We report here a scalable, catalytic one-pot approach to enantiopure and unmodified β2-amino acids. A newly developed confined imidodiphosphorimidate (IDPi) catalyzes a broadly applicable reaction of diverse bis-silyl ketene acetals with a silylated aminomethyl ether, followed by hydrolytic workup, to give free β2-amino acids in high yields, purity, and enantioselectivity. Importantly, both aromatic and aliphatic β2-amino acids can be obtained using this method. Mechanistic studies are consistent with the aminomethylation to proceed via silylium-based asymmetric counteranion-directed catalysis (Si-ACDC) and a transition state to explain the enantioselectivity is suggested on the basis of density functional theory calculation.

We report ah ighly enantioselective catalytic protonation of bis-silyl ketene acetals.O ur method delivers abranched carboxylic acids,including nonsteroidal anti-inflammatory arylpropionic acids such as Ibuprofen, in high enantiomeric purity and high yields.T he process can be incorporated in an overall deracemization of a-branched carboxylic acids,i nvolving ad ouble deprotonation and silylation followed by the catalytic asymmetric protonation. Carboxylic acids are not only valuable synthetic intermedi-Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

In this paper we explore and propose a methodology for the scale-up of continuous biphasic liquid/liquid reactions under super-heating conditions.

The continuous flow reaction of various aryl or heteroaryl bromides in toluene in the presence of THF (1.0 equiv) with sec‐BuLi (1.1 equiv) provided at 25 °C within 40 sec the corresponding aryllithiums which were acylated with various functionalized N,N‐dimethylamides including easily enolizable amides at −20 °C within 27 sec, producing highly functionalized ketones in 48–90 % yield (36 examples). This method was well suited for the preparation of α‐chiral ketones such as naproxene and ibuprofen derived ketones with 99 % ee. A one‐pot stepwise bis‐addition of two different lithium organometallics to 1,1,3,3‐tetramethyurea (TMU) provided unsymmetrical ketones in 69–79 % yield (9 examples).

No abstract