 (w), 2984 (s), 1733
-1
1
(s), 1120 (m), 710 (s) cm
3
. H NMR (200 MHz, CDCl ): δ 7.94
(
m, 4H), 7.50-7.32 (m, 6H), 4.24 (t, J ) 6.3 Hz, 4H), 2.48 (t,
J ) 7.2 Hz, 4H), 2.35 (m, 4H), 1.97 (quint, J ) 6.8 Hz, 4H),
1
1
1
3
.47 (m, 4H).
3
C NMR (50 MHz, CDCl ): δ 209.7, 166.7,
33.0, 130.4, 129.7, 128.6, 64.4, 42.8, 39.2, 23.4, 23.1. MS
-
1
1
(
EI): 153 (8), 105 (100), 84 (29), 77 (25), 55 (11). Anal. Calcd
for C26 : C, 71.21; H, 6.90. Found: C, 71.09; H, 6.74.
-Br om o-1-n itr o-2-ph en yloctan e (32). Overall yield (1.27
g, 4.04 mmol, 84%) based on 6-bromo-1-hexene (4e) (1.01 g,
.2 mmol) and nitrostyrene (0.72 g, 4.80 mmol). Reaction
(vs), 1603 (w), 1538 (vs), 702 (s) cm
.
H NMR (300 MHz,
H
30
O
6
CDCl ): δ 7.22-7.08 (m, 5H), 4.16 (q, J ) 7.2 Hz, 2H), 3.78
3
8
(q, J ) 7.1 Hz, 2H), 3.54 (d, J ) 10.8 Hz, 1H), 3.31-3.23 (m,
1H), 1.92-1.54 (m, 4H), 1.37 (d, J ) 4.3, 6.0 Hz, 6H), 1.21 (t,
J ) 7.1 Hz, 3H), 1.04-0.92 (m, 2H), 0.55 (t, J ) 7.1 Hz, 3H).
6
1
3
conditions: -10 °C, 10 h. Purification by flash chromatogra-
3
C NMR (75 MHz, CDCl ): δ 168.2, 167.5, 140.2, 128.4, 128.3,
phy (hexanes/ether ) 19:1). IR (neat): 2930 (s), 1550 (s), 1450
128.2, 127.0, 87.9, 61.4, 61.0, 58.6, 45.0, 40.2, 33.5, 25.7, 25.5,
-1
1
+
(m), 1380 (s), 700 (s) cm
.
H NMR (200 MHz, CDCl
3
): δ 708
21.4, 14.0, 13.6. MS (EI): 379 (M , 5), 241 (17), 189 (71), 172
(57), 117 (98), 69 (100). Anal. Calcd for C20
H, 7.70; N, 3.96. Found: C, 63.30; H, 7.55; N, 3.68.
(
3
m, 5H), 4.48 (t, J ) 7.6 Hz, 2H), 3.35 (quint, J ) 7.6 Hz, 1H),
6
H29NO : C, 63.31;
.27 (t, J ) 6.7 Hz, 2H), 1.75-1.52 (m, 4H), 1.30-1.05 (m, 6H).

Functionalized Dialkylzincs via a Boron-Zinc Exchange
J . Org. Chem., Vol. 61, No. 23, 1996 8239
Eth yl 3-Bu ten yla cr yla te (40). Allylzinc bromide prepared
from allyl bromide (7.2 g, 60 mmol) in THF (10 mL) and cut
zinc foil (4.71 g, 72 mmol) in THF (5 mL) according to the
2.30-2.15 (m, 1H), 2.10-1.81 (m, 6H), 1.50-1.35 (m, 1H), 1.11
1
3
(s, 3H), 1.01 (s, 3H).
3
C NMR (50 MHz, CDCl ): δ 199.7,
137.0, 132.5, 128.2, 127.8, 46.1, 40.9, 38.4, 36.7, 33.2, 27.8, 26.0,
3
+
procedure of Gaudemar was added at -70 °C to a solution of
23.1, 21.9. MS (EI): 242 (M , 5), 122 (19), 105 (100), 77 (26).
CuCN‚2LiCl (prepared from CuCN (5.37 g, 60 mmol) and LiCl
Anal. Calcd for C17
H, 9.14.
H22O: C, 84.25; H, 9.15. Found: C, 84.14;
(5.09 g, 120 mmol)) in THF (60 mL). The reaction mixture
was stirred at -30 °C for 45 min and was cooled back to -78
An a lytica l Da ta of P r od u cts 49-54 of Ta ble 2 P r e-
p a r ed Accor d in g to th e Typ ica l P r oced u r e A. Cyclo-
h exyl P h en yl Keton e (49).44 Overall yield (1.10 g, 86%)
based on cyclohexene (0.62 g, 7.5 mmol) and benzoyl chloride
(0.95 g, 6.75 mmol). Reaction conditions: 0 °C, 3 h (B/Zn-
exchange) and -10 °C, 10 h (reaction with electrophile).
Purified by flash chromatography (hexanes/ether ) 9:1). The
°
C. Ethyl (R-bromomethyl)acrylate (10.4 g, 54 mmol) was
added, and the reaction mixture was allowed to warm to 0 °C
and was worked up as usual. The residue obtained after
evaporation of the solvents was purified by distillation afford-
ing the acrylate 40 as a colorless liquid (6.47 g, 42 mmol, 77%
yield; bp 81-83 °C/32 mbar). IR (neat): 2980 (vs), 1720 (vs),
-
1
1
44
1
635 (s), 1450 (m), 1370 (m), 1310 (m) cm
.
H NMR (200
spectral data are identical with the literature.
MHz, CDCl
3
): δ 6.11 (d, J ) 1.5 Hz, 1H), 5.76 (ddt, J ) 17.1,
Eth yl 2-(2,3-Dip h en ylp r op yl)a cr yla te (50). Overall yield
(4.24 g, 95%) based on stilbene (3.0 g, 16.5 mmol) and ethyl
R-(bromomethyl)acrylate17 (2.90 g, 15.0 mmol). Reaction
conditions: rt, 3 h (B/Zn-exchange) and -20 °C, 1 h (reaction
with electrophile). Purified by flash chromatography (hexanes/
ether ) 9:1). IR (neat): 3030 (m), 1720 (s), 1500 (m), 1450
1
4
2
1
0.2, 6.5 Hz, 1H), 5.48 (q, J ) 1.4 Hz, 1H), 5.03-4.90 (m, 2H),
.16 (q, J ) 7.2 Hz, 2H), 2.40-2.32 (m, 2H), 2.25-2.13 (m,
1
3
H), 1.26 (t, J ) 7.2 Hz, 3H). C NMR (50 MHz, CDCl
67.0, 140.1, 137.6, 124.6, 115.0, 60.5, 32.4, 31.2, 14.1. MS
3
): δ
+
(EI): 154 (M , 1), 126 (19), 111 (29), 81 (100), 53 (23), 41 (67).
-
1
1
Anal. Calcd for C
H, 9.14.
Eth yl 2-(6-Ca r beth oxy-6-h ep ten yl)a cr yla te (42). Pre-
9
H
14
O
2
: C, 70.10; H, 9.15. Found: C, 69.75;
(m), 1130 (m), 700 (s) cm
.
3
H NMR (200 MHz, CDCl ): δ
7.30-7.13 (m, 10H), 6.11 (s, 1H), 5.34 (s, 1H), 4.18 (q, J ) 7.0
1
3
Hz, 2H), 3.36-2.60 (m, 5H), 1.28 (t, J ) 7.1 Hz, 3H). C NMR
(50 MHz, CDCl ): δ 165.3, 142.1, 138.5, 137.1, 127.4, 126.4,
pared according to the typical procedure A in 77% overall yield
3
1
7
(
0.97 g) using ethyl R-(bromomethyl)acrylate (0.78 g, 4.05
126.1, 124.1, 123.7, 58.8, 45.0, 41.3, 36.6, 12.4. MS (EI): 294
(6), 203 (100), 181 (72), 157 (57), 129 (72), 114 (85), 86 (69), 55
mmol) and the acrylate 40 (0.80 g, 5.2 mmol). Reaction
conditions: -20 °C, 1 h. Purified by flash chromatography
(
(62). Anal. Calcd for C20
81.57; H, 7.61.
