A convenient and genuine equivalent to HZrCp2Cl generated in situ from ZrCp2Cl2-DIBAL-H

Article abstract of DOI:10.1021/ol061202o

Slow addition of 1 equiv of ¹Bu₂AlH to ZrCp ₂Cl₂ in THF provides a convenient route to either HZrCp₂Cl-¹Bu₂AlCl (Reagent I) or HZrCp ₂Cl (Reagents II and III). The latter represents a highly convenient route to genuine HZrCp₂Cl, while Reagent I is useful for regio- and stereoselective conversion of 1- and 2-alkynes into (E)-1-iodo-1-alkenes and (E)-2-iodo-2-alkenes, respectively.

Full text of DOI:10.1021/ol061202o

ORGANIC
LETTERS
2006
Vol. 8, No. 17
3675-3678
A Convenient and Genuine Equivalent
to HZrCp2Cl Generated in Situ from
ZrCp2Cl2−DIBAL-H
Zhihong Huang and Ei-ichi Negishi*
Herbert C. Brown Laboratories of Chemistry, Purdue UniVersity, 560 OVal DriVe,
West Lafayette, Indiana 47907-2084
negishi@purdue.edu
Received May 16, 2006
ABSTRACT
Slow addition of 1 equiv of iBu2AlH to ZrCp2Cl2 in THF provides a convenient route to either HZrCp2Cl-iBu2AlCl (Reagent I) or HZrCp2Cl
(Reagents II and III). The latter represents a highly convenient route to genuine HZrCp2Cl, while Reagent I is useful for regio- and stereoselective
conversion of 1- and 2-alkynes into (E)-1-iodo-1-alkenes and (E)-2-iodo-2-alkenes, respectively.
Despite the well-established significance of HZrCp2Cl1,2 in
organic synthesis3 including its hydrozirconation of alkenes2a
and alkynes1b,2b as well as reduction of various other organic
compounds,3,4 its use has been plagued with difficulties in
maintaining its purity over an extended period of time at
the satisfactory level.3d This has made it desirable to develop
procedures for its in situ generation and use. Thus, various
methods have been devised, including treatment of consider-
ably more stable and less expensive ZrCp2Cl2 with many
different hydride sources, such as LiAlH4,5,6 NaAlH2-
as modifications of some of these original procedures
involving LiAlH46 and tBuMgCl.9 And yet, none of these in
situ generation methods appears to be a true equivalent to
isolated and pure HZrCp2Cl. The use of basic metal hy-
drides, such as LiAlH4 and NaAlH2(OCH2CH2OMe)2, is
usually complicated by the production of undesirable byprod-
ucts that interfere with the desired reactions with HZrCp2Cl
and/or cause technical difficulties, such as very sluggish and
tedious filtration for their removal. The initially formed
t
reagent generated by treating ZrCp2Cl2 with BuMgCl is
(OCH2CH2OMe)2,5 LiBH(sBu)3,5,7 and BuMgCl,5,8 as well
iBuZrCp2Cl, whose hydrogen-transfer hydrozirconation is
much slower than that with HZrCp2Cl.5,8 Its acceleration
through the use of various catalysts does speed up the desired
hydrozirconation, but fails to match the results obtainable
with pure HZrCp2Cl.9
t
(1) (a) Wailes, P. C.; Weigold, H. J. Organomet. Chem. 1970, 24, 405.
(b) Wailes, P. C.; Weigold, H.; Bell, A. P. J. Organomet. Chem. 1971, 27,
373.
(2) (a) Hart, D. W.; Schwartz, J. J. Am. Chem. Soc. 1974, 96, 8115. (b)
Hart, D. W.; Blackburn, T. F.; Schwartz, J. J. Am. Chem. Soc. 1975, 97,
679.
(3) (a) Schwartz, J.; Labinger, J. A. Angew. Chem., Int. Ed. 1976, 15,
333. (b) Wipf, P.; Jahn, H. Tetrahedron 1996, 52, 12853. (c) Negishi, E.
In Organometallics in Synthesis: A Mannual, 2nd ed.; Schlosser, M., Ed.;
Wiley: New York, 2002; Chapter 8, pp 925-1002. (d) Lipshutz, B. H.;
Pfeiffer, S. S.; Noson, K.; Tomioka, T. In Titanium and Zirconium in
Organic Synthesis; Marek, I., Ed.; Wiley-VCH: Weinheim, Germany, 2002;
Chapter 4, pp 110-148.
(5) Negishi, E.; Miller, J. A.; Yoshida, T. Tetrahedron Lett. 1984, 25,
3407.
(6) Buchwald, S. L.; LaMaire, S. J.; Nielsen, R. B.; Watson, B. T.; King,
S. M. Tetrahedron Lett. 1987, 28, 3895.
(7) Lipshutz, B. H.; Keil, R.; Ellsworth, E. L. Tetrahedron Lett. 1990,
31, 7257.
(8) Swanson, D. R.; Nguyen, T.; Noda, Y.; Negishi, E. J. Org. Chem.
1991, 56, 2590.
(4) White, J. M.; Tunoori, A. R.; Georg, G. I. J. Am. Chem. Soc. 2000,
122, 11995.
(9) Makabe, H.; Negishi, E. Eur. J. Org. Chem. 1999, 969.
10.1021/ol061202o CCC: $33.50
© 2006 American Chemical Society
Published on Web 07/27/2006

