Photoinduced synthesis of diorganozinc and organozinc iodide reagents [2]

Full text of DOI:10.1021/ja980318f

5114
J. Am. Chem. Soc. 1998, 120, 5114-5115
Scheme 1
Photoinduced Synthesis of Diorganozinc and
Organozinc Iodide Reagents
Andre´ B. Charette,* Andre´ Beauchemin, and
Jean-Franc¸ois Marcoux
De´partement de Chimie, UniVersite´ de Montre´al
Que´bec, Canada H3C 3J7
ReceiVed January 28, 1998
Scheme 2
In the past few years, organozinc derivatives have been found
to be increasingly useful reagents for carrying out organic
transformations.1 The relatively low reactivity of the carbon-
zinc bond toward electrophilic reagents has made them ideal
precursors to more reactive species via transmetalation reactions2
or Lewis acid-catalyzed addition reactions to carbonyl groups.3
Consequently, one significant advantage of these reagents is that
highly functionalized derivatives can be prepared. Although there
are several methods to prepare dialkylzincs (A) (R*2Zn where
R* is an enantiomercially pure group), they usually require excess
Et2Zn followed by a distillation to remove excess reactants and/
or the presence of a transition-metal catalyst (Scheme 1).4-6
Although mixed diorganozinc reagents (B) (R*ZnR′) have been
invoked as intermediates,7,8 very few methods for their clean
synthesis are available.9 Conversely, access to functionalized
organozinc halides (C) (R*ZnX) has been traditionally ac-
complished by the direct insertion of activated zinc into a carbon-
iodine bond,10 by treating an organolithium or Grignard reagent
with ZnX211 or, more recently, by a Pd-, Mn/Cu- or Ni-catalyzed
Et2Zn insertion into C-X bond.12
Table 1. Effect of Irradiation on the Conversion of 1 to 2
entry
x
solvent (temp °C)
t (h)
convsn to 2a (%)
1
2
3
4
5
1.0
1.0
2.0
10.0
1.0
CD2Cl2 (23)
neat (80)
neat (80)
48
48
48
6
<10
45 (3)b
70 (3)b
>90 (3)b
90
neat (80)
CD2Cl2 (23)c
3
a The conversion of 2 was determined by H NMR of the crude
reaction mixture. The remaining material was starting iodide 1 and
Et2Zn. b Mixed diorganozinc 2 was converted into 3 upon removal of
excess Et2Zn. c Reaction mixture was irradiated with a GE sunlamp
(275 W) in a pyrex NMR tube.
1
Our interest in the synthesis of chiral, functionalized zinc
carbenoid reagents (D) for the cyclopropanation reaction of
unfunctionalized olefins prompted us to devise a unified route to
diorganozincs (A, B) and organozinc iodides (C). Ideally, this
route would avoid the use of excess diethyl- or diisopropylzinc
reagent and/or the use of a transition metal as a catalyst. This is
an essential requirement since these additional species might
jeopardize the subsequent conversion of these reagents into chiral
zinc carbenoids (Scheme 2).13 The accessibility to pure and
homogeneous organozinc reagents is an essential first-step toward
the efficient synthesis of chiral zinc carbenoid reagents. Herein,
we report a new general route to diorganozinc reagents (A, B)
and organozinc iodides (C) that is based on the facile equilibration
of organozinc reagents and alkyl iodides under photochemical
conditions.
(1) (a) Knochel, P.; Langer, F.; Longeau, A.; Rottla¨nder, M.; Stu¨demann,
T. Chem. Ber. 1997, 130, 1021-1027. (b) Knochel, P.; Singer, R. D. Chem.
ReV. 1993, 93, 2117-2188.
(2) See, for example: Lipshutz, B. H.; Woo, K.; Gross, T.; Buzard, D. J.;
Tirado, R. Synlett 1997, 477-478 and references therein.
(3) Soai, K.; Niwa, S. Chem. ReV. 1992, 92, 833-856.
(4) Preparation of diorganozinc via an iodine-zinc exchange: (a) Rozema,
M. J.; Sidduri, A.; Knochel, P. J. Org. Chem. 1992, 57, 1956-1958. (b)
Micouin, L.; Knochel, P. Synlett 1997, 327-328.
(5) Preparation of diorganozinc from olefins via a nickel-catalyzed
hydrozincation: (a) Vettel, S.; Vaupel, A.; Knochel, P. Tetrahedron Lett. 1995,
36, 1023-1026. (b) Vettel, S.; Vaupel, A.; Knochel, P. J. Org. Chem. 1996,
61, 7473-7481.
