Amination intramolecular reductive

Piperidines bearing a masked aldehyde function in the e-position are easily transformed into quinolizidine compounds through intramolecular reductive amination after deprotection (acetal precursors) or oxidative cleavage (tv e-diols). Some examples are given below. 

V-( 1,1 -dimcthylbut-3-cnyl)-hydroxylamine followed by intramolecular 1,3-dipolar cycloaddition, was easily converted into the polyhydroxylated quinolizidine 192 by removal of the isopropylidene group and hydrogenolysis of the N-O bond in the presence of Raney-nickel accompanied by intramolecular reductive amination (Scheme 35) <2001CC915>. 

Protected pyrazoline derivatives 429 can be transformed by conventional ozonolysis methodology to the corresponding aldehydes 430, then the Cbz protecting group is removed and the intramolecular reductive amination using... 

Xenovinine 195, a natural alkaloid, was obtained by catalytic hydrogenolysis of carbamate 194 and subsequent intramolecular reductive amination of the in /-////-generated A-deprotected ketopyrrolidine <1999T8915>. Enantiodivergent synthesis of 195 with the same reductive amination as final step was also reported (Scheme 45) <1998EJO 955>. 

Catalytic reduction (Raney-Ni, H2) of the nitroso acetal-mesylate 243 resulted in reductive cleavage of both N-O bonds followed by intramolecular reductive amination and finally intramolecular iV-alkylation providing the masked 7-epiaustraline alkaloid 244 (Scheme 65) <1998JA7357>. 

When DHAP-dependent aldolases are used as catalyst of the aldol reaction, a phosphorylated azido or amino polyhydroxyketone is obtained. The phosphate may be cleaved enzymatically or reductively cleaved under the hydrogenation conditions of the next step in which the azide is reduced to the amine. Intramolecular imine formation occurs spontaneously when the azide is reduced. The intramolecular reductive amination is the second key step of the aldolase-mediated synthesis of iminocyclitols. In general, delivery of hydrogen onto five- and six-membered ring imines occurs from the face opposite to the C4 hydroxyl group. 

Scheme 1.64). The Ag(I)-mediated cyclization afforded dipole 306 for 1,3-dipolar cycloaddition with methyl vinyl ketone to yield adducts 307 and the C(2) epimer as a 1 1 mixture (48%). Hydrogenolytic N—O cleavage and simultaneous intramolecular reductive amination of the pendant ketone of the former dipolarophile afforded a mixture of alcohol 308 and the C(6) epimer. Oxidation to a single ketone was followed by carbonyl removal by conversion to the dithiolane and desulfurization with Raney nickel to afford the target compound 305 (299). By this methodology, a seven-membered nitrone (309) was prepared for a dipolar cycloaddition reaction with Al-methyl maleimide or styrene (301). 

Williams and co-workers form the C(7)-C(8) bond first through the addition of benzyl anion to an aziridino aldehyde 317 <20020L3711, 2004JOC2825>. The resulting hydroxyl group is protected and the -methoxybenzyl (PMB) group is removed and the hydroxyl-oxidized to aldehyde 319 (Scheme 62). An intramolecular reductive amination was used to form the final bond of the tricycle. 

In 1923 the bacterium Acinetobacter suboxydans was isolated and, starting in 1930, was used for the industrial oxidation of L-sorbitol to L-sorbose in the Reichstein-Griissner synthesis of vitamin C[39]. Bayer uses the same type of reaction, but instead of Acinetobacter the bacterium Gluconobacter suboxydans is used in the oxidation of N-protected 6-amino-L-sorbitol to the corresponding 6-amino-L-sorbose, which is an intermediate in miglitol production (Fig. 19-7). 1-Desoxynojirimydn is produced by chemical intramolecular reductive amination of 6-amino-L-sorbose. In contrast, the... 

Alternatively, compound 14 was oxidized with sodium periodate, followed by reduction with sodium borohydride in ethanol to afford 18 (Scheme 3). Hydrolysis of the isopropy-lidene group in 18 with 50% aqueous trifluoroacetic acid followed by hydrogenation of the azide group and then intramolecular reductive amination and protection of the imine group afforded 19. Selective mesylation of the primary hydroxyl group in 19 followed by silylation and subsequent removal of the benzyloxycarbonyl group and then cyclization with sodium acetate afforded 20. Deprotection of 20 led to me50-quinuclidine-3,5-diol (3). 

In related work esters 222 and 223 were each converted to the respective alkaloids (-)-lupinine 224 and (-)-5-epitashiromine 225 by sequences which featured intramolecular reductive amination reactions <04T5433>. Reduction of advanced intermediate 226 with LAH, followed by hydrogenolysis and deketalization gave 1-deoxy-D-gulonojirimycin 227 <04TL5355>. COaMe... 

Other examples of intramolecular reductive amination reactions resulting from amines formed from azido compounds are shown below. Excellent diastereoselectivities were observed for the reduction of the intermediate imines in the latter two cases (Scheme 37).W8H50]... 

SCHEME 6 Synthesis of (+)-spectalme (4) via intramolecular reductive amination. 

SCHEME 7 Synthesis of (+)-spectalin (4) using intramolecular reductive amination via alkyne hydrosilylation-oxidation strategy. 

SCHEME 8 Synthesis of (—)-deoxoprosophylline(8) using intramolecular reductive amination via Sml2-mediated cross-coupling. 

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