Aminoalcohol Carbamates

The concept of structural modification amongst the aminoalcohol carbamates has crept up due to the introduction of non-polar functions on the unsubstituted N of the carbamoyl moiety in the following general formula ... 

In the reaction of an aminoalcohol with a methyl imidazole-AT-carboxylate or tert-butyl imidazole-AT-peroxycarboxylate, selective acylation of the amino function can be achieved11903 to give the carbamate and peroxycarbamate, respectively, the hydroxy groups of which can be further acylated ... 

A cyclic carbamate (see also Chapter 7) is obtained in the reaction of an aminoalcohol with CDI [190]... 

In analogy to the preceding Section 7.1.5 the insertion of a C=0 or C=S group between an amino and a hydroxy function of 1,3-aminoalcohols using CDI or ImCSIm yields six-membered heterocycles with a carbamate or thiocarbamate structure. 

Another fruitful investigation was based upon the cyanohydrin of ketone 60. This substance (75) undergoes hydride reduction to the corresponding aminoalcohol, which forms cyclic carbamate 76 on... 

Oxidative carbonylation is not necessarily associated with C - C bond formation. Indeed, heteroatom carbonylation may occur exclusively, as in the oxidative carbonylation of alcohols or phenols to carbonates, of alcohols and amines to carbamates, of aminoalcohols to cyclic carbamates, and of amines to ureas. All these reactions are of particular significance, in view of the possibility to prepare these very important classes of carbonyl compounds through a phosgene-free approach. These carbonylations are usually carried out in the presence of an appropriate oxidant under catalytic conditions (Eqs. 31-33), and in some cases can be promoted not only by transition metals but also by... 

Similarly, lipase-catalyzed kinetic resolution has also been applied to intermediate nitrile alcohol 46 (Scheme 14.14). Best results were obtained by using immobilized Pseudomonas cepacia (PS-D) in diisopropyl ether, leading to excellent yield and enantiomeric excess of the desired (5)-alcohol 46a, along with (/J)-nitrile ester 47. Reduction of 46a with borane-dimethylsulhde complex, followed by conversion to the corresponding carbamate and subsequent lithium aluminum hydride reduction gave rise to the desired (S)-aminoalcohol intermediate 36, a known precursor of duloxetine (3). 

Enantiomerically pure aminoalcohols, which are readily available by reduction of a-amino acids, can be converted into alkoxycarbonylating reagents suitable for the solid-phase synthesis of oligocarbamates (Figure 16.26). Particularly convenient alkoxycarbonylating reagents are 4-nitrophenyl carbonates, which can be prepared from alcohols and 4-nitrophenyl chloroformate, and which react smoothly with aliphatic primary or secondary amines to yield the corresponding carbamates. 

In 1975 Sharpless and coworkers discovered the stoichiometric aminohydrox-ylation of alkenes by alkylimido osmium compounds leading to protected vicinal aminoalcohols [1,2]. Shortly after, an improved procedure was reported employing catalytic amounts of osmium tetroxide and a nitrogen source (N-chlo-ro-N-metallosulfonamides or carbamates) to generate the active imido osmium species in situ [3-8]. Stoichiometric enantioselective aminohydroxylations were first reported in 1994 [9]. Finally, in 1996 the first report on a catalytic asymmetric aminohydroxylation (AA) was published [10]. During recent years, several reviews have covered the AA reaction [11-16]. 

An interesting offshoot of the work on osmium-catalyzed dihydroxylations is vicinal hydroxyamination [24]. Here, imido analogs of OSO4 react with olefins to produce /5-aminoalcohols by a cw-addition process. The oxyamination reaction can be made catalytic in OSO4 by employing chloramine salts of arylsulfonamides (ArS02NClNa) or carbamates. 

Avino et al. [288] have adapted the NPEOC and Fmoc anchors for the attachment of various O-protected a,co-aminoalcohols as weH as 3 -a mi rio-3 -deoxy nucleosides to LCAA-CPG (Figure 19.12). The supports obtained were derived from the known Hnkers (Section 19.3.1.3 and Section 19.3.2.2) by solid-phase transformation of the hydroxyl Hnker into the carbamate by the reachon with l,T-carbonyldiimidazole foUowed by aminoalcohol treatment The authors have found that both anchors, NPEOC and Fmoc, can be cleaved by standard ammonolysis without the need for DBU, but the former gives a cleaner product. 

Besides the amide bond present in peptides, the carbamate and urea groups constitute additional chemically stable linkages for oligomeric compounds. The first syntheses of oligocarbamates on solid supports were based on the sequential condensation of aminoalcohols derived from a-amino acids shown in Scheme 2.7.1. 

Supported chiral bispidine-derived aminoalcohols were screened in the addition of diethylzinc to benzaldehyde [133]. These immobilized ligands were obtained in three steps from eompound 186 isolated from iV-Boc-piperidin-4-one (Scheme 79). The hydroxyl function of 186 was first linked onto ehloromethylated polystyrene to afford polymer 187. The carbamate was then removed under elassical conditions and reaction of the resulting polymer with chiral epoxides led to ehiial polymeric bispidine-derived aminoalcohols 188. 

Deprotonation by s-BuLi/(—)-sparteine of racemic N,N-dibenzyl-3-cyclopropylpropyl carbamate 117 selected only the pro-S-proton of the (ii)-substrate, leading to a powerful KR leaving an enantiomerically enriched unreacted (S)-117 [76]. The diastereomericaUy enriched lithiated compound 118 could react with an electrophile to give 1,2-aminoalcohol derivative 119 of high enantiomeric excess. 

Carbamates Isocyanates Hydroxynitriles Aminoalcohols Amides (Carboxamides)... 

The reaction has recently been developed further by use of the milder reagents PhIO and PhI(OAc)2, respectively, within the iodine(III)-mediated intramolecular pyrrolidine formation from alkenes. For example, the combined use of iodoso-benzene and trimethylsilyl triflate generates reaction conditions that enable an efficient aminooxygenation of urea precursors 61. Because of the acidic reaction conditions, the final carbon-heteroatom bond formation cannot proceed toward diamination, and aminooxygenation products 62 are obtained selectively. The free aminoalcohols are conveniently obtained by acidic cleavage of the cyclic carbamate [51]. 

M. Tamura, M. Honda, K. Noro, Y. Nakagawa, K. Tomishige, Heterogeneous Ce02-catalyzed selective synthesis of cyclic carbamates from CO2 and aminoalcohols in acetonitrile solvent, J. Catal. 305 (2013) 191-203. 

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