22 2
H O : C, 81.60; H, 7.53. Found: C,
hexanes/ether ) 19:1). IR (neat): 2930 (m), 1720 (s), 1630
m), 1180 (s), 1030 (m) cm
-
1 1
(
.
H NMR (200 MHz, CDCl
3
): δ
Dieth yl (1,2,3-Tr ip h en ylp r op yl)m a lon a te (51). Overall
yield (5.81 g, 90%) based on diethyl benzylidenemalonate (3.72
g, 15.0 mmol) and stilbene (3.0 g, 16.5 mmol). Reaction
conditions: rt, 3 h (B/Zn-exchange) and 0 °C, 24 h (reaction
with electrophile). Purified by flash chromatography (hexanes/
ether ) 4:1). The product was isolated as a 7:3 mixture of
diastereoisomers. IR (neat): 1750 (s), 1600 (m), 1500 (s), 1450
5
7
.85 (s, 2H), 5.23 (s, 2H), 3.93 (q, J ) 7.1 Hz, 4H), 2.03 (t, J )
1
3
.2 Hz, 4H), 1.30-1.05 (m, 6H), 1.03 (t, J ) 7.1 Hz, 6H).
): δ 167.0, 140.8, 123.9, 60.2, 31.5, 28.5,
8.0, 14.0. MS (EI): 268 (1), 223 (21), 194 (54), 121 (94), 81
100), 41 (62). Anal. Calcd for C15 : C, 67.14; H, 9.01.
Found: C, 66.94; H, 9.11.
C
NMR (75 MHz, CDCl
2
(
3
24 4
H O
-
1
1
Dieth yl (6-Ca r beth oxy-1-p h en yl-6-h ep ten yl)m a lon a te
3
(s), 1030 (s), 700 (s) cm . H NMR (200 MHz, CDCl ): δ 7.29
(
43). Prepared according to the typical procedure A in 83%
(m, 15H), 4.19 (m, 2H), 3.73 (m, 4H), 3.37 (m, 1H), 3.00-2.49
(m, 2H), 1.20 (t, J ) 7.1 Hz, 2.18H), 0.97 (t, J ) 7.2 Hz 0.82H),
overall yield (1.36 g) based on diethyl benzylidenemalonate
1.01 g, 4.05 mmol) and 40 (0.80 g, 5.2 mmol). Reaction
conditions: 0 °C, 10 h. Purified by flash chromatography
1
3
(
0.82 (t, J ) 7.2 Hz, 0.82H), 0.68 (t, J ) 7.1 Hz, 2.18H).
C
NMR (50 MHz, CDCl
3
): δ 168.6, 168.5, 167.6, 141.2, 140.2,
(
1
5
hexanes/ether ) 9:1). IR (neat): 2940 (s), 1760 (s), 1730 (s),
140.0, 139.4, 139.2, 137.0, 130.3, 130.0, 129.7, 129.2, 129.1,
128.8, 128.2, 128.1, 127.8, 127.6, 127.3, 127.2, 127.0, 126.7,
126.6, 125.9, 125.6, 61.7, 61.3, 61.1, 60.9, 56.2, 56.0, 51.7, 51.2,
49.0, 48.5, 39.7, 39.5, 14.1, 13.9, 13.7, 13.5. MS (EI): 339 (9),
250 (16), 181 (100), 131 (18), 103 (22), 84 (42). Anal. Calcd
-
1
1
030 (s), 700 (s) cm
3
. H NMR (200 MHz, CDCl ): δ 7.14 (m,
H), 5.99 (s, 1H), 5.33 (s, 1H), 4.16 (q, J ) 7.1 Hz, 2H), 4.08
(
q, J ) 7.1 Hz, 2H), 3.78 (q, J ) 7.1 Hz, 2H), 3.55 (d, J ) 11.0
Hz, 1H), 3.30 (m, 1H), 2.10 (m, 2H), 1.60 (m, 2H), 1.21 (t, J )
.2 Hz, 3H), 1.19 (t, J ) 7.2 Hz, 3H), 1.50-1.00 (m, 4H), 0.83
7
30 4
for C28H O : C, 78.11; H, 7.02. Found: C, 77.96; H, 7.41.
1
3
(t, J ) 7.1 Hz, 3H). C NMR (75 MHz, CDCl
3
): δ 168.2, 167.6,
2-(2-Ca r beth oxy-2-pr op en yl)bicyclo[2.2.1]h epta n e (52).
Overall yield (2.03 g, 93%) based on norbornene (1.15 g, 12
mmol) and ethyl R-(bromomethyl)acrylate17 (2.03 g, 10.5
mmol). Reaction conditions: rt, 40 h (B/Zn-exchange) and -20
°C, 1 h (reaction with electrophile). Purified by flash chro-
matography (hexanes/ether ) 19:1). The product was isolated
as a endo:exo (2:1) mixture of isomers. IR (neat): 2950 (vs),
1
4
2
66.9, 140.5, 128.1, 128.0, 126.6, 124.0, 61.2, 60.8, 60.2, 58.6,
5.3, 33.5, 31.3, 27.9, 26.4, 13.9, 13.8, 13.4. MS (EI): 404 (7),
44 (31), 198 (54), 131 (49), 91 (100), 41 (29). Anal. Calcd for
23 32 6
C H O : C, 68.29; H, 7.97. Found: C, 67.99; H, 8.01.
(
-)-(1S,2S)-6,6-Dim et h yl-2-(3-ca r b et h oxy-3-b u t en yl)-
bicyclo[3.1.1]h ep ta n e (47). Prepared according to the typi-
cal procedure A in 85% overall yield (0.99 g) based on (-)-â-
pinene (0.71 g, 5.2 mmol) and ethyl R-(bromomethyl)acrylate
2870 (s), 1720 (vs), 1630 (m), 1455 (m), 1175 (s) cm-
(200 MHz, CDCl ): δ 6.05 (s, 1H), 5.41 (s, 1H), 4.12 (q, J )
7.1 Hz, 2H), 2.30-1.90 (m, 5H), 1.80-0.90 (m, 8H), 1.22 (t, J
1
.
1
H NMR
1
7
3
(
0.86 g, 4.5 mmol). Reaction conditions: -20 °C, 1 h. Purified
by flash chromatography (hexanes/ether ) 95:5). [R]25
15.7 (c 2.61, benzene). IR (neat): 2935 (vs), 1719 (vs), 1630
13
)
) 7.1 Hz, 3H). C NMR (50 MHz, CDCl ): δ 167.2, 140.5,
139.7, 124.6, 124.2, 60.2, 40.4, 40.1, 39.8, 39.7, 38.4, 37.6, 37.0,
36.5, 35.0, 34.5, 29.9, 29.7, 28.6, 22.3, 14.0. MS (EI): 208 (5),
3
D
-
(
-
1
1
m), 1468 (m), 1184 (s), 1159 (s) cm
.
H NMR (300 MHz,
CDCl
2
3
): δ 6.03 (s, 1H), 5.41 (s, 1H), 4.12 (q, J ) 7.1 Hz, 2H),
114 (10), 95 (100), 67 (23). Anal. Calcd for C13
H, 9.68. Found: C, 74.90; H, 9.98.
20 2
H O : C, 74.96;
.26-2.16 (m, 3H), 1.91-1.76 (m, 6H), 1.50-1.37 (m, 4H), 1.22
13
(
t, J ) 7.2 Hz, 3H), 1.11 (s, 3H), 0.91 (s, 3H). C NMR (50
3 -( 2 -C a r b e t h o x y -2 -p r o p e n y l ) -( 1 S , 2 R ) -2 , 6 , 6 -
tr im eth ylbicyclo[3.1.1]h ep ta n e (53). Overall yield (1.26 g,
84%) based on R-pinene (0.95 g, 7.0 mmol) and ethyl R-(bro-
momethyl)acrylate17 (1.16 g, 6.0 mmol). Reaction conditions:
rt, 40 h (B/Zn-exchange) and -20 °C, 1 h (reaction with
electrophile). Purified by flash chromatography (hexanes/ether
) 19:1). The product was isolated as a 3:2 mixture of
diastereoisomers. IR (neat): 2900 (vs), 1720 (vs), 1630 (m),
MHz, CDCl ): δ 167.5, 141.6, 124.2, 60.7, 46.6, 41.7, 41.3, 38.9,
3
+
3
5
(
6.7, 33.9, 30.6, 28.4, 26.7, 23.5, 22.6, 14.4. MS (EI): 230 (M ,
), 177 (20), 161 (28), 133 (38), 121 (34), 93 (40), 82 (100), 69
: C, 76.75; H, 10.47. Found:
89). Anal. Calcd for C16
H
26
O
2
C, 76.57; H, 10.28.
