It comprises the one-pot sequential reduction to aldehyde with DIBAL-H at −78 °C and subsequent in situ addition of Grignard reagents. Remarkably, our method is friendly with serine and threonine derivatives without the requisite to protect the β-hydroxy group. With this tool in hand, we thought on the possibility to extend the scope of the aforementioned one-pot procedure to the synthesis of enantiomerically pure allylic amines. It has been rported earlier the one-pot preparation of N-protected allylic amines via tandem DIBAL-H reduction–Wittig olefination of N-protected α-amino esters [17]. However, that preliminary study was limited to the use of phosphonium ylide reagents and commonly t-Boc (iBoc and Ac were used once) as N-protecting group. To the best of our knowledge, no further studies on the reaction conditions have been carried out. Instead, the method was applied to N-Ac aspartic, and N-Ac and N-Boc glutamic acid dialkyl esters, this time using a stabilized phosphonate ester [18]. This strategy was used later on in the synthesis of aminopeptidase A inhibitors [19]. Similarly, N-methylproline methyl ester was reacted in a similar one-pot fashion during the synthesis of nine-membered ring lactams [20]. Finally, a one- pot reduction-olefination involving an α-amino β-hydroxy ester and a phosphonium salt, both bearing free hydroxy groups, has been used in the synthesis of (−)-α-conhydrine [21].
It comprises the one-pot sequential reduction to aldehyde with DIBAL-H at −78 °C and subsequent in situ addition of Grignard reagents. Remarkably, our method is friendly with serine and threonine derivatives without the requisite to protect the β-hydroxy group. With this tool in hand, we thought on the possibility to extend the scope of the aforementioned one-pot procedure to the synthesis of enantiomerically pure allylic amines. It has been rported earlier the one-pot preparation of N-protected allylic amines via tandem DIBAL-H reduction–Wittig olefination of N-protected α-amino esters [17]. However, that preliminary study was limited to the use of phosphonium ylide reagents and commonly t-Boc (iBoc and Ac were used once) as N-protecting group. To the best of our knowledge, no further studies on the reaction conditions have been carried out. Instead, the method was applied to N-Ac aspartic, and N-Ac and N-Boc glutamic acid dialkyl esters, this time using a stabilized phosphonate ester [18]. This strategy was used later on in the synthesis of aminopeptidase A inhibitors [19]. Similarly, N-methylproline methyl ester was reacted in a similar one-pot fashion during the synthesis of nine-membered ring lactams [20]. Finally, a one- pot reduction-olefination involving an α-amino β-hydroxy ester and a phosphonium salt, both bearing free hydroxy groups, has been used in the synthesis of (−)-α-conhydrine [21].
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