XPhos (CAS 564483-18-7) is the most broadly competent ligand in the Buchwald family — enabling Suzuki-Miyaura, Buchwald-Hartwig, Negishi, Heck, and Sonogashira couplings with a single, air-stable phosphine. Its molecular identity (C₃₃H₄₉P, MW 476.72 g/mol) is verified independently through PubChem [004]. Developed by Professor Stephen Buchwald's group at MIT and commercialized through MilliporeSigma, XPhos has become the default choice for initial reaction screening in pharmaceutical process chemistry worldwide. The global phosphine ligand market — in which Buchwald ligands like XPhos hold a dominant R&D share — was valued at $452 million in 2025 and is projected to reach $685 million by 2032 [003].
What Makes XPhos Structurally Unique?
XPhos (2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl) combines three structural features that drive its exceptional catalytic performance [001]:
| Property | Value |
|---|---|
| CAS Number | 564483-18-7 |
| Molecular Formula | C₃₃H₄₉P |
| Molecular Weight | 476.72 g/mol |
| Melting Point | 187–190 °C |
| Purity | ≥98% |
| SMILES | CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C2=C(P(C3CCCCC3)C4CCCCC4)C=CC=C2 |
- Two cyclohexyl groups on phosphorus provide electron-rich character essential for oxidative addition to aryl chlorides — the most abundant and economical class of electrophiles
- Three isopropyl substituents on the lower ring create steric bulk that promotes the catalytically active mono-ligated Pd(0) species
- The biphenyl backbone enables Pd-arene interactions that stabilize reactive intermediates
Professor Buchwald's group demonstrated the ligand's power in the *Journal of the American Chemical Society* (2007, Vol. 129, pp. 3358-3366), showing that XPhos-based catalysts achieve outstanding efficiency with heteroaryl halides — substrates that had historically poisoned less robust catalyst systems [002].
Which Cross-Coupling Reactions Can XPhos Catalyze?
Sigma-Aldrich documentation lists XPhos as suitable for Suzuki-Miyaura, Buchwald-Hartwig, Heck, Hiyama, Negishi, Sonogashira, and Stille couplings — making it one of the most broadly scoped ligands in the entire Buchwald portfolio [001].
The ligand is particularly effective with unactivated aryl chlorides and heteroaryl substrates (pyridines, pyrimidines, thiophenes, indoles) — compound classes that dominate pharmaceutical synthesis and frequently challenge simpler phosphine ligands [002].
How Does XPhos Compare to Other Buchwald Ligands?
| Ligand | CAS | Specialty | Best For |
|---|---|---|---|
| **XPhos** | 564483-18-7 | Universal scope | Broad substrate compatibility |
| SPhos | 657408-07-6 | Suzuki specialist | Electron-rich aryl chlorides |
| RuPhos | 787618-22-8 | C–N coupling | Primary amines, anilines |
| tBuXPhos | 564483-19-8 | C–O coupling | Phenol/aryl halide coupling |
| BrettPhos | 1070663-78-3 | Amide coupling | Primary amides, sulfonamides |
XPhos's unique position as the "generalist" makes it the most frequently selected ligand for initial reaction screening — only switching to a specialist (RuPhos for C–N, tBuXPhos for C–O) when XPhos proves insufficient.
What Are the Commercial Options for Purchasing XPhos?
XPhos is exclusively available through MilliporeSigma (Sigma-Aldrich) under catalog number 638064, protected by U.S. Patents 7,223,879, 6,307,087, and 6,395,916 [001].
| Pack Size | Approximate Price |
|---|---|
| 1 g | $185 |
| 5 g | $344 |
| 25 g | $1,220 |
| 100 g | $3,350 |
For most research and small-scale process development, the 5 g pack represents the cost-efficiency optimum at $68.80/g [001].
What Is the Market Outlook for Phosphine Ligands?
The global phosphine ligand market — in which Buchwald-type biaryl phosphines represent a significant and growing segment — was valued at $452 million in 2025 and is projected to reach $685 million by 2032, growing at a compound annual growth rate of 6.2% [003]. This growth is driven by expanding pharmaceutical R&D pipelines, increasing drug candidate complexity requiring sophisticated cross-coupling, and the agrochemical industry's shift toward selective active ingredients.
Frequently Asked Questions
Q: What is XPhos used for?
XPhos is a Buchwald biaryl phosphine ligand used in palladium-catalyzed cross-coupling reactions including Suzuki-Miyaura, Buchwald-Hartwig, Negishi, Heck, and Sonogashira couplings. It is particularly effective with heteroaryl halides and unactivated aryl chlorides [001].
Q: What is the CAS number of XPhos?
564483-18-7 [001].
Q: Is XPhos air-stable?
Yes. Unlike earlier-generation phosphine ligands that required glovebox handling, XPhos is air-stable at ambient conditions — a critical practical advantage for routine laboratory use [001].
Q: How does XPhos compare to SPhos?
Both are highly universal Suzuki-Miyaura ligands. XPhos offers broader cross-coupling scope (Suzuki + Buchwald-Hartwig + Negishi + Heck + Sonogashira), while SPhos provides marginally higher activity specifically for electron-rich aryl chloride Suzuki couplings [001].
Q: What is the molecular weight of XPhos?
476.72 g/mol [001].
Q: Where can I buy XPhos?
XPhos is available from MilliporeSigma (catalog #638064) in 1 g, 5 g, 25 g, and 100 g pack sizes. It is patent-protected (US 7,223,879) and exclusively distributed through Sigma-Aldrich [001].
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*For procurement inquiries about XPhos and related Buchwald ligands, contact our team.*
References & Sources
https://www.sigmaaldrich.com/US/en/product/aldrich/638064
Journal of the American Chemical Society | 2007 | DOI: 10.1021/ja068577p
https://www.qyresearch.com/reports/5879844/phosphine-ligands
https://pubchem.ncbi.nlm.nih.gov/
