The Barbier-Type Alkylation of Aldehydes with Alkyl Halides in the Presence of Metallic Strontium

Abstract

In the presence of metallic strontium, the Barbier-type alkylation of aldehydes with alkyl iodides proceeded smoothly at −15 °C under an argon atmosphere to afford the corresponding alkylated alcohols in moderate to good yields. The unusual addition reaction of ethyl benzoate with tert-butyl iodide took place to give the p-tert-butylated alkylated product (the 1,6-adduct of the benzoate) in 55% yield. Using strontium isopropoxide, the Meerwein–Ponndorf–Verley-type reduction of the aldehyde proceeded smoothly under reflux conditions in 2-propanol.

Superior Alkylating Agents for Bulky Esters/Ketones via Strontium‐Mediated Barbier‐Type Reaction

“…Few studies on the preparation and reactivity of organostrontium compounds were found in the literature, besides our study. We have been investigating synthetic reactions using strontium compounds and have reported that the alkylation of aldehydes or imines with alkyl iodides, and dialkylation of esters with alkyl iodides proceeded smoothly using metallic strontium to afford the corresponding adducts in good yields. On the strontium method, the reaction as one‐pot protocol, so‐called Barbier procedure, proceeds smoothly at ambient temperature to give the corresponding adduct in excellent yield (Scheme b).…”

The Chemistry of Alkylstrontium Halide Analogues, Part 2: Barbier‐Type Dialkylation of Esters with Alkyl Halides

“…Interestingly, the reactions proceeded smoothly to give the products in good yields with esters that have an α proton (Entries 3-7 in Table 3). In previous studies, [12] the results for the alkylation of aldehydes that have an α proton or of imines that are derived from enolizable aldehydes were poor. One of the reasons may be that alkylstrontium halide analogues have a strong nucleophilicity, as well as a strong basicity, which obstructs the alkylation of these kinds of aldehydes or imines.…”

“…[10,11] We have investigated synthetic reactions using strontium compounds and have already reported the alkylation of aldehydes or imines with alkyl iodides using metallic strontium. [12] When we extended our investigation to include esters, we found that the Barbier-type alkylation of esters with alkyl iodides using strontium metal proceeded smoothly to afford the corresponding adducts in good yields. To the best of our knowledge, such reactions are hitherto unknown in the literature, and we wish to describe our results herewith.…”

Chemoselective Ketone Synthesis by the Strontium‐mediated Alkylation or Arylation of N,N‐Dimethylamides or Urea

“…[26][27][28][29] We previously reported that the alkylation of aldehydes or imines and the dialkylation of esters proceeded smoothly with the combination of metallic strontium and alkyl iodides under mild conditions. [30,31] The key feature of these transformations is that the organostrontium reagents can be readily prepared by the reaction of strontium metal and alkyl halides, in the same manner as organomagnesium reagents. Strontium has an electronegativity (0.95) comparable to lithium but with a larger ionic radius (Sr 2 + = 118 pm) than lanthanum, suggesting that it may combine the high reactivity of organolithium species with the monoalkylation characteristics of organolanthanide reagents.…”