Aldehyde-functionalized silanes

Aldehyde-functionalized Silanes New Compounds to Improve the Immobilization of Biomolecules... 

We have synthesized aldehyde-functionalized silanes as a new class of spacer molecules for silica surfaces. The aldehyde group can be used to attach biomolecules directly to the surface, with no bifunctional crosslinking species required (Fig. IB) [3]. As many immobilization problems are closely related to the use of the crosslinking agent (e.g., glutaraldehyde tends to form undesirable polymers) [4], the development of a one-step immobilization method is a significant improvement. 

It presents a comparison of the observed GOD activities with activity of GOD physisorbed on native, underivatized CPG. An increase of enzyme activity over a time of four weeks was observed. The first bar shows the absorption of the sample immobilized without any reagent on native CPG. The second bar results from immobilization using APTES/GA, and the last two bars show the activity of GOD immobilized using aldehyde-functionalized silanes with the same chain length (C7) but differing in the number of substituent efrioxy groups. 

The following advantages of the immobilization using aldehyde-functionalized silanes have been demonstrated in our preliminary study. 

Our measures to overcome these problems include the preparation of aldehyde-functionalized silanes as a new class of spacer molecules for silica surfaces, the application of a series of such compounds with up to three ethoxy groups and different chain length of the anchor group to the surface of controlled pore glass (CPG) as a model substrate, the immobilization of glucose oxidase (GOD) and systematic activity studies over a period of four weeks. 

Keywords Hydroformylation / Aldehyde-Functionalized Silanes / Regioselectivity... 

J. Grobe, C. Bruning, M. Wessels, "Aldehyde-functionalized Silanes New Compounds to Improve the Immobilization of Biomolecules", in Organosilicon Chemistry II From Molecules to Materials (Eds. N. Auner, J. Weis), VCH, Weinheim, 1996, p. 243. 

Many other functional silane coupling agents are available from commercial suppliers, including hydroxyl, aldehyde, acrylate and methacrylate, and anhydride compounds. Substrate modification procedures similar to those discussed above can be used with these reagents to link a biomolecule to an inorganic surface or particle. 

The ruthenium carbene catalysts 1 developed by Grubbs are distinguished by an exceptional tolerance towards polar functional groups [3]. Although generalizations are difficult and further experimental data are necessary in order to obtain a fully comprehensive picture, some trends may be deduced from the literature reports. Thus, many examples indicate that ethers, silyl ethers, acetals, esters, amides, carbamates, sulfonamides, silanes and various heterocyclic entities do not disturb. Moreover, ketones and even aldehyde functions are compatible, in contrast to reactions catalyzed by the molybdenum alkylidene complex 24 which is known to react with these groups under certain conditions [26]. Even unprotected alcohols and free carboxylic acids seem to be tolerated by 1. It should also be emphasized that the sensitivity of 1 toward the substitution pattern of alkenes outlined above usually leaves pre-existing di-, tri- and tetrasubstituted double bonds in the substrates unaffected. A nice example that illustrates many of these features is the clean dimerization of FK-506 45 to compound 46 reported by Schreiber et al. (Scheme 12) [27]. 

Eliminations. When functionalized silanes in which a potential leaving group is attached to a /3-atom or to a vinylogously related atom are treated with TBAF, fragmentation ensues. New uses of this process are preparations of 2,3-dimethylene-2,3-dihydrothiophene," substituted 1,2,3-butatrienes, chiral allylic alcohols, and a-fluoroketones. The precursors for the allylic alcohols are the alkylation products (with aldehydes) of 2-(trimethylsilyl)ethyl sulfoxides, and those for the fluoroketones are 1-silyl-l-hydroxymethyloxiranes. 

The reduction of both ketones and aldehydes using silanes has been developed using a discrete Cp Ni-NHC catalyst [74,75]. A variety of aldehydes and ketones were reduced with excellent functional group tolerance in moderate to high yields with low catalyst loading (Figure 13.31). 

