Highly Efficient, General Procedure for the Preparation of Alkylzinc Reagents from Unactivated Alkyl Bromides and Chlorides

Abstract

Alkylzinc bromides have been efficiently prepared by the direct insertion of zinc metal (dust, powder, granule, shot), activated with 1−5 mol % I 2 , into alkyl bromides in a polar aprotic solvent. The zinc reagents thus formed undergo Ni-and Pd-catalyzed cross-coupling with aryl halides to produce functionalized alkylarenes in excellent yields.

Synthetic Studies on (+)‐Biotin, Part 11: Application of Cinchona Alkaloid‐Mediated Asymmetric Alcoholysis of meso‐Cyclic Anhydride in the Total Synthesis of (+)‐Biotin

“…tained using the Huo procedure [14] from ethyl 5-bromopentanoate, was carried out in the presence of Pd@D296 (d < 100 nm, 0.01 mmol/ g) at 35 8C in a mixture of THF and toluene for 12 h, As expected, this improved Fukuyama-type cross-coupling reaction proceeded well to provide the desired hydroxy ester 8 in 85% yield.…”

Ni‐Catalyzed Reductive Allylation of Unactivated Alkyl Halides with Allylic Carbonates

“…The 2-phenyl carbonate 2 g, however, behaved differently from the 2-alkyl-substituted analogues, providing moderate and excellent yields for 1 a and 1 b, respectively ( Table 2, entries 11 and 12). The coupling reactions of 1 a and 1 b with 1-alkyl-substituted allyl substrates 2 h-2 k were generally highly efficient ( Table 2, entries [13][14][15][16][17][18][19][20]. Poor results were delivered for 1-phenyl allylic carbonate 2 l due to extensive homocoupling (Table 2, entries [21][22].…”

Differentiating CBr and CCl Bond Activation by Using Solvent Polarity: Applications to Orthogonal Alkyl–Alkyl Negishi Reactions

“…The nBuZnBr for these studies was prepared as a solution in DMI by oxidative addition of activated Zn dust into nBuBr following a procedure reported by Huo; [17] this method of organozinc preparation is preferred as it requires relatively little synthetic effort, is efficient and produces no inorganic byproducts. [18] The optimal solvent ratio in the cross-coupling reaction involving 1-bromo-4-chlorobutane and nBuZnBr was found to be 1:2 DMI:THF, where a 12.2:1 apparent selectivity [19] (C alkyl À Br:C alkyl À Cl) was obtained ( Table 1, entry 1); increasing the proportion of DMI relative to THF was detrimental to the apparent selectivity (entries 2-5).…”

“…Following this study, a general one-pot double alkyl-alkyl Negishi orthogonal reaction sequence (Scheme 3) was devised whereby a bifunctional bromochloroalkane was [a] nBuZnBr (1.0 m in DMI) was prepared according to Huo's method. [17] [b] Percent conversion was assessed by GCMS analysis using undecane as a calibrated internal standard. [20] Reactions were performed in duplicate and the average conversions are reported.…”