Traceless solid-phase synthesis

Plunkett MJ, Ellman JA. A silicon-based linker for traceless solid-phase synthesis. J Org Chem 1995 60 6006-6007. 

B. A. Lorsbach, R. B. Miller, M. J. Kurth, Reissert-Based Traceless Solid-Phase Synthesis Isoquinoline, and Isoxazoline-Containing Heterocycles , J. Org. Chem. 1996, 61, 8716-8717. 

Recently, palladium-catalyzed carbonylation of chloropyrimido[4,5-d]pyrimidines has been reported (Equation 51) <2006W0065703>. Raney nickel-mediated desulfurization of alkylthiopyrimido[4,5-, pyrimidines was described in GHEC(1984), and has been applied recently both in the desulfurization of reduced species (Equation 52) <2001WO64679> and for cleavage of sulfur linkages in traceless solid-phase synthesis <1999BMCL965,... 

T. Ruhland, K. Andersen and H. Pedersen, Selenium-linking strategy for traceless solid-phase synthesis Direct loading, aliphatic C-H bond formation upon cleavage and reaction monitoring by gradient MAS NMR spectroscopy, J. Org. Chem., 1998, 63, 9204-9211. 

P rez, R., Beryozkina, T., Zbruyev, O.I., Haas, W. and Kappe, C.O., Traceless solid phase synthesis of bi-cyclic dihydropyrimidones using multidirectional cyclization cleavage, /. Comb. Chem., 2002,4, 501-510 and references cited therein. 

The Traceless Solid-Phase Synthesis of Organic Molecules... 

Pourbaix C, Carreaux F, Carboni B, Deleuze H, Boronate linker for traceless solid-phase synthesis, Chem. Commun., 14 1275-1276, 2000. 

Traceless solid-phase synthesis of 2,6,9-trisubstituted purines from resin-bound 6-thiopurines <02T7911>, and microwave assisted solid-phase synthesis of 2,6,9-trisubstituted purines <02TL6169> have been described. A resin-capture and release strategy toward combinatorial libraries of 2,6,9-trisubstituted purines has been reported <02JCO183>. Alkylated purines chlorinated at the 6,8- or 2,6,8-positions can be captured onto a solid support and further elaborated by aromatic substitution or via palladium catalyzed crosscoupling reactions <02JA1594>. 

Scheme 14.8 Traceless solid-phase synthesis of olomoucine analogs developed by Schultz and coworkers [58],...

Ruhland et al. synthesized polystyrene-bound selenium 72 and applied it to traceless solid-phase synthesis of a library of aryl alkyl ethers 73 (Scheme 48) [93]. 

Based on this methodology, a traceless solid-phase synthesis of 4,5-diarylated... 

Moreover, cyclative cleavage is an often used technique that has been developed into a powerful tool for traceless solid-phase synthesis. One example of particular... 

In the traceless, solid-phase synthesis of hetero-annulated l,3-oxazine-6-ones, significant rate enhancement was observed across a range of steps carried out using microwave heating (Scheme 4.15)." ° In a similar traceless, solid-phase approach, a number of 2,4,6-trisubstituted thiazolo[4,5-rf]pyridine-5,7-dione derivatives have been prepared using microwave heating as a key step. An amino ester resin was first swollen in DMSO then an isocyanate was added, and the reaction mixture was heated to 150 °C to yield a thiazolourea, which was converted to the final product in another three steps on the support before a final cleavage protocol (Scheme 4.16). 

On the other hand, a traceless solid-phase synthesis of 2,3-disubstituted indoles 115 was developed using PdCl2(PPh3)2 as the precatalyst, tetramethylgaunidine (TMG) as the base and under double coupling conditions. Solution-phase conditions, in this case, caused incomplete reactions, and large quantities of multiple acetylene insertion side products were observed, presumably due to the poor solubility of the inorganic bases. 

Sodium benzenesulfinate resin 43 can also be used to prepare a traceless solid-phase synthesis for 3,4-dihydropyrimidine-2-ones 54 and 55 (Scheme 12.13). This strategy highlighted the sulfinate acidification to yield resin-bound benzenesulfinic acid 52, followed by the condensation of urea or thiourea with aldehydes and sulfinic acid. A one-pot cyclization-dehydration process with 1,3-dicarbonyl compounds or )8-ketoesters (generated in situ by treating the latter reagents with KOH/EtOH) afforded 54, while cyclization with a mixture of pyrrolidine and /8-ketoacid in ethanol followed by the addition of TsOH HaO gave the ester form of 55. When THF was used as a solvent, the free carboxylic acid form of 55 was obtained in comparable yields. 

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