Production of novel isoquinoline-containing functional reagents and new developmet

本文报道了一种新型的化学选择性叔丁氧基羰基化试剂，1-叔丁氧基-2-叔丁氧基羰基- 1,2 -二氢异喹啉（BBDI），该试剂由异喹啉与Boc_2O反应制备而得。BBDI对酸性底物在无碱条件下的叔丁基羰基化反应较碱性底物容易，而用Boc_2O对酚类、羧酸等酸性化合物的叔丁基化反应则需要一定的碱。羧酸酯的合成是有机化学中生产天然和合成有用化合物的最基本和关键的方法之一。研究了羧酸和醇的活性衍生物之间的偶联反应。这些程序是相当有趣的，特别是涉及到多肽或复杂的生物活性化合物，如大环内酯的操作。以BBDI为缩合试剂，在电子锅中进行了简单温和的n保护氨基酸酯化反应。该方案有几个优点，包括使用几乎等摩尔量的醇，不需要添加剂，不发生外消旋作用。接下来，我们在简单温和的条件下，在Boc_2O存在下，开发了一种新的bbdi催化n保护氨基酸的酯化反应。虽然已经报道了多种酸催化酯化反应的方法，但使用BBDI等近中性催化剂尚未进行广泛的研究。进一步研究发现，用6-甲氧基异喹啉等富电子异喹啉衍生的BBDI型试剂催化酯化可缩短反应时间。羧酸酰胺的合成是有机化学中生产天然和合成有用化合物如肽的最基本和关键的方法之一。我们成功地获得了一种简单而温和的酰胺，它使用了几乎等量的各种羧酸、胺和BBDI，而不需要任何添加剂。少

We reported a novel and chemoselective tert-butoxycarbonylation reagent, 1-tert-butoxy-2-tert-butoxycarbonyl-1, 2-dihydroisoquinoline (BBDI), which was easily prepared in quantitative yield by the reaction of isoquinoline with Boc_2O. BBDI effected easily the tert-butoxycarbonylation for acidic substrates in the absence of bases rather than basic ones, while that for acidic compounds such as phenols, carboxylic acids using Boc_2O required some base. The synthesis of carboxylic esters is one of the most fundamental and pivotal protocols for producing natural and synthetically useful compounds in organic chemistry. The coupling reactions between activated derivatives of carboxylic acids and alcohols have been employed. These procedures are of considerable interest, especially as relate to the manipulation of peptides or complicated biologically active compounds such as macrolides. A simple and mild esterification of N-protected amino acids using BBDI as a novel condensing reagent in a on … More e-pot method was developed. This protocol has several advantages including the use of nearly equimolar amounts of alcohols, no requirement for additives, and no racemization occurs. Next, we developed a novel BBDI-catalyzed esterification of N-protected amino acids in the presence of Boc_2O under simple and mild conditions. Although a variety of methods for acid-catalyzed esterification reactions have been reported, the use of a nearly neutral catalyst such as BBDI has not been extensively investigated. Further, it was found that catalytic esterification using BBDI typed reagent derived from electron-rich isoquinoline such as 6-methoxyisoquinoline shortened a reaction time. The synthesis of carboxylic amide is one of the most fundamental and pivotal protocols for producing natural and synthetically useful compounds such as peptides in organic chemistry. We succeeded a simple and mild amidation that uses nearly equimolar amounts of a variety of carboxylic acids and amines and BBDI without the need for any additives. Less