Addition of Tertiary Amines

More details about multiple radical adducts of Cjq can be found in Chapter 10. 

Primary and secondary amines can add to Cjq as nucleophiles (Section 3.3). Tertiary amines can not form similar addition products, rather an electron transfer imder formation of zwitterions is often observed (Section 3.3). However, a photochemical reaction of tertiary amines with Cjq is possible and leads to complex mixtures of addition products [52-62]. The product distribution strongly depends on conditions such as temperature and the presence of either light or oxygen. If oxygen is thoroughly excluded, 9 is the major product (Figrue 6.8) in the photoaddition of triethylamine [56, 59]. It can be isolated in low yields. 

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Synthesis of Silicone Monomers and Intermediates. Another important reaction for the formation of Si—C bonds, in addition to the direct process and the Grignard reaction, is hydrosdylation (eq. 3), which is used for the formation of monomers for producing a wide range of organomodified sihcones and for cross-linking sihcone polymers (8,52—58). Formation of ether and ester bonds at sihcon is important for the manufacture of curable sihcone materials. Alcoholysis of the Si—Cl bond (eq. 4) is a method for forming silyl ethers. HCl removal is typically accomphshed by the addition of tertiary amines or by using NaOR in place of R OH to form NaCl. 

Particularly, diisopropylamine and dibutylamine showed high o/t/io-selectivity. Addition of tertiary amines, such as triethylamine, tripropylamine, and tripentylamine was ineffective in the"ortAo-selectivity. In this system A-bromoamine never generates. 

Reaction conditions can be modified to accelerate the rate of lithiation when necessary. Addition of tertiary amines, especially TMEDA, facilitates lithiation53 by coordination at the lithium and promoting dissociation of aggregated structures. Kinetic and spectroscopic evidence indicates that in the presence of TMEDA lithiation of methoxybenzene involves the solvated dimeric species (BuLi)2(TMEDA)2.54 The reaction shows an isotope effect for the o-hydrogcn, establishing that proton abstraction is rate determining.55 It is likely that there is a precomplexation between the methoxybenzene and organometallic dimer. 

Interestingly, bases and water have different effect on stability of BENA and intermediate SENA. Additives of tertiary amines stabilize SENAs (191), whereas bases cause spontaneous decomposition of BENAs. SENAs are hydrolytically unstable, whereas BENAs are inert toward water under neutral conditions. 

Based on nucleophilic addition, racemic allenyl sulfones were partially resolved by reaction with a deficiency of optically active primary or secondary amines [243]. The reversible nucleophilic addition of tertiary amines or phosphanes to acceptor-substituted allenes can lead to the inversion of the configuration of chiral allenes. For example, an optically active diester 177 with achiral groups R can undergo a racemization (Scheme 7.29). A 4 5 mixture of (M)- and (P)-177 with R = (-)-l-menthyl, obtained through synthesis of the allene from dimenthyl 1,3-acetonedicar-boxylate (cf. Scheme 7.18) [159], furnishes (M)-177 in high diastereomeric purity in 90% yield after repeated crystallization from pentane in the presence of catalytic amounts of triethylamine [158], Another example of a highly elegant epimerization of an optically active allene based on reversible nucleophilic addition was published by Marshall and Liao, who were successful in the transformation 179 — 180 [35], Recently, Lu et al. published a very informative review on the reactions of electron-deficient allenes under phosphane catalysis [244]. 

The two functional groups implicated in a coupling require attention to effect the reaction. The ammonium group of the C02H-substituted component must be converted into a nucleophile by deprotonaton (Figure 1.7). This can be done in situ by the addition of a tertiary amine to the derivative dissolved in the reaction solvent, or by addition of tertiary amine to the derivative in a two-phase system that allows removal of the salts that are soluble in water. The carboxy-containing component is... 

This kinetic feature is observed by using primary and secondary amines, both aromatic and aliphatic. Tertiary amines263 (and other substances unable to produce substitution products such as 2-hydroxypyridine264) may act as a catalyst in apolar solvents, in a series of runs carried out without changing the initial concentration value of substrate and of amines, it was found that the addition of tertiary amines enhances kabs values. 

Highly efficient and stereoselective addition of tertiary amines to electron-deficient alkenes is used by Pete et al. for the synthesis of necine bases [26,27], The photoinduced electron transfer of tertiary amines like Af-methylpyrrolidine to aromatic ketone sensitizers yield regiospecifically only one of the possible radical species which then adds diastereospecifically to (5I )-5-menthyloxy-2-(5//)-furanone as an electron-poor alkene. For the synthesis of pyrrazolidine alkaloids in approximately 30% overall yield, the group uses a second PET step for the oxidative demethylation of the pyrrolidine. The resulting secondary amine react spontaneously to the lactam by intramolecular aminolysis of the lactone (Scheme 20) [26,27]. 

