Chemoselective Reduction by Cp2Zr(H)Cl (Schwartz's Reagent)

Full text of DOI:10.1071/CH03321

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Aust. J. Chem. 2004, 57, 383
Chemoselective Reduction by Cp2Zr(H)Cl (Schwartz’s Reagent)
HeedongYunA
A Department of Chemistry, Columbia University, New York, NY 10027, USA
(e-mail: hy2013@columbia.edu).
Manuscript received: 20 December 2003.
Final version: 23 January 2004.
Heedong Yun received a B.S. in 1999 from Seoul National University. He obtained an M.A. from Columbia University in 2003 and currently he is
pursuing a Ph.D. under the guidance of Samuel Danishefsky on the total synthesis of biologically active marine natural products.
of the chemistry of organozirconocenes has focussed on carbon–carbon
and carbon–heteroatom bond formations.[6] Recently, however, it has
been recognized that the title reagent is also especially useful for effecting
chemoselective reductions of carbonyl groups and other compounds.
Background and Preparation
Since the preparation of the first organochlorobis(cyclopentadienyl)
zirconium complex by Wailes and Weigold in 1970,[1] organozirconocenes
have emerged as one of the most useful classes of transition metal deriva-
tives in organic synthesis. The wide range of transformations mediated by
zirconocenes and the easy preparation of such species have contributed to
the broad appeal of such reagents. In particular, Schwartz and coworkers
pioneered the use of hydrozirconation for the functionalization of organic
compounds.[2] Cp2Zr(H)Cl (Scheme 1) was first prepared by Wailes et al.[1]
by reduction of Cp2ZrCl2 with LiAlH4 in tetrahydrofuran[3] as well as by
magnesium metal reduction. This reagent is also prepared by reduction with
LiAl(OBut)3H[4] and Red-Al.[5] Much of the development
Cl
Cl
[HϪ]
H
Zr
Zr
Cl
Scheme 1.
Applications
O
OK
KH
Reduction of 2◦ Amides or Lactams to Imines
RЈ
RЈ
N
R
N
R
Zirconium(iv) salts of 2◦ amides or lactams were transformed by Schwartz’s
reagent to N-substituted imines (Scheme 2).[7] The method represents con-
trolled reduction of amides and lactams to the corresponding imines, a
transformation that is otherwise very difficult to achieve because imines are
reduced more rapidly than carboxamides by most metal hydride reagents.
H
OZrCp2H
H
Cp2Zr(H)Cl
RЈ
RЈ
R
N
R
N
Scheme 2.
Reduction of 3◦ Amides to Aldehydes
A convenient procedure for the conversion of 3◦ amides to aldehydes under
very mild conditions was introduced (Scheme 3).[8] The ketone functionality
also present in the molecule is reduced to an alcohol together with amide
reduction. Of additional particular interest is that in the presence of an ester
functionality, a 3◦ amide can be reduced selectively to the corresponding
aldehyde in very good yield.
O
O
Cp2Zr(H)Cl
NEt2
H
O
30min, 94%
O
OH
Reduction of Phosphine Oxides or Sulfides to Phosphines
Cp2Zr(H)Cl
15min, 74%
OMe
NEt2
OMe
H
Reduction of phosphine oxides or sulfides can be achieved using several
reagents.[9] The most popular reductants are silanes which can be used gen-
erally in the presence of other functionalities. However the other reducing
agents are not so selective and many functionalities are sensitive to reduction
by them. Schwartz’s reagent selectively reduced a variety of functionalized
phosphine oxides or sulfides efficiently (Scheme 4).[10]
6
6
O
O
O
Scheme 3.
Ph
Ph
Ph
Ph
2 eq. Cp2Zr(H)Cl
P
X
P
References
R
R
[1] (a) P. C. Wailes, H. Weigold, Organomet. Chem. 1970, 24, 405.
doi:10.1016/S0022-328X(00)80281-8
X ϭ O, S
R ϭ Et, Cy, But, Ph
(b) P. C. Wailes, H. Weigold, A. P. Bell, Organomet. Chem. 1971, 27,
373. doi:10.1016/S0022-328X(00)82168-3
[2] (a) J. Schwartz, in New Applications of Organometallic Reagents in
Organic Synthesis (Ed. D. Seyferth) 1976, p. 46 (Elsevier: Amsterdam).
(b) Schwartz’s reagent is commercially available from various suppliers,
for example Aldrich catalog number 22367-0.
[3] Buchwald and coworkers developed an experimentally simple procedure
for large scale preparations.
S. L. Buchwald, S. J. La Maire, R. B. Nielsen, B. T. Watson, S. M.
King, Org. Synth. 1993, 71, 77.
[4] P. C. Wailes, H. Weigold, Inorg. Synth. 1979, 19, 223.
[5] D. B. Carr, J. Schwartz, J. Am. Chem. Soc. 1979, 101, 3521.
[6] P. Wipf, H. Jahn, Tetrahedron 1996, 52, 12853. doi:10.1016/0040-
4020(96)00754-5
Scheme 4.
[7] D. J. A. Schedler, J. Li, B. Ganem, J. Org. Chem. 1996, 61, 4115.
doi:10.1021/JO960286J
[8] J. M. White, A. R. Tunoori, G. I. Georg, J. Am. Chem. Soc. 2000, 122,
11995. doi:10.1021/JA002149G
[9] D. G. Gilheany, C. M. Mitchell, The Chemistry of Organophosphorous
Compounds (Ed. F. R. Hartley) 1990, Vol. 1, p. 152 (John Wiley:
New York, NY).
[10] M. Zablocka, B. Delest, A. Igau, A. Skowronska, J.-P. Majoral,
Tetrahedron Lett. 1997, 38, 5997. doi:10.1016/S0040-4039(97)01365-8
© CSIRO 2004
10.1071/CH03321
0004-9425/04/040383