Quaternary ammonium: formal

Compounds containing a nitrogen atom with four attached groups also exist, but the nitrogen atom must carry a formal positive charge. Such compounds are called quaternary ammonium salts. 

The novel highly substituted spiro[4.4]nonatrienes 98 and 99 are produced by a [3+2+2+2] cocyclization with participation of three alkyne molecules and the (2 -dimethylamino-2 -trimethylsilyl)ethenylcarbene complex 96 (Scheme 20). This transformation is the first one ever observed involving threefold insertion of an alkyne and was first reported in 1999 by de Meijere et al. [81]. The structure of the product was eventually determined by X-ray crystal structure analysis of the quaternary ammonium iodide prepared from the regioisomer 98 (Ar=Ph) with methyl iodide. Interestingly, these formal [3+2+2+2] cycloaddition products are formed only from terminal arylacetylenes. In a control experiment with the complex 96 13C-labeled at the carbene carbon, the 13C label was found only at the spiro carbon atom of the products 98 and 99 [42]. 

Quaternary phosphonium salts, having the general formulation [R4P+X ], are formal analognes of quaternary ammonium salts. While there are structural similarities in structure (general tetrahedral) and modes of formation, there are also fhndamental differences in the natures of the two types of compounds. 

The enantioselective formal total synthesis of 4-demethoxydaunomycin was accomplished in the laboratory of M. Shibasaki. The key intermediate was prepared from an enantiomerically enriched frans- 3-amino alcohol, which was first exhaustively methylated to the corresponding quaternary ammonium salt. This salt was then treated with excess n-BuLi to afford the desired allylic alcohol in moderate yield. 

Nitrogen compounds with four alkyl groups bonded to the nitrogen—thereby giving the nitrogen a positive formal charge—are called quaternary ammonium salts. Their names consist of the names of the alkyl groups in alphabetical order, followed by anunonium (all in one word), and then the name of the counterion as a separate word. 

During the enantioselective formal synthesis of 4-demethoxy-daunomycin, BuLi proves to be the base of choice for a Hofmann elimination process of the quaternary ammonium salt of a trans-/3-amino alcohol to obtain the corresponding allylic alcohol with a slight erosion of ee (eq 61). Other bases such as KHMDS and KOtBu afford 1,4-dimethoxy-naphthalene as a result of an undesired consequent dehydration. 

Formally this approach also covers a host of similar reactions where other salts of the acid (most often the potassium salts, but alternatively various quaternary ammonium type salts and even some tertiary amine salts) are involved, and then reacted with (usually) the bromo-derivative of the alkyl or aryl group that is to be eslerified with the acid or acids in question. Because of the versatility and convenience of this approach, it has largely displaced the silver salt method, but formally... 

The general mechanism of substitution is a two-step process shown in equation (1) comprising formation (step a) and decomposition (step b) of a quaternary ammonium ion (1). This is a formal represen-... 

The fomth formula shows a quaternary ammonium salt, derived formally by replacing all four hydrogen atoms of the salt NH4CI with organic radicals. The free bases, the hydroxides of the quaternary ammonium ion, exist in addition to the neutral salts. 

Important derivatives of ammonia are the tetraalkyl ammonium salts. The cation in these salts has four organic groups attached to the nitrogen atom and is called a quaternary ammonium ion. In a quaternary ammonium ion, the nitrogen atom has a formal charge of -l-l. Two examples of such cations are shown in the margin. 

The TEAF system can be used to reduce ketones, certain alkenes and imines. With regard to the latter substrate, during our studies it was realized that 5 2 TEAF in some solvents was sufficiently acidic to protonate the imine (p K, ca. 6 in water). Iminium salts are much more reactive than imines due to inductive effects (cf. the Stacker reaction), and it was thus considered likely that an iminium salt was being reduced to an ammonium salt [54]. This explains why imines are not reduced in the IPA system which is neutral, and not acidic. When an iminium salt was pre-prepared by mixing equal amounts of an imine and acid, and used in the IPA system, the iminium was reduced, albeit with lower rate and moderate enantioselectivity. Quaternary iminium salts were also reduced to tertiary amines. Nevertheless, as other kinetic studies have indicated a pre-equilibrium with imine, it is possible that the proton formally sits on the catalyst and the iminium is formed during the catalytic cycle. It is, of course, possible that the mechanism of imine transfer hydrogenation is different to that of ketone reduction, and a metal-coordinated imine may be involved [55]. 

Amino groups are capable of becoming dissociated among themselves or with other functions by two types of hydrogen bonding, formally represented eis 62 and 63. In the former the amine acts as a weak protonic acid, and must therefore be primary or secondary (or an ammonium compound other than quaternary). On the other hand, in 63 it acts as a weak base, sharing its p electrons, and can be any type of amine (but not an ammonium compound). 

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