Tertiary amine, sterically hindered

Preparation of B-fluoroborazines cannot be effected from trifluoro-borane and amines by a Brown-Laubengayer type of reaction. However, direct synthesis of B-fluoroborazine rings has been reported recently and involves the dehydrofluorination of primary amine-trifluoroborane adducts with the aid of the adducts of sterically hindered tertiary amines with trifluoroborane. 2,4,6-Trifluoroborazines and ammoniumtetra-fluoroborates sl) are obtained in excellent yield. 

In an important experiment, Mukaiyama and coworkers enolized carbonyl compounds under much milder conditions (low temperatures) with dialkylboryl triflate and a sterically hindered tertiary amine base such as 2,6-lutidine (2,6-dimethylpyridine) or diisopropylethylamine (DPEA).95-97 Less-hindered bases led to formation of a stable borane-amide complex (Lewis acid-Lewis base) and prevented the reaction with the carbonyl compound. Masamune et al,98 and Evans et a/.99100 carried out a study to investigate the reasons for the selective enolate formation. They showed that it depends on the boron ligand, base, solvent and the group attached to the carbonyl moiety. Ketones give (Z)-enolates with often excellent selectivity, whereas r-butyl thiolates give selectively the ( )-enolates (equations 32 and 33).100 101 Evans suggests that reactions with 9-BBN triflate are often under thermodynamic control.15 In equation... 

Further, formation of quaternary salts can interfere in the ready removal of hydrogen halide by tertiary amines such as dimethylaniline, pyridine, or quinoline.58 To overcome this, Hiinig and Kiessel59 successfully applied sterically hindered tertiary amines, e.g., ethyldiisopropylamine and 7V-ethyldi-(cyclohexyl)amine for instance, removing hydrogen bromide from 1,2-di-bromo-2-methylpropane by potassium hydroxide in ethylene glycol60 gave unsatisfactory yields of l-bromo-2-methyl-l-propene ... 

Enolization Direct enolization can occur during the coupling reaction. During coupling, conversion of the incoming amino acid to an activated ester increases the acidity of the a-carbon (Scheme 20.4). This can tend to favor enolization, which leads to rearrangement about the a-carbon. In SPPS, sterically hindered tertiary amines are used in an effort to minimize base-catalyzed removal of the a-carbon proton. 

Even more sterically hindered tertiary amines were studied by Lunazzi and coworkers . In a series of iV,iV-diisopropyl , A-t-butyl-neopentyl and N-t-butyladamantyl amines " some of the NMR detectable dynamic processes are of inversion-rotation type. Scheme 3 summarizes the possible interconversions in the diisopropyl series For the neopentyl derivative 38 for example, the DNMR ( H and shows two successive processes during the cooling procedure, with barriers of 8.9 and 7.7 kcalmol . MM2-82 calculations of 39 define 3 possible rotamers around the R—C—N—Ip dihedral angle (Figure 4). Since the G+ and gauche and gauche ) are... 

We first attempted to make the ammonium salts more stable using steric hindrance. We prepared a variety of sterically encumbered ammonium salts via the sequence shown in Equation 2. Although we could prepare a vau iety of hindered tertiary amines, successful quaternlzatlons were achieved only with methyl groups. These salts were more stable to phenoxlde than n-Bu NBr by factors of 10-50, demonstrating that steric hindrance can ay a significant part in stabilization of phase transfer catalysts. However, none of these salts were more effective than n-Bu NBr as phase transfer agents, probably due to their less lipophilic nature, and we turned our attention to other systems. 

The arylation of aliphatic amines has been difficult under metal-free conditions, but intramolecular arylations using aminoalkyl-substituted iodonium salts to yield indolines were viable (Scheme 5b) [94]. The groups of Olofsson and Adolfsson recently accomplished a metal-free arylation of secondary amides at room temperature (Scheme 5c) [95], A chemoselectivity study revealed a substantial orthoeffect, allowing selective transfer of a TRIP moiety and providing access to sterically hindered tertiary amides that are inaccessible by metal-catalyzed arylations. 

Secondary amines also yield linear polypeptides, when their nucleophilicity is not reduced by steric hindrance (e.g., dimethylamine or piperidine). Imidazole is an exception mainly yielding cyclic polypeptides. Cyclic polypeptides are also formed by sterically hindered secondary amines and by tertiary amines. Thermal polymerizations also yield cyclic polypeptides. Mechanisms and preparative aspects of aU these polymerizations are discussed in Chap. 15. 

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. ... 

The first step can be frozen out if a tertiary amine is used which, for steric reasons, is unable to add to and to transfer protons. This is valid for the tertiary amine tetrakisdimefhylaminoethylene (TDAE). Upon electron transfer the Cjq radical monoanion salt Cgg[TDAE] is formed (Chapter 2) [84]. The second step, the formation of the zwitterion, was directly observed by using the less hindered DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) and isolating the green diamagnetic zwitterion complex CjqDBU (Figure 3.7) by precipitation in benzene [83]. In solution, this complex stays in equilibrium with the dissociated Cjq and DBU radicals. 

Primary and secondary amines attack the nitrosyl nitrogen via pathways that are both first and second order in the amine concentration [26,119]. This is followed by dissociation to give primary alcohols or nitrosoamines [120, 121] however, tertiary amines and sterically hindered amines do not react. 

Without additives, radical formation is the main reaction in the manganese-catalyzed oxidation of alkenes and epoxide yields are poor. The heterolytic peroxide-bond-cleavage and therefore epoxide formation can be favored by using nitrogen heterocycles as cocatalysts (imidazoles, pyridines , tertiary amine Af-oxides ) acting as bases or as axial ligands on the metal catalyst. With the Mn-salen complex Mn-[AI,AI -ethylenebis(5,5 -dinitrosalicylideneaminato)], and in the presence of imidazole as cocatalyst and TBHP as oxidant, various alkenes could be epoxidized with yields between 6% and 90% (in some cases ionol was employed as additive), whereby the yields based on the amount of TBHP consumed were low (10-15%). Sterically hindered additives like 2,6-di-f-butylpyridine did not promote the epoxidation. 

The relationship between the structure of the tertiary amine and the intrinsic rate of racemization was clear. This effect has been studied before by Williams,[32 among others. Two families of bases were compared trialkylamines and 4-alkylmorpholines. The trends were most clearly expressed in the experiments using Boc-Ser(OBzl)-NCA. The rate was decreased within each family as the steric bulk of the amine was increased. This result was consistent with the direct enolization mechanism that requires a close approach of the tertiary amine for the abstraction of the a-proton. The rate was much lower with 4-alkyl-morpholines than with trialkylamines because of the decreased basicity of the former (triethylamine and 4-ethylmorpholine have similar structures TEA is actually more hindered). The most favorable results with respect to racemization were obtained when a weak base was combined with a sterically hindered substituent, as with 4-cyclohexylmorpholine. In the case of Boc-Phe-NCA, the same trends were seen, except that racemization by the 4-alkylmorpholines was so slow that the differences within that family were not significant. 

Notes. The TNBSA test was found to be efficient for primary amines, including sterically hindered amines as seen in our probes with the tertiary amine of Aib. 

---