(
-)-(1S,2S)-6,6-Dim eth yl-2-(2-oxo-2-ph en yleth yl)bicyclo-
3.1.1]h ep ta n e (48). Prepared according to the typical pro-
cedure A in 82% overall yield (0.93 g) based on (-)-â-pinene
0.71 g, 5.2 mmol) and benzoyl chloride (0.63 g, 4.5 mmol).
Reaction conditions: -20 °C, 4 h. Purified by flash chroma-
[
-
1
1
1160 (s), 1030 (m), 940 (m) cm
3
. H NMR (300 MHz, CDCl ):
(
δ 6.06 (s, 0.4H), 6.04 (s, 0.6H), 5.46 (s, 0.4H), 5.44 (s, 0.6H),
4.10 (m, 2H), 2.57-1.30 (m, 10H), 1.23 (t, J ) 7.1 Hz, 3H),
2
5
13
tography (hexanes/ether ) 9:1) [R]
IR (neat): 3064 (w), 2908 (s), 1686 (vs), 1448 (m), 751 (s), 690
(
7
D
) -19.0 (c 3.06, benzene).
1.10 (m, 3H), 0.94 (m, 5H), 0.86 (s, 1H). C NMR (75 MHz,
-
1
1
s) cm
.
H NMR (200 MHz, CDCl
3
): δ 7.87-7.83 (m, 2H),
(44) Kondo, T.; Akazome, M.; Tsuji, Y.; Watanabe, Y. J . Org. Chem.
1990, 55, 1286.
.45-7.35 (m, 3H), 3.05-3.01 (m, 2H), 2.75-2.55 (m, 1H),

8
240 J . Org. Chem., Vol. 61, No. 23, 1996
Langer et al.
CDCl
4
3
3
): δ 167.3, 167.2, 140.4, 139.8, 125.2, 124.4, 60.3, 49.0,
8.2, 43.5, 43.4, 41.9, 40.9, 39.3, 38.7, 36.7, 34.9, 34.7, 34.2,
4.0, 32.3, 27.9, 27.6, 23.0, 22.9, 21.3, 16.1, 14.1. MS (EI): 250
1.24 (m, 53H), 0.86 (t, J ) 7.0 Hz, 6H). 13C NMR (125 MHz,
3
318 K, CDCl ): δ 72.1, 37.6 (2C), 31.94, 31.91, 29.8-29.6 (16C),
29.35, 29.32, 25.7 (2C), 22.7 (2C), 14.1 (2C). MS (EI): 423 (1),
406 (18), 297 (39), 278 (2), 97 (60), 83 (100). Anal. Calcd for
(
1), 137 (73), 93 (59), 83 (100), 69 (66), 55 (68), 41 (41). Anal.
Calcd for C16 : C, 76.75; H, 10.42. Found: C, 76.54; H,
0.60.
-(Tr iisopr opylsilyloxy)-3-allylcyclopen tan e (54). Over-
H
26
O
2
C
29
H
60O: C, 82.00; H, 14.24. Found: C, 81.95; H, 14.13.
1
Typ ica l P r oced u r e B for th e On e-P ot Hyd r obor a tion ,
1
Bor on -Zin c Exch a n ge a n d Asym m etr ic Ad d ition to
Ald eh yd es. P r ep a r a tion of (R)-Eth yl 7-Hyd r oxy-2-m e-
t h ylen ed od eca n oa t e (56o) (en t r y 15 of Ta b le III). (a)
Hydroboration: A 50 mL two-neck flask equipped with an
argon inlet and a rubber septum was charged under argon with
ethyl 3-butenylacrylate (40) (1.47 g, 9.1 mmol). Diethylborane
(0.83 g, 9.0 mmol) was added at -10 °C over 15 min. The
reaction was allowed to slowly warm to rt and was stirred for
2 h. The volatiles were evaporated under vacuum (0.3 mmHg)
affording the crude hydroboration product (1.72 g).
(b) Boron-Zinc Exchange: To the organoborane prepared
above was added Et
2
Zn (2.0 mL, 19.5 mmol) at 0 °C. After
0.5 h, the excess diethylzinc and formed triethylborane were
evaporated (0.3 mmHg, 50 °C, 4 h). The resulting dialkylzinc
was diluted with toluene (4 mL) and was ready to use for the
next step.
all yield (0.18 g, 2.9 mmol, 72% yield) based on 4-(triisopro-
pylsilyl)-1-cyclopentene (0.90 g, 4.0 mmol) and allyl bromide
(4.84 g, 40 mmol). Reaction conditions: 0 °C, 3 h (B/Zn-
exchange) and 0 °C, 1 h (reaction with electrophile). Purifica-
tion by flash chromatography (hexanes/ether ) 10:1). The
product was obtained as a 3:2 mixture of diastereomers. IR
-
1
1
(neat): 2935 (s), 1465 8), 1060 (s), 885 (s), 680 (s) cm
.
H
NMR (300 MHz, CDCl
3
): δ 5.75 (m, 1H), 4.93 (m, 2H), 4.29
1
3
(
m, 1H), 2.25-1.05 (m, 9H), 1.00 (s, 21H). C NMR (75 MHz,
CDCl
3
): δ 138.3, 138.1, 114.8, 74.2, 74.0, 43.0, 42.6, 42.4, 41.0,
4
0.5, 37.4, 36.8, 36.1, 35.9, 35.8, 30.0, 29.7, 18.0, 12.2, 12.1.
MS (EI): 239 (60), 131 (87), 103 (62), 75 (100), 61 (55). Anal.
Calcd for C17 34OSi: C, 72.27; H, 12.13. Found: C, 72.12; H,
2.09.
Eicosa n a l (59). The aldehyde 59 was prepared according
H
1
2
5
(c) Asymmetric addition: A suspension of (1R,2R)-1,2-bis-
to the procedure developed by Corey. A suspension of PCC
0.72 g, 3.3 mmol) and Celite (2 g) in CH Cl (5 mL) was cooled
to 0 °C, and eicosanol (58) (0.90 g, 3.0 mmol) in CH Cl (10
(trifluoromethanesulfonamido)cyclohexane (55) (42 mg, 0.112
(
2
2
mmol) and titanium(IV) isopropoxide (0.80 g, 2.81 mmol) in
toluene (1 mL) was warmed to 50 °C for 0.5 h and cooled to
2
2
mL) was added. After 10 h of stirring at rt, the brown slurry
was filtered over a short silica column which was eluted with
-60 °C. The dialkylzinc prepared above was added via
syringe, and the resulting yellowish-green reaction mixture
was warmed to -20 °C and was stirred for 20 min at this
temperature. Hexanal (140 mg, 1.40 mmol) was added and
the reaction mixture was stirred at this temperature for 12 h.
It was quenched with a saturated aqueous NH4Cl solution (50
mL), and the precipitate formed was dissolved by adding
aqueous HCl (10%). The aqueous phase was extracted with
ether (2 × 50 mL). The combined organic phase was dried
CH
2
Cl
9 (0.84 g, 94% yield) as a colorless solid (mp 50-51 °C; lit.:
7-79 °C). IR (KBr): 2920 (vs), 2740 (w), 1710 (vs), 1470 (s),
2
(400 mL) affording after evaporation of the solvents
4
5
5
7
1
1
410 (m), 715 (s), 700 (m). H NMR (200 MHz, CDCl ): δ 9.72
3
(
(
t, J ) 1.8 Hz, 1H), 2.38 (td, J ) 7.3, 1.9 Hz, 2H), 1.60-1.45
13
m, 2H), 1.40-1.05 (m, 32H), 0.84 (t, J ) 6.5 Hz, 3H).
C
NMR (50 MHz, CDCl
3
): δ 202.7, 43.9, 31.9, 30.0 (9C), 29.6,
+
2
2
9.4, 29.3 (2C), 29.1, 22.7, 22.0, 14.1. MS (EI): 296 (M , 1),
78 (9), 96 (49), 82 (84), 68 (56), 57 (100), 43 (98). Anal. Calcd
40O: C, 81.01; H, 13.60. Found: C, 81.02; H, 13.53.
