Hemi-aminals

These and other interesting results allow quantitative insight into the rate of breakdown of N-(hydroxymethyl) compounds (i.e., carbinolamines (hemi-aminals)), the reaction mechanisms of which we examined in Sect. 8.7.3 (see, in particular, Fig. 8.20) [80 - 82], These carbinolamines, we recall, are major metabolic intermediates in oxidative N-dealkylation reactions resulting from cytochrome P450 catalyzed hydroxylation of the C-atom adjacent to the... 

For the synthesis of CIO carba derivatives, a better leaving gronp than hydroxyl is nsnally preferred. The anomeric finoride , bromide, acetate, benzoate and phenyl-snlphonyl gronps have all been nsed and some of the chemistry that has been achieved is shown in Scheme 25. AllylsUanes tend to provide /S-confignred prodncts by axial attack on the oxoninm ion species (Scheme 25C) whereas larger nncleophiles snch as electron-rich aromatics add by attack on the a face (Scheme 25D). For nitrogen nncleophiles, Haynes and CO workers have employed the CIO anomeric bromide intermediate that gives the ClO-a hemi-aminal prodncts (Scheme 25E), some of which exhibit remarkable stability (Chart 1) . ... 

The precursor of the 2-dRL lesion is the C(l ). The carbocation formed upon its oxidation [reaction (2)] could react with water giving rise to a labile hemi-aminal [reaction (3)] that would readily hydrolyze giving rise to the 2-dRL lesion and an unaltered base [reaction (5)]. 

Mass spectrometry was used to determine the structure of dimeric hemi-aminals of C30 Nuphar alkaloids, including the position of the hydroxyl group (71). Ions formed as a result of loss of OH, H20, SH, CH2S, and CH3S are... 

Benzotriazol-l-yl)alkoxymethyllithiums 451 and 2-lithiooxazolidines 452 are two types of acyllithium reagents which can be considered as protected formyl anions with hemi-aminal structure. 

The heterocyclic hemi-aminal 44 was formed as a model for the synthesis of the marine alkaloids zoanthamine and zoanthenol and is derived from the cyclic imine formed by the reduction of an appropriated substituted azide <07H(72)213>. A pyrrolidine-fused azepine has been isolated from the venom of the ant Myrmicaria melanogaster and assigned as 45 based upon GC and FT-IR comparison with synthetic material <07JNP160>. The axially chiral doubly bridged biphenyl azepine 46 has been synthesised and used with oxone as an epoxidation catalyst in a biphasic system <070BC501>. 

Diacetoxyiodo)benzene in combination with simple bromide salts in ethanol can be used for the regios-elective ethoxybromination of a wide range of enamides, giving synthetically versatile a-bromo hemi-aminals [98]. 

Stress metab. from the Japanese radish Daikon (Raphanus sativus var. hortensis) (Cruciferae) inoculated with Pseudomonas cichorii. Gum. [a] 0 (c, 0.52 in CHCI3). Unusual hemi-aminal struct. Occurs as a mixt. of diastereoisomers ratio ol-OH P-OH estimated as 2.5 1. 

Analysis of DCLs by a combination of high-performance liquid chromatography (HPLC) and MS (LC-MS) has proven very powerful, provided the library members are stable enough to allow chromatographic separation. LC-MS analysis can yield both the quantity and the identity of individual library members. Care should be taken that the exchange between library members is slow on the timescale of the experiment. This is usually the case for hydrazone and disulfide libraries, without requiring special precautions. It has recently been reported that even the composition of DCLs of hydrolytically labile imines can be analyzed directly by HPLC, provided an acidic mobile phase is used. Beau et al. successfully used a common reversed-phase HPLC solvent system based on acetonitrile/water mixtures containing 0.1% trifluoroacetic acid [10]. Imine hydrolysis is slow under these conditions because at low pH the zwitterionic hemi-aminal intermediate that is believed to be important in the hydrolysis process is more difficult to attain (Scheme 2.1). 

Scheme 2.1 The mechanism for imine hydrolysis under acidic conditions is believed to involve the decomposition of the zwitterionic hemi-aminal intermediate as the rate-determining step (10). The rate of...

Pre-forming the electrophilic species in this reaction has greatly increased its utility and the diversity of substrates that have been exploited. Species that have been used include aminal 15, hemi-aminal 16, imine 17, and iminium ion 18. 

Functionalized iminium salts 24 can be readily prepared by a number of methods and allows the reaction to be conducted at lower temperatures and in non-protic solvents thus allowing other, more sensitive active hydrogen species to participate in this reaction. These methods can include alkylation of existing imine 22, cleavage of aminals 25 or hemi-aminals 23 with acetyl chloride or trimethylsilyl iodide/chloride, or in a direct fashion from carbonyl derivative 26 with amine salts or with trimethylsilyl amines. 

For example, consider a recent communication on the synthesis of P-amino acids.Hemi-aminal 31, under the influence of boron trifluoride, could be converted to acyl iminium ion 33. Capture of the electrophilic species 33 with the ketene acetal 32 provided ready access to 34. These advanced intermediates could be transformed into the desired P-amino acids 35. 

The hemi-aminal or enamide intermediates can also be used for C-C bond formation, via iminium ion intermediates, as in a short synthesis of crispine 4.155 (Scheme 4.57). °... 

Af-Allylacetamide as a substrate directs the hydroformylation in the P-position of the amide group, which is explained by coordination ofthe amide unitto rhodium (Scheme 4.38) [32]. The preferred formation of an intermediate six-membered metaiiacycie (A) forces the production of the branched aldehyde. Noteworthy, the terminal aldehyde that is formed via the seven-membered ring B after formation of a hemi-aminal and dehydration may undergo a second hydroformylation step to eventually produce l-acetylpyrrolidine-2-carbaldehyde [82]. 

As shown in Scheme 14.9a,b, an efficient protocol for the stereoselective synthesis of 1,3-syn and -anti tetrahydropyrimidinones (syn- and anti- 2) could be developed [13]. The modular procedure is based on a stereodivergent cycliza-tion of readily available urea-type substrates 41 by intramolecular allylic substitution. The cychzation proceeds with excellent yield (up to 99%) and selectivity (up to dr > 20 1), purely based on substrate control. The product pyrimidines 42 can be readily transformed into the corresponding free syn- and anti-amines 43. Furthermore, also a novel domino sequence for the rapid assembly of 1,3-syn-substituted oxazines 46 could be realized [14]. Mechanistically, the one-pot procedure is based on a three-step sequential process involving a hemi-aminalization... 

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