Schwartz's Reagent, Zirconocene chloride hydride
Schwartz's Reagent, Zirconocene chloride hydride
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Sandra Forbes
Zirconocene chloride hydride is capable of facilitating an efficient reduction process, converting tertiary amides into aldehydes while tolerating the presence of esters. When alkynes and alkenes undergo hydrozirconation with Schwartz's reagent, zirconium-containing products are generated, which, for instance, can be subjected to carbonylation reactions.
Recent Literature
The development of a highly efficient protocol for the in situ generation of Schwartz reagent offers a convenient and practical approach for two significant chemical transformations. It enables the reduction of amides to aldehydes and the regioselective hydrozirconation-iodination of alkynes and alkenes. These single-step processes are characterized by extremely short reaction times, outstanding compatibility with various functional groups, and the utilization of cost-effective and long-term storage-stable reducing agents.
Y. Zhao, V. Snieckus, Org. Lett., 2014, 16, 390-393.
DOI: 10.1021/ol403183a
The reduction of tertiary amides to aldehydes utilizing Cp₂Zr(H)Cl exhibits a number of prominent advantages. Firstly, the reaction proceeds with an extremely short reaction time, enabling efficient synthesis. Moreover, it yields aldehydes in very high quantities while demonstrating excellent chemoselectivity, selectively targeting the desired functional group transformation. Secondly, the reaction circumvents the need for elaborate workup procedures, simplifying the post-reaction purification steps. It also does not demand strictly anhydrous conditions, enhancing its operational convenience. Lastly, the reaction shows minimal substrate dependence, indicating its broad applicability across a variety of substrates.
J. M. White, A. R. Tunoori, G. I. Georg, J. Am. Chem. Soc., 2000, 122, 11995-11996.
DOI: 10.1021/ja002149g
Chromium serves as a catalyst to facilitate a photochemical alkylation reaction of aldehydes, which proceeds with linear selectivity. The alkylzirconium species required for the reaction are generated in situ through the reaction of a diverse array of alkenes with Schwartz's reagent. Notably, this reaction demonstrates a high degree of functional group tolerance and can be carried out at ambient temperature under the irradiation of visible light.
Y. Hirao, Y. Katayama, H. Mitsunuma, M. Kanai, Org. Lett., 2020, 22, 8584-8588.
DOI: 10.1021/acs.orglett.0c03180
Zirconocene hydride functions as a catalyst, enabling a mild and efficient approach for the semireduction of both secondary and tertiary amides to imines. In this process, secondary amides undergo conversion to yield a wide variety of imines with notably high yields and exceptional chemoselectivity. Furthermore, a reductive transamination of tertiary amides can also be successfully carried out when a primary amine is present, and this reaction occurs under ambient temperature conditions.
R. A. Kehner, G. Zhang, L. Bayeh-Romero, J. Am. Chem. Soc., 2023, 145, 4921-4927.
DOI: 10.1021/jacs.2c11786
Zirconocene hydride acts as a catalyst to mediate a mild semireduction methodology for the conversion of both secondary and tertiary amides to their corresponding imines. For secondary amides, this catalytic system affords a diverse range of imines with excellent yields and remarkable chemoselectivity. In addition, under the influence of a primary amine at room temperature, a reductive transamination reaction of tertiary amides can be effectively realized.
R. A. Kehner, G. Zhang, L. Bayeh-Romero, J. Am. Chem. Soc., 2023, 145, 4921-4927.
DOI: 10.1021/jacs.2c11786
Y. Zhao, V. Snieckus, Org. Lett., 2014, 16, 390-393.
DOI: 10.1021/ol403183a
The utilization of non-C₂-symmetric ProPhenol ligands enables the realization of a catalytic and asymmetric vinylation reaction of N-Boc imines through hydrozirconation. This reaction pathway results in the formation of allylic amines with excellent yields and enantioselectivities. Furthermore, this work presents a highly efficient asymmetric synthesis strategy for the selective serotonin reuptake inhibitor (SSRI) (-)-dapoxetine.