N. Saito, T. Katayama, Y. Sato, Org. Lett. 2008, 10, 3829-3832. Nickel-catalyzed highly regioselective multicomponent coupling of ynamides, aldehydes and silane a new access to functionalized enamides. 

A novel and versatile method for preparing polymer-supported reactive dienes was recently developed by Smith [26]. PS-DES (polystyrene diethyl-silane) resin 28 treated with trifluoromethanesulfonic acid was converted to a polymer-supported silyl triflate 29 and then functionalized with enolizable a,jS-unsaturated aldehydes and ketones to form silyloxydienes 30 and 31 (Scheme 4.4). These reactive dienes were then trapped with dienophiles and the Diels Alder adducts were electrophilically cleaved with a solution of TFA. 

The hydrosilylation of carbonyl compounds by EtjSiH catalysed by the copper NHC complexes 65 and 66-67 constitutes a convenient method for the direct synthesis of silyl-protected alcohols (silyl ethers). The catalysts can be generated in situ from the corresponding imidazolium salts, base and CuCl or [Cu(MeCN) ]X", respectively. The catalytic reactions usually occur at room tanperature in THE with very good conversions and exhibit good functional group tolerance. Complex 66, which is more active than 65, allows the reactions to be run under lower silane loadings and is preferred for the hydrosilylation of hindered ketones. The wide scope of application of the copper catalyst [dialkyl-, arylalkyl-ketones, aldehydes (even enoUsable) and esters] is evident from some examples compiled in Table 2.3 [51-53],... 

Enones and enoates undergo 1,2-reduction [115, 191]. Lipshutz et al. reported the effective protection of carbonyl functions by the triisopropylsilyl acyl silane group (TIPS), which allowed the selective conversion of alkenes or alkynes to the corresponding zirconocene complexes [24]. The aldehyde could subsequently be regenerated by desilylation with TBAF [186]. 

While trifluoro and other halosilanes function by increased electrophilicity at silicon, nucleophilic reactivity of allylic silanes can be enhanced by formation of anionic adducts (silicates). Reaction of allylic silanes with aldehydes and ketones can... 

Although the titanium-based methods are typically stoichiometric, catalytic turnover was achieved in one isolated example with trialkoxysilane reducing agents with titanocene catalysts (Scheme 28) [74], This example (as part of a broader study of enal cyclizations [74,75]) was indeed the first process to demonstrate catalysis in a silane-based aldehyde/alkyne reductive coupling and provided important guidance in the development of the nickel-catalyzed processes that are generally more tolerant of functionality and broader in scope. 

Silyltitanation of 1,3-dienes with Cp2Ti(SiMe2Ph) selectively affords 4-silylated r 3-allyl-titanocenes, which can further react with carbonyl compounds, C02, or a proton source [26]. Hydrotitanation of acyclic and cyclic 1,3-dienes functionalized at C-2 with a silyloxy group has been achieved [27]. The complexes formed undergo highly stereoselective addition with aldehydes to produce, after basic work-up, anti diastereomeric (3-hydroxy enol silanes. These compounds have proved to be versatile building blocks for stereocontrolled polypropionate synthesis. Thus, the combination of allyltitanation and Mukayiama aldol or tandem aldol-Tishchenko reactions provides a short access to five- or six-carbon polypropionate stereosequences (Scheme 13.15) [28],... 

Attempts to make C2-symmetric ferrocenes by double lithiation of a bis-acetal met with only limited success . A second lithiation of the ferrocenylacetal 298 leads to functionalization of the lower ring of the ferrocene, in contrast with the second adjacent lithiation of the oxazolines described below. This can be used to advantage if, for example, the first-formed aldehyde 301 is protected in situ by addition of the lithiopiperazine 53 °, directing f-BuLi to the lower ring (Scheme 139) °. The same strategy can be used to introduce further functionalization to products related to 302. For example, silane 303, produced in enantiomerically pure form by the method of Scheme 138, may be converted to the ferrocenophane 304 by lithiopiperazine protection, lithiation and functionalization (Scheme 140) . 

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