Novel asymmetric indium-mediated Barbier-type addition reactions: The synthesis of allylborane reagents and chiral tertiary alcohols

Indium metal was used to synthesize a variety of organometallic intermediates that were taken on in the addition reaction with ketone substrates to provide the corresponding alcohol products in moderate to excellent yields. This type of reaction has proven to be an effective method in the synthesis of alcohol products, which are desirable synthetic building blocks. Specifically, the indium-mediated addition reactions were conducted in an asymmetric fashion, using either the commercially available (+)-(1S,2 R)-2-amino-1,2-diphenylethanol or B-chlorodiisopinocampheylborane as the chiral directors. It was found that indium effectively promoted the allylation of both aliphatic and aromatic ketones under Barbier-type reaction conditions. By simply mixing indium(0), (+)-(1S,2 R)-2-amino-1,2-diphenylethanol, pyridine, allyl bromide, and the desired ketone in one-pot, the corresponding homoallylic tertiary alcohols were obtained in up to 80% ee. This reaction was also found to promote the chemoselective allylation of an aldehyde functionality in the presence of a ketone in good diastereoselectivity (64% de). The methodology was extended to the indium-mediated propargylation of acetophenone using propargyl bromide and it was found that the presence of the Lewis acid, In(OTf)3 produced the corresponding homoallenic alcohol in 85% yield and excellent regioselectivity (14:1; allenyl:propargyl). The asymmetric indium-mediated chemoselective propargylation of the aldehyde in the presence of a ketone provided the corresponding secondary homopropargylic alcohol in excellent diastereoselectivity of 95% de.;Indium metal generated several allyl- and allenylindium intermediates, which were reacted with dDIP-Cl in one-pot. It was found that indium effectively promoted the transfer of these groups to boron forming the corresponding borane reagents. The newly formed borane reagents were reacted with ketones to produce the corresponding alcohol products in high yields and excellent enantioselectivity (94% ee). Using this method the methallylation and cinnamylation of ketones provided the highest enantioselectivities, while the propargylation provided low enantiomeric excesses. However, the allylboranes are typically generated in several steps and there currently are not a wide variety of substituted and functionalized versions of these reagents. This was the first example of the direct synthesis of allylboranes that contained substitutions and functionalities from the corresponding allyl bromide, thereby expanding the utility of the DIP-Cl reagent.