2- Amino alcohols synthesis

Ferrocenyl amido complexes, with Zr(IV), 4, 773 Ferrocenyl amino alcohols, synthesis, 6, 202 Ferrocenylated ODN, characteristics, 1, 909—910 Ferrocenyl diols, chiral, synthesis, 6, 204 Ferrocenyldiphenylphosphines, preparation, 6, 202 Ferrocenylimines mercuration, 2, 433 into platinacycles, 8, 511... 

In combination with the range of standard transformations of alcohols, alkenes, and vinylsulfides, these silicon-tethered additions of functionalized radicals offer a versatile and stereoselective approach to amino alcohol synthesis. Whereas vinyl and 2-oxoethyl radicals have not yet been demonstrated as competent participants in the various intermolecular additions reported in the literature, the temporary tether approach allows such functionalized fragments to be installed in an efficient and stereoselective manner. Synthesis of the aminosugar daunosamine from achiral precursors shows how this concept, employing hydrazone radical acceptors, can be merged with asymmetric catalysis to achieve practical synthetic advances. 

However, a reversal of the diastereofacial selectivity may arise when the substrate has, in a or position of the side chain, a group prone to complexation with the Lewis acid. Then, the use of bidentate Lewis acids such as MgBr2, TiCU or ZnC allows the reaction to proceed under a chelation control model, providing preferentially the syn adduct for a 1,4-chelation and the anti adduct for a 1,5-chelation. This was exploited in the stereoselective synthesis of both diastereomers, simply by changing the chelation conditions on the substrate . An impressive amount of work was done with various a-alkoxy aldehydes as a route to carbohydrate chemistry. Similarly, a-amino aldehydes were used as substrates for /3-amino alcohol synthesis . ... 

PROPYNYLLITHIUM LITHIUM, 1-PROPYNYL- (4529-04-8), 76, 214 Protected vicinal amino alcohols, synthesis of, 77, 78... 

For the amino alcohols synthesis, see Sumitomo Chem (1976) JP Patent 839405... 

Table 6.2. Variation of the amines in the 1,3-amino alcohol synthesis by using 4-trifluoromethyl-benzal-dehyde as constant building block...

The dihydrothiazine oxide (73) gives the (Z)-allylic sulfoxide (77), which (/,/2 = 90 min) is slowly converted to a mixture of ( )-allylic sulfoxides (78) that are epimeric at the sulfur atom. This well-precedented transformation of (77) to the thermodynamically more stable (78) involves conformational inversion of the sulfenate ester (79a) to (79b). At any stage of this equilibrium, treatment with a thiophile such as trimethyl phosphite can stereospecifically lead to the (F -hydroxy carbamate (74) (Scheme 13) <84JA7861>. This versatile transformation has been applied to stereospecific vicinal amino alcohol synthesis. 

T. Fey, M. Holscher, H. Keul, H. Hocke, Alternating poly(ester am-ide)s from succinic anhydride and a, co-amino alcohols synthesis and thermal characterization, Polym. Int. 52 (2003) 1625-1632. 

Most of the above examples demonstrate that the amino-alcohol moiety can be synthesised with a high degree of stereocontrol. Furthermore, the formation of heterocyclic intermediates, in particular oxazolidinones and oxazolines above, is often a crucial factor in exercising this control. Hence, ring fragmentations of, -heterocycles, produced by methods other than allylic functionalisation, persist as an important area within amino-alcohol synthesis. 

Amino-alcohol synthesis may also be achieved by the simple, classical addition of amines to oxiranes. However, even today such procedures are often limited by poorly nucleophilic amines, incompatibility of some epoxides with reaction conditions and poor regioselectivity of addition. It has been shown that compared to the use of Si02 or kl20-, the Na-exchanged Y-type zeolite resin ZCP-50 mediates such additions with consistently improved regio-... 

Various other reductive methods have been applied to amino-alcohol synthesis. (S)-(-)-3-Piperidinol was synthesised from both L-glutamic acid and (S)-malic acld. The routes involved cycli-sations of amino-alcohols in which the amino moiety was established by azide and nitrile reductions with H /Pd-C and LiAlH j respectively. Acyl cyanides were reduced to optically active amino-... 

The stability of a-azido substituents in boronic esters was first observed in exploratory studies [29]. Azido groups are compatible with several standard reactions of boronic esters, including chain extension with (dichloromethyl)lithium and substitution of the resulting a-chloro substituent. After peroxidic deboronation, reduction of the azido group with lithium aluminum hydride led to an asymmetric amino alcohol, (5S,6S)-BuCH(NH2)CH(OH)Bu, in 98% diastereopurity [29]. Details ofa more recent amino alcohol synthesis are shown below in Scheme 8.31. 

In an effort to further evaluate the generality of this concept, we were particularly attracted to evaluate novel methods for the synthesis of chiral 1,3-diamine motifs and of 1,3-aminoalcohol functionahties, both of which constitute particularly important structural elements in various bioactive natural products and medicinal compounds. Because of their prevalence, a number of strategies for the construction of such systems have been reported. Inspired by our domino concept in combination with certain hmitations of existing methods, in particular, with respect to modularity and convergence, a more direct and flexible procedure for 1,3-diamine and 1,3-amino alcohol synthesis based on stereoselective intramolecular allylic substitution reaction seemed desirable. 

SCHEME 40.13. Carboamination reaction of substituted chiral amino alcohol synthesis of disubstituted morpholines. 

Fey T, Holscher M, Keul H, Hocker H (2003a), Alternating poly(ester amide)s from succinic anhydride and amino alcohols synthesis and thermal characterisation , Pol. Int., 52 (10), 1625-1632. 

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