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

Abstract

Ketone synthesis via the addition of organometallic reagents to amides has long been investigated. In many cases, it is necessary to control the solvent, reaction temperature, and adhere to strict nucleophile stoichiometry for each combination of amide and organometallic reagent. Strontium, with an electronegativity comparable to lithium but a larger ionic radius, may display high reactivity with the characteristics of monoalkylation. Here, we show that the monoalkylation of various N,N-dimethylamide derivatives with alkyl iodides to afford the ketones proceeds smoothly under generally mild temperature conditions. By this method, not only aromatic amides but also α-proton-bearing aliphatic amides were suitable substrates for ketone synthesis. In addition, we found that tetramethylurea, typically a poor electrophile, also reacted to afford benzophenone in good yield with excellent selectivity.

One-Shot Deprotonative Metalation/Transmetalation/Polymerization of Halothiophenes Catalyzed by Nickel Complex for Polythiophene Synthesis

“…Lowering the reaction temperature to room temperature also resulted in giving the corresponding polythiophene 3, when MgCl 2 , CaCl 2 , 12 and ZnCl 2 were employed. In contrast, the use of SrCl 2 , 13 resulted in giving polymer 3 in a much lower yield and that of BaCl 2 14 and MnCl 2 15 did not afford the polymer at room temperature. Cooling of the mixture of 2-bromo-3-hexylthiophene (1) and divalent metal chloride at -78 °C in THF resulted in forming the precipitate of the metal salt.…”

Continuous Flow Acylation of (Hetero)aryllithiums with Polyfunctional N,N‐Dimethylamides and Tetramethylurea in Toluene

“…Finally, we have extended this acylation in continuous flow to a semi‐batch telescoped procedure for the preparation of unsymmetrical ketones of type 5 using TMU ( 4 ) as a C1‐building block (Scheme 5). [8a,27] Thus, the treatment of a mixture of ArBr ( 8 ) and TMU ( 4 ) in toluene with sec ‐BuLi at −20 °C for 50 sec in continuous flow provided the tetrahedral intermediate 15 which was poured into a toluene solution of various organolithiums R−Li ( 7 , R = Bu, (Het)Ar or Bn). These organolithiums were conveniently prepared via direct metalation, using sec ‐BuLi and TMEDA (1.0 equiv) in toluene at −20 °C (10‐30 min) in batch.…”

Practical method for hydroxyl-group protection using strontium metal and readily available silyl chlorides

“…7–10 Our group has already reported the smooth alkylation of aldehydes 11 or imines 12 and the dialkylation of an ester 13 using metallic Sr and alkyl iodide under mild conditions. 14 The electronegativity of Sr is close to that of Li and Mg (Li = 0.98, Mg = 1.31, Sr = 0.95 on the Pauling scale, respectively), 15 but Sr has a larger ionic radius (Li + = 76, Mg 2+ = 72, Sr 2+ =118 in pm, respectively). 16 The reaction of Sr metal with alcohols results in strontium alkoxide, where the bond distance between Sr and O is large, with an increase in the partial negative charge of oxygen.…”

“…Surprisingly, when DMF or DMA was chosen as a solvent, methyl iodide did not necessarily generate methyl strontium iodide (entries 3–6). 14 A slight decrease in the yield was observed when DMF was used as the solvent (entry 5); however, a decrease in the yield was not observed with DMA (entry 6). Furthermore, the reduction in the amount of Sr metal from 1.5 equivalents to 1.0 equivalents did not decrease the yield (entry 7).…”