On the other hand, addition of tertiary amines accelerated hydrogenation of some compounds over Raney nickel [6I. In hydrogenation of halogen derivatives over palladium [62] or Raney nickel [63] the presence of at least one equivalent of sodium or potassium hydroxide was found necessary. 

Reaction conditions can be modified to accelerate the rate of lithiation when necessary. Addition of tertiary amines, especially TMEDA, accelerates lithiation42 by... 

In a detailed study on phosphonate diester and phosphonamidate synthesis, Hirschmann, Smith, and co-workers reported that pyrophosphonate anhydrides may be produced as side products during conversion of phosphonate monoesters into phosphonochloridates. 72 They recommended adding the phosphonate monoester to a solution of the chlorinating agent (thionyl chloride or oxalyl chloride) to minimize formation of the less reactive anhydrides. They also found that addition of tertiary amines (e.g., TEA) to the phosphonochloridates, prior to addition of the alcohol or amine component, results in formation of a phospho-nyltrialkylammonium salt that is more reactive than the corresponding phosphonochloridate and leads to better yields of the phosphonate esters and amides. 

The Mitsunobu etherification of polystyrene-bound phenols is usually conducted in THF or NMP, simply by adding the alcohol, the phosphine, and DEAD. Some authors claim that the addition of tertiary amines is beneficial [148], but this seems not always to be the case [146], It is, of course, important that neither the support nor any of the... 

Hoffmann, N., Bertrand, S., Marinkovic F S. and Pesch, J. (2006) Efficient radical addition of tertiary amines to alkenes using photochemical electron transfer. Pure and Applied Chemistry, 78, 2227-2246. 

Bertrand, S., Hoffmann, N., and Pete, J.P. (2000) Highly efficient and stereoselective radical addition of tertiary amines to electron-deficient alkenes-application to the enantioselective synthesis of necine bases. European Journal of Organic Chemistry, 82, 2227—2238. 

A. Krushevska, A. Lasztity, M. Kotrebai, R. M. Barnes, Addition of tertiary amines in the semiquantitative, multi-element inductively coupled plasma mass spectrometric analysis of biological materials, J. Anal. Atom. Spectrom., 11 (1996), 343D352. 

Recently, an efficient photocatalytic method has been reported for the radical addition of tertiary amines to electron-deficient double bonds (Scheme 59) [134]. N-methylpyrrolidine was added to the furanone 216. The radical attack occurred specifically anti with respect to the menthyloxy substituent, and the adducts 217 and 218 were isolated in high yields in the presence of sensitizers having electron-rich substituents or in the presence of semiconductors like Ti02-However, the configuration of the chiral center in the a-position of the nitrogen atom could not be controlled. Although the diastereoselectivity was almost the... 

Recently Betrand et al. have reported the sensitized intermolecular addition of tertiary amines derived from pyrrolidines to (5R)-5-menthyloxy-2[5//]-furanone (328) using ketonic sensitizers (Scheme 73, Table 13) [329]. 

The addition occurs with complete facial selectivity on the furanone ring. The method has been generalized to the addition of tertiary amines and A-protected secondary amines to electron-deficient olefins (Table 13). 

A further example of photochemically induced addition to the enone double bond in (25) has been reported. In this example irradiation using benzophe-none as the radical producing agent in methanol results in a 51% yield of the adduct (26). Pete and his co-workers have reported the sensitized addition of tertiary amines such as (27) to the furanone double bond in (28). The reaction involves electron transfer from the amine to the sensitiser which ultimately... 

Bertrand, S., Glapski, C., Hoffmann, N., Pete, J. P, Highly Efficient Photochemical Addition of Tertiary Amines to Electron Deficient Alkenes. Diastereoselective Addition to (5R) 5 Menthyloxy 2 5H furanone, Tetrahedron Lett. 1999, 40, 3169 3172. 

Intriguing but confusing information is available in two Chemical Abstracts references to Chinese publications. A 1988 abstract d reports the behavior of phenol under Reimer-Tiemann reaction conditions with the addition of tertiary amines. The authors claim that the para. ortho ratio is reversed from that normally observed and 60% yield of p-hydroxybenzaldehyde, 7% yield of o-hydroxybenzaldehyde and only 1% tars are obtained when phenol is subjected to the new conditions. One year later a report appeared in which it is claimed that the use of tertiary amines under phase-transfer conditions increases the yield of ortho product. The authors report a yield of 79% of salicylaldehyde from phenol using 0.37% catalyst (the nature of the catalyst is not mentioned in the abstract and the Chinese publication is not available to this author), and 35% sodium hydroxide at 55-60 °C for 90 min. Surely, these results (or the translation) warrant checking. 

The reversibility of the addition of tertiary amine is even more pronounced. The initiation is very slow and insignificant towards the end of polymerization when the concentration of monomer is greatly reduced. Therefore, the conversion curves at that stage of the process show an internal first order character in monomer but second order in respect to the initial monomer concentration. 

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