Schwartz's Reagent, Zirconocene chloride hydride
Zirconocene chloride hydride enables an efficient reduction of tertiary amides to aldehydes, in which esters are tolerated. Hydrozirconation of alkynes and alkenes with Schwartz's reagent gives zirconium products, that for example can be carbonylated.
Recent Literature
A highly efficient in situ generation of the Schwartz reagent provides a
convenient method for the reduction of amides to aldehydes and the
regioselective hydrozirconation-iodination of alkynes and alkenes. These
single-step processes proceed in very short reaction time, show excellent
functional group compatibility, and use inexpensive and long-storage stable
reducing reagents.
Y. Zhao, V. Snieckus, Org. Lett., 2014,
16, 390-393.
The reduction of tertiary amides to aldehydes via Cp2Zr(H)Cl shows
several distinct advantages: The reaction requires a very short reaction time
and provides very high yields of the aldehydes with good chemoselectivity.
Furthermore, the reaction does not require extensive workup procedures, nor does
it require scrupulously dry conditions. Additionally, substrate dependence is minimal.
J. M. White, A. R. Tunoori, G. I. Georg, J. Am. Chem. Soc., 2000,
122, 11995-11996.
Chromium catalyzes a photochemical, and linear-selective alkylation of
aldehydes with alkylzirconium species generated in situ from a wide range of
alkenes and Schwartz's reagent. The reaction proceeded with high functional
group tolerance at ambient temperature under visible-light irradiation.
Y. Hirao, Y. Katayama, H. Mitsunuma, M. Kanai,
Org. Lett., 2020, 22, 8584-8588.
Zirconocene hydride catalyzes a mild method for the semireduction of both
secondary and tertiary amides to imines. While secondary amides furnish a
diverse array of imines in very good yield with excellent chemoselectivity, a
reductive transamination of tertiary amides is also achievable in the presence
of a primary amine at room temperature.
R. A. Kehner, G. Zhang, L. Bayeh-Romero, J. Am. Chem. Soc.,
2023, 145, 4921-4927.
Zirconocene hydride catalyzes a mild method for the semireduction of both
secondary and tertiary amides to imines. While secondary amides furnish a
diverse array of imines in very good yield with excellent chemoselectivity, a
reductive transamination of tertiary amides is also achievable in the presence
of a primary amine at room temperature.
R. A. Kehner, G. Zhang, L. Bayeh-Romero, J. Am. Chem. Soc.,
2023, 145, 4921-4927.
Y. Zhao, V. Snieckus, Org. Lett., 2014,
16, 390-393.
The use of a non-C2-symmetric ProPhenol ligands enables a catalytic and
asymmetric vinylation of N-Boc imines via hydrozirconation providing
allylic amines in excellent yields and enantioselectivities. A very short,
asymmetric synthesis of the selective serotonine reuptake inhibitor (SSRI) (-)-dapoxetine
is also reported.
B. M. Trost, C.-I Hung, D. C. Koester, Y. Miller, Org. Lett.,
2015,
17, 3778-3781.
Hydrozirconation of an alkyne with the Schwartz reagent forms a vinyl
zirconium intermediate, which directly undergoes a copper-catalyzed
electrophilic enamidation with dioxazolones. High functional group tolerance of
hydrozirconation enables the use of functionalized alkynes including esters.
S. Banjo, K. Nakata, E. Nakasuji, S. Yasui, N. Chida, T. Sato, Org. Lett., 2022, 24,
8662-8666.
Addition of in situ generated Schwartz reagent to widely available isocyanates
enables a chemoselective, high-yielding, and versatile synthesis of variously
functionalized formamides. The reaction tolerates the presence of sensitive
functionalities (esters, nitro groups, nitriles, alkenes).
V. Pace, K. de la Vega-Hernández, E. Urban, T. Langer, Org. Lett.,
2016, 18, 2750-2753.
A tethered alkene functionality can be used as a traceless directing group
for a zirconium catalyzed reductive cleavage of Csp3 and Csp2
carbon-heteroatom bonds, including C-O, C-N, and C-S bonds. The reaction is
especially useful for cleavage of homoallylic ethers and the removal of terminal
allyl and propargyl groups.
C. Matt, F. Kölblin, J. Streuff,
Org. Lett., 2019, 21, 6909-6913.
A general, mild, and efficient reductive cleavage of aryl O-carbamates to
phenols using the Schwartz reagent is selective and tolerates a large number of
functional groups. The cleavage may be carried out by direct or by an economical
in situ procedure; and, notably, establishes a synthetic connection to the
directed ortho metalation strategy.
J. Morin, Y. Zhao, V. Snieckus, Org. Lett., 2013,
15, 4102-4105.
A Cr-catalyzed asymmetric cross aza-pinacol coupling of aldehydes and N-sulfonyl
imines provides β-amino alcohols bearing vicinal stereocenters. This protocol
proceeds in a radical-polar crossover manner from the intermediacy of an α-amino
radical instead of a ketyl radical.
H. Hu, Z. Wang, J. Am. Chem. Soc.,
2023, 145, 20775-20781.
A general method for the reductive phosphination of amides in one pot provides
α-amino phosphonates in very good yields. The reaction covers a broad scope of
substrates such as secondary and tertiary amides.
Y. Gao, Z. Huang, R. Zhuang, J. Xu, P. Zhang, G. Tang, Y. Zhao, Org. Lett., 2013,
15, 4214-4217.
An unprecedented hydroalumination of C=O bonds catalyzed by zirconocene
dichloride enables a site-selective deprotection of peracetylated functional
substrates. A mixed metal hydride, with 1:1 zirconium/aluminum stoichiometry, is
the reductive species.
T. Courant, M. Gavel, R. M. Q. Renard, V. Gandon, A. Y. P. Joosten, T.
Lecourt, J. Org. Chem., 2021, 86,
9280-9288.
A combination of Cp2ZrCl2 and DIBAL-H promotes a
regioselective cleavage of primary acetates on a broad scope of substrates,
ranging from carbohydrates to terpene derivatives, with a high tolerance toward
protecting groups and numerous functionalities found in natural products and
bioactive compounds.
M. Gavel, T. Courant, A. Y. P. Joosten, T. Lecourt,
Org. Lett., 2019, 21, 1948-1952.
