α-氨基酰胺衍生物的不对称合成

Asymmetric synthesis of α-aminoamides derivatives

探索不对称合成α-氨基酰胺衍生物的方法。方法以(R)-1-苯乙胺为起始原料,首先合成手性氨甲酰基硅烷,然后,该手性氨甲酰基硅烷分别与非手性亚胺、手性亚胺反应,最终得到立体选择性加成产物α-氨基酰胺衍生物。结果与结论合成了5个α-氨基酰胺衍生物,其中6c、8a和8c是高立体选择性产物。手性氨甲酰基硅烷与亚胺的反应具有立体选择性,其立体选择性大小与亚胺双键氮原子和碳原子上所连的烃基有关,因此通过选择不同的烃基可实现不对称合成α-氨基酰胺衍生物的目的。

As the representatives of the smallest subunit of peptides and proteins, oz-aminoamides are impor- tant synthetic targets. Construction of such species by establishing the carbon-carbon bond on the alpha posi- tion to the carbonyl group is often accomplished by the Ugi reaction, which affords an a-（ N-acyl-N-alkyl- amino） amide containing a new stereogenic center at the alpha-carbon atom. Several limitations of this ap- proach have been observed, so it was urgent to report an approach which directly affords a high diastereose- lective o^-aminoamides. It was found that the addition of imine by carbamoylsilanes promoted by stoichimet- ric amounts of BF3 -EtEO could afford a-aminoamides. However for efficient applications within these areas, enantioenriched substrates are required. After exploring the potential of both single and double stereodifferen- tiation in these addition reactions by incoporating chiral N-auxiliaries into the imine and/or carbamoylsilane components, so a chiral carbamoylsilane 4 were synthesized using （R）-l-phenylethylamine as startingmaterial. The reactions of chiral carbamoylsilane 4 with imines 5a ,5b ,5c and chiral imines 7a ,7b ,7c can af- ford stereoselective addition products 6b ,6c ,8a, 8b and 8c, in which 6c ,Sa and 8c are highly stereoselective products. A comparison of the results obtained from 5b ,5c ,Ta ,Tb and 7c indicates that the chiral carbamoyl- silane possesses stereoselectivity which is directly related to substituted group on C = N double bond of im- ines. Thereby, a possible route to enantiopure α-aminoamides is proposed.