Schwartz's reagent

{{chembox

| verifiedrevid = 401437383

| Name =

| ImageFile = Cp4Zr2H2Cl2.png

| ImageSize = 154px

| ImageFile1 = Schwartz's-reagent-dimer-from-xtal-3D-bs-17-ar.png

| ImageSize1 = 150px

| IUPACName = Chloridohydridozirconocene

| OtherNames = Cp₂ZrClH, zirconocene chloride hydride

| SystematicName = chloridobis(η⁵-cyclopentadienyl)hydridozirconium

| Section1 = {{Chembox Identifiers

| CASNo = 37342-97-5

| CASNo_Ref = {{cascite|correct|CAS}}

| EC_number = 253-479-5

| UNII = S84D01XQGL

| UNII_Ref = {{fdacite|correct|FDA}}

| PubChem = 53384630

| ChemSpiderID = 28605366

| SMILES = [cH-]1cccc1.[cH-]1cccc1.Cl[ZrH+2]

| InChI = 1/2C5H5.ClH.Zr.H/c2*1-2-4-5-3-1;;;/h2*1-5H;1H;;/q2*-1;;+3;/p-1/r2C5H5.ClHZr/c2*1-2-4-5-3-1;1-2/h2*1-5H;2H/q2*-1;+2

| InChIKey = GBJQOFBMEJYDAU-CFXPZLBWAB

| StdInChI = 1S/2C5H5.ClH.Zr.H/c2*1-2-4-5-3-1;;;/h2*1-5H;1H;;/q2*-1;;+3;/p-1

| StdInChIKey = GBJQOFBMEJYDAU-UHFFFAOYSA-M

}}

| Section2 = {{Chembox Properties

| Formula = C₁₀H₁₁ClZr

| MolarMass = 257.87 g/mol

| Appearance = White solid

| Density =

| MeltingPt =

| BoilingPt =

| Solubility =

}}

| Section3 = {{Chembox Hazards

| GHSPictograms = {{GHS02}}{{GHS05}}

| GHSSignalWord = Danger

| HPhrases = {{H-phrases|228|261|314}}

| PPhrases = {{P-phrases|210|231+232|240|241|260|264|280|301+330+331|303+361+353|304+340|305+351+338|310|321|363|370+378|402+404|405|501}}

| MainHazards =

| FlashPt =

| AutoignitionPt =

}}

| Section4 =

| Section5 =

| Section6 =

}}

Schwartz's reagent is the common name for the organozirconium compound with the formula (C₅H₅)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.{{cite journal|doi=10.1002/ejoc.201800852|title=Recent Developments and Synthetic Applications of Nucleophilic Zirconocene Complexes from Schwartz's Reagent|journal=European Journal of Organic Chemistry|volume=2018|issue=35|pages=4828–4844|year=2018|last1=Pinheiro|first1=Danielle L. J.|last2=De Castro|first2=Pedro P.|last3=Amarante|first3=Giovanni W.|s2cid=102770378}}

Preparation

The complex was first prepared by Wailes and Weigold.{{cite journal | first1= P. C.|last1= Wailes |first2= H.|last2= Weigold | title = Hydrido complexes of zirconium I. Preparation | journal = J. Organomet. Chem. | year = 1970 | volume = 24 | pages = 405–411 | doi = 10.1016/S0022-328X(00)80281-8 | issue = 2}} It can be purchased or readily prepared by reduction of zirconocene dichloride with lithium aluminium hydride:

: (C₅H₅)₂ZrCl₂ + {{1/4}} LiAlH₄ → (C₅H₅)₂ZrHCl + {{1/4}} LiAlCl₄

This reaction also affords (C₅H₅)₂ZrH₂, which is treated with methylene chloride to give Schwartz's reagent {{cite journal|journal=Org. Syntheses|doi=10.15227/orgsyn.071.0077 |first1=Stephen L. |last1=Buchwald|first2=Susan J. |last2=LaMaire|first3=Ralph B. |last3=Nielsen|first4=Brett T. |last4=Watson|first5=Susan M. |last5=King|title=Schwartz's Reagent|date=1993 |volume=71 |page=77 }}

