Schwartz's reagent


Schwartz's reagent is the common name for the organozirconium compound with the formula 2ZrHCl, sometimes called zirconocene hydrochloride or zirconocene chloride hydride, and is named after Jeffrey Schwartz, a chemistry professor at Princeton University. This metallocene is used in organic synthesis for various transformations of alkenes and alkynes.

Preparation

The complex was first prepared in crude form by Wailes and Weigold. It can be purchased or readily prepared by reduction of zirconocene dichloride with lithium aluminium hydride:
In practice this reaction also affords 2ZrH2, which is treated with methylene chloride to give the mixed hydride chloride. An alternative procedure that generated Schwartz's Reagent from dihydride has also been reported.

Structure

The dimetallic structure has been confirmed by MicroED. The results are consistent with FT-IR spectroscopy, which established that the hydrides are bridging. Solid state NMR spectroscopy also indicates a dimeric structure. The X-ray crystallographic structure for the methyl compound 4Zr2H22 compound is analogous.

Uses in organic synthesis

Schwartz's reagent can be used for a number of reactions. It has been shown that it can be used to reduce amides to aldehydes. Reducing tertiary amides with Schwartz's reagent can reach efficient yields, but primary and secondary amides will show decreased yields. The use of Schwartz's reagent in this manner will not require any added heat and can be done quickly, and reduction of the alcohol form is not a problematic side reaction as it can be with other reducing agents. Schwartz's reagent will selectively reduce the amide over any readily reducible esters that may be present in the reaction mixture.
Vinylation of ketones in high yields is a possible use of Schwartz's reagent.
Schwartz's reagent is used in the synthesis of some macrolide antibiotics, -motuporin, and antitumor agents.

Hydrozirconation

Hydrozirconation is a form of hydrometalation. Substrates for hydrozirconation are alkenes and alkynes. With terminal alkynes the terminal vinyl zirconium product is predominantly formed. Secondary reactions are nucleophilic additions, transmetalations, conjugate additions, coupling reactions, carbonylation and halogenation.
Computational studies indicate that hydrozirconation occurs from the interior portion.
When treated with one equivalent of Cp2ZrClH, diphenylacetylene gives the corresponding alkenylzirconium as a mixture of cis and trans isomers. With two equivalents of hydride, the endproduct was a mixture of erythro and threo zircono alkanes:
In 1974 Hart and Schwartz reported that the organozirconium intermediates react with electrophiles such as hydrochloric acid, bromine and acid chlorides to give the corresponding alkane, bromoalkanes, and ketones:
The corresponding organoboron and organoaluminum compounds were already known, but these are air-sensitive and/or pyrophoric whereas organozirconium compounds are not.

Scope

In one study the usual regioselectivity of an alkyne hydrozirconation is reversed with the addition of zinc chloride:
One example of a one-pot hydrozirconation - carbonylation - coupling is depicted below:
With certain allyl alcohols, the alcohol group is replaced by nucleophilic carbon forming a cyclopropane ring: The selectivity of the hydrozirconation of alkynes has been studied in detail. Generally, the addition of the Zr–H proceeds via the syn-addition. The rate of addition to unsaturated carbon-carbon bonds is terminal alkyne > terminal alkene ≈ internal alkyne > disubstituted alkene Acyl complexes can be generated by insertion of CO into the C–Zr bond resulting from hydrozirconation. Upon alkene insertion into the zirconium hydride bond, the resulting zirconium alkyl undergoes facile rearrangement to the terminal alkyl and therefore only terminal acyl compounds can be synthesized in this way. The rearrangement most likely proceeds via β-hydride elimination followed by reinsertion.