A Proton Sponge

Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan 

Superbases for Organic SyrUhesis Guanidines, Amidines, Phosphazenes and Related Organocatalysts Edited by Tsutomu Ishikawa 2009 John Wiley Sons, Ltd. ISBN 978-0 70-51800-7 

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The Lewis acid of choice for most of the cyclization reactions is ethylaluminum dichloride, because of its exceptional properties it is a mild Lewis acid, and, as an organometallic compound, can serve as a proton sponge , and thereby inhibit competitive protodesilyla-tion37. The desired precursors reacted smoothly with 1.1 equivalents of ethylaluminum dichloride in toluene or dichloromethane at low temperature to generate diastereoselectively the desired spiro[4.5]decanones38. 

Larhed et al. investigated enantioselective Heck reactions with 2,3-dihydrofuran as alkene [86]. In the coupling with phenyl triflate, conditions previously reported by Pfaltz [87] were attempted under microwave irradiation. Interestingly, the catalytic system Pd2(dba)3/(4S)-4-t-butyl-2-[2-(diphenylphosphanyl)phenyl]-4,5-dihydro-l,3-oxazole, identified by the Swiss team, was found suitable for high-temperature microwave-assisted enantioselective Heck reactions (Scheme 76). Using a proton sponge as a base and benzene as a solvent gave the best conversions (Scheme 76). At tempera-... 

Reaction of Chlorodimethyl(2,3,4,5-tetramethyl-2,4-cyclopentadien-l-yl)silane with Silica Materials. Chlorodimethyl-(2,3,4,5-tetramethyl-2,4-cyclopentadien-l-yl)silane (excess) was added to a mixture of amine-functionalized silica with hexanes in a drybox. 2,6-Di-tert-butylpyridine (excess) was added as a proton sponge. The mixture was allowed to react while stirring for 24 h. The solid was filtered and washed with hexanes and THF in the drybox. The solid was then contacted with another aliquot of chlorodimethyl-(2,3,4,5-tetramethyl-2,4-cyclopentadien-l-yl)silane and the procedure was repeated. 

The hydrofluoride of a proton sponge is used in MeCN as fluoride ion donor benzoyl chloride is transformed into benzoyl fluoride107 (reaction 10). 

The kinetics and mechanism of proton transfer from diarylcyanomethanes to a proton-sponge, c/i-l,2-bis(diethylaminomethyl)cyclohexane, in acetonitrile has been studied. 

Some consideration was given to appropriate bases for this oxidation system. Pyridine and sodium bicarbonate had been shown to be useful earlier and were included. Additional bases considered were a proton sponge (1,8-Bis(dimethylamino)naphthalene) and, as stated above, pyridine N-oxide. Because of the low solubilities in CXL systems of NaHCOs and the proton-sponge, pyridine was selected for these exploratory studies. 

Majetich reports a general intramolecular Lewis acid allylation protocol for the synthesis of bicy-clo[5.4.0]undecen-3-ones (168) and bicyclo[4.4.0]decen-3-ones (170), which are 1,6-addition products (Scheme 27). The same precursors, (167) and (169), when submitted to the fluoride ion cyclization protocol, also afford 1,2- and 1,4-addition products.73 Typically, ethylaluminum dichloride, a proton sponge Lewis acid, is used in order to minimize adventitious protonic desilylation. Other 0,y-unsatu-rated silanes also undergo similar intramolecular Lewis acid catalyzed additions for example, the si-lylpropargylic enones (171) undergo intramolecular cyclization to the allenylspiro system (172).74... 

Using the reversed mode strategy, the reaction of acid chlorides with a tertiary amine in the presence of a proton sponge readily produces ketenes ... 

Fig. 6. A proton-sponge (a) l,8-Bis(dimethylamino)napthalene in the pristine form (b) after protonation using 1,2-dichloro maleic acid. The contour maps of the corresponding Laplacians are shown at logarithmic intervals in (c) and (d), respectively (reproduced with permission from Mallinson et al. [56,57]).

Mallinson et al. [56,57] have carried out experimental and theoretical charge density determinations on a proton sponge compound, bis(dimethyamino)-napthalene (DMAN), in both pristine and protonated forms (Fig. 6). They used positional and thermal parameters of hydrogen atoms from an independent neutron diffraction experiment and treated the thermal... 

It is convenient to note here that l,8-bis(dimethylamino)naphthalene and related compounds are very strong bases and act as a proton sponge, removing H+ and forming N H- N H-bonds that are symmetrical and nearly linear. 

Phenyltrichlorostannane reacts with 1 surplus amine to yield the hexacoordinate tin compound 2c only. An elimination of HCl from 2c seems to be impossible. Even reaction with a proton sponge, Ai, A, A, A -tetramethylnaphthalene-1,8-diamine, failed. 2c crystallizes in a non-centrosymmetric monoclinic space group (Cc). The molecule involves the all-d5 configuration of the salen type ligand. The angle (93.9°) of C19-Sn-Cl indicates a real cis arrangement of the chlorine atom and the phenyl group (Fig. 2) [2]. 

Although Pd(0) complexes are catalytically active as is, Pd(II) salts have also been used the reducing atmosphere of CO converts Pd(II) to Pd(0) in situ. A proton sponge such as Et3N also must be present to tie up the acidic byproduct, HX. Equations 12.37,77 12.38,78 and 12.3979 provide a few examples of Pd-catalyzed carbonylation. 

At around the same time, Ellman and coworkers [52] also reported similar results for anchona-catalyzed sulfinyl transfer reactions to those obtained by the Shibata group [51]. They found that the parent anchona alkaloids effectively catalyzed the sulfinyl transfer reaction of tert-butanesulfinyl chloride (rac-74) and a variety ofbenzyl alcohols in the presence of a proton sponge (2.5 equiv). For example, in the presence of 10 mol% of quinidine (2) and 2.5 equivalents of a proton sponge, sulfinyl transfer with 2,4,6-trichlorobenzyl alcohol (77) provided the sulftnate ester 78 in 92% yield and with 90% ee (Scheme 11.37). 

MCF-7 cells and their xenograph tumors, and compared with DOX-loaded pH-insensitive micelles made of PLLA-PEG with folate targeting groups (PHlM/f) [99]. The cellular localization of the nanoparticles was confirmed by confocal microscopy (Fig. 10.13). DOX delivered by PHSM/f was found uniformly distributed in the cytosol as well as in the nucleus, while DOX/PHlM/f was entrapped in endosome and multivesicular bodies. It was thus hypothesized that PHis, which is known to have an endosomal membrane-disruption activity induced by a proton sponge mechanism of its imidazole groups [209, 210], disrupted the compartment membrane and released DOX into the cytosol. As a result, DOX/PHSM/f showed much higher in vitro and in vivo anticancer activities toward DOX-resistant cells (Fig. 10.14). 

T4.5 Start from Section 4.14 Superacids and superbases which covers classical examples of superbases, nitrides, and hydrides of s-block elements. However, there are several groups of superbases that you can look at. For example, amides (diisopropylamide related) are commonly used superbases. More modem are phosphazene bases which are neutral rather bulky compounds containing phosphorus and nitrogen. An interesting topic is a proton sponge (or Alder s base) and its derivatives as well as several theoretical and practical approaches used in rational design of superbases. 

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