An alternative procedure that generated Schwartz's reagent from dihydride has also been reported.{{cite journal | first1=Peter|last1= Wipf |first2=Hidenori|last2= Takahashi |first3=Nian |last3=Zhuang| title=Kinetic vs. thermodynamic control in hydrozirconation reactions| journal=Pure Appl. Chem.| volume= 70 | issue=5| year=1998| pages=1077–1082| url = http://www.iupac.org/publications/pac/1998/pdf/7005x1077.pdf| doi=10.1351/pac199870051077|s2cid= 94092883 }} Moreover, it's possible to perform an in situ preparation of (C₅H₅)₂ZrHCl from zirconocene dichloride by using LiH. This method can also be used to synthesize isotope-labeled molecules, like olefines by employing Li²H or Li³H as reducing agents.{{Cite journal |last1=Zippi |first1=E. M. |last2=Andres |first2=H. |last3=Morimoto |first3=H. |last4=Williams |first4=P. G. |date=1994-04-01 |title=Preparation and Use of Tritiated Schwartz' Reagent (ZrCp2Cl3H) |url=https://doi.org/10.1080/00397919408020780 |journal=Synthetic Communications |volume=24 |issue=7 |pages=1037–1044 |doi=10.1080/00397919408020780 |issn=0039-7911|url-access=subscription }}

Schwartz's reagent has a low solubility in common organic solvents.{{Cite journal |last1=Wipf |first1=Peter |last2=Jahn |first2=Heike |date=1996-09-30 |title=Synthetic applications of organochlorozirconocene complexes |url=https://dx.doi.org/10.1016/0040-4020%2896%2900754-5 |journal=Tetrahedron |language=en |volume=52 |issue=40 |pages=12853–12910 |doi=10.1016/0040-4020(96)00754-5 |issn=0040-4020|url-access=subscription }} The trifluoromethanesulfonate (C₅H₅)₂ZrH(OTf) is soluble in THF.{{Cite journal |last1=Luinstra |first1=Gerrit A. |last2=Rief |first2=Ursula |last3=Prosenc |first3=Marc H. |date=1995-04-01 |title=Synthesis and Reactivity of Cp₂ZrH(OSO₂CF₃), a Soluble Monomeric Alternative for Schwartz's Reagent, and the Solid-State Structure of Its Dimer, [Cp₂Zr(OSO₂CF₃)(-H)]₂.0.5THF |url=https://doi.org/10.1021/om00004a003 |journal=Organometallics |volume=14 |issue=4 |pages=1551–1552 |doi=10.1021/om00004a003 |issn=0276-7333|url-access=subscription }}

Structure

The complex adopts the usual "clam-shell" structure seen for other Cp₂MX_n complexes.{{Cite journal |last1=Wipf |first1=Peter |last2=Jahn |first2=Heike |date=1996-09-30 |title=Synthetic applications of organochlorozirconocene complexes |url=https://dx.doi.org/10.1016/0040-4020%2896%2900754-5 |journal=Tetrahedron |language=en |volume=52 |issue=40 |pages=12853–12910 |doi=10.1016/0040-4020(96)00754-5 |issn=0040-4020|url-access=subscription }} The dimetallic structure has been confirmed by Microcrystal electron diffraction.{{cite journal |last1=Jones |first1=Christopher G. |last2=Asay |first2=Matthew |last3=Kim |first3=Lee Joon |last4=Kleinsasser |first4=Jack F. |last5=Saha |first5=Ambarneil |last6=Fulton |first6=Tyler J. |last7=Berkley |first7=Kevin R. |last8=Cascio |first8=Duilio |last9=Malyutin |first9=Andrey G. |last10=Conley |first10=Matthew P. |last11=Stoltz |first11=Brian M. |last12=Lavallo |first12=Vincent |last13=Rodríguez |first13=José A. |last14=Nelson |first14=Hosea M. |title=Characterization of Reactive Organometallic Species via MicroED |journal=ACS Central Science |volume=5 |issue=9 |pages=1507–1513 |date=6 September 2019 |doi=10.1021/acscentsci.9b00403|pmid=31572777 |doi-access=free |pmc=6764211 }} 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 (C₅H₅)₄Zr₂H₂(CH₃)₂ compound is analogous.{{cite journal|author=Rossini, A. J.|author2=Mills, R. W.|author3=Briscoe, G. A.|author4=Norton, E. L.|author5=Geier, S. J.|author6=Hung, I.|author7=Zheng, S.|author8=Autschbach, J.|author9=Schurko, R. W.|title=Solid-State Chlorine NMR of Group IV Transition Metal Organometallic Complexes|journal=Journal of the American Chemical Society|year=2009|volume=131|issue=9|pages=3317–3330|doi=10.1021/ja808390a|pmid=19256569|bibcode=2009JAChS.131.3317R }}

