Imines amine protection

A number of imine derivatives have been prepared as amine protective groups, but few of these have seen extensive use. The most widely used are the benzylidene... 

A number of imine derivatives have been prepared as amine protective groups, but most of these have not seen extensive use. The most widely used are the ben-zylidene and diphenylmethylene derivatives. The less used derivatives are listed, for completeness, with their references at the end of this section. For the most part, they are prepared from the aldehyde and the amine by water removal cleavage is effected by acid hydrolysis. 

Trifluoroalanine has also been prepared by reducing trifluoropyruvate imines (ethyl trifluoropyruvate is available commercially it is prepared either from per-fluoropropene oxide or by trifluoromethylation of ethyl or f-butyl oxalate). These imines are obtained by dehydration of the corresponding aminals or by Staudinger reaction. They can also be obtained by palladium-catalyzed carbonylation of trifluoroacetamidoyl iodide, an easily accessible compound (cf. Chapter 3) (Figure 5.4). Reduction of the imines affords protected trifluoroalanines. When the imine is derived from a-phenyl ethyl amine, an intramolecular hydride transfer affords the regioisomer imine, which can further be hydrolyzed into trifluoroalanine. ... 

Mukaiyama and coworkers have pioneered many routes to the total syntheses of rare carbohydrates such as the 2-amino-2-deoxypentoses [75]. In 1982, they reported that the potassium enolate derived from the magnesium salt of the (/ )-atrolactic acid derivative 85 adds to 2,3-0-isopropylidene-D-glyceraldehyde in a highly stereoselective manner giving, after alcohol protection, imine hydrolysis and amine protection, the D-arabinopentoate derivative 86 (Scheme 13.35). Further elaboration leads to 2-acetamido-2-deoxy-D-arabinose 87. In a similar fashion, starting from (5 )-atrolactic acid, 2-acetamido-2-deoxy-D-ribose 88 was prepared [76]. 

The cyclohexylidene protecting group has been employed in several syntheses. A preparation of 2,3-0-cyclohexylidene-4-deoxy-L-threose (445) fi om L-( + )-diethyltartrate (lb) in seven steps illustrates one synthetic application (Scheme 99). Conversion of the monobenzyl protected alcohol 443 to its tosylate followed by reduction with sodium borohydride provides the deoxy intermediate 444, which is reductively deprotected and Swem oxidized to 445 in good overall yield. Treatment with benzylamine provides an imine that undergoes a stereoselective carbon-carbon bond forming reaction with a-lithio-A, A -dimethylacetamide in the presence of the Lewis acid zinc bromide to furnish, after Cbz-amine protection, the j9-aminoamide 446. This is converted in four steps to A -acetyl-L-daunosamine (447), a sugar moiety particularly important as the carbohydrate constituent of the anthracycline antibiotics [149]. 

The metal coordination complexes of both sahcylaldehyde phenyhiydrazone (91) and sahcylaldoxime provide antioxidant (92) protection and uv stabihty to polyolefins (see Antioxidants). In addition, the imines resulting from the reaction of sahcylaldehyde and aromatic amines, eg, p- am in oph en o1 or a-naphthylamine, can be used at very low levels as heat stabiLizers (qv) in polyolefins (93). 

The imine, prepared from an amine and (C5H4N)(Me3C JH2)CO (TiC, toluene, reflux, 12 h NaOH, 80% yield), can be cleaved with coned. HCl (reflux). The protective group was used to direct a-alkylation of amines. 

A trifluoromethylsulfonamide can be prepared from a primary amine to allow monoalkylation of that amine. The triflamide is not stable to strong base, which causes elimination to an imine, but when used to protect an indole, it is cleaved with K2CO3 in refluxing methanol. ... 

The reductive amination of ketones can be carried out under hydrogen pressure in the presence of palladium catalysts. However, if enantiopure Q -aminoketones are used, partial racemization of the intermediate a-amino imine can occur, owing to the equilibration with the corresponding enam-ine [102]. Asymmetric hydrogenation of racemic 2-amidocyclohexanones 218 with Raney nickel in ethanol gave a mixture of cis and trans 1,2-diamino cyclohexane derivatives 219 in unequal amounts, presumably because the enamines are intermediates, but with excellent enantioselectivity. The two diastereomers were easily separated and converted to the mono-protected cis- and trans- 1,2-diaminocyclohexanes 220. The receptor 221 has been also synthesized by this route [103] (Scheme 33). 

PreUminary studies on the racemic reaction of protected imines with ni-tromethane showed that the thiourea and the amine mutually weakened their reactivities. However, the bifunctional amino-thiourea led to good results. Enantioselectivity of the adduct depended on the protecting group, P(0)Ph2 affording the best results (76% ee). Then, other aromatic imines substrates were successfully phosphorylated with good to high enantioselec-tivities (63-76% ee). 

Hydroamination of alkynes offers a straightforward preparation of a variety of amines, enamines, and imines.79 Numerous reports have appeared in the literature on this process. However, almost all these reactions have been carried out in organic solvents, which usually require the protection of functional groups or harsh conditions. Recently, Marinelli et al. have reported an Au(III)-catalyzed hydroamination of alkynes in... 

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