Chemical Synthesis

Gold Catalyst

Introduction

Hashmi, Toste, Echavarren, and Haruta, among others, have fueled the advance of gold into the forefront of transition metal catalysis.1,2 Phosphine ligated gold(I) complexes have risen as powerful C–C, C–N, and C–O bond forming catalysts due to the ease with which they can activate C=C and C=C bonds thus allowing for unique rearrangements or reactions with various nucleophiles. Gold catalysis provides an excellent method to construct complex chemical architectures in a mild manner that would be difficult to achieve using other reaction paradigms. As illustrated below, the active catalysts are typically prepared by the addition of a silver activator to a gold halide precatalyst, although there are examples of isolable gold catalysts.

Sigma-Aldrich is proud to offer a treasure-trove of gold precatalysts and silver salts, as well as an extensive portfolio of unsaturated building blocks to accelerate your research success in this exciting field.

References: 

  1. For recent examples, see: (a) Shapiro, N. D.; Toste, F. D. J. Am. Chem. Soc., 2007,  129, 4160. (b) Jiménez-Núñez, E.; Echavarren, A. M. Chem. Commun. 2007, 333. (c) Echavarren, A. M. et al. Angew. Chem., Int. Ed. 2006, 45, 5452. (d) Haruta, M. Nature 2005, 437, 1098. (e) Luzung, M. R et al. J. Am. Chem. Soc. 2004, 126, 10858. (f) Hashmi, A. S. K. Gold. Bull. 2004, 37, 51. 
  2.  For recent reviews, see: (a) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem., Int. Ed. 2006, 45, 7896. (b) Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006, 4555. (c) Zhang, L. et al. Adv. Synth. Catal. 2006, 348, 2271. (d) Hashmi, A. S. K. Angew. Chem., Int. Ed., 2005, 44, 6990.
  3. For a comprehesion review on gold catalysis, see: Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180.

 

Advantages

  • Catalysts readily activate alkenes, alkynes, and alkenes in a myriad of transformations
  • Promote regio-, diastereo-, and enantioselective processes
  • Catalysts are typically air- and water-stable and reactions can be performed in an “open flask”
  • Exceptional functional group tolerance
  • Market exclusivity for selected gold catalysts

 

Representative Applications

Rearrangement of Allylic Acetates

Marion et al. reported the catalyzed isomerization of allylic acetates. Using a gold complex with a N-heterocyclic carbine ligand, the researchers reported the first gold catalyzed allylic rearrangement. To illustrate the versatility of the catalyst, several allyl acetates were rearranged with excellent yields.

Rearrangement of Allylic Acetates image

Reference:
Marion, N. et al. Org. Lett. 2007, 9, 2653.

Isomerization of Allenyl Carbinol Esters

Buzas et al. reported the synthesis of a series of 1,3-butadien-2-ol from different allenes using a gold complex as catalyst. Butadiene building blocks are of interest for Diels-Alder reactions, [4+1] cycloaddition and asymmetric hydrogenation. The catalyst utilized in this reaction is a gold complex with XPhos as a ligand. With a low loading of 1mol%, the authors were able to synthesize a variety of butadiene with yields up to 100%.

Isomerization of Allenyl Carbinol Esters image

Reference:
Buzas, A. K. et al. Org. Lett. 2007, 9, 985.

Intramolecular [4+2] Cycloadditions of Arylalkynes or 1,3-Enynes with Alkenes

Echavarren and co-workers reported the synthesis of pycnantuquinones A derivatives, catalyzed by [4+2] cycloaddition of dienynes. Using a stable crystalline gold complex based on the Buchwald ligand, the researchers were able to synthesize a family of derivatives with good yields.

Intramolecular [4+2] Cycloadditions of Arylalkynes or 1,3-Enynes with Alkenes image

Reference:
Nieto-Oberhuber, C. et al. J. Am. Chem. Soc. 2008, 130, 269.



Cyclopropanation

The Toste group demonstrated that olefins undergo stereoselective cyclopropanation (cis) with propargyl esters in the presence of in situ generated Ph3PAuSbF6 and is thus a complement to the trans selectivity observed in transition metal catalyzed cyclopropanation of olefins using α-diazoacetates.

 

Isomerization of 1,6-Enynes

Echavarren and others have studied a variety of gold catalyzed cyclizations of 1,6-enynes with or without the presence of nucleophiles. A variety of gold(I) catalysts are active, including Ph3PAuCH3, Ph3PAuSbF6, and Au[P(t-Bu)2(o-biphenyl)]SbF6 complexes. The reactions can tolerate heteroatoms located between the olefin and alkyne moieties.

Isomerization of 1,5-Enynes

Under gold(I) catalysis, 1,5-enynes of varying substitution patterns rearrange to give bicyclo[3.1.0]-hexenes in a high yielding, stereocontrolled fashion. For optically active substrates, the reaction can occur with efficient chirality transfer. The catalyst system utilizes Ph3PAuCl in combination with AgBF4, AgPF6, or AgSbF6 activators.



Isomerization of 1,4-Enynes (Rautenstrauch Rearrangement)

The Rautenstrauch rearrangement of 1,4-enynes provides an expeditious route to a diverse portfolio of functionalized cyclopentanones. Chiral 1-ethynyl-2-propenyl pivalates efficiently rearrange enantioselectively under mild conditions. Either Ph3PAuSbF6 or Ph3PAuOTf (both generated in situ) can be used, depending on the identity of the substrates.