Our initial target for this study was the mixed diorganozinc 2.
As expected, when iodide 114 was stirred with 1 equiv of
diethylzinc in CD2Cl2, less than 10% of the desired diorganozinc
(6) Preparation of homodialkylzincs via a boron-zinc exchange: (a)
Langer, F.; Devasagayaraj, A.; Chavant, P.-Y.; Knochel, P. Synlett 1994, 410-
412. (b) Langer, F.; Schwink, L.; Devasagayaraj, A.; Chavant, P.-Y.; Knochel,
P. J. Org. Chem. 1996, 61, 8229-8243.
1
was observed by H NMR (Table 1, entry 1).
Knochel has previously shown that the use of an excess Et2Zn
without any solvent at 80 °C is necessary to favorably induce
the equilibrium on the side of the more stable diorganozinc reagent
(or of the more volatile iodoethane). Accordingly, the exchange
reaction occurred quantitatively when 10 equiv of Et2Zn was used
to produce 2. Unfortunately, the mixed diorganozinc 2 was
completely converted into the diorganozinc reagent 3 upon
removal of excess Et2Zn and EtI (Table 1, entries 2-4). HoweVer,
we haVe found that a faVorable equilibrium occurred in solution
at room temperature with only 1 equiV of Et2Zn when a solution
of the iodide and Et2Zn in CH2Cl2 is irradiated at λ g 280 nm
(7) Knochel has postulated that mixed diorganozinc reagents were formed
as intermediates to homodiorganozinc reagents: (a) ref 4. (b) Micouin, L.;
Oestreich, M.; Knochel, P. Angew. Chem., Int. Ed. Engl. 1997, 36, 245-246.
(8) Mixed diorganozinc reagents are prone to undergo the following Schlenk
equilibrium: 2R*ZnR′ h R*2Zn + R′2Zn. However, when R* contains a
functional group that is electron-withdrawing or that can stabilize the zinc
center by an intramolecular chelate, the mixed diorganozinc should then be
favored over the two other species. For a discussion of the Schlenk equilibrium
of organozinc compounds, see: Charette, A. B.; Marcoux, J.-F. J. Am. Chem.
Soc. 1996, 118, 4539-4549 and references therein.
(9) A method for the preparation of TMSCH2ZnR has been reported
recently: (a) Berger, S.; Langer, F.; Lutz, C.; Knochel, P.; Mobley, T. A.;
Reddy, C. K. Angew. Chem., Int. Ed. Engl. 1997, 36, 1496-1498. (b) Lutz,
C.; Knochel, P. J. Org. Chem. 1997, 62, 7895-7898.
(13) Excess diethylzinc would obviously produce an achiral cyclopropana-
ting reagent whereas the presence of a catalytic amount of a transition metal
led to the formation of unsuitable reactive species: (a) Kanai, H.; Hiraki, N.;
Iida, S. Bull. Chem. Soc. Jpn. 1983, 56, 1025-1029. (b) Kanai, H.; Nishiguchi,
Y.; Matsuda, H. Bull. Chem. Soc. Jpn. 1983, 56, 1592-1597. (c) Takai, K.;
Kakiuchi, T.; Utimoto, K. J. Org. Chem. 1994, 59, 2671-2673.
(14) Prepared from the known diol in 4 steps (1. TBDMSCl, imidazole; 2.
BnBr, NaH; 3. TBAF, THF; 4. Tf2O, NaI, collidine, CH2Cl2, acetone 73%
overall yield). For the diol synthesis, see: Wala, R.; Zarnowki, J.; Antkowiak,
W. Z. Rocz. Chem. 1969, 43, 833-844.
(10) Rieke, R. D.; Li, P. T.-J.; Burns, T. P.; Uhm, S. T. J. Org. Chem.
1981, 46, 4323-4324.
(11) Boersma, J. In ComprehensiVe Organometallic Chemistry; Wilkinson,
G.; Stone, F. G. A.; Abel, E. W., Eds.; Pergamon Press: NY 1982; Vol 2, p
823-862.
(12) (a) Stadtmu¨ller, H.; Tucker, C. E.; Vaupel, A.; Knochel, P. Tetrahedron
Lett. 1993, 34, 7911-7914. (b) Klement, I.; Knochel, P.; Chau, K.; Cahiez,
G. Tetrahedron Lett. 1994, 35, 1177-1180. (c) Vaupel, A.; Knochel, P. J.
Org. Chem. 1996, 61, 5743-5753.
