Linker acetal

The Leznoff acetal linker 69 was used to anchor an aldehyde to the solid support and following a series of reactions, the aldehyde was released by acidic cleavage [78]. An application of this resin was demonstrated for a biaryl aldehyde library synthesis which incorporated a Suzuki-Miyaura reaction (Scheme 37) [79]. Cleavage was effected by a solution of 3 M HC1... 

Bleicher KH, Wareing JR. Phil Acetic Acid A new linker for solid phase organic synthesis. Tetrahedron Lett 1998 39 4591 1594. 

Chamoin S, Houldsworth S, Kruse CG, Bakker WI, Snieckus V. The Suzuki-Miyaura cross coupling reactions on solid support. Link to solution phase directed ortho metalation. The Leznoff acetal linker approach to biaryl and heterobiaryl aldehydes. Tetrahedron Lett 1998 39 4179-4182. 

Fig. 2 Deshielding of polyplexes. After endocytosis of polyplexes into endosomes, deshielding by cleavage of PEG hydrazone or acetal linkers...

The successfully generated chalcones could be cleaved by treatment with trifluoro-acetic acid or used for the subsequent synthesis of pyrimidines [45], Condensation of the polymer-bound chalcones with benzamidine hydrochloride under microwave irradiation for 30 min furnished the corresponding pyrimidines in good yields after TFA-induced cleavage. This new robust support/linker system for SPOT synthesis has been demonstrated to be compatible with a range of organic reactions and highly applicable for microwave conditions. 

After linker coupling, a positive Kaiser test is observed (note 8), which indicates a small amount of free NH2. The free NH2 can be capped with acetic anhydride. The above dried MicroTubes (1) were treated with a 100 mL solution of acetic anhydride (0.5 M) and DIEA (0.6 M) in DCM for 1-2 h. After the supernatant was removed by aspiration, the MicroTubes were washed three times with DMF, MeOH, and DCM and dried under vacuum for 3h after a final washing with ethyl ether. The Kaiser test was negative. 

O-stannylene acetals,84 glycals and 1,2-anhydrosugars,85 and to selective de-O-benzylation of position-2 with TIBAL, DIBAL-H57 or Lewis acid catalysts,86 or to the one-pot access to 3-O-benzyl-4,6-0-benzylidene glucosides by tandem catalysis recently reported.87 The 1,2-lactones recently reported by Linker and co-workers35 are also synthons which provide... 

Scheme 27. Synthesis of bis(pyrazol-l-yl)acetic acids with solid phase linkers (68).

In our first attempt to bind linker-modified bis(pyrazol-l-yl)acetic acids to a solid phase we used Merrifield resin, which is one of the most popular solid phase supports. Since Merrifield polymer was designed to bind carboxylic acids, we used the ester methyl 2,2-bis(3,5-dimethylpyrazol-l-yl)-3-hydroxypropionate (52) instead of the 2,2-bis(3,5-dimethylpyrazol-l-yl)-3-hydroxypropionic acid (49). 

Acetals and ketals are very important protecting groups in solution-phase synthesis, but only a few constructs have been used as linkers in solid-phase synthesis (Tab. 3.3). The THP-linker (22) (tetrahydropyran) was introduced by Ellman [54] in order to provide a linker allowing the protection of alcohols, phenols and nitrogen functionalities in the presence of pyridinium toluene sulfonate, and the resulting structures are stable towards strong bases and nucleophiles. Other acetal-linkers have also been used for the attachment of alcohols [55, 56]. Formation of diastereomers caused by the chirality of these linkers is certainly a drawback. Other ketal tinkers tike... 

A dendrimer containing a dye as core was synthesized by Zhang and coworkers (Fig. 7.7) [39, 40]. The feoc-protected amine endgroups of this [Gl] dendrimer were equipped with a 4-(hydroxymethyl)phenoxy acetic acid (HMPA) linker performing several reaction steps to obtain the red colored dendritic support (14). 

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