1,2-Metallate Rearrangement as a Toolbox for the Synthesis of Allylic Alcohols

Abstract

The development of new methods and protocols for the synthesis of biologically active substances remains one of the most important pillars in organic chemistry, and one of these privileged structural motifs are allylic alcohols. The method of choice to date for the synthesis of these is the Nozaki–Hiyama–Takai–Kishi reaction. We describe here a valuable alternative to the synthesis of allylic alcohols via 1,2-metallate rearrangement. In this work, various vinyl boronic esters with different functional groups have been applied in the Hoppe–Matteson–Aggarwal reaction. In addition, two monoterpenoids were constructed via this convergent synthetic strategy.

Latest Developments of the Julia–Kocienski Olefination Reaction: Mechanistic Considerations

“…Stereogenic centers in the α-position to the boron atom or in the allylic position in the case of the second reacting partner are generally very stable under the standard reaction conditions, and in the case of boron-containing reagents, they are also readily available using various synthetic methods. From a mechanistic point of view, the 1,2-metallated rearrangement proceeds while the configuration is preserved [ 59 ], meaning this method is highly suitable for 1,2-disubstituted olefins with a stereogenic center in the allylic position. This strategy has already been exploited several times in the context of natural product synthesis [ 60 ].…”

Stereoselective Construction of β-chiral Homoallyl Functionalities by Substrate- and Reagent-Controlled Iterative 1,2-Metallate Rearrangements

“…As expected, the use of carbamate 6 in this sequence resulted in the formation of the opposite diastereoisomer 9b , with a lower yield and selectivity (37% o3s, 3:1, Table , entry 2). As observed in our previous study, the low yields obtained from the combination of carbamates and vbe 8 can probably be attributed to a combination of inferior leaving group quality (Cb) and poor migration ability of the unsubstituted vinyl residue . Notably, the yield dropped significantly (37% vs 60%), while the diastereomeric ratio (3:1 vs 2.4:1) remained comparable to that of the secondary alcohol.…”

“…As observed in our previous study, 8 the low yields obtained from the combination of carbamates and vbe 8 can probably be attributed to a combination of inferior leaving group quality (Cb) and poor migration ability of the unsubstituted vinyl residue. 10 Notably, the yield dropped significantly (37% vs 60%), while the diastereomeric ratio (3:1 vs 2.4:1) remained comparable to that of the secondary alcohol. This trend was not observed when unsubstituted vbe 8 was used.…”