R)-1-Br om o-6-p en ta cosa n ol (60). Prepared according to
4
(MgSO ), and evaporating of the solvents afforded a crude oil
which was purified by chromatography (hexanes/ether ) 3:1)
for C20
H
leading to analytically pure 56o (257 mg, 72% yield, 95% ee).
(
2
5
[
R]
An a lytica l Da ta of Com p ou n d s 56a -w of Ta ble III
P r ep a r ed Accor d in g to th e Typ ica l P r oced u r e B. (S)-
-P h en yl-1-n on a n ol (56a ). Yield (495 mg, 87%, 92% ee)
D
) +0.3 (c 3.34, CHCl
3
).
the typical procedure B (see below). Yield (310 mg, 69%, 92%
ee) based on 5-bromo-1-pentene (4e) (2.24 g, 15.0 mmol)
(
Ca u tion ! Bis(5-bromopentyl)zinc may decompose in an
1
explosive manner at higher temperatures. Reaction temper-
atures below 10 °C and a protecting shield should be used.)
and eicosanal (59) (300 mg, 1.01 mmol). Reaction conditions:
ether, 0 °C, 12 h. Purified by chromatography (hexanes/ether
based on octene (1.25 g, 10.2 mmol) and benzaldehyde (275
mg, 2.60 mmol). Purified by chromatography (hexanes/ether
)
10:1). The enantiomeric excess was determined by integra-
1
tion of the H NMR signals of the (S)-O-acetylmandelic ester
5
:1) and isolated as a colorless solid (mp 63-64 °C). The
2
5
1
derivative at δ 5.96 (s) and 5.95 (s) (ratio 96:4). [R]
D
) -24.2
) -25.6 (c 3.12, CHCl ). IR
(neat): 3350 (s), 3030 (w), 2920 (vs), 2860 (s), 1450 (m), 1030
enantiomeric excess was determined by integration of the H
1g
25
(c 6.60, CHCl
3
); lit.:2 [R]
D
3
NMR signals of the (S)-O-acetylmandelic ester derivative at
δ 3.38 (t) and 3.22 (t) (ratio 96:4). [R]
IR (KBr): 3320 (m), 2930 (vs), 2860 (s), 1470 (m), 720 (w). H
2
5
D
) +1.0 (c 0.99, CHCl1
3
).
1
(m). H NMR (200 MHz, CDCl
3
): δ 7.33-7.24 (m, 5H), 4.66
(
(
t, J ) 6.6 Hz, 1H), 1.97 (s, 1H), 1.75-1.67 (m, 2H), 1.39-1.18
NMR (200 MHz, CDCl
3
): δ 3.57 (s, 1H), 3.40 (t, J ) 7.3 Hz,
1
3
m, 12H), 0.86 (t, J ) 7.1 Hz, 3H).
C NMR (75 MHz,
2
H), 1.89-1.79 (m, 3H), 1.47-1.14 (m, 42H), 0.86 (t, J ) 6.2
1
3
CDCl
9.5 (2C), 29.2, 25.8, 22.6, 14.1. MS (EI): 220 (M , 1), 107
100), 77 (30), 57 (18). Anal. Calcd for C15 24O: C, 81.76; H,
0.98. Found: C, 81.68; H, 11.15.
3
): δ 145.0, 128.4 (2C), 127.4, 125.9 (2C), 74.7, 39.1, 31.8,
Hz, 3H). C NMR (50 MHz, CDCl
2.7, 31.9, 29.7 (13C), 29.4, 28.2, 25.6, 24.8, 22.7, 14.1. MS
EI): 430 (6), 428 (6), 297 (99), 179 (82), 97 (66), 69 (62), 57
100). Anal. Calcd for C25 51BrO: C, 67.09; H, 11.48.
3
): δ 71.8, 37.6, 37.2, 33.9,
+
2
(
1
3
(
(
H
H
(
S)-(E)-4-Tetr a d ecen -6-ol (56b). Yield (291 mg, 75%, >
Found: C, 66.97; H, 11.36.
S)-10-Non a cosa n ol (57). To Bu
mL) prepared from n-BuLi (1.4 M solution in hexanes 1.4 mL,
2
7
96% ee) based on octene (2.64 g, 23.5 mmol) and hexanal (180
(
2
Cu(CN)Li
2
in THF (1
mg, 1.83 mmol). Reaction conditions: rt, 12 h, using Ti(Ot-
3
0
Bu)
1
4
.
Purification by chromatography (hexanes/ether ) 10:
2
mmol) and CuCN (89 mg, 1.0 mmol) was added at -60 °C
). The enantiomeric excess was determined by integration
of the H NMR signals at δ 5.89 (s) and 5.65 (m) of the (S)-
(R)-1-bromo-6-pentacosanol (60) (89 mg, 0.20 mmol) in THF
1
(2 mL). The reaction mixture was warmed to 0 °C and stirred
2
5
O-acetylmandelic ester derivative (ratio: >98:<2). [R]
1.6 (c 5.49, CHCl ). IR (neat): 3350 (s), 2930 (s), 2840 (s),
470 (m), 1385 (w), 970 (m). H NMR (200 MHz, CDCl ): δ
D
)
for 1 h. After the usual workup, the crude product was
purified by chromatography (hexanes/ether/CHCl 10:1:1) af-
fording the desired product as a colorless solid (78 mg, 95%;
-
1
3
3
1
3
4
6
25
5.61 (dt, J ) 15.3, 6.4 Hz, 1H), 5.43 (ddt, J ) 15.3, 6.9, 1.0 Hz,
mp 80-80.5 °C, lit.: 81-81.5 °C). [R]
D
) 0.0 (c 1.05, CHCl
) 2.18 (c 1.1, CHCl ). IR
KBr): 3340 (m), 3240 (m), 2920 (vs), 2850 (m), 1470 (m), 720
3
);
4
6
25
25
1H), 4.01 (m, 1H), 1.99 (q, J ) 7.0 Hz, 2H), 1.48-1.18 (m, 17H),
lit.: [R]
D
) 0 (c 2.5, CHCl
3
), [R]
D
3
0
.92-0.83 (m, 6H). 13C NMR (50 MHz, CDCl
): δ 133.3, 131.8,
3
(
(
1
73.2, 37.3, 34.2, 31.8, 29.5, 29.2, 25.5 (2C), 22.6, 22.3, 14.1,
m). H NMR (500 MHz, 318 K, CDCl
3
): δ 3.55 (s, 1H), 1.44-
+
1
3.6. MS (EI): 212 (M , 1), 194 (1), 99 (94), 57 (100), 43 (13).
Anal. Calcd for C14
H, 13.24.
H28O: C, 79.18; H, 13.29. Found: C, 79.23;
(
45) (a) Dominguez, X. A.; Barragan, V. J . Org. Chem. 1965, 30,
2
1
049. (b) Dave, P.; Byun, H.-S.; Engel, R. Synth. Commun. 1986, 16,
(
S)-(E)-3-Meth yl-2-d od ecen -4-ol (56c). Yield (250 mg,
343.
6
2%, >96% ee) based on octene (2.22 g, 19.8 mmol) and (E)-
(46) (a) Bentley, H. R.; Henry, J . A.; Irvine, D. S.; Mukerji, D.;
Spring, F. S. J . Chem. Soc. 1955, 596. (b) Beckmann, S.; Sch u¨ hle, H.