B. M. Trost, C.-I Hung, D. C. Koester, Y. Miller, Org. Lett., 2015, 17, 3778-3781.
DOI: 10.1021/acs.orglett.5b01755
Hydrozirconation of an alkyne in the presence of the Schwartz reagent leads to the formation of a vinyl zirconium intermediate. This intermediate subsequently undergoes a direct copper - catalyzed electrophilic enamidation reaction with dioxazolones. The remarkable functional group tolerance of the hydrozirconation step makes it feasible to use functionalized alkynes, encompassing those with ester functionalities.
S. Banjo, K. Nakata, E. Nakasuji, S. Yasui, N. Chida, T. Sato, Org. Lett., 2022, 24, 8662-8666.
DOI: 10.1021/acs.orglett.2c03497
The in - situ generation of the Schwartz reagent followed by its addition to readily accessible isocyanates facilitates a chemoselective, high - yielding, and highly versatile synthetic approach for the preparation of variously functionalized formamides. Notably, this reaction is well - tolerated in the presence of sensitive functional groups, including esters, nitro groups, nitriles, and alkenes.
V. Pace, K. de la Vega-Hernández, E. Urban, T. Langer, Org. Lett., 2016, 18, 2750-2753.
DOI: 10.1021/acs.orglett.6b01226
A tethered alkene moiety can serve as a traceless directing group in a zirconium - catalyzed reductive cleavage reaction targeting Csp³ and Csp² carbon - heteroatom bonds, encompassing C - O, C - N, and C - S bonds. This reaction holds particular utility for the cleavage of homoallylic ethers and the elimination of terminal allyl and propargyl groups.
C. Matt, F. Kölblin, J. Streuff, Org. Lett., 2019, 21, 6909-6913.
DOI: 10.1021/acs.orglett.9b02572
A broad - spectrum, mild, and highly efficient reductive cleavage of aryl O - carbamates to phenols, employing the Schwartz reagent, exhibits remarkable selectivity and is compatible with a vast array of functional groups. This cleavage can be executed either through a direct approach or via an economical in - situ process. Significantly, it forges a synthetic link to the directed ortho - metalation strategy.
J. Morin, Y. Zhao, V. Snieckus, Org. Lett., 2013, 15, 4102-4105.
DOI: 10.1021/ol401547d
A chromium - catalyzed asymmetric cross aza - pinacol coupling reaction between aldehydes and N - sulfonyl imines has been developed, which yields β - amino alcohols with adjacent stereocenters. This reaction protocol proceeds via a radical - polar crossover mechanism, wherein the key intermediate is an α - amino radical rather than a ketyl radical.
H. Hu, Z. Wang, J. Am. Chem. Soc., 2023, 145, 20775-20781.
DOI: 10.1021/jacs.3c08493
A one - pot, general approach for the reductive phosphination of amides has been established, which enables the efficient synthesis of α - amino phosphonates with exceptionally high yields. This reaction demonstrates a wide substrate scope, encompassing both secondary and tertiary amides.
Y. Gao, Z. Huang, R. Zhuang, J. Xu, P. Zhang, G. Tang, Y. Zhao, Org. Lett., 2013, 15, 4214-4217.
DOI: 10.1021/ol4019419
Zirconocene dichloride - catalyzed hydroalumination of C=O bonds, facilitates site - selective deprotection of peracetylated functional substrates. The reductive species responsible for this transformation is a mixed metal hydride with a 1:1 zirconium/aluminum stoichiometry.
T. Courant, M. Gavel, R. M. Q. Renard, V. Gandon, A. Y. P. Joosten, T. Lecourt, J. Org. Chem., 2021, 86, 9280-9288.
The synergy between Cp₂ZrCl₂ and DIBAL - H facilitates regioselective cleavage of primary acetates across a diverse array of substrates, spanning from carbohydrates to terpene derivatives. This reaction system exhibits remarkable tolerance towards protecting groups and a multitude of functionalities commonly present in natural products and bioactive compounds.
M. Gavel, T. Courant, A. Y. P. Joosten, T. Lecourt, Org. Lett., 2019, 21, 1948-1952.
DOI: 10.1021/acs.orglett.8b03947
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