Synthesis of trans-1,2-dimetalloalkenes through reductive anti-dimagnesiation and dialumination of alkynes

Abstract

Polar reactive organometallic species have been key reagents in synthesis for more than a century. Stereodefined 1,2-dimetallated alkenes offer promising synthetic utility; however, few methods are available for their preparation due to their relatively low stability. Here we report the reductive anti-1,2-dimetallation of alkynes to stereoselectively generate trans-1,2-dimagnesio- and 1,2-dialuminoalkenes, which are stable and have been demonstrated in organic synthesis. These stereodefined 1,2-dimetallated alkenes are prepared through the use of a sodium dispersion as a reducing agent, and organomagnesium and organoaluminium halides as reduction-resistant electrophiles. Highly nucleophilic 1,2-dimagnesioalkenes serve as dual Grignard reagents and have been demonstrated to react with various electrophiles to afford anti-difunctionalized alkenes. The 1,2-dialuminoalkenes react with paraformaldehyde with dearomatization of the aryl moieties to form the corresponding dearomatized 1,4-diols, with the overall reaction being regarded as alkynyl-directed dearomatization of arenes. X-ray crystallographic analysis further supports the formation of trans-1,2-dimagnesio- and 1,2-dialuminoalkenes, with computational studies providing insight into the mechanism of dearomative difunctionalization.

Stereoselective Synthesis of Tetraarylethylenes Enabled by Reductive anti‐1,2‐Dimetallation of Alkynes

“…slightly lower efficacy (entry 3). According to our previous report, [13] 1,2-dimagnesiation of alkynes proceeded with various Grignard reagents other than (TMS) 2 CHMgCl. However, in the present reaction, the use of methylmagnesium chloride (MeMgCl), cyclopentylmagnesium bromide (cPentMgBr), tertbutylmagnesium chloride (tBuMgCl), and (trimethylsilyl)methylmagnesium bromide ((TMS)CH 2 MgBr) significantly lowered the yield of 3 aa (entries 4-7).…”

“…We have previously reported the anti-1,2-dimagnesiation and dialumination of alkynes to afford the corresponding trans-1,2-dimetalloalkenes. [13] Although the resulting trans-1,2-dimagnesioalkenes could be trapped by various electrophiles including trialkoxyboranes, aldehydes, epoxides, and alkyl chlorides, the attempted Kumada-type coupling [14] using an aryl iodide as an electrophilic coupling partner did not work well. Herein, we disclose that transmetalation of the 1,2-dimagnesioalkenes to zinc chloride [15] allows us to achieve the Negishi coupling reaction [16] with aryl iodides, thus enabling the synthesis of a wide variety of TAEs in regio-and stereoselective manners (Scheme 1d).…”

“…We have previously reported the anti ‐1,2‐dimagnesiation and dialumination of alkynes to afford the corresponding trans ‐1,2‐dimetalloalkenes [13] . Although the resulting trans ‐1,2‐dimagnesioalkenes could be trapped by various electrophiles including trialkoxyboranes, aldehydes, epoxides, and alkyl chlorides, the attempted Kumada‐type coupling [14] using an aryl iodide as an electrophilic coupling partner did not work well.…”

Stereo- and regioselective boryllithiation and -sodiation of alkynes: reductive approach using flow microreactors

“…1b-1d), we have been investigting "reductive" approaches for difunctionalizations of alkynes. [31][32][33] Among these, we envisioned that the reductive diboration of alkynes 32 would provide a clue to the development of excellent borylmetallation (Fig. 1e).…”

One-Pot, Three-Component Assembly of Sulfides Using a Sulfoxide Reagent as a Sulfur Dication Equivalent

“…We demonstrate that a wide variety of Grignard reagents along with organolithium and organozinc reagents were viable substrates in our coupling platform, thus enabling diversity in substituents of sulfide products. With ever-increasing methods to prepare various organomagnesium and organozinc reagents, our method presented herein will find widespread use in the modular synthesis of sulfides for synthetic and medicinal applications.…”