β‐Hydroxy‐tetrahydroquinolines from Quinolines Using Chloroborane: Synthesis of the Peptidomimetic FISLE‐412

Abstract

A new synthetic protocol provides a simple and direct method to generate functionalized β-hydroxy-tetrahydroquinolines (THQs). Hydroboration of quinolines using chloroboranes followed by oxidation led to the formation of functionalized β-hydroxy-tetrahydroquinolines. High regio and diastereoselectivities were observed in α or γ substituted quinolines and the trans diastereomer of β-hydroxy-THQ was the major isostere. This new protocol was utilized to build the novel antibody-targeted lupus peptidomimetic FISLE-412.

Double Hydroboration of Quinolines via Borane Catalysis: Diastereoselective One Pot Synthesis of 3‐Hydroxytetrahydroquinolines

“…For example, in