i
An obvious combination of Bu2AlH and ZrCp2Cl2 was
briefly investigated by us in 1980 with the goal of catalyzing
hydroalumination of alkenes with ZrCp2Cl2 (eq 1 in Scheme
1). This attempt failed, but the corresponding reaction of
Scheme 2
Scheme 1
contrast with other known procedures for the preparation of
HZrCp2Cl by treating ZrCp2Cl2 with LiAlH4, Red-Al, or
other basic metal hydrides, the iBu2AlH-ZrCp2Cl2 reaction
was not seriously plagued with over-reduction of ZrCp2Cl2
to produce H2ZrCp212 or very sluggish and tedious filtration
of the byproducts. The latter feature permits convenient and
i
facile removal of Bu2AlCl‚THF by washing it through a
sintered glass filter leading to in situ generation and direct
use of HZrCp2Cl (Reagent II) without its transfer, reweigh-
ing, or, more dangerously, long-term storage. It goes without
saying that this reaction also provides an unprecedentedly
clean and convenient route to isolated and pure HZrCp2Cl
(Reagent III) that can be stored and used (Scheme 2).
As the results summarized in Table 1 indicate, Reagent I
is a convenient reagent for hydrometalation of both terminal
(entries 1-10) and internal (entries 11 and 12) alkynes as
well as alkenes (entries 13 and 14). One unexpected but
synthetically useful finding is that the hydrometalation-
iodinolysis of 2-alkynes run at e25 °C (entries 11 and 12)
is highly regioselective (g98%) as long as 1.5 equiv of
Reagent I is used.13 This reagent is also convenient and
satisfactory for a recently reported direct reduction of amides
to aldehydes4 at 23 °C (eq 3 in Scheme 3). Despite many
favorable results shown in Table 1 and Scheme 3, Reagent
I is clearly not a genuine equivalent to HZrCp2Cl. In some
iBu3Al with alkenes in the presence of a catalytic amount of
ZrCp2Cl2 led to a hydrogen-transfer hydroalumination of
alkenes10 (eq 2 in Scheme 1). A year earlier, Schwartz re-
ported an intriguing but complex 1:3 reaction of ZrCp2Cl2
with iBu2AlH in benzene shown in eq 3 in Scheme 1.11 We
confirmed the reported results. Furthermore, we have found
that the 1:3 stoichiometry is independent of the initial ratio
i
of ZrCp2Cl2 and Bu2AlH. Thus, the reaction fails to give
HZrCp2Cl.
Despite the uninspiring results shown in Scheme 1, the
i
reaction of ZrCp2Cl2 with Bu2AlH was reexamined in
THF. Thus, iBu2AlH was slowly added to 1 molar equiv of
ZrCp2Cl2 dissolved in THF at 0 °C, and the reaction was
monitored by NMR spectroscopy. It induced precipitation
of HZrCp2Cl, which was accompanied by complete disap-
pearance of the Cp signals for ZrCp2Cl2 [1H NMR: δ 6.25
(s); 13C NMR: δ 116.60 (s)]. These findings indicated clean
formation of a 1:1 mixture of HZrCp2Cl and iBu2AlCl‚THF
(Reagent I) according to eq 1 in Scheme 2. In marked
i
cases, the presence of Bu2AlCl can be detrimental, as
indicated by three mutually related cases of the hydrozir-
conation-Pd-catalyzed cross-coupling tandem reactions (eqs
Table 1. Hydrometalation-Iodinolysis of Alkynes and Alkenes with ZrCp2Cl2-DIBAL-H in THF (Reagent I)
a All isolated products were isomerically g98% pure by 1H and 13C NMR spectroscopy. b The use of iBu2AlD gave the â-deuterio derivative in 90% yield
with g98% D incorporation in the â position. c The alkene indicated was hydrometalated, and the corresponding iodoalkanes were the products obtained in
the indicated yields.
3676
Org. Lett., Vol. 8, No. 17, 2006

