The first catalytic method for diastereo‐ and enantioselective synthesis of allylic boronates bearing a Z‐trisubstituted alkenyl fluoride is disclosed. Boryl substitution is performed with either a Z‐ or E‐allyldifluoride and is catalyzed by bisphosphine/Cu complexes, affording products in up to 99 % yield with >98:2 Z/E selectivity and 99:1 enantiomeric ratio. A variety of subsequent modifications are feasible, and notable examples are diastereoselective additions to aldehydes/aldimines to access homoallylic alcohols/amines containing a fluorosubstituted stereogenic quaternary center.
…I believe that every militant chemist can confirm it:that one must distrust the almost-the-same…, the practically identical, the approximate, the or-even, all surrogates and all patchwork. The differences can be small, but they can lead to radically different consequences…; the chemist's trade consists in good part in being aware of these differences, knowing them close up, and foreseeing their effects. "
Synthesis of complex bioactive molecules is substantially facilitated by transformations that efficiently and stereoselectively generate polyfunctional compounds. Designing such processes is hardly straightforward, however, especially when the desired route runs counter to the inherently favored reactivity profiles. Furthermore, in addition to being efficient and stereoselective, it is crucial that the products generated can be easily and stereodivergently modified. Here, we introduce a catalytic process that delivers versatile and otherwise difficult-to-access organoboron entities by combining an allenylboronate, a hydride, and an allylic phosphate. Two unique selectivity problems had to be solved: avoiding rapid side reaction of a Cu−H complex with an allylic phosphate, while promoting its addition to an allenylboronate as opposed to the commonly utilized boron−copper exchange. The utility of the approach is demonstrated by applications to concise preparation of the linear fragment of pumiliotoxin B (myotonic, cardiotonic) and enantioselective synthesis and structure confirmation of netamine C, a member of a family of anti-tumor and anti-malarial natural products. Completion of the latter routes required the following noteworthy developments: (1) a two-step all-catalytic sequence for conversion of a terminal alkene to a monosubstituted alkyne; (2) a catalytic S N 2′-and enantioselective allylic substitution method involving a mild alkylzinc halide reagent; and (3) a diastereoselective [3+2]-cycloaddition to assemble the polycyclic structure of a guanidyl polycyclic natural product.
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