Z. Naturforsch. 1968, 23b, 471.
2-methyl-2-butenal (170 mg, 2.02 mmol). Purification by
chromatography (hexanes/ether ) 10:1). The enantiomeric

Functionalized Dialkylzincs via a Boron-Zinc Exchange
J . Org. Chem., Vol. 61, No. 23, 1996 8241
1
excess was determined by integration of the H NMR signals
and 3.89 (t) of the (S)-O-acetylmandelic ester derivative (ratio
at δ 5.23 (q) and 5.44 (q) of the (S)-O-acetylmandelic ester
96.5:3.5). [R]25
) -22.4 (c 3.17, benzene). IR (neat): 3430
1
D
2
5
derivative (ratio >98:<2). [R]
D
) -2.2 (c 4.16, CHCl
3
). IR
(m), 2960 (vs), 1710 (vs), 1290 (s), 1160 (s), 760 (m). H NMR
(200 MHz, CDCl ): δ 7.34-7.26 (m, 5H), 4.70-4.65 (m, 1H),
4.08-4.02 (m, 2H), 2.10 (s, 1H), 1.88-1.60 (m, 4H), 1.17 (s,
(
neat): 3350 (m), 2925 (vs), 2860 (s), 1470 (m), 1380 (m), 1005
3
1
(
m). H NMR (200 MHz, CDCl
3
): δ 5.46-5.40 (m, 1H), 3.95
1
3
(
3
3
t, J ) 6.6 Hz, 1H), 1.59-1.46 (m, 9H), 1.25 (s, 12H), 0.86 (m,
3
9H). C NMR (50 MHz, CDCl ): δ 178.6, 144.5, 128.5 (2C),
1
3
H). C NMR (50 MHz, CDCl
3
): δ 138.3, 120.7, 78.1, 34.8,
127.6, 125.8 (2C), 74.0, 64.1, 38.7, 35.3, 27.2 (3C), 25.1. MS
+
1.9, 29.6, 29.5, 29.3, 25.9, 22.6, 14.1, 13.0, 10.8. MS (EI): 198
(EI): 250 (M , 3), 120 (53), 107 (96), 103 (91), 57 (100). HRMS.
+
(
M , 2), 180 (16), 95 (44), 85 (100), 82 (33), 81 (44), 68 (55).
22 3
Calcd for C15H O : 250.1569. Found: 250.1561.
Anal. Calcd for C13
H, 13.22.
H
26O: C, 78.72; H, 13.21. Found: C, 78.82;
(S)-1-Cycloh exyl-4-p iva loxy-1-bu ta n ol (56i). Yield (85
mg, 22%, 78% ee) based on allyl pivalate (4.95 g, 34.8 mmol)
and cyclohexanecarboxaldehyde (170 mg, 1.52 mmol). Purified
by chromatography (hexanes/ether ) 3:1). The enantiomeric
(
S)-1-P h en yl-1-u n d eca n ol (56d ). Yield (500 mg, 88%, >
6% ee) based on decene (3.19 g, 22.8 mmol) and benzaldehyde
255 mg, 240 mmol). Reaction conditions: ether, 0 °C.
9
(
1
excess was determined by integration of the H NMR signals
Purification by chromatography (hexanes/ether ) 10:1). The
at δ 3.99 (m) and 3.75 (m) of the (S)-O-acetylmandelic ester
1
25
enantiomeric excess was determined by integration of the H
derivative (ratio 89:11). [R]
D
3
) -5.0 (c 2.61, CHCl ). IR
1
NMR signals at δ 5.98 (s) and 5.96 (s) of the (S)-O-acetylman-
(neat): 3440 (m), 2925 (vs), 1730 (vs), 1290 (s), 1160 (s).
NMR (200 MHz, CDCl ): δ 4.06 (t, J ) 6.0 Hz, 2H), 3.38-
3.32 (m, 1H), 1.78-1.10 (m, 16H), 1.17 (s, 9H). C NMR (50
MHz, CDCl ): δ 178.6, 75.7, 64.4, 43.7, 38.7, 30.3, 29.2, 27.8,
27.2 (3C), 26.5, 26.3, 26.1, 25.2. MS (EI): 248 (1), 103 (39),
H
2
5
delic ester derivative (ratio >98:<2). [R]
D
) -20.1 (c 6.71,
3
1
3
3
CHCl ). IR (neat): 3450 (s), 3065 (w), 2920 (vs), 2850 (s), 1445
1
(
m), 1025 (m). H NMR (300 MHz, CDCl
3
): δ 7.37-7.28 (m,
3
5
0
1
2
H), 4.68 (t, J ) 6.6 Hz, 1H), 1.90 (s, 1H), 1.83-1.27 (m, 18H),
1
3
.91 (t, J ) 6.5 Hz, 3H). C NMR (75 MHz, CDCl
3
): δ 145.0,
95 (28), 71 (100), 57 (53). Anal. Calcd for C15
H, 11.01. Found: C, 69.89; H, 10.70.
28 3
H O : C, 70.27;
28.3 (2C), 127.3, 125.9 (2C), 74.6, 39.1, 31.9, 29.5-29.2 (5C),
+
5.8, 22.6, 14.1. MS (EI): 248 (M , 3), 107 (100), 91 (13), 79
(S)-1-(1-Cycloh exen yl)-4-pivaloxy-1-pen tan ol (56j). Yield
(272 mg, 52%, 95% ee) based on 3-butenyl pivalate (2.52 g,
16.1 mmol) and cyclohexenecarboxaldehyde (215 mg, 1.95
mmol). Purified by chromatography (hexanes/ether ) 5:1).
The enantiomeric excess was determined by integration of the
(37), 41 (15). Anal. Calcd for C17H28O: C, 82.20; H, 11.36.
Found: C, 82.15; H, 11.38.
(
S)-1-(1-Cycloh exen yl)-1-u n d eca n ol (56e). Yield (350
mg, 73%, >96% ee) based on decene (2.09 g, 14.9 mmol) and
cyclohexenecarboxaldehyde (210 mg, 1.91 mmol). Purification
by chromatography (hexanes/ether ) 20:1). The enantiomeric
1
H NMR signals at δ 5.45 (s) and 5.67 (s) of the (S)-O-
2
5
acetylmandelic ester derivative (ratio 97.5:2.5). [R]
D
) +2.5
1
excess was determined by integration of the H NMR signals
(c 4.73, CHCl
(s), 1190 (s), 1030 (m). H NMR (200 MHz, CDCl
1H), 4.03 (t, J ) 6.5 Hz, 2H), 3.93 (t, J ) 6.6 Hz, 1H), 2.00 (s,
3
). IR (neat): 3420 (s), 2920 (vs), 1720 (s), 1290
1
at δ 5.46 (m) and 5.67 (m) of the (S)-O-acetylmandelic ester
3
): δ 5.62 (s,
2
5
derivative (ratio >98:<2). [R]
D
3
) +1.8 (c 11.9, CHCl ). IR
1
3
(
neat): 3340 (s), 2920 (vs), 2855 (s), 1440 (m), 920 (m), 840
w), 800 (w). H NMR (300 MHz, CDCl
t, J ) 6.7 Hz, 1H), 2.05-1.84 (m, 5H), 1.64-1.42 (m, 6H),
.23 (s, 16H), 0.85 (t, J ) 6.7 Hz, 3H). C NMR (75 MHz,
): δ 140.1, 122.9, 76.7, 34.8, 31.9, 29.6 (4C), 29.3, 25.8,
4.9, 23.3, 22.7 (3C), 14.0. MS (EI): 252 (M , 3), 234 (21),
35 (30), 121 (24), 111 (83), 107 (72), 94 (100). Anal. Calcd
32O: C, 80.89; H, 12.78. Found: C, 80.64; H, 12.60.
S)-[(1S,2S)-6,6-Dim eth ylbicyclo[3.1.1]h ept-2-ylm eth yl]-
5H), 1.66-1.23 (m, 10H), 1.16 (s, 9H).
CDCl ): δ 178.6, 139.7, 123.3, 76.5, 64.2, 38.7, 34.2, 28.5, 27.2
(3C), 25.0, 23.2, 22.6 (2C), 22.2. MS (EI): 250 (1), 166 (27),
C NMR (50 MHz,
1
(
3
): δ 5.60 (s, 1H), 3.90
3
(
1
1
3
111 (53), 67 (56), 57 (100), 41 (65). Anal. Calcd for C16
C, 71.60; H, 10.51. Found: C, 71.65; H, 10.66.