Uses in organic synthesis

Schwartz's reagent reduces amides to aldehydes.{{cite journal | first1= M. W. |last1=Leighty|first2= J. T.|last2= Spletstoser |first3=Gunda I. |last3=Georg | title=Mild Conversion of Tertiary Amides to Aldehydes Using Cp₂ZrHCl (Schwartz's Reagent)| journal=Org. Synth.| volume= 88| year=2011| pages=427–437|doi=10.1002/0471264229.os088.39|isbn=978-0471264224|url=https://orgsyn.org/demo.aspx?prep=v88p0427|url-access=subscription}}

Vinylation of ketones in high yields is a possible use of Schwartz's reagent.{{cite journal | first1= H. |last1=Li|first2= P. J. |last2=Walsh | title=Catalytic Asymmetric Vinylation and Dienylation of Ketones| journal=J. Am. Chem. Soc.| volume= 127|issue=23| year=2005| pages=8355–8361| doi= 10.1021/ja0425740|pmid=15941269|bibcode=2005JAChS.127.8355L }}

Schwartz's reagent has been used in the synthesis of some macrolide antibiotics,{{cite journal | first1= Matthew O.|last1= Duffey|first2= Arnaud |last2=Le Tiran |first3= James P. |last3=Morken | title=Enantioselective Total Synthesis of Borrelidin| journal=J. Am. Chem. Soc.| volume= 125|issue= 6| year=2003| pages=1458–1459| doi = 10.1021/ja028941u|pmid= 12568588|bibcode= 2003JAChS.125.1458D}}{{cite journal | first1= J. |last1=Wu|first2= J. S. |last2=Panek | title=Total Synthesis of (−)-Virginiamycin M₂: Application of Crotylsilanes Accessed by Enantioselective Rh(II) or Cu(I) Promoted Carbenoid Si–H Insertion| journal=J. Org. Chem.| volume= 76| issue=24 | year=2011| pages=9900–9918 | doi =10.1021/jo202119p|pmid=22070230}} (−)-motuporin,{{cite journal | first1= T.|last1= Hu|first2= J. S.|last2= Panek | title= Total Synthesis of (−)-Motuporin| journal=J. Org. Chem.| volume= 64|issue= 9| year=1999| pages=3000–3001 | doi = 10.1021/jo9904617|pmid= 11674393}} and antitumor agents.{{cite journal | first= K. C. |last=Nicolaou| title=Total Synthesis of Apoptolidin: Completion of the Synthesis and Analogue Synthesis and Evaluation| journal=J. Am. Chem. Soc.| volume= 125| year=2003|issue=50| pages=15443–15454 | doi = 10.1021/ja030496v|pmid=14664590|bibcode=2003JAChS.12515443N |display-authors=etal}}

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,{{cite journal

|title =Allylic alcohols by alkene transfer from zirconium to zinc: 1-[(tert-butyldiphenylsilyl)oxy]-dec-3-en-5-ol

|journal=Organic Syntheses

|date=1998

|volume=9

|issue=74

|pages=205

|url = http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv9p0143

| access-date = 2013-03-23

| quote = Organic Syntheses, Coll. Vol. 9, p.143 (1998); Vol. 74, p.205 (1997).

}} conjugate additions,[http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv9p0640 Conjugate Addition Of A Vinylzirconium Reagent: 3-(1-Octen-1-Yl)Cyclopentanone], Organic Syntheses, Coll. Vol. 9, p.640 (1998); Vol. 71, p.83 (1993). coupling reactions, carbonylation and halogenation.

Computational studies indicate that hydrozirconation occurs from the interior portion.{{cite journal | first1= E. Y.|last1= Pankratyev|first2= T. V.|last2= Tyumkina|first3= L. V.|last3= Parfenova|first4= S. L.|last4= Khursan|first5= L. M. |last5=Khalilov|first6= U. M. |last6=Dzhemilev | title=DFT and Ab Initio Study on Mechanism of Olefin Hydroalumination by XAlBuⁱ₂ in the Presence of Cp₂ZrCl₂ Catalyst. II.(1) Olefin Interaction with Catalytically Active Centers| journal=Organometallics| volume= 30 | issue=22| year=2011| pages=6078–6089| doi = 10.1021/om200518h}}{{cite journal | first1=Juping |last1=Wang |first2=Huiying |last2=Xu |first3=Hui |last3=Gao |first4=Cheng-Yong |last4=Su |first5=Cunyuan |last5=Zhao |first6=David Lee |last6=Phillips| title=DFT Study on the Mechanism of Amides to Aldehydes Using Cp₂Zr(H)Cl| journal=Organometallics| volume=29 | issue=1| year=2010| pages=42–51 | doi = 10.1021/om900371u}}

