Enantiospecific Synthesis of ortho-Substituted Benzylic Boronic Esters by a 1,2-Metalate Rearrangement/1,3-Borotropic Shift Sequence

Abstract

Coupling reactions between benzylamines and boronic esters have been investigated. ortho-Lithiated benzylamines react with boronic esters and a N-activator to afford ortho-substituted benzylic boronic esters with formal 1,1′-benzylidene insertion into the C–B bond. The reaction occurs by a SN2′ elimination and 1,2-metalate rearrangement of the N-activated boronate complex to afford a dearomatized intermediate, which undergoes a Lewis-acid catalyzed 1,3-borotropic shift to afford the boronic ester products in high yield and with excellent enantiospecificity. The use of enantioenriched α-substituted benzylamines gave the corresponding secondary boronic esters with high ee.

Enantiospecific Synthesis of ortho‐Substituted 1,1‐Diarylalkanes by a 1,2‐Metalate Rearrangement/anti‐SN2′ Elimination/Rearomatizing Allylic Suzuki–Miyaura Reaction Sequence

“…Thee lectronics of the aryl iodide appeared to have limited effect on reactivity and both electron-donating (6aab)a nd electron-withdrawing substituents (6aac)were well tolerated, as were halides (6aad, 6aae, 6aaf)a nd ortho-substitution (6aag). Coupled product 6iaa was formed in 50 % 1 HNMR yield and 91:9 e.r.,c orresponding to an enantiospecificity of 84 %from (R)-1 i.Since 4ia is formed in 96:4 e.r., [9] this result indicates that the g-selective allylic Suzuki-Miyaura crosscoupling (4ia to 6iaa)proceeds in 87 %es. Simple ortho-bromo benzylamine 1b underwent smooth coupling to provide 6baa in 67 %y ield.…”

“…[18] Furthermore,n aphthylamine 1a,w hich has been used extensively as as ubstrate in these studies,i ss table with respect to the 1,3-borotropic shift: heating 4aa in the presence of NaBPh 4 ,i nl ine with our previously reported conditions, [9] provided no evidence of the borotropic shift product (Scheme 4B). [18] Furthermore,n aphthylamine 1a,w hich has been used extensively as as ubstrate in these studies,i ss table with respect to the 1,3-borotropic shift: heating 4aa in the presence of NaBPh 4 ,i nl ine with our previously reported conditions, [9] provided no evidence of the borotropic shift product (Scheme 4B).…”

“…[9] Enantioenriched a-methyl o-bromo benzylamines were transformed into dearomatized intermediate 4 through a1 ,2-metalate rearrangement/anti-S N 2' elimination reaction triggered by N-activation of arylboronate complex 2' ' (Scheme 1B). [9] Enantioenriched a-methyl o-bromo benzylamines were transformed into dearomatized intermediate 4 through a1 ,2-metalate rearrangement/anti-S N 2' elimination reaction triggered by N-activation of arylboronate complex 2' ' (Scheme 1B).…”

Enantiospecific Synthesis of ortho‐Substituted 1,1‐Diarylalkanes by a 1,2‐Metalate Rearrangement/anti‐SN2′ Elimination/Rearomatizing Allylic Suzuki–Miyaura Reaction Sequence

“…We recently reported am ethod for the enantiospecific synthesis of ortho-substituted secondary benzylic boronic esters. [9] Enantioenriched a-methyl o-bromo benzylamines were transformed into dearomatized intermediate 4 through a1 ,2-metalate rearrangement/anti-S N 2' elimination reaction triggered by N-activation of arylboronate complex 2' ' (Scheme 1B). Subsequent suprafacial 1,3-borotropic shift provided the secondary a-methyl benzylic boronic esters (5)w ith excellent levels of enantiopurity.W er ecognized that the stereospecific cross-coupling of these enantioenriched benzylic boronic esters with an aryl electrophile,i nl ine with reports from Crudden, [7] would provide access to the valuable 1,1-diarylalkane motif.…”

A Versatile Bis‐Allylboron Reagent for the Stereoselective Synthesis of Chiral Diols

“…On the other hand, the b-branched and sterically less demanding isovaleric aldehyde (entry 11) gave the desired product in 73 % ee. [39,43] Indeed, bis-borinate 13 underwent two-fold allyl transfer to ar ange of aliphatic and aromatic aldehydes in good yields ranging from 62 to 74 %( Table 2). This result is consistent with previously reported computational models.…”