New General Method for Regio- and Stereoselective Allylic Substitution with Aryl and Alkenyl Coppers Derived from Grignard Reagents

Abstract

Allylic substitution with sp(2)-carbon reagents (aryl and alkenyl anions) was realized by using allylic picolinates and copper reagents derived from RMgBr and CuBr x Me(2)S to afford anti S(N)2' products regio- and stereoselectively. Steric and electronic factors in the reagents and the size of the methylene substituents around the allylic moiety marginally affected the selectivity. The reaction system was compatible with alkyl reagents as well. Furthermore, the substitution was applied to construction of a quaternary center and synthesis of (-)-sesquichamaenol. Electron-withdrawing nature of the pyridyl group and chelation of the C(=O)-C(5)H(4)N to MgBr(2) generated in situ were found to be responsible for the high efficiency of the substitution.

Installation of the imidazole ring on chiral substrates via allylic substitution

“…We have published the substitution of secondary allylic picolinates with copper reagents derived from RMgBr and CuBr$Me 2 S to afford anti S N 2 0 products with high stereoselectivity and regioselectivity. 14 The picolinoxy leaving group is responsible for the high efficiency in selectivity and reactivity. The substitution was expanded with copper reagents derived from aryl lithiums 15 and alkynyl lithiums.…”

Salicylate‐Directed C−O Bond Cleavage: Iron‐Catalyzed Allylic Substitution with Grignard Reagents

“…To wardt he idea, we here presenta northo-ester-directed ironcatalyzed allylic substitution with Grignardr eagents (Scheme1d). [10][11][12] The methodology applies environmentally benign and easily availablee thyl salicylate as ad irecting leaving group and Fe(acac) 3 as catalyst, [13] thus greatlye xpanding synthetic applicationsina llylic substitution reactions.…”

“…The efficiency of the reaction of hexyl Grignard reagent 2e with 1k was moderate, while the regioselectivity of the linear and branched products was excellent (entry 5). The substrate (1m)w ith long chain alkyl reactede fficiently with both alkyl and aromatic Grignardr eagents (entries [6][7][8][9][10][11]. Alkyl Grignardr eagents led to higher regioselectivities of the reactions compared to aromatic Grignardr eagent, probablyd ue to the steric effect of the R groups.T he double bond geometry of cis-allyl substrate (1n) droped to 2.5:1( Z:E)i nt he product (entry 12), indicating that CÀOb ond cleavage is af ast step and CÀCb ondf ormation is a potentialr ate-determining step of the reaction.…”

Studies on Enantioselective Total Synthesis of Ascospiroketal B (I)

“…Commercially available D-mannitol (15) was converted to aldehyde 16 by conversion of two 1,2-diol moieties to 1,3-dioxolane protecting groups and subsequent oxidative cleavage of the remaining 1,2-diol in 46% overall yields. 5 Takai protocol for the introduction of (E)-selective vinyl iodide, 6 TFA-mediated deprotection of the dioxolane protectiong group in MeOH, 7 and PMB-mono-protection of the resulting primary alcohol provided the secondary alcohol 17 in 51% three-step yields. Mitsunobu inversion of the secondary hydroxyl group in 17, 8 methanolysis of the benzoate using K 2 CO 3 in MeOH, and TBS-protection of the resulting alcohol provided the vinyl iodide 18 in 45% overall yields.…”