28 3
H O :
CDCl
3
+
2
1
(S)-11-P iva loxy-4-u n d ecen -6-ol (56k ). Yield (261 mg,
41%, 95% ee) using 4-pentenyl pivalate (2.81 g, 16.5 mmol)
and (E)-2-hexenal (230 mg, 2.34 mmol). Reaction conditions:
for C17
H
(
4
rt, Ti(Ot-Bu ). Purified by chromatography (hexanes/ether )
p h en ylm eth a n ol (56f). Yield (70 mg, 17%, >96% de) as a
colorless solid (mp 59-60 °C) using (-)-â-pinene (2.56 g, 18.8
mmol) and benzaldehyde (185 mg, 1.74 mmol). Purification
by chromatography (hexanes/ether ) 10:1). The diastereo-
meric excess was determined by integration of the 1H NMR
signals at δ 0.83 (s) and 0.94 (s) of the (S)-O-acetylmandelic
5:1). The enantiomeric excess was determined by integration
1
of the H NMR signals at δ 4.01 (t) and 3.91 (t) of the (S)-O-
2
5
acetylmandelic ester derivative (ratio >97.5:<2.5). [R]
D
)
-0.2 (c 4.26, CHCl
3
). IR (neat): 3340 (m), 2940 (vs), 1730 (vs),
1
1485 (s), 1285 (s), 1160 (s). H NMR (200 MHz, CDCl
3
): δ
5.60 (dt, J ) 15.4, 6.6 Hz, 1H), 5.41 (dd, J ) 15.4, 7.0 Hz, 1H),
4.00 (t, J ) 6.7 Hz, 3H), 1.97 (q, J ) 7.0 Hz, 2H), 1.63-1.31
2
5
ester derivative (ratio >98:<2). [R]
D
3
) -40.5 (c 2.79, CHCl ).
1
3
IR (neat): 3300 (s), 3050 (w), 2910 (s), 1460 (m), 1025 (m),
65 (m). H NMR (200 MHz, CDCl
(m, 11H), 1.16 (s, 9H), 0.87 (t, J ) 7.3 Hz, 3H). C NMR (50
1
7
4
3
3
): δ 7.34-7.18 (m, 5H),
3
MHz, CDCl ): δ 178.6, 133.1, 132.0, 73.0, 64.3, 38.7, 37.1, 34.2,
+
.64 (m, 1H), 2.30-2.19 (m, 2H), 1.95-0.74 (m, 10H), 1.13 (s,
28.6, 27.2 (3C), 25.9, 25.1, 22.3, 13.6. MS (EI): 270 (M , 1),
252 (1), 125 (25), 103 (99), 99 (61), 85 (29), 57 (100). Anal.
1
3
H), 0.95 (s, 3H). C NMR (50 MHz, CDCl ): δ 145.4, 128.4
3
(
2
1
2C), 127.4, 125.8 (2C), 72.7, 47.5, 47.1, 41.3, 38.7, 37.3, 33.7,
Calcd for C16
11.30.
30 3
H O : C, 71.07; H, 11.18. Found: C, 71.18; H,
+
8.1, 26.4, 23.3, 22.2. MS (EI): 244 (M , 3), 226 (12), 159 (22),
22 (41), 107 (100), 105 (46), 79 (75). Anal. Calcd for
(S)-2-Meth yl-10-p iva loxy-4-d eca n ol (56l). Yield (407 mg,
60%, 90% ee) using 5-hexenyl pivalate (3.67 g, 20.0 mmol) and
3-methylbutanal (215 mg, 2.50 mmol). Purified by chroma-
tography (hexanes/ether ) 5:1). The enantiomeric excess was
C
17
H
24O: C, 83.55; H, 9.90. Found: C, 83.65; H, 9.88.
(
S)-Cycloh exylp h en ylm eth a n ol (56g). Yield (290 mg,
6
7%, 80% ee) as a colorless solid (mp 66 °C) using cyclohexene
1
(
1.54 g, 18.8 mmol) and benzaldehyde (240 mg, 2.26 mmol).
determined by integration of the H NMR signals at δ 4.00 (t)
2
5
Purified by chromatography (hexanes/ether ) 10:1). [R]
-
D
)
and 3.94 (t) of the (S)-O-acetylmandelic ester derivative (ratio
36.0 (c 2.25, ether). The enantiomeric excess was determined
95:5). [R]25
D
) +6.1 (c 2.31, CHCl
(vs), 1725 (vs), 1370 (m), 1290 (m), 1170 (s). H NMR (200
MHz, CDCl ): δ 4.02 (t, J ) 6.6 Hz, 2H), 3.64 (s, 1H), 1.74-
1.15 (m, 14H), 1.16 (s, 9H), 0.89 (d, J ) 6.6 Hz, 3H), 0.86 (d,
3
). IR (neat): 3400 (m), 2920
1
1
by integration of the H NMR signals at δ 5.46 (d) and 5.48
d) of the (S)-O-acetylmandelic ester derivative (ratio 90:10).
IR (KBr): 3413 (s), 3087 (w), 2917 (vs), 2849 (s), 1444 (m),
(
3
1
13
7
(
65 (m), 698 (m). H NMR (200 MHz, CDCl
3
): δ 7.34-7.19
J ) 6.6 Hz, 3H). C NMR (50 MHz, CDCl ): δ 178.6, 69.9,
64.4, 46.9, 38.7, 37.9, 29.3, 28.5, 27.2 (3C), 25.9, 25.5, 24.6,
23.5, 22.1. MS (EI): 215 (6), 113 (20), 103 (100), 85 (37), 69
3
1
3
m, 5H), 4.31 (d, J ) 7.1 Hz, 1H), 1.99-0.90 (m, 12H).
C
NMR (50 MHz, CDCl ): δ 143.6, 128.1 (2C), 127.3, 126.6 (2C),
7
1
3
+
9.3, 44.9, 29.2, 28.8, 26.4, 26.0, 25.9. MS (EI): 190 (M , 49),
07 (100), 79 (35), 41 (13). Anal. Calcd for C13 18O: C, 82.06;
(38), 57 (84). Anal. Calcd for C16
Found: C, 70.44; H, 11.73.
32 3
H O : C, 70.54; H, 11.84.
H
H, 9.53. Found: C, 81.92; H, 9.76.
S)-1-P h en yl-4-p iva loxy-1-bu ta n ol (56h ). Yield (280 mg,
0%, 93% ee) based on allyl pivalate (4.95 g, 34.8 mmol) and
(S)-Eth yl 7-(4-Cya n op h en yl)-7-h yd r oxy-2-m eth ylen e-
h ep ta n oa te (56m ). Yield (437 mg, 69%, 80% ee) using 40
(2.16 g, 14.0 mmol) and 4-cyanobenzaldehyde (286 mg, 2.20
mmol). Purified by chromatography (hexanes/ether ) 3:1).
The enantiomeric excess was determined by integration of the
(
7
benzaldehyde (170 mg, 1.60 mmol). Purified by chromatog-
raphy (hexanes/ether ) 3:1). The enantiomeric excess was
1
1
determined by integration of the H NMR signals at δ 4.03 (t)
H NMR signals at δ 5.46 (m) and 5.38 (m) of the (S)-O-

8
242 J . Org. Chem., Vol. 61, No. 23, 1996
Langer et al.
2
5
acetylmandelic ester derivative (ratio 90:10). [R]
D
) -10.5
(S)-5-(ter t-Bu tyld im eth ylsiloxy)-1-(cycloh exen -1-yl)-1-
p en ta n ol (56r ). Yield (280 mg, 63%, 94% ee) based on 4-(tert-
butyldimethylsiloxy)-1-butene (1.86 g, 10.0 mmol) and cyclo-
hexenecarboxaldehyde (165 mg, 1.50 mmol). Purified by
chromatography (hexanes/ether ) 8:1). The enantiomeric
(
(
(
c 3.34, CHCl
3
). IR (neat): 3480 (s), 2940 (vs), 2230 (s), 1720
vs), 1630 (m), 840 (m). H NMR (200 MHz, CDCl
1
3
): δ 7.57
d, J ) 8.0 Hz, 2H), 7.40 (d, J ) 8.4 Hz, 2H), 6.07-6.06 (m,
1
7
(
H), 5.72-5.71 (m, 1H), 4.68 (t, J ) 6.0 Hz, 1H), 4.13 (q, J )
1
.2 Hz, 2H), 2.70 (s, 1H), 2.23 (t, J ) 7.0 Hz, 2H), 2.05-1.20
excess was determined by integration of the H NMR signals
1
3
m, 6H), 1.24 (t, J ) 7.2 Hz, 3H). C NMR (50 MHz, CDCl
3
):
at δ 5.46 (s) and 5.67 (s) of the (S)-O-acetylmandelic ester
δ 167.2, 150.4, 140.5, 132.1 (2C), 126.4 (2C), 124.6, 118.8,
10.8, 73.4, 60.5, 38.8, 31.6, 28.1, 25.0, 14.1. MS (EI): 269
1), 156 (7), 120 (12), 105 (43), 91 (100), 77 (34). Anal. Calcd
for C17 : C, 71.06; H, 7.37; N, 4.87. Found: C, 71.01;
H, 7.53; N, 5.18.
