Pyrrole‐Protected β‐Aminoalkylzinc Reagents for the Enantioselective Synthesis of Amino‐Derivatives

Chiral β‐aminoalkylzinc halides were prepared starting from optically pure commercial β‐amino‐alcohols. These amino‐alcohols were converted to the corresponding N‐pyrrolyl‐protected alkyl iodides which undergo a zinc insertion in the presence of LiCl (THF, 25 °C, 10–90 min). Subsequent Negishi cross‐coupling or acylation reactions with acid chlorides produced amino‐derivatives with retention of chirality. Diastereoselective CBS‐reductions of some prepared N‐pyrrolyl‐ketones provided 1,3‐subsituted N‐pyrrolyl‐alcohols with high diastereoselectivity. Additionally, a deprotection procedure involving an ozonolysis allowed the conversion of the pyrrole‐ring into a formamide without loss of optical purity. Chiral β‐aminoalkylzinc halides for enantioselective amine synthesis: Chiral β‐N‐pyrrolyl‐alkyl iodides prepared from commercial β‐amino‐alcohols undergo zinc insertion in the presence of LiCl (THF, 25 °C, 10–90 min). Negishi cross‐coupling or acylation quenching reactions produced a range of chiral β‐N‐pyrrolyl derivatives that may be converted into 1,3‐amino‐alcohols and other chiral amino‐derivatives. Subsequent ozonolysis allowed the conversion of the pyrrole moiety into formamides without loss of optical purity.