View source for 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     = Cp<sub>2</sub>ZrClH, zirconocene chloride hydride
| SystematicName = chloridobis(η<sup>5</sup>-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 = C<sub>10</sub>H<sub>11</sub>ClZr
| 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 [[empirical formula|formula]] (C<sub>5</sub>H<sub>5</sub>)<sub>2</sub>ZrHCl, 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]].<ref>{{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}}</ref>

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

: (C<sub>5</sub>H<sub>5</sub>)<sub>2</sub>ZrCl<sub>2</sub>  +  {{1/4}}&nbsp;LiAlH<sub>4</sub>  →  (C<sub>5</sub>H<sub>5</sub>)<sub>2</sub>ZrHCl  +  {{1/4}}&nbsp;[[Lithium tetrachloroaluminate|LiAlCl<sub>4</sub>]]

This reaction also affords (C<sub>5</sub>H<sub>5</sub>)<sub>2</sub>ZrH<sub>2</sub>, which is treated with [[methylene chloride]] to give Schwartz's reagent <ref name=buchwald>{{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 }}</ref>

An alternative procedure that generated Schwartz's reagent from dihydride has also been reported.<ref name=wpif2>{{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 }}</ref> Moreover, it's possible to perform an ''in situ'' preparation of (C<sub>5</sub>H<sub>5</sub>)<sub>2</sub>ZrHCl from zirconocene dichloride by using LiH. This method can also be used to synthesize isotope-labeled molecules, like olefines by employing Li<sup>2</sup>H or Li<sup>3</sup>H as reducing agents.<ref>{{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 }}</ref>

Schwartz's reagent has a low solubility in common organic solvents.<ref>{{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 }}</ref>  The trifluoromethanesulfonate (C<sub>5</sub>H<sub>5</sub>)<sub>2</sub>ZrH(OTf) is soluble in THF.<ref>{{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 Cp<sub>2</sub>ZrH(OSO<sub>2</sub>CF<sub>3</sub>), a Soluble Monomeric Alternative for Schwartz's Reagent, and the Solid-State Structure of Its Dimer, [Cp<sub>2</sub>Zr(OSO<sub>2</sub>CF<sub>3</sub>)(-H)]<sub>2</sub><big>.</big>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 }}</ref>

==Structure==
The complex adopts the usual "clam-shell" structure seen for other Cp<sub>2</sub>MX<sub>n</sub> complexes.<ref>{{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 }}</ref> The dimetallic structure has been confirmed by [[Microcrystal electron diffraction]].<ref>{{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 }}</ref>  The results are consistent with [[Fourier-transform infrared spectroscopy|FT-IR spectroscopy]], which established that the hydrides are bridging. [[Solid-state nuclear magnetic resonance|Solid state NMR]] spectroscopy also indicates a dimeric structure.  The X-ray crystallographic structure for the methyl compound (C<sub>5</sub>H<sub>5</sub>)<sub>4</sub>Zr<sub>2</sub>H<sub>2</sub>(CH<sub>3</sub>)<sub>2</sub> compound is analogous.<ref>{{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 }}</ref>

==Uses in organic synthesis==
Schwartz's reagent reduces [[amide]]s to [[aldehyde]]s.<ref name=leig>{{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 Cp<sub>2</sub>ZrHCl (Schwartz's Reagent)| journal=[[Organic Syntheses|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}}</ref>

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

Schwartz's reagent has been used in the synthesis of some [[macrolide antibiotics]],<ref name=duffey>{{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}}</ref><ref name=wu>{{cite journal | first1= J. |last1=Wu|first2= J. S. |last2=Panek | title=Total Synthesis of (−)-Virginiamycin M<sub>2</sub>: 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}}</ref> (−)-motuporin,<ref name=hu>{{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}}</ref> and antitumor agents.<ref name=nic>{{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}}</ref>

==Hydrozirconation==
'''Hydrozirconation''' is a form of [[hydrometalation]].  Substrates for hydrozirconation are [[alkene]]s and [[alkyne]]s. With terminal alkynes the terminal vinyl zirconium product is predominantly formed. Secondary reactions are [[nucleophilic addition]]s, [[transmetalation]]s,<ref>{{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).
}}</ref> [[conjugate addition]]s,<ref>[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).</ref> [[coupling reaction]]s, [[carbonylation]] and [[halogenation]].

