Fluorinated alcohol mediated N,N′-dialkylation of amino acid derivatives via cascade [1,5]-hydride transfer/cyclization for concise synthesis of tetrahydroquinazoline

Abstract

Structurally diverse amino acids and their ester derivatives were conveniently N,N′-dialkylated via TFE promoted cascade condensation/[1,5]-hydride transfer/cyclization for straightforward construction of tetrahydroquinazolines incorporating various amino acids.

peri-Interactions in 1,8-bis(dimethylamino)naphthalene ortho-ketimine cations facilitate [1,5]-hydride shift: selective synthesis of 1,2,3,4-tetrahydrobenzo[h]quinazolines

“…21 Subsequently, the acid-catalyzed variant ( 3 → 5 ) of this cyclization was developed leading to a significant increase in the rate and yields in comparison with the thermal variant. 22–26 For the mentioned reactions (Scheme 1), there are three main factors that are favorable for the tert -amino effect: (1) the effective pyrrolidine-based hydride-donating part: the tert -amino effect in general is more pronounced for amines with secondary or tertiary carbon substituents 14,27,28 while the simple NMe group does not produce good results, even if the hydride-acceptor is an active N -alkylated Schiff base as in 6 (Scheme 2); 29 (2) increased hydride-accepting ability of the C(R 1 )NR 2 group due to the accepting (CF 3 , CO 2 Et) or at least not donating (H) nature of the substituent R 1 ; and (3) relatively high hydrolytic stability of the precursor imines 1 and 4 because of the presence of the R 2 substituent in comparison with N -unsubstituted imines (R 2 = H).…”

Diastereoselective Bidirectional C(sp3)−H Bond Functionalization of Piperazine Compounds

“…[3] Cascade [1,n]-hydride transfer ( [1,n]-HT)/cyclization represents one of the main approaches to activate the C(sp 3 )À H bonds α to heteroatom or aromatic rings. [4] It is well developed for the construction of CÀ C, [5] CÀ O [5b,6] or CÀ N [7] bonds and offers rapid access to polycyclic compounds. [1,n]-HT/cyclization occurs under either thermal conditions [7b] or the catalysis of Lewis acids [5c,e,8] and Brønsted acids.…”