Catalytic Enantioselective 1,2‐Diboration of 1,3‐Dienes: Versatile Reagents for Stereoselective Allylation

Abstract

Polyketides are an important class of natural products that often possess potent biological activity and intriguing chemical structures. Among the methods for constructing these ensembles, the stereoselective addition of allyl metal reagents [1] -particularly allyl boron reagents [2] -to prochiral carbonyls holds particular prominence. With Type I allylation reagents, [3] which react through closed transition states, this reaction not only delivers functionality that is strategically positioned for establishing appropriate oxygenation patterns, but its stereochemical predictability allows ready access to acetate, propionate, and isobutyrate synthetic equivalents. A limitation of many allylation reactions, however, is that they deliver products bearing a terminal alkene; if one desires additional substitution or functionality on the olefin, additional synthetic manipulations are often required. [4] In this regard, the vinylogous aldol reaction has proven particularly important as it delivers enoate-derived homoallylic alcohols. Unfortunately, even with the tremendous emphasis placed on the development of catalytic enantioselective vinylogous aldol reactions, an efficient syn-selective asymmetric propionate version is still unavailable, as is a version that delivers quaternary centers.[5] Herein, we document the first examples of the enantioselective catalytic 1,2-diboration of 1,3-dienes (Scheme 1). As depicted in Scheme 1, the 1,2-diboration of 1,3-dienes delivers allyl boron reagents (A) that are perfectly configured to participate in highly selective allylation reactions.[6-8] Importantly, with an appropriate oxidative work-up, these reactions deliver vinylogous aldol equivalents that directly address the above-described synthesis limitations. Also of significant consequence, is that the allyl boron in the allylation product B may be subject to other useful bondforming reactions, [9] which allow for chain-extending polyketide synthesis.To develop the catalytic synthesis strategy in Scheme 1, efforts were first extended toward the development of an enantioselective 1,2-diboration of terminal dienes.[10] A recent study in our laboratory showed that enantioselective 1,4-diboration of trans-1,3-dienes could be accomplished with [Pt(dba) 3 ] and a chiral phosphonite ligand. [11,12] Although evaluation of alternate phosphorous donors revealed ligands that furnished the desired 1,2-diboration, the selectivity was suboptimal. A more reliable strategy for obtaining the 1,2-diboration product was to replace the trans-diene substrate with cis-1,3-dienes. This approach furnished 1,2-diboration products (3:1 to > 20:1 1,2/1,4 selectivity) across a range of substrates and generally occurred with excellent enantioselection. After optimization, the ligand structures and reaction conditions depicted in Scheme 2 were found to be optimal. With respect to polypropionate synthesis, the diboration of cis pentadiene is paramount and this was found to occur in excellent enantioselectivity (95:5 e.r.) and good yield with ligand L2 (...

Asymmetric Diboration of Terminal Alkenes with a Rhodium Catalyst and Subsequent Oxidation: Enantioselective Synthesis of Optically Active 1,2‐Diols

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Synthesis of Medicinally Relevant Terpenes: Reducing the Cost and Time of Drug Discovery

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Highly Selective Copper‐Catalyzed Hydroboration of Allenes and 1,3‐Dienes

“…[19] Hydroboration of 1,3-diene derivatives: The hydroboration of 1,3-dienes is a useful reaction for synthesizing allylboranes and homoallylboranes, which are important intermediates in organic synthesis. [20,21] We anticipated that analogous catalytic systems for allenes could be applicable to the selective hydroboration of 1,3-diene derivatives (Scheme 8). By employing 1,3-cyclohexadiene (8 a) as a substrate and HB-A C H T U N G T R E N N U N G (pin) as a hydroboration reagent, an allylborane (9 a) was selectively isolated in 81 % yield with DTBMAr-Xan (for the structure, see Figure 1…”