S)-Eth yl 7-Hyd r oxy-7-[(S)-4-isop r op en ylcycloh exen -
-yl]h ep ta n oa te (56n ). Yield (210 mg, 71%, 85% de) based
derivative (ratio 97:3). [R]25
D
3
) 2.0 (c 3.0, CHCl ). IR (neat):
1
(
3340 (s), 2920 (vs), 1460 (m), 1250 (s), 1100 (s), 840 (s), 770
1
(m). H NMR (200 MHz, CDCl
6.4 Hz, 1H), 3.58 (t, J ) 6.4 Hz, 2H), 2.05-1.14 (m, 15H), 0.86
(s, 9H), 0.03 (s, 6H). 13C NMR (50 MHz, CDCl
3
): δ 5.60 (s, 1H), 3.91 (t, J )
H
21NO
3
3
): δ 139.9, 123.0,
(
76.6, 63.1, 34.5, 32.7, 25.9 (3C), 24.9, 23.3, 22.6 (2C), 22.1, 18.3,
+
1
-5.3 (2C). MS (EI): 298 (M , 1), 149 (60), 131 (36), 107 (39),
93 (54), 81 (93), 75 (100). Anal. Calcd for C17
68.40; H, 11.48. Found: C, 68.24; H, 11.50.
on 40 (0.88 g, 5.70 mmol) and (S)-perillaldehyde (150 mg, 0.97
mmol). Purified by chromatography (hexanes/ether ) 3:1).
The diastereomeric excess was determined by integration of
the H NMR signals at δ 6.10-6.12 (m) and 6.07-6.09 (m) of
the (S)-O-acetylmandelic ester derivative (ratio 92.5:7.5).
34 2
H O Si: C,
(S)-7-Br om o-1-(4-cya n op h en yl)-1-h ep ta n ol (56s). Yield
(503 mg, 85%, 88% ee) based on 6-bromo-1-hexene (2.61 g, 16.0
mmol) and 4-cyanobenzaldehyde (262 mg, 2.00 mmol). Puri-
fied by chromatography (hexanes/ether ) 3:1). The enantio-
1
2
5
[
1
R]
D
) -44.7 (c 4.70, CHCl
715 (s), 1635 (m), 1285 (s), 990 (m). H NMR (200 MHz,
): δ 6.10-6.08 (m, 1H), 5.61 (s, 1H), 5.48-5.46 (m, 1H),
.68-4.66 (m, 2H), 4.15 (q, J ) 7.2 Hz, 2H), 3.93 (t, J ) 6.4
Hz, 1H), 2.30-1.41 (m, 16H), 1.69 (s, 3H), 1.25 (t, J ) 7.1 Hz,
3
). IR (neat): 3400 (m), 2940 (vs),
1
1
meric excess was determined by integration of the H NMR
CDCl
3
signals at δ 3.37 (t) and 3.32 (t) of the (S)-O-acetylmandelic
4
ester derivative (ratio 94:6). [R]25
D
3
) -14.8 (c 9.23, CHCl ).
IR (neat): 3430 (s), 2940 (vs), 2230 (s), 840 (m). 1H NMR (200
MHz, CDCl
1
3
3
1
2
1
H). C NMR (50 MHz, CDCl
3
): δ 167.2, 149.5, 140.8, 139.5,
24.2, 121.9, 108.5, 76.0, 60.4, 41.0, 34.7, 31.7, 30.3, 28.3, 27.3,
5.2, 23.9, 20.7, 14.1. MS (EI): 306 (M , 2), 288 (3), 156 (100),
49 (37), 133 (37), 105 (40), 91 (52). Anal. Calcd for
: C, 74.47; H, 9.87. Found: C, 74.33; H, 9.91.
R)-Eth yl 7-Hyd r oxy-2-m eth ylen ed od eca n oa te (56o).
3
): δ 7.57 (d, J ) 8.2 Hz, 2H), 7.41 (d, J ) 8.2 Hz,
2H), 4.71-4.65 (m, 1H), 3.35 (t, J ) 6.7 Hz, 2H), 2.30 (s, 1H),
+
13
1.82-1.64 (m, 4H), 1.41-1.31 (m, 6H). C NMR (50 MHz,
3
CDCl ): δ 150.2, 132.2 (2C), 126.44 (2C), 118.8, 110.9, 73.6,
+
C
19
H
30
O
3
38.9, 33.9, 32.5, 28.4, 27.9, 25.2. MS (EI): 297(M , 3), 295
+
(
(M , 3), 205 (7), 149 (5), 133 (16), 132 (100), 104 (15). Anal.
Yield (257 mg, 72%, 95% ee) based on 40 (1.47 g, 9.07 mmol)
Calcd for C14H18BrNO: C, 56.77; H, 6.12; N, 4.73. Found: C,
and hexanal (140 mg, 1.40 mmol). Purified by chromatography
56.42; H, 6.18; N, 4.69.
(
hexanes/ether ) 3:1). The enantiomeric excess was deter-
(S)-7-Br om o-1-cycloh exyl-1-h ep ta n ol (56t). Yield (60
mg, 11%, 60% ee) based on 6-bromo-1-hexene (2.61 g, 16.0
mmol) and cyclohexanecarboxaldehyde (222 mg, 2.0 mmol).
Purified by chromatography (hexanes/ether ) 5:1). The enan-
1
mined by integration of the H NMR signals at δ 5.48 (s) and
5
2
.37 (s) of the (S)-O-acetylmandelic ester derivative (ratio 97.5:
2
5
.5). [R]
D
3
) +0.3 (c 3.34, CHCl ). IR (neat): 3420 (m), 2930
1
1
(
vs), 1720 (vs), 1630 (m), 940 (m), 820 (w). H NMR (200 MHz,
CDCl ): δ 6.46 (m, 1H), 5.44 (m, 1H), 4.13 (q, J ) 7.1 Hz, 2H),
.50 (s, 1H), 2.26-2.20 (m, 2H), 1.86 (s, 1H), 1.60-1.20 (m,
tiomeric excess was determined by integration of the H NMR
3
signals at δ 3.37 (t) and 3.30 (t) of the (S)-O-acetylmandelic
3
1
ester derivative (ratio 80:20). [R]25
D
3
) -6.4 (c 2.81, CHCl ).
1
3
1
4H), 1.23 (t, J ) 7.2 Hz, 3H), 0.82 (t, J ) 6.0 Hz, 3H).
): δ 167.2, 140.8, 124.2, 71.60, 60.4, 37.3,
7.0, 32.8, 32.7, 28.4, 25.2, 25.1, 22.5, 14.0, 13.9. MS (EI): 238
4), 185 (21), 156 (45), 139 (100), 128 (28). Anal. Calcd for
C
IR (neat): 3350 (s), 2910 (vs), 2850 (s), 1450 (m), 1260 (m). H
NMR (200 MHz, CDCl ): δ 3.38 (t, J ) 6.7 Hz, 2H), 3.31 (m,
1H), 1.83-1.17 (m, 22H), 13C NMR (50 MHz, CDCl
): δ 76.0,
NMR (50 MHz, CDCl
3
(
C
3
3
3
43.5, 33.9, 33.8, 32.7, 29.2, 28.8, 28.1, 27.7, 26.5, 26.3, 26.1,
25.7. MS (EI): 260 (1), 258 (1), 195 (20), 193 (15), 113 (26),
15
H
28
O
3
: C, 70.27; H, 11.01. Found: C, 69.99; H, 11.07.
(
S)-1-P h en yl-4-(t r iisop r op ylsiloxy)-1-b u t a n ol (56p ).
95 (100). Anal. Calcd for C13
Found: C, 56.44; H, 9.13.
H25BrO: C, 56.32; H, 9.09.
