Carbonyl linkers

Dressman BA, Singh U, Kaldor SW. Solid phase synthesis of urea libraries using a diversifiable thiophenoxy carbonyl linker. Tetrahedron Lett 1998 39 3631-3634. 

Dressman, B. A. Singh, U. Kaldor, S. W. Solid Phase Synthesis of Urea Libraries Using a Diversifiable Thiophenoxy Carbonyl Linker, Tetrahedron Lett. 1998, 39. 3631. 

The chromium carbonyl linkers 1.40 (98) and 1.41 (99) were prepared from commercial triphenylphospine resin and respectively from pre-formed p-arene chromium carbenes and Fischer chromium amino carbenes. Their SP elaboration is followed by cleavage with pyridine at reflux for 2 h (1.40) and with iodine in DCM for 1 h at rt (1.41) both linkers produce the desired compounds in good yields. A similar cobalt carbonyl linker 1.42 (100) was prepared as a mixmre of mono- (1.42a) and bis- (1.42b) phosphine complex, either from pre-formed alkyne complexes on triphenylphosphine resin or by direct alkyne loading on the bisphosphine cobalt complex traceless cleavage was obtained after SP transformations by aerial oxidation (DCM, O2, hp, 72 h, rt) and modified alkynes were released with good yields and... 

The Mizoroki-Heck reaction promoted by microwave irradiation was first described by Laihed and Hallberg [205]. For easy catalyst recovery, solid-supported systems were often used. An a-heteroatom-substituted carbonyl linker has been utilized in solid-phase approaches to oxinolines by Pummerer cyclization [206]. The reaction performed with s/c = 20 in the presence of phosphine ligands (ratio ligand/palladium-precursor = 1 1) in 88-99% yield at 7 h reaction time. 

The development of suitable linkers is a continuous area of interest in solid-supported synthesis. Based on their previously explored traceless linking strategy using HASC (a-heteroatom-substituted carbonyl) linkers employing Smb, Procter and coworkers have demonstrated the use of a novel sulfur-based linker for the synthesis of the tetra-... 

Proliferous Polymerization. Eady attempts to polymerize VP anionicaHy resulted in proliferous or "popcorn" polymerization (48). This was found to be a special form of free-radical addition polymerization, and not an example of anionic polymerization, as originally thought. VP contains a relatively acidic proton alpha to the pyrroHdinone carbonyl. In the presence of strong base such as sodium hydroxide, VP forms cross-linkers in situ probably by the following mechanism ... 

Anthranilic acid derivatives of genus D that possess carbamate and urea linkers (W contains an oxygen or nitrogen atom directly linked to the carbonyl carbon, e.g., compounds 18 and 19 respectively) were claimed as GPR109A agonists in a patent application [65]. 

Perhaps a better design for a bis-hydrazide compound to modify carboxylate particles would include a short PEG spacer arm between the two hydrazide groups. This type of linker would result in a hydrophilic surface due to the presence of the PEG spacers, while providing the terminal hydrazide functionality necessary for coupling to carbonyl compounds. Unfortunately, this type of compound is not currently available, so the aliphatic bis-hydrazides are the only choice. 

H-donor for both the intramolecular hydrogen bond with the amide linker carbonyl the carboxylic acid group is deprotonated. 

The reaction of 8 with oxygen (Scheme 1) leads to the bis-carbonyl-0-oxide 10 and can be seen either as a reaction of two carbene centers or as a reaction of two radical centers, giving a bis-peroxide. The IR and UV data suggest that there is little interaction between the two carbonyl centers via the linker. 

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