Department of Chemistry, University of Houston, Houston, Texas 77204, USA.
Nat Chem. 2015 Dec;7(12):1024-7. doi: 10.1038/nchem.2364. Epub 2015 Oct 19.
The α-alkylation of ketones and their derivatives by the addition of their corresponding enolates to alkyl halides is a fundamental synthetic transformation, but its utility is limited because the key bond-forming step proceeds in a bimolecular nucleophilic substitution fashion. Here we describe how an umpolung strategy that involves the addition of Grignard reagents to α-epoxy N-sulfonyl hydrazones-directed by the alkoxide of the 1-azo-3-alkoxy propenes formed in situ via base-induced ring opening of the epoxide-leads to the syn-selective production of α-alkyl-β-hydroxy N-sulfonyl hydrazones with α-quaternary centres. This transformation is remarkable in its ability to incorporate an unprecedented range of carbon-based substituents, which include primary, secondary and tertiary alkyl, as well as alkenyl, aryl, allenyl and alkynyl groups. Subsequent hydrolysis of the β-hydroxy N-sulfonyl hydrazone products produces the corresponding β-hydroxy ketones. In addition to hydrolysis, the hydrazone products are poised to undergo numerous different known synthetic transformations via well-established chemistry, which would provide access to a wide array of useful structures.
酮及其衍生物的α-烷基化反应是通过相应的烯醇盐与卤代烷加成来实现的，这是一种基本的合成转化，但由于关键的成键步骤是以双分子亲核取代的方式进行，因此其应用受到限制。在这里，我们描述了一种反转策略，该策略涉及到格氏试剂与α-环氧 N-磺酰腙的加成，该加成由原位形成的 1-偶氮-3-烷氧基丙烯的烷氧基导向，该加成通过环氧开环形成。这种转化能够引入前所未有的一系列碳基取代基，包括伯、仲和叔烷基，以及烯基、芳基、烯丙基和炔基，这是非常显著的。随后水解β-羟基 N-磺酰腙产物可得到相应的β-羟基酮。除了水解之外，腙产物还可以通过成熟的化学方法进行多种不同的已知合成转化，从而获得广泛的有用结构。
