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.
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.
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.
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 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.