[[Computational chemistry|Computational studies]] indicate that hydrozirconation occurs from the interior portion.<ref name=pank>{{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 XAlBu<sup>i</sup><sub>2</sub> in the Presence of Cp<sub>2</sub>ZrCl<sub>2</sub> Catalyst. II.(1) Olefin Interaction with Catalytically Active Centers| journal=[[Organometallics]]| volume= 30 | issue=22| year=2011| pages=6078–6089| doi = 10.1021/om200518h}}</ref><ref name=wang>{{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 Cp<sub>2</sub>Zr(H)Cl| journal=[[Organometallics]]| volume=29 | issue=1| year=2010| pages=42–51 | doi = 10.1021/om900371u}}</ref>
When treated with one equivalent of Cp<sub>2</sub>ZrClH, [[diphenylacetylene]] gives the corresponding alkenylzirconium as a mixture of [[cis isomer|cis and trans isomer]]s. With two equivalents of hydride, the endproduct was a mixture of [[erythro]] and [[threo]] zircono alkanes:

:[[Image:Alkynehydrozirconation1970.svg|600px|Alkyne hydrozirconation Weigold 1970]]
In 1974 Hart and Schwartz reported that the organozirconium intermediates react with [[electrophile]]s such as [[hydrochloric acid]], [[bromine]] and [[acid chloride]]s to give the corresponding [[alkane]], [[bromoalkane]]s, and [[ketone]]s:<ref>{{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 }}</ref>
 
:[[Image:AlkenehydrozirconationSchwarz1974.svg|600px|Alkene hydrozirconation Schwarz 1974]]
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]]:<ref>{{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 }}</ref><ref>The electrophile in this reaction is [[iodine]]. The additive is believed to promote [[kinetic reaction control]].</ref>

:[[Image:HydrozirconationReversedregioselectivity.svg|650px|Hydrozirconation with reversed regioselectivity Zhang 2007]]

One example of a [[one-pot synthesis|one-pot]] hydrozirconation - carbonylation - coupling is depicted below:<ref>{{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}}</ref><ref>Reagents: [[phenylacetylene]], Schwartz's reagent, [[tetraphenylpalladium]] and the [[iodane]] [[diphenyliodonium]][[tetrafluoroborate]] ([[phenyl]] group donor)</ref>

:[[Image:Hydrozirconationcarbonylationcoupling.svg|600px|Hydrozirconation carbonylation coupling Kang 2002]]

With certain [[allyl alcohol]]s, the [[Alcohol (chemistry)|alcohol]] group is replaced by nucleophilic carbon forming a [[cyclopropane]] ring:<ref>{{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 }}</ref> The selectivity of the hydrozirconation of alkynes has been studied in detail.<ref name=sun>{{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}}</ref><ref name=panek>{{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}}</ref> 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 <ref name=wpif>{{cite journal | first1=Peter |last1=Wipf |first2=Heike|last2= Jahn| title=Synthetic applications of organochlorozirconocene complexes| journal=[[Tetrahedron (journal)|Tetrahedron]]| volume= 52 | issue=40| year=1996| pages=12853–12910| doi=10.1016/0040-4020(96)00754-5}}</ref> [[Acyl]] complexes can be generated by insertion of [[Carbon monoxide|CO]] into the C–Zr bond resulting from hydrozirconation.<ref name=bertelo>{{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}}</ref> 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.

==Further reading==
*{{cite journal | first1=D. W. |last1=Hart |first2=J. |last2=Schwartz| title=Hydrozirconation. Organic Synthesis via Organozirconium Intermediates. Synthesis and Rearrangement of Alkylzirconium(IV) Complexes and Their Reaction with Electrophiles| journal=[[J. Am. Chem. Soc.]]| volume=96 | issue=26| year=1974 | pages=8115–8116 | doi = 10.1021/ja00833a048|bibcode=1974JAChS..96.8115H }}
*{{cite journal | first1=J. |last1=Schwartz |first2=J. A. |last2=Labinger| title=Hydrozirconation: A New Transition Metal Reagent for Organic Synthesis | journal=[[Angew. Chem. Int. Ed.]]| volume= 15 | issue=6| year=2003| pages=330–340| doi =10.1002/anie.197603331}}
*{{cite journal | first1=Donald W. |last1=Hart |first2=Thomas F. |last2=Blackburn |first3=Jeffrey |last3=Schwartz| title=Hydrozirconation. III. Stereospecific and regioselective functionalization of alkylacetylenes via vinylzirconium(IV) intermediates| journal=[[J. Am. Chem. Soc.]]| volume= 97 | issue=3| year=1975| pages=679–680 | doi = 10.1021/ja00836a056|bibcode=1975JAChS..97..679H }}

==References==
{{reflist|30em}}

==External links==
{{commons category}}
*[http://orgchem.chem.uconn.edu/namereact/schwartz.html Examples in organic synthesis] at the University of Connecticut website
{{Cyclopentadienide complexes}}
[[Category:Metallocenes]]
[[Category:Organozirconium compounds]]
[[Category:Cyclopentadienyl complexes]]
[[Category:Reagents for organic chemistry]]
[[Category:Chloro complexes]]
[[Category:Hydrido complexes]]
[[Category:Zirconium(IV) compounds]]