Alkylamines,chiral synthesis

O-Alkylation of 4-hydroxy-3-morpholino-l,2,5-thiadiazole 132 has been achieved with the chiral cyclic chloro-methyl sulfite 133 which subsequently suffers ring opening on treatment with simple alcohols <2001RCB436> or alkylamines <2002RJ0213> to afford the timolol analogues 134 with very little racemization (Scheme 20). This indicated an almost exclusive attack of the oxy anion on the exocyclic carbon atom and is a significant improvement on the previous oxirane method, which suffers from racemization. An alternative biocatalytic asymmetric synthesis of (A)- and (R)-timolol has also appeared <2004S1625>. 

As the latter were not easily accessible by chemical synthesis at that time, new methods of preparing these ferrocene derivatives were developed and introduced in 1969. It was then proved that the U-4CRs of chiral a-ferrocenyl-alkylamines can form diastereomeric a-aminoacid derivatives stereo-selectively, and it was further shown that after the reaction the a-ferrocenyl groups of the products can be replaced by protons, thus resynthesizing the chiral a-ferrocenyl-alkylamines simultaneously." Later, the development of this ferrocene chemistry was given up since such syntheses cannot form the products in sufficient quantity and stereoselective purity. ... 

Careful inspection of the reported photocatalytic reactions may demonstrate that reaction products can not be classified, in many cases, into the two above categories, oxidation and reduction of starting materials. For example, photoirradiation onto an aqueous suspension of platinum-loaded Ti02 converts primary alkylamines into secondary amines and ammonia, both of which are not redox products.34) ln.a similar manner, cyclic secondary amines, e.g., piperidine, are produced from a,co-diamines.34) Along this line, trials of synthesis of cyclic imino acids such as proline or pipecolinic acid (PCA) from a-amino acids, ornithine or lysine (Lys), have beer. successfuL35) Since optically pure L-isomer of a-amino acids are available in low cost, their conversion into optically active products is one of the most important and practical chemical routes for the synthesis of chiral compounds. It should be noted that l- and racemic PCA s are obtained from L-Lys by Ti02 and CdS photocatalyst, respectively. This will be discussed later in relation to the reaction mechanism. 

In order to search for conformationally restricted 5-HT2A/2C receptor agonists, a useful method for the synthesis of an enantiomerically pure heterocyclic tetrahydrobenzo[l,2-ft 4,5-fc Jdifuran based alkylamines was developed. The route to the core structure is illustrated below. Thus, when the ehlorobromo compound was treated with Mg in the presence of EtMgBr, the tetrahydrobenzodifuran was obtained. This was further functionalized by reaction with a chiral acyl chloride and AlCl, followed by reduction of the ketone carbonyl group with triethylsilane in trifluoroacetic acid <01JMC1003>. 

All four 2,3,5-tri- -benzoyl-D-pentofuranosyl cyanides with the 1,2-trans-stereochemlstry have been synthesized from the correspond -ing l- -acetates (with MeoSiCN-SnClh) their c.d. spectra have been interpreted by the exciton chirality method.The synthesis of a-aminonitriles by addition of hydrogen cyanide and alkylamines to D-glucose, D-galactose, and D-mannose has been reexamined, and new products have been obtained depending upon the conditions as well as the sugar. As shown in Scheme 11, the o-aminonitriles... 

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