Lithiation-borylation methodology in the total synthesis of natural products
Lithiation-borylation methodology in the total synthesis of natural products
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DOI：
10.1038/s44160-021-00012-1
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发表时间：
2022-02-01
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通讯作者：
Aggarwal, Varinder K.
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作者：
Yeung, Kay;Mykura, Rory C.;Aggarwal, Varinder K.
显示出广泛底物范围的稳健合成方法在复杂有机分子的合成中具有很大的实用性。在该竞技场内，使用硼酸酯的合成方法是特别有用的，因为它们以非常高水平的立体选择性经历各种各样的转化。特别地，硼酸酯可以使用对映体富集的金属类卡宾进行单一或多重同系化。将合适的对映体富集的类卡宾锂或类卡宾镁加成到硼酸酯上，随后进行1，2-迁移，得到具有高度立体控制的同系硼酸酯。这个过程被称为锂化-硼化，可以是迭代的，它允许碳链以惊人的精度一次延伸一个原子。迭代同源化被比作分子装配线，类似于大自然装配天然产物的方式，例如，在聚酮合酶机制中。本文综述了锂化-硼化化学在天然产物合成中的应用，硼酸酯是一种多用途的中间体，它能与亲核试剂发生1，2-迁移反应，并将邻近的离去基团排出。这种反应性使得碳链能够以高立体控制一次一个原子地生长。本文综述了锂化硼化方法的基本原理及其在天然产物合成中的应用。
Robust synthetic methods that show a broad substrate scope are of great utility in the synthesis of complex organic molecules. Within this arena, synthetic methods that employ boronic esters are especially useful because they undergo a wide variety of transformations with very high levels of stereoselectivity. In particular, boronic esters can undergo single or multiple homologations using enantioenriched metal carbenoids. The addition of a suitable enantioenriched lithium or magnesium carbenoid to a boronic ester, with subsequent 1,2-migration, gives a homologated boronic ester with high stereocontrol. This process, termed lithiation-borylation, can be iterative, which allows a carbon chain to be extended one atom at a time with remarkable precision. The iterative homologation has been likened to a molecular assembly line and resembles the way nature assembles natural products, for example, in polyketide synthase machinery. The application of lithiation-borylation chemistry to the synthesis of a broad variety of natural products is discussed in this Review.Boronic esters are versatile intermediates that readily accept nucleophiles and then undergo 1,2-migration, expelling a neighbouring leaving group. Such reactivity enables carbon chains to be grown one atom at a time with high stereocontrol. This Review examines the fundamentals of lithiation-borylation methodology and its application to natural product synthesis.