Reagent II does appear to serve as a genuine and satisfactory
equivalent to isolated and pure HZrCp2Cl. Even so, fast
addition or use of an excess iBu2AlH must be avoided so as
not to generate H2ZrCp2.
Scheme 3
The following experiments involving the use of Reagents
I and II are representative.
(1E,3S)-4-(tert-Butyldimethylsiloxy)-1-iodo-3-methyl-1-
butene (use of Reagent I): To ZrCp2Cl2 (321 mg, 1.1
mmol) in THF (2.5 mL) cooled to 0 °C was added slowly a
i
solution of Bu2AlH (156 mg, 1.1 mmol) in THF (0.5 mL)
under argon. The resultant suspension was stirred for 30 min
at 0 °C, followed by addition of a solution of (3S)-4-(tert-
butyldimethylsiloxy)-3-methyl-1-butyne (198 mg, 1.0 mmol)
in THF (0.5 mL). The mixture was warmed to room
temperature and stirred until a homogeneous solution resulted
(ca. 1 h) and then cooled to -78 °C, followed by addition
of I2 (330 mg, 1.3 mmol) in THF (1.5 mL). After 30 min at
-78 °C, GLC analysis indicated that the starting material
had been completely consumed, and the desired product was
formed in 94% yield by GLC. The reaction mixture was
quenched with 1 N HCl, extracted with ether, washed
successively with saturated Na2S2O3, NaHCO3, and brine,
dried over MgSO4, filtered, and concentrated. Flash chro-
matography (silica gel, hexanes) afforded 293 mg (90%) of
the title compound.14
(3E,5E,7E)-1-(tert-Butyldimethylsilyl)-3,5,7-decatrien-
1,9-diyne (5b) (use of Reagent II): To ZrCp2Cl2 (321 mg,
1.1 mmol) in THF (2.5 mL) in a two-necked flask was
4-6 in Scheme 3). In eq 4, Reagent I is highly satisfactory.
In eq 5, however, an undesired participation by Bu2AlCl
seriously diverts the course of the reaction. This side reaction
is currently under investigation.
Another somewhat unexpected aspect of the hydrozir-
conation with Reagent I is that the desired hydrozirconation
is accompanied by a slow reverse transmetalation in which
the alkenyl group generated by hydrozirconation is trans-
ferred from Zr to Al to eventually give an equilibrium
mixture. The reversible nature of the slow transmetalation
can be readily observed, as exemplified in Scheme 4.
i
i
added dropwise a solution of Bu2AlH (156 mg, 1.1 mmol)
in THF (0.5 mL) at 0 °C. The resultant suspension was stirred
for 30 min at 0 °C. The supernatant liquid was filtered
through a sintered glass filter attached to the flask under
argon. The white solid (HZrCp2Cl) remaining in the reactor
was washed with THF (2.0 mL). To HZrCp2Cl thus pre-
pared was added a solution of 3b (190 mg, 1.0 mmol) in
THF (1.0 mL) at room temperature. After 1 h, a homoge-
neous solution thus obtained was cooled to 0 °C, and a
solution of dry ZnBr2 (261 mg, 1.0 mmol) in THF (1.0 mL)
was added. After 30 min, (E)-BrCHdCHCtCSiMe3 (242
mg, 1.2 mmol) and Pd(PPh3)4 (23 mg, 0.02 mmol) in
DMF (2.0 mL) were added, and the resultant mixture was
stirred at room temperature and monitored by GLC analysis.
The reaction was complete in 5 h, and the reaction mixture
was quenched with aqueous NH4Cl, extracted with ether,
washed successively with saturated NaHCO3 and brine, dried
over MgSO4, filtered, and concentrated to give the crude
product as a viscous oil. To the crude product were added
MeOH (4.0 mL) and K2CO3 (138 mg, 1.0 mmol). The
resultant mixture was stirred at room temperature for 1 h,
quenched with water, extracted with ether, dried over MgSO4,
filtered, and concentrated. Flash chromatography (silica gel,
Scheme 4
(11) Carr, D. B.; Schwartz, J. J. Am. Chem. Soc. 1979, 101, 3521.
(12) For an alternate approach to prepare a hydridoziconocene chlor-
ide derivative, i.e., HZr(MeCp)2Cl, by mixing Zr(MeCp)2Cl2 with H2Zr-
(MeCp)2, see: Erker, G.; Schlund, R.; Kru¨ger, C. Organometallics 1989,
8, 2349.
(13) For the use of 2.0 equiv of HZrCp2Cl, see: Panek, J. S.; Hu, T. J.
Org. Chem. 1997, 62, 4912.
As amply demonstrated in Scheme 5 summarizing the
results of highly demanding cases of oligoenyne syntheses,
(10) Negishi, E.; Yoshida, T. Tetrahedron Lett. 1980, 1501.
Org. Lett., Vol. 8, No. 17, 2006
(14) Zeng, F.; Negishi, E. Org. Lett. 2002, 4, 703.
3677

Scheme 5 a
a Reagents and conditions: (a) (i) dry ZnBr2, (ii) 2% Pd(PPh3)4, THF-DMF. (b) Same as (a) except that 2 equiv each of 5b and HZrCp2Cl
were used and that the cross-coupling reaction was carried out at 50 °C.
hexanes) afforded the title compound (5b) (186 mg, 77%
over 2 steps).
Supporting Information Available: Experimental pro-
1
cedures and H and 13C NMR spectroscopic data for 9
terminally silylated oligoenynes including 4b, 5b, 8, and
9, iodoalkenes, and 3-pyridinecarboxaldehyde-R-d1. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. We thank the National Science Foun-
dation (CHE-0309613), the National Institutes of Health (GM
36792), and Purdue University for support of this work.
Technical assistances provided by B. Liang, A. Mitin, and
G. Zhu are gratefully acknowledged.
OL061202O
3678
Org. Lett., Vol. 8, No. 17, 2006