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:

:Image:Alkynehydrozirconation1970.svg

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:{{Cite journal | last1 = Hart | first1 = D. W. | last2 = Schwartz | first2 = J. | title = Hydrozirconation. Organic Synthesis via Organozirconium Intermediates. Synthesis and Rearrangement of Alkylzirconium(1V) Complexes and Their Reaction with Electrophiles | doi = 10.1021/ja00833a048 | journal = Journal of the American Chemical Society | volume = 96 | issue = 26 | pages = 8115–8116 | year = 1974 | bibcode = 1974JAChS..96.8115H }}

:Image:AlkenehydrozirconationSchwarz1974.svg

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:{{cite journal | doi = 10.1021/ja075215o | volume=129 | title=Directed Hydrozirconation of Propargylic Alcohols | year=2007 | journal=Journal of the American Chemical Society | pages=12088–12089 | last1 = Zhang | first1 = Donghui| issue=40 | pmid=17850152 | pmc=2669288 | bibcode=2007JAChS.12912088Z }}The electrophile in this reaction is iodine. The additive is believed to promote kinetic reaction control.

:Image:HydrozirconationReversedregioselectivity.svg

One example of a one-pot hydrozirconation - carbonylation - coupling is depicted below:{{cite journal | doi = 10.1039/b110983a | issue=4 | title=Palladium-catalyzed coupling reaction of acylzirconocene chlorides with hypervalent iodonium salts: synthesis of aryl-substituted ketones | year=2002 | journal=Journal of the Chemical Society, Perkin Transactions 1 | pages=459–461 | last1 = Kang | first1 = Suk-Ku}}Reagents: phenylacetylene, Schwartz's reagent, tetraphenylpalladium and the iodane diphenyliodonium tetrafluoroborate (phenyl group donor)

:Image:Hydrozirconationcarbonylationcoupling.svg

With certain allyl alcohols, the alcohol group is replaced by nucleophilic carbon forming a cyclopropane ring:{{cite journal | doi = 10.1039/b203762a | issue=12 | title=A one-pot access to cyclopropanes from allylic ethers via hydrozirconation–deoxygenative ring formation | year=2002 | journal=Chemical Communications | pages=1308–1309 | last1 = Gandon | first1 = Vincent| pmid=12109129 }} The selectivity of the hydrozirconation of alkynes has been studied in detail.{{OrgSynth | first1=R. C. |last1=Sun |first2=M. |last2=Okabe |first3=D. L. |last3=Coffen|first4=J. |last4=Schwartz | title=Conjugate Addition of a Vinylzirconium Reagent: 3-(1-Octene-1-yl)cyclopentanone | collvol = 9| year=1998 | collvolpages=640 | prep = cv9p0640}}{{cite journal | last1=Panek |first1=J. S.|last2= Hu |first2=T.| title= Stereo- and Regiocontrolled Synthesis of Branched Trisubstituted Conjugated Dienes by Palladium(0)-Catalyzed Cross-Coupling Reaction| journal=J. Org. Chem.| volume= 62| issue=15| year=1997| pages=4912–4913|doi=10.1021/jo970647a}} 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 {{cite journal | first1=Peter |last1=Wipf |first2=Heike|last2= Jahn| title=Synthetic applications of organochlorozirconocene complexes| journal=Tetrahedron| volume= 52 | issue=40| year=1996| pages=12853–12910| doi=10.1016/0040-4020(96)00754-5}} Acyl complexes can be generated by insertion of CO into the C–Zr bond resulting from hydrozirconation.{{cite journal | first1=Christopher A.|last1= Bertelo|first2= Jeffrey |last2=Schwartz| title=Hydrozirconation. II. Oxidative homologation of olefins via carbon monoxide insertion into the carbon-zirconium bond| journal=J. Am. Chem. Soc.| volume=97 | issue=1| year=1975| pages=228–230 | doi = 10.1021/ja00834a061|bibcode= 1975JAChS..97..228B}} 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.