Carbamates, reduction with

Many carbamates have been used as protective groups. They are arranged in this chapter in order of increasing complexity of stmcture. The most useful compounds do not necessarily have the simplest stmctures, but are /-butyl (BOC), readily cleaved by acidic hydrolysis benzyl (Cbz or Z), cleaved by catalytic hy-drogenolysis 2,4-dichlorobenzyl, stable to the acid-catalyzed hydrolysis of benzyl and /-butyl carbamates 2-(biphenylyl)isopropyl, cleaved more easily than /-butyl carbamate by dilute acetic acid 9-fluorenylmethyl, cleaved by /3-elimination with base isonicotinyl, cleaved by reduction with zinc in acetic acid 1-adamantyl, readily cleaved by trifluoroacetic acid and ally], readily cleaved by Pd-catalyzed isomerisation. 

The carbamate, prepared from the 4-nitrophenyl carbonate, is cleaved by reduction with dithiothreitol (DTT) and TEA to give the aniline, which triggers fragmentation, releasing the amine. ... 

The carbamates, derived from the reaction of 8-aminoquinoline with phenyl or ethyl chloroformate, upon reduction with NaBH4 gave the... 

An alternative method for cleaving carbamates is exhaustive reduction with LiAlFLt to yield methylamines (Entry 3, Table 3.22). Entry 9 in Table 3.22 is an example of the nucleophilic cleavage of a carbamate with sodium methoxide. The mild reaction conditions required in the case are attributable to the structure of the amine (a vinylogous amide) these conditions are unlikely to lead to the cleavage of simple A-alkyl- or A, A-dialkylcarbamates, although A-arylcarbamates are also susceptible to nucleophilic cleavage (Entry 6, Table 3.26). 

Reduction of vinylogous carbamate 36 with sodium cyanoborohydride in acidic methanol gave exclusively the equatorial aminoester 38. Eschenmoser and co-workers (181 have explained this result by invoking a stereoelectroni-cally controlled anti peri planar addition of hydride ion on the iminium ion 37. 

The structures of the ds-hydroindole 130 (Ar = Ph) and the trans-hydroindole 131 (Ar = Ph) were established by their conversion to ( )-a- and ( )-(3-lycorane (57 and 58), respectively. In the event, catalytic hydrogenation of the double bond in the hydroindoles 130 and 131 (Ar = Ph) over 5% Pd/C in AcOH proceeded with concomitant N-debenzylation to provide the corresponding secondary amines, which were then allowed to react with methyl chloroformate to furnish the corresponding carbamates 132 and 133. On heating in POCl3, 132 and 133 underwent Bischler-Napieralski cyclization to provide the 7-oxo-a- and -(3-lycoranes 134 and 135, which were then converted to 57 and 58, respectively, by reduction with LiAlH4. 

Another approach to the lycorane skeleton involving an intramolecular Diels-Alder reaction commenced with the conversion of the unsaturated nitrile 138 to the imine 139 by sequential reduction with diisobutylaluminum hydride followed by condensation with but-3-enylamine (Scheme 13) (118). When 139 was acy-lated with chloroethyl chloroformate in the presence of Hiinig base and the resulting dienamide heated at 140°C, the bicyclic carbamate 141 was isolated. If it is assumed that the Diels-Alder reaction proceeded via an exo transition state,... 

The oxazolidin-2-ones 53 (R = H=CCH=CH2 or COEt) are obtained in a one-pot reaction of amino alcohol carbamates 52 with sodium hydroxide, followed by allyl bromide or propi-onyl chloride (94TL9533). A modified procedure for the preparation of chiral oxazolidin-2-ones 56 from a-amino acids 54, which avoids the hazardous reduction of the acids with borane and the intermediacy of water-soluble amino alcohols, is treatment of the methyl ester of the amino acid with ethyl chloro-formate to give 55, followed by reduction with sodium borohydride and thermal ring-closure of the resulting carbamate f95SC561). The 2-prop-ynylcarbamates 57 (R = Ts, Ac, Bz, Ph or allyl) cyclize to the methyleneoxazolidinones 58 under the influence of silver cyanate or copper(I) chloride/triethylamine (94BCJ2838). 

The first reported synthesis of cyprodime utilized as starting material the highly potent opioid agonist 4,14/J-dimethoxy-iV-methylmorphinan-6-one (24) which is available from oxymorphone in six steps [72]. A-Demethyla-tion was achieved with the 2,2,2-trichloroethyl carbamate to give (25) which was cleaved reductively with activated zinc and ammonium chloride to afford /V-normorphinan (26). Alkylation with cyclopropylmethyl chloride provided cyprodime (23). 

By treatment of an alkene with phenyltellurinyl trifluoroacetate in combination with ethyl carbamate and boron trifluoride in refluxing chloroform, the addition product 5 was obtained in good yield and with complete diastereoselectivity. The stereochemistry of the product was confirmed on comparison with an authentic sample and is in agreement with the proposed mechanism. Further reduction with hydrazine gave the phenyltelluro derivative 6 in high yield, whereas heating provided the corresponding ru-oxazolidinone 725-28. 

By contrast, high stereoselectivity was observed in the cyclization of unsaturated acyclic amides and carbamates, the preferential formation of the trans- or m-isomer is dependent on the experimental conditions. Hence, by treating 7V-acetyl-5-hcxcn-2-amine with mercury(II) acetate in tetrahydrofuran (kinetic conditions), followed by reduction with sodium borohydride, trans-l-acetyl-2,5-dimethylpyrrolidine (4. R = CH3) was obtained in 98 % yield and only traces of the cu-isomer were shown to be present by H and 13C NMR81. 

The reaction of diallyl ether with mercury(II) nitrate in dichloromethane in the presence of an alkyl carbamate proceeds with total stereoselectivity and moderate yield. Under these conditions (thermodynamic control) the reaction gave, after reductive cleavage, the more stable diequatorial alkyl 3,5-dimelhyl-4-morpholine carboxylate 1124. 

Reaction of allylic alcohol 396 with paraformaldehyde using a catalytic amount of p-toluenesulfonic acid gave cyclic carbamate 397, which upon reduction with lithium aluminum hydride afforded aminodiol 398. Oxidative cleavage of the double bond of 398, achieved by dry silica gel ozonization (80JA5968) of the trifluoro acetate salt of aminodiol 398, gave ( )-5-epi-desosamine (399) (Scheme 49). 

Lebrun and coworkers reported a convenient synthesis to a range of phenanthroindo- and quinolizidine natural products [62]. In this approach, the alkaloids (+)-antofine [( )-3] (n-1) and (+)-cryptopleurine [(+)-5] (n=2), were synthesized by Pictet-Spengler cyclization of 72 [2-arylmethyl-piperidine (n=2) and -pyrrolindine (n=l)], Scheme (7). The intermediate compounds were obtained by sequential iV-deprotection-reduction of the parent enecarbamates 71, which were obtained from Homer reaction of phosphorylated carbamates 70 with the appropriate aldehyde (69). 

Chiral oxazolidones are readily prepared from carbamates of a-amino esters by reduction with NaBHa-Lil in refluxing THF. Note that imides (A-acyloxazolidinones) are reduced to alcohols, therefore the reduction represents a method for recovery of both chiral products and auxiliaries. ... 

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