Bases 1,4-Diazabicyclo octane

Together with a shift of the proton from the a-carbon to the alkoxide oxygen, the tertiary amine is eliminated from the addition product to yield the unsaturated product 3. Early examples of the Baylis-Hillman reaction posed the problem of low conversions and slow reaction kinetics, which could not be improved with the use of simple tertiary amines. The search for catalytically active substances led to more properly adjusted, often highly specific compounds, with shorter reaction times." Suitable catalysts are, for example, the nucleophilic, sterically less hindered bases diazabicyclo[2.2.2]octane (DABCO) 6, quinuclidin-3-one 7 and quinuclidin-3-ol (3-QDL) 8. The latter compound can stabilize the zwitterionic intermediate through hydrogen bonding. ... 

Separation of relatively pure para-cresol from mixed cresols using an organic solvent and thereafter formation of a solid crystalline complex with the solvent has been reported. Piperazine and DABCO (diazabicyclo-octane) have been found to be very effective as extracting agents in this process of separation. There is very little effect of m-cresol in this process. The values of separation factor approach infinity as 100% p-cresol-base complex is crystallized. The yield of p-cresol was impressive with some aliphatic polar solvents, but... 

Details are given of the synthesis of new methacrylate monomers containing pendant quaternary ammortirrm moieties based on diazabicyclo-octane. The monomers were homopolymers using azobismethylpropionarrride dihydrochloride as initiator. The monomers and polymers were characterised by elemental analysis, TGA, DSC, FTIR and carbon 13 NMR. Antimicrobial activities were investigated against S.aureus and E.coli. 41 refs. 

Figure 2.32 Examples of structures based on paddle wheel dimer units. In the copper trimesate HKUST-1, (top, left and right), dimeric copper units link four trimesate ligands into a three-dimensional framework, leaving the apical coordination site accessible to other ligands (such as water molecules). In the pillared layered zinc terephthalate of Dybtsev et al. porous planar zinc terephthalate sheets (shown) are linked via the diamine diazabicyclo-octane (N(C2H4)3N) coordinated at the apical sites.

In the presence of a base such as l,4-diazabicyclo[2.2.2]octane (DABCO) or tri-alkylphosphines, conjugated carbonyl compounds such as esters and amides add to aldehydes via the a-carbon to give a-alkenyl-P-hydroxy esters or amides. This sequence is called the Baylis-Hillman reaction and a simple example is... 

A practical and efficient set of conditions were developed using a stoichiometric base catalyst, l,4-diazabicyclo[2,2,2]octane (DABCO)... 

The high selectivity that the system shows to pyrazine 20 compared to the stronger base pyridine, indicates that the diamine is chelated between the carboxylic acid functions as in 21. Spectroscopic evidence in the form of upfield shifts in the NMR spectra of the complexes supports such structures. Not only aromatic diamines are accommodated but also aliphatics such as l,4-diazabicyclo[2.2.2]octane (DABCO) in complex 22. Typically, exchange rates into and out of these complexes are such that they appear fast on the NMR time scale at ambient temperature, but exchange can be frozen out at low temperatures20. For DABCO, an activation barrier of 10.5 kcal M 1 was observed at Tc = 208 °K. 

In a more recent study, Wannberg and Larhed reported solid-supported aminocar-bonylations employing molybdenum hexacarbonyl as a solid source of carbon monoxide [37]. Carbon monoxide is smoothly liberated at the reaction temperature upon the addition of the strong base l,8-diazabicyclo[2.2.2]octane (DBU). In this transfor-... 

DABCO = l,4-diazabicyclo[2,2,2]octane (triethylene diamine) (22) is a moderately basic amine, removable by sublimation, that causes enantiomeriza-tion of amino acid residues that have been reacted to form Schiff s bases (RR C=NCHR2CO-). 

The main steps in the currently accepted catalytic cycle of the Heck reaction are oxidative addition, carbopalla-dation (G=G insertion), and / -hydride elimination. It is well established that both, the insertion as well as the elimination step, are m-stereospecific. Only in some cases has formal /r/ / i--elimination been observed. For example, exposure of the l,3-dibromo-4-(dihydronaphthyloxy)benzene derivative 16 and an alkene 1-R to a palladium source in the presence of a base led to a sequential intra-intermolecular twofold Heck reaction furnishing the alkenylated tetracyclic products 17 in good to excellent yields (Scheme 9). " In the rate-determining step, the base removes a proton in an antiperiplanar orientation from the benzylic palladium intermediate. The best amine base was found to be l,4-diazabicyclo[2.2.2]octane, which apparently has an optimal shape for this proton abstraction. 