S0002-7863(98)00318-7 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/06/1998

Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 20, 1998 5115
(Table 1, entry 5).15 This spectacular rate enhancement for alkyl
group exchange is possible only between dialkylzincs and alkyl
iodides.16
Table 2. Synthesis of Organozinc Reagents from Alkyl Iodides
As a follow-up of this observation, several other alkyl iodides
were submitted to the reaction conditions to produce the mixed
diorganozinc reagents (B) (Table 2). In all the cases, control
experiments showed that less than 10% of the desired mixed
diorganozinc reagent was produced if an equimolar mixture of
the alkyl iodide and diethylzinc were stirred under these condition
but without irradiation. The alkyl group exchange occurred
smoothly and in very high yields with primary iodides containing
chelating groups upon irradiation (Table 2, entries 1-5).17 Even
a secondary iodide was transformed into the corresponding mixed
diorganozinc reagent in high yield under these conditions (Table
2, entry 2). In cases where the stability of the desired mixed
diorganozinc was comparable to that of the starting material, the
use of the more reactive diisopropylzinc led to an higher yield
for the mixed diorganozinc (Table 2, entries 8 and 9). Access to
the diorganozinc reagents (A) was achieved by irradiating a
solution containing 0.5 equiv of diethyl- or diisopropylzinc and
1 equiv of the alkyl iodide (Table 2, entries 10-13). The double
alkyl group exchange occurred rapidly with alkyl iodides contain-
ing chelating or basic groups (Table 2, entries 10 and 11). As
previously observed, the use of diisopropylzinc was necessary to
obtain high conversions with less reactive iodides.
We then turned our attention to the synthesis of organozinc
iodides using the same procedure. Gratifyingly, very high
conversions to organozinc iodides were observed if R2Zn (R )
Et, i-Pr) was substituted with EtZnI or i-PrZnI (Table 2, entries
14-20). The reaction times were usually longer that those
necessary for the synthesis of the diorganozinc reagents. This
observation is probably a consequence of the lower reactivity of
EtZnI (or i-PrZnI) compared to that of Et2Zn (or i-Pr2Zn) in this
exchange process. Generally, isopropylzinc iodide generally
produced higher yields of the corresponding alkylzinc iodide (see
Table 2, entries 16 vs 17 and 18 vs 19).
To further confirm the high conversion observed by NMR or
GC, two of these organozinc reagents were prepared on 1-mmol
scale and submitted to known transformations (eq 1-2). The
irradiation time had to be slightly longer for complete conversion
to the desired diorganozinc and the yields for these reactions were
similar to those reported in the literature for the same transforma-
tions.18
Application of this methodology to the synthesis of chiral zinc
carbenoid reagents is in progress and will be reported in due
course.
Acknowledgment. This research was supported by the NSERC
(Canada), an Alfred P. Sloan Research Fellow, Merck Frosst Canada,
F.C.A.R. (Que´bec), and the Universite´ de Montre´al. A.B. thanks the
1
a Conversions were determined by H NMR and/or GC analysis of
the crude reaction mixture using an internal standard. In all cases, any
remaining materials were identified to be the starting reagents. b <10%
conversions were observed in all the cases if the reactions were not
irradiated at g280 nm.
(15) The mixture was irradiated in a Pyrex NMR tube (λ g 280 nm) with
a GE sunlamp (275 W). Photoreactions could also be performed in Pyrex
flask or NMR tube (λ g 280 nm) using a Hanovia 450 W Hg medium-pressure
UV lamp in a water-cooled quartz immersion apparatus as the light source.
(16) The mechanism for the facile exchange is not known at this time but
it might involve the formation of an exciplex between the alkyl iodide and
diethylzinc. Both species were recovered unchanged when irradiated separately.
For a discussion of the UV spectra of dialkylzincs, see: Young, P. J.; Gosavi,
R. K.; Connor, J.; Strausz, O. P.; Gunning, H. E. J. Chem. Phys. 1973, 58,
5280-5283.
(17) In all cases, a stoichiometric amount of EtI or i-PrI was formed and
observed by NMR and/or GC.
(18) Experimental details and other control experiments are provided in
the Supporting Information.
NSERC Postgraduate Scholarship (PGS A). We thank Prof. Denis Gravel
for may helpful discussions.
Supporting Information Available: Typical experimental procedures
and NMR spectra data of all the compounds (9 pages, print/PDF). See
any current masthead page for ordering information and Web access
instructions.
JA980318F