Yield (365 mg, 60%, 50% ee) based on 3-triisopropylsiloxy-1-
propene (2.54 g, 11.8 mmol) and benzaldehyde (200 mg, 1.88
mmol). Purified by chromatography (hexanes/ether ) 10:1).
The enantiomeric excess was determined by integration of the
(R)-1-Br om o-7-d od eca n ol (56u ). Yield (409 mg, 77%, 90%
ee) based on 6-bromo-1-hexene (2.61 g, 16.0 mmol) and hexanal
(200 mg, 2.00 mmol). Purified by chromatography (hexanes/
ether ) 10:1 and then 5:1). The enantiomeric excess was
1
H NMR signals at δ 3.65 (t) and 3.49 (t) of the (S)-O-
2
5
1
acetylmandelic ester derivative (ratio 75:25). [R]
D
) -17.0
determined by integration of the H NMR signals at δ 3.38 (t)
(
(
7
3
(
c 3.23, CHCl
3
). IR (neat): 3370 (m), 2945 (s), 1470 (m), 1110
and 3.32 (t) of the (S)-O-acetylmandelic ester derivative (ratio
1
25
m), 885 (m), 760 (w), 700 (m). H NMR (200 MHz, CDCl
3
): δ
.32-7.19 (m, 5H), 4.70-4.63 (m, 1H), 3.72 (t, J ) 6.0 Hz, 2H),
.25 (s, 1H), 1.90-1.78 (m, 2H), 1.67-1.59 (m, 2H), 1.09-0.99
95:5). [R]
D
3
) -0.3 (c 7.71, CHCl ). IR (neat): 3350 (m), 2940
1
(vs), 2865 (s), 1470 (m), 1260 (m), 1020 (m), 720 (w). H NMR
(200 MHz, CDCl ): δ 3.53 (s, 1H), 3.37 (t, J ) 6.8 Hz, 2H),
1.86-1.79 (m, 5H), 1.39-1.27 (m, 14H), 0.86 (t, J ) 6.4 Hz,
3H). 13C NMR (50 MHz, CDCl
): δ 71.8, 37.4, 37.2, 33.9, 32.7,
3
1
3
m, 21H).
3
C NMR (50 MHz, CDCl ): δ 145.0, 128.2 (2C),
1
2
27.1, 125.8 (2C), 74.1, 63.6, 36.7, 29.3, 18.3 (6C), 11.9 (t, J )
9 Hz, 3C). MS (EI): 322 (M , 1), 131 (100), 91 (12), 75 (13).
3
+
31.8, 28.8, 28.1, 25.4, 25.3, 22.6, 14.0. MS (EI): 248 (2), 246
(2), 195 (29), 193 (28), 101 (78), 95 (57), 69 (22), 55 (96), 43
Anal. Calcd for C19
0.54; H, 10.45.
S)-5-(ter t-Bu t yld im et h ylsiloxy)-1-p h en yl-1-p en t a n ol
56q). Yield (360 mg, 82%, 92% ee) based on 4-(tert-butyldi-
methylsiloxy)-1-butene (1.86 g, 10.0 mmol) and benzaldehyde
159 mg, 1.50 mmol). Purified by chromatography (hexanes/
34 2
H O Si: C, 70.75; H, 10.62. Found: C,
7
(28), 41. Anal. Calcd for C12
Found: C, 54.33; H, 9.43.
H25BrO: C, 54.34; H, 9.50.
(
(
(S)-7-Iod o-1-p h en yl-1-h ep ta n ol (56v). Yield (330 mg,
58%, 86% ee) based on 6-iodo-1-hexene (3.46 g, 16.5 mmol) and
benzaldehyde (190 mg, 1.79 mmol). Purified by chromatog-
raphy (hexanes/ether ) 20:1 and then 6:1 and 1:1). The
(
ether ) 8:1 then 5:1). The enantiomeric excess was deter-
1
1
mined by integration of the H NMR signals at δ 3.57 (t) and
enantiomeric excess was determined by integration of the H
3
4
(
.42 (t) of the (S)-O-acetylmandelic ester derivative (ratio 96:
NMR signals at δ 3.15 (t) and 3.10 (t) of the (S)-O-acetylman-
2
5
25
). [R]
D
) -8.6 (c 0.7, EtOH). IR (neat): 3360 (m), 2940
delic ester derivative (ratio 93:7). [R]
D
3
) 14.6 (c 3.22, CHCl ).
1
vs), 2860 (s), 1470 (w), 1100 (s), 770 (m), 700 (m). H NMR
200 MHz, CDCl ): δ 7.32-7.18 (m, 5H), 4.58 (t, J ) 5.8 Hz,
H), 3.55 (t, J ) 6.5 Hz, 2H), 2.32 (s, 1H), 1.77-1.13 (m, 6H),
IR (neat): 3380 (s), 3040 (w), 2940 (vs), 2860 (s), 1495 (m),
(
3
1455 (m), 920 (m), 700 (s). 1H NMR (200 MHz, CDCl
3
): δ 7.33-
1
0
1
2
1
6
7.24 (m, 5H), 4.63 (t, J ) 6.1 Hz, 1H), 3.15 (t, J ) 6.9 Hz, 2H),
1
3
13
.85 (s, 9H), 0.00 (s, 6H). C NMR (50 MHz, CDCl
28.3 (2C), 127.3, 125.8 (2C), 74.4, 63.0, 38.7, 32.5, 25.9 (3C),
2.0, 18.2, -5.4 (2C). MS (EI): 257 (1), 147 (47), 117 (23),
07 (27), 105 (45), 75 (100). Anal. Calcd for C17
9.33; H, 10.27. Found: C, 69.49; H, 10.08.
3
): δ 144.9,
1.97 (s, 1H), 1.85-1.62 (m, 4H), 1.42-1.18 (m, 6H). C NMR
3
(50 MHz, CDCl ): δ 144.8, 128.4 (2C), 127.5, 125.8 (2C), 74.6,
+
38.9, 33.4, 30.3, 28.4, 25.6, 7.2. MS (EI): 318 (M , 2), 107
H
30
O
2
Si: C,
(100), 79 (17). Anal. Calcd for C13
Found: C, 49.10; H, 6.03.
H19IO: C, 49.07; H, 6.02.

Functionalized Dialkylzincs via a Boron-Zinc Exchange
S)-10-Iod o-2-m eth yl-4-d eca n ol (56w ). Yield (180 mg,
J . Org. Chem., Vol. 61, No. 23, 1996 8243
(
Ack n ow led gm en t. We thank the Deutsche Fors-
chungsgemeinschaft (SFB 260) and the Fonds der
Chemischen Industrie for the generous support of this
research. We thank the BASF AG (Ludwigshafen),
Witco AG (Bergkamen), Chemetall (Frankfurt), and
SIPSY (Avrill e´ , France) for generous gift of chemicals.
3
2
2%, 73% ee) based on 6-iodo-1-hexene (3.46 g, 16.5 mmol) and
-methylbutanal (160 mg, 1.85 mmol). Purified by chroma-
tography (hexanes/ether ) 20:1 and then 10:1). The enantio-
meric excess was determined by integration of the 1H NMR
signals at δ 3.16 (t) and 3.10 (t) of the (S)-O-acetylmandelic
2
5
ester derivative (ratio 86.5:13.5). [R]
D
3
) 5.5 ° (c 1.46, CHCl ).
IR (neat): 3350 (m), 2940 (vs), 2860 (s), 1465 (m), 1370 (w).
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
1
H NMR (200 MHz, CDCl
3
): δ 3.63 (s, 1H), 3.15 (t, J ) 7.0 Hz,
spectra of all new compounds (132 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
2
H), 1.85-1.63 (m, 3H), 1.43-1.13 (m, 11H), 0.88 (d, J ) 6.7
1
3
3
Hz, 3H), 0.87 (d, J ) 6.5 Hz, 3H). C NMR (50 MHz, CDCl ):
δ 69.7, 46.7, 37.8, 33.4, 30.4, 28.5, 25.3, 24.5, 23.4, 22.0, 7.2.
MS (EI): 280 (1), 241 (17), 196 (9), 155 (5), 97 (57), 87 (41), 80
(21), 69 (100), 57 (30), 43 (50). Anal. Calcd for C11
H23IO: C,
4
4.31; H, 7.77. Found: C, 44.54; H, 8.02.
J O961129N