Silver nitrate displayed a pronounced effect on the selectivity of silylation [380, 392, 440, 441], The treatment of uridine (63) with 2.2 molar equiv. of each fm-butylchloro-dimethylsilane and silver nitrate in oxolane led to the exclusive formation of 5 -0-silyl derivative 64 in 95% isolated yield [380], Under analogous conditions, 1,2-0-isopropylidene-ct-D-glucofuranose was selectivity silylated at 0-6, and 1,2-0-isopro-pylidene-oc-D-xylofuranose at 0-5, with 94-96% yield [442]. Combination of silver nitrate with pyridine resulted in disilylation of nucleosides at 0-5 and 0-2 with excellent selectivity. Interestingly, the selectivity for secondary hydroxyl groups is reversed with a combination of silver nitrate and l,4-diazabicyclo[2.2.2]octane as a base. Such a disilylation led to 3, 5 -6 -0-(/ert-butyldimethylsilyl) derivatives in as high yields as 94%. Other soluble silver salts, e.g., silver perchlorate, behaved similarly [380],... 

A nice example of grinding-induced crystal engineering is the formation of a hydrogen bonded cocrystal between ferrocene dicarboxylic acid and 1,4-diazabicyclo [2.2.2] octane (DABCO). The ferrocene dicarboxylic acid exists in the solid as a hydrogen bonded dimer based on two repeats of the carboxylic acid dimer synthon (solid A). Grinding with DABCO (solid B) gives rise to a new solid, C, in which the carboxylic acid dimers have been broken and replaced by an acid-amine synthon, Figure 8.25.30... 

The deprotonation step, either by the sensitizer radical anion or by some adventitious base, is essential for the formation of any amine derived products. This step can be prevented if the a-hydrogens are arranged in a plane orthogonal to the singly occupied nitrogen n-orbital a requirement which is met for the radical cation of l,4-diazabicyclo[2.2.2]octane (DABCO). The low oxidation potential, due to the interaction of the pair of transannular nitrogens, makes this an excellent electron transfer quencher. Yet, no product formation is observed as a result of these interactions, with the possible exception of the zwitterionic adducts formed with highly electrophilic ketones [193]. 

Historically, the most effective N-based organic catalysts were nucleophilic unhindered tertiary amines such as DABCO (diazabicyclo[2.2.2]octane, 1) [23], qui-nuclidine (2), 3-hydroxy quinuclidine (3-HDQ, 3), 3-quinuclidone (4) and indoli-zine (5) (Fig. 5.1) [24]. A direct correlation has been found between pKa and the activity of the quinuclidine-based catalysts the higher the pKa, the faster the rate [25]. More recently, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 6), considered as a hindered and non-nucleophilic base, was shown to be a better catalyst than DABCO, or 3-HDQ [26]. The reason for the increased reactivity for this catalyst was attributed to stabilization of the zwitterionic enolate by delocalization of the positive charge. Other N-based catalysts such as N,N-(dimethylamino)pyridine... 

The reaction of l,4-diazabicyclo[2.2.2]octane (DABCO)-derived quaternary ammonium salts with electrophilic alkenes in the presence of a base opens a stereoselective route to highly substituted 2,3-dihydrofurans <2005S2188>. An ammonium ylide is initially formed that attacks the Michael acceptor. The resulting enolate finally expels DABCO in an O-alkylation reaction, affording fra j -2,3-disubstituted dihydrofurans as the major products (Equation 65) <2005S2188>. 

Besides the above mentioned cinchona based system, to date only a few nitrogen-based chiral ligands have been reported to work under catalytic conditions70-72. The C2-symmetrical l,4-diazabicyclo[2.2.2]octane (DABCO) derivative l70 and the isoxazolidines 2 and 371 are examples. The main problem with most of the other amines tested stems from the formation of ligand-osmate ester complexes which are too stable. Although with these ligands the levels of enantiomeric excess are still not satisfactory, the successful osmium turnover gives hope for future improvements. 

BASES Ascarite. Barium hydroxide. 1,8-Bis(dimethylamino)naphthaIene. n-Butyl-amine. I, S-Diazabicyclo 4.3.0]nonene-5 (DBN). l,4-Diazabicydo 2.2.2]octane-... 

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