Cyclization of ε-Acetylenic Carbonyls (Conia-Ene Reaction)

The non-catalyzed Conia-ene reaction provides access to methylenecyclopentanes without the need for deprotonation, however, the high temperatures required often result in diminished yields. Toste and co-workers reported a mild catalytic version of this reaction that proceeds under neutral conditions at ambient temperatures.

5-Endo-dig Carbocyclizations

While the gold(I)-catalyzed Conia-ene cycloisomerization is limited to terminal γ-alkynes, the related 5-endo-dig reaction allows for cyclization onto non-terminal δ-alkynes providing access to cyclopentene derivatives. This synthetic methodology can be applied to the preparation of simple bicyclic molecules, as well as in heterocycle synthesis (below) and halogenated cyclopentenes via alkynyl halide precursors.

Propargyl Claisen Rearrangement

The gold catalyst [(Ph3PAu)3O]BF4 provides access to a variety of homoallenic alcohols via a rapid two-step, one-pot sequence of a Claisen rearrangement of a propargyl vinyl ether followed by reduction of the aldehyde functionality. The reactions are generally high yielding and the robust catalyst system also shows superb ability to relay resident chirality into the allene products.

Stereoselective Synthesis of Dihydropyrans

Using gold(I) catalysis, 2-substituted dihydropyrans are readily prepared from propargyl vinyl ethers in a stereocontrolled fashion.

Hydroamination of Alkenes and Alkynes
Widenhoefer and He have explored a variety of gold catalyzed hydroamination reactions with alkenes and alkynes, and both intra- and intermolecular variants were studied. Using either Au(I) or Au(III) catalysts, amines, pyrrolidines, imines, and indoles can be easily accessed.

Hydrofunctionalization of Allenes with C, N, and O Nucleophiles

Vinylated tetrahydrofurans, tetrahydropyrans, pyrrolidines, and piperidines can be readily prepared from the corresponding heteroatom functionalized allenes using Au[P(t-Bu)2(o-biphenyl)]Cl and one of several silver activators. Alternatively, allene tethered indoles can be used in the preparation of carbazole derivatives.

 

Stereoselective Synthesis of Functionalized Dihydrofurans

Gagosz and co-workers have prepared a variety of 2,5-dihydrofurans via formation of an allene intermediate followed by cycloisomerization. The rapid reactions occur in the presence of Ph3PAuNTf2, and complete chirality transfer is observed.

Ring Expansions of Alkynylcycloalkanols

1-Alkynylcycloalkanols rapidly rearrange to the corresponding 2-alkylidenecycloalkanones in the presence of several gold catalysts. The high yielding reactions provide a single olefin isomer when internal alkynes are employed.

Acetylenic Schmidt Reaction

In the presence of a gold catalyst, pyrroles of varying substitution patterns can be prepared by an intramolecular acetylenic Schmidt reaction of homopropargyl azides.

 


Product Information


Product Product Name Structure Add to Cart
404217

Chloro(trimethylphosphine)gold(I), 99%


288225 Chloro(triethylphosphine)gold(I), 97%
254037 Chloro(triphenylphosphine)gold(I), 99.9+%
677922

Bis(trifluoromethanesulfonyl)imidate-(triphenylphosphinegold(I) 0.5 toluene adduct


665177

Chloro(tris(4-trifluoromethylphenyl)phosphinegold(I), 99%


679771

[1,1'-biphenyl-2-yl(di-tert-butyl)phosphine]chlorogold(I), 98%


665185

Bis(diphenylphosphinomethane)dichlorodigold(I), 97%


665142

Tris(triphenylphosphinegold)oxonium tetrafluoroborate


677876

Trichloro(pyridine)gold(III), 97%


1,3-Bis(2,6-diisopropylphenyl-imidazol-2-ylidene)gold(I) chloride
(Acetonitrile)[(2-biphenyl)di-tert-butylphosphine]gold(I) hexafluoroantimonate
Dichloro(2-pyridinecarboxylato)gold
2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl gold(I) bis(trifluoromethanesulfonyl)imide
2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl gold(I) chloride
Chloro[tris(2,4-di-tert-butylphenyl)phosphite]gold
481130

Gold(I) chloride, 99.9% (metals basis)

AuCl
379948

Gold(III) chloride, 99.99+%

AuCl3
G4022

Gold(III) chloride trihydrate, ≥49.0% as Au

HAuCl4 • 3H2O
298174

Sodium tetrachloroaurate(III) dihydrate, 99%

NaAuCl4 • 2H2O
398470

Gold(III) bromide hydrate, 99.9%

AuBr4 • xH2O
674583

Silver perchlorate, 97%

AgClO4
176427

Silver p-toluenesulfonate, ≥99%

Ag(OSO2C6H4CH3)
176435

Silver trifluoromethanesulfonate, ≥99%

Ag(OSO2CF3)
550256

Silver methanesulfonate

Ag(OSO2CH3)
T62405

Silver trifluoroacetate, 98%

Ag(CO2CF3)
208361

Silver tetrafluoroborate, 98%

AgBF4
227722

Silver hexafluorophosphate, 98%

AgPF6
227730

Silver hexafluoroantimonate(V), 98%

AgSbF6
668001

Silver bis(trifluoromethanesulfonyl)imide, 97%

AgN(OSO2CF3)2