((2-Fluoro-6-(methoxymethoxy)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-1-yl)ethynyl)triisopropylsilane is a multifunctional, protected naphthyl building block that combines a masked terminal alkyne, a pinacol boronate and a protected phenolic group on a fluorinated naphthalene core. The compound is catalogued with CAS number 2621932-37-2 and has an empirical formula of C29H42BFO4Si and a molecular weight of approximately 512.54 Da. Its design reflects contemporary medicinal-chemistry practice of installing orthogonal synthetic handles on an aromatic scaffold to permit rapid, sequential diversification in late-stage synthesis.
The protected ethynyl function is present as a triisopropylsilyl (TIPS) ether of a terminal alkyne. The TIPS group is selected because it is robust to many reaction conditions used in multistep synthesis yet is removable under mild fluoride-mediated conditions to liberate the terminal alkyne for downstream transformations such as Sonogashira couplings, copper-catalysed azide�alkyne cycloadditions (CuAAC), oxidative homocouplings or intramolecular cyclisations. The inclusion of an ethynyl handle installed as a TIPS derivative therefore enables timed exposure of the alkyne reactivity at a chosen synthetic stage while avoiding side reactions earlier in the sequence.
The molecule also bears a pinacol boronate ester (4,4,5,5-tetramethyl-1,3,2-dioxaborolane) appended to the naphthalene ring. Boronate esters of this class are widely employed as partners in Suzuki�Miyaura cross-coupling reactions, providing a stable yet versatile organoboron species that can undergo palladium-catalysed transmetalation to install diverse aryl or vinyl fragments. The presence of a boronate on the same ring as an alkynyl substituent allows orthogonal cross-coupling strategies that can selectively exploit the boronate or the alkyne at different stages, facilitating convergent assembly of complex polyaryl or heteroaryl architectures.
A third functional element is the methoxymethyl (MOM)-protected phenolic oxygen (methoxymethoxy), which protects a naphthalen-1-ol motif from undesired reactions during early steps and can be deprotected under acidic conditions when the free phenol is required for further derivatisation or for installation of hydrogen-bonding or metal-binding motifs. The 2-fluoro substituent on the naphthalene ring provides electronic modulation and a metabolic-stability element commonly exploited in drug discovery, as C�F substitution frequently influences lipophilicity, binding interactions and bioavailability without contributing large steric bulk.
The combined presence of TIPS-alkyne, pinacol boronate and MOM protection on a single fluorinated naphthyl core makes this intermediate particularly useful in discovery chemistry where rapid exploration of structure�activity relationships is needed. Typical workflow options include initial Suzuki coupling to replace the boronate with a diverse aryl partner while retaining the masked alkyne, subsequent desilylation and CuAAC or Sonogashira coupling to append polar or heterocyclic fragments, and late-stage MOM deprotection to expose a phenolic handle for hydrogen bonding or conjugation. Alternatively, the exposed terminal alkyne (after desilylation) may be used in intramolecular cyclisations to build fused polycyclic systems that are difficult to access by other routes.
From a synthetic-methodology perspective, installation of the ethynyl group is commonly achieved by alkynylation of a prefunctionalised aryl halide or by �inverse� alkynylation using alkynyl halides under metal-promoted conditions, while boronate esters are introduced through Miyaura borylation of an aryl halide or via directed borylation of the aromatic ring. The selection of TIPS as the alkyne protecting group and pinacol as the boronate protecting diol reflects standard practice for robustness and commercial availability. Chemists handling this intermediate typically store it under inert atmosphere at low temperature to maximise stability, and they confirm structure and purity by NMR, HRMS and chromatographic methods prior to use.
Overall, ((2-fluoro-6-(methoxymethoxy)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-1-yl)ethynyl)triisopropylsilane serves as an enabling fragment for modular synthesis, especially in programmes that require orthogonal functional-group manipulation on a fluorinated aromatic scaffold. Its utility is rooted in the well-established chemistries of silyl-protected alkynes, organoboron cross-couplings and acid-labile oxygen protection strategies, which together enable efficient, chemoselective construction of complex molecules.
References
Dudnik AS & Gevorgyan V (2010) Formal inverse Sonogashira reaction: direct alkynylation of arenes and heterocycles with alkynyl halides. Angewandte Chemie International Edition 49 12 2096�2098. DOI: 10.1002/anie.200906755
Lennox AJJ & Lloyd-Jones GC (2014) Selection of boron reagents for Suzuki�Miyaura coupling. Chemical Society Reviews 43 412�443. DOI: 10.1039/c3cs60197h
Kanwal I, Mujahid A, Rasool N, Rizwan K, Malik A, Ahmad G, Shah SAA, Rashid U & Nasir NM (2020) Palladium and copper catalysed Sonogashira cross coupling: an excellent methodology for C�C bond formation over 17 years � a review. Catalysts 10 443. DOI: 10.3390/catal10040443
|
GHS07 Warning Details
Discovory and Applicatios