Günter Markus, Gais Hans-Joachim
Institut für Organische Chemie der Rheinisch-Westfälischen Technischen Hochschule Aachen, Professor-Pirlet-Strasse 1, D-52056 Aachen, Germany.
J Org Chem. 2003 Oct 17;68(21):8037-41. doi: 10.1021/jo030171x.
An asymmetric synthesis of fused bicyclic amino acids having a hexahydro-cyclopenta[c]pyridine skeleton and carrying besides an enone structural element a substituent at the beta-position is described. The key steps of the synthesis are a highly selective allylation of N-tert-butylsulfonyl imino ester with bis(allylsulfoximine)titanium complexes and a highly diastereoselective Pauson-Khand cycloaddition of sulfonimidoyl-substituted gamma,delta-unsaturated alpha-amino acid esters carrying a substituent at the beta-position and a propargyl group at the N-atom. The cyclization is accompanied by a reductive cleavage of the sulfoximine group of the primary cyclization product. Surprisingly, the removal of the sulfoximine group proceeds with inversion of the configuration at the S-atom and gives N-methyl-phenylsulfinamide with >/=98% ee. Deprotection of the bicyclic N-tert-butylsulfonyl-protected amino acid ester was accomplished through treatment with CF(3)SO(3)H under anhydrous conditions. The enantio- and diastereomerically pure sulfoximine-substituted gamma,delta-unsaturated alpha-amino acid esters used as starting material were obtained through a highly regio- and diastereoselective allylation of N-tert-butylsulfonyl imino ester with acyclic bis(allylsulfoximine)titanium complexes, described previously.
本文描述了一种具有六氢环戊[c]吡啶骨架的稠合双环氨基酸的不对称合成方法，该氨基酸除烯酮结构单元外，在β位还带有一个取代基。合成的关键步骤包括N-叔丁基磺酰基亚氨基酯与双（烯丙基亚砜亚胺）钛配合物的高度选择性烯丙基化反应，以及在β位带有取代基且在N原子处带有炔丙基的磺酰亚胺基取代的γ,δ-不饱和α-氨基酸酯的高度非对映选择性Pauson-Khand环加成反应。环化反应伴随着初级环化产物中亚砜亚胺基团的还原裂解。令人惊讶的是，亚砜亚胺基团的去除在S原子处构型翻转的情况下进行，并得到对映体过量（ee）≥98%的N-甲基苯亚磺酰胺。双环N-叔丁基磺酰基保护的氨基酸酯的脱保护通过在无水条件下用CF(3)SO(3)H处理来完成。用作起始原料的对映体和非对映体纯的亚砜亚胺取代的γ,δ-不饱和α-氨基酸酯是通过N-叔丁基磺酰基亚氨基酯与无环双（烯丙基亚砜亚胺）钛配合物的高度区域和非对映选择性烯丙基化反应获得的，该反应已在之前描述过。
