Iron-Catalyzed Cross-Coupling of Propargyl Ethers with Grignard Reagents for the Synthesis of Functionalized Allenes and Allenols.

Daniels Posevins,Jan‐E. Bäckvall,Aitor Bermejo‐López

doi:10.1002/anie.202106742

Daniels Posevins, Jan‐E. Bäckvall + Show 1 more

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https://doi.org/10.1002/anie.202106742

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Abstract

Herein we disclose an iron‐catalyzed cross‐coupling reaction of propargyl ethers with Grignard reagents. The reaction was demonstrated to be stereospecific and allows for a facile preparation of optically active allenes via efficient chirality transfer. Various tri‐ and tetrasubstituted fluoroalkyl allenes can be obtained in good to excellent yields. In addition, an iron‐catalyzed cross‐coupling of Grignard reagents with α‐alkynyl oxetanes and tetrahydrofurans is disclosed herein, which constitutes a straightforward approach towards fully substituted β‐ or γ‐allenols, respectively.

Highlights

In the present work we have studied iron-catalyzed cross-coupling of less reactive propargylic ethers with Grignard reagents
Other oxygenbased leaving groups tested, such as pivalate, carbonate, phosphonate, and mesylate provided the desired allene 2 aa in poor yields together with the 1,3-enyne 3 as the main product. These results demonstrate the compatibility problems with fluoroalkyl group-containing substrates in these attempted SN2’-type cross-coupling reactions
[a] Reaction conditions: 0.2 M solution of propargyl methyl ether 1 (0.3 mmol) in PhMe, Fe(acac)3 (5 mol %) with dropwise addition of Grignard reagent (1.5 equiv). [b] Isolated yield. [c] Using 10 mol % of TMEDA as an additive. [d] 2.0 equiv of PhMgBr was used and the reaction time was 4 h. [e] The reaction time was 12 h and 1 k was recovered in 43 % yield

Summary

Because of the demand of new efficient methods for the

The use of other Grignard reagents such as n- alkyl substituents in the R1 and R2 positions afforded the BuMgCl and PhMgBr in the reaction with 1 af afforded the corresponding g-allenols 5 b–5 e in 56–85 % yields under the corresponding trifluoromethyl allenes 2 ab and 2 ac in 43 % standard reaction conditions (entries 2 and 3, Table 3). Afforded the corresponding allene 2 d in 72 % yield Trisubstituted g-allenol 5 i was prepared by cross-coupling of (entry 6). TBS-protected CF3 and CHF2 4 i with MeMgBr under the standard reaction conditions in group-containing a-allenols 2 e and 2 f were prepared in a moderate 55 % yield (entry 8).

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MeMgBr BnMgCl MeMgBr PhMgBr

Findings

Conflict of Interest