1 aldehyde protection amines

This approach offers unique opportunities for the generation of multi-functionalized cyclic 2-azadiene systems. A wide variation of the substitution pattern at the positions N-1 and C-6 can be determined by an appropriate choice of the aldehyde and amine. Various substituents can easily be introduced at the C-3 position via addition/elimination reactions on the sensitive imidoyl chloride moiety [24]. Upon reaction with bi-functional reagent, an adequately AT-protected 2(lH)-pyrazinone was elaborated into C-nucleoside analogues (Scheme 8). The desired skeleton and functionalities were obtained by oxidation-cyclization reaction followed by photochemical removal of the protective o-nitrobenzyl group [25]. 

Examples of the protection of alkynes, carboxylic acids, alcohols, phenols, aldehydes, amides, amines, esters, ketones, and alkenes are also indexed on p. xvii. Section (designated with an A 15A, 30A, etc.) with protecting group reactions are located at the end of pertinent chapters. 

MgS04, the tetracycles 2-648 were obtained with excellent diastereoselectivity in reasonable yield. The reaction presumably starts with a condensation of the aldehydes 2-645 with the benzyl-protected amine moiety of 2-644 to give an iminium ion which can subsequently cyclize to afford the spirocyclic intermediates 2-646. A [3,3] sigmatropic Cope rearrangement then forms the nine-membered cyclic enamines 2-647 which, after protonation, act as the starting point for another indole iminium cyclization to provide the tetracycles 2-648 via 2-647. 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

A novel Mannich reaction between A -alkoxycarbonylpyrroles 739, formaldehyde, and primary amine hydrochlorides catalyzed by Y(OTf)3 gave a monoaminoalkylation product 741 some times in good yield (14-81%) in aqueous media (Scheme 146) <2001TL461>. When formaldehyde was replaced by acetaldehyde or benzaldehyde, no reaction occurred. There was no formation of the 2,7-diazabicyclo[2.2.1]hept-5-ene 740 (through the aza-Diels-Alder reaction of an N-protected pyrrole with an aldehyde and amine salts by catalysis with triflate). 

Other acetals such as Se,Se- [40], S,Se- [26] and AT,Se-acetals [41, 42] have also been used to generate Se-, S- and AT-substituted alkyl radicals. This strategy is one of the most efficient for the preparation of 1-amido substituted alkyl radicals from aldehydes [Eq. (17)]. Conversion of the aldehyde to an AT,Se-acetal is achieved by conversion to the imine and treatment with ClCOOEt and (z-Bu)2AlSePh. Starting from lactaldehyde 61, the AT,Se-acetal 62 is prepared without racemization. Radical allylation affords the protected amine 63 in 65 % yield [43]. 

In general, imines are too reactive to be used to protect carbonyl groups. In a synthesis of juncusol, however, a bromo- and an iodocyclohexylimine of two identical aromatic aldehydes were coupled by an Ullmann coupling reaction modified by Ziegler." The imines were cleaved by acidic hydrolysis (aq. oxalic acid, THF, 20°C, 1 h, 95% yield). Imines of aromatic aldehydes have also been prepared to protect the aldehyde during ring metalation with, -BuLi. Imines have been used successfully to protect amines and are stable to phase transfer alkylations. 

Coupling of the 4-amino-4-deoxy-ribonic acid derivative 54, obtained from L-serine aldehyde, and amine 55 furnished the amide 56, which underwent hydrolysis of the Boc protecting gronp followed by N-methylation to provide the oxazole 57 (Scheme 8)." ... 

The primary alcohol in 133 was protected as the benzoyl ester 134 before removal of the aldehyde-protecting group in order to prevent hemiacetal formation between the Cn-OH and the C2i-aldehyde functions. The indole amine in 134 was tosylated under basic conditions, accompanied by some epimerization occurring at C-20, to produce the epimeric mixture 136. The aldehyde function in 136 was converted to a silyl enol ether, and then a hydroxy group was introduced at the C-20 position by treatment with... 

Examples of the protection of acetylenes, carboxylic acids, alcohols, phenols, aldehydes, amides, amines, esters, ketones, and olefins are also... 

Similar aldehydes 143a-b, 143e were also applied by the Cdrdova group, this time in combination with Boc-protected imines 23a, 23c-d (Scheme 5.56). Again, L-proline 1 was successfully utilized to yield the allylic Boc-protected amines 146 in reasonable yield and E/Z selectivity, but excellent enantioselectivity (all >99% ee) [85],... 

Interesting examples for conjugate additions mediated by chiral amines have been described by Alexakis et al. (Scheme 36), who used the nitroalkene 151 as a Michael acceptor in organocatalytic enamine-catalyzed conjugate addition reactions 149, 150, 153). Michael reaction of 151 with propionaldehyde 60 in the presence of the diamine catalyst 152 (15 mol%) gave 153 as a mixture of four diastereomers in good yield. Subsequent aldehyde protection and conversion of the... 

A multi-component catalytic asymmetric aziridination of aldehydes employs a protected amine and ethyl diazoacetate as reactants and an (5)-VAPOL boroxinate catalyst, giving aziridine-2-carboxylic esters in up to 99% ee. It works for some cases where preformed imines failed. ... 

Treating the protected amine 141 in the presence of the Rh-BIPHEPHOS catalyst (see Figure 3) under hydroformylation conditions, leads to enamide 142. The consecutive reactions are hydroformylation to give the linear aldehyde, cyclization to give aminoacetal and the elimination of water. Compound 142 is a key intermediate in the synthesis o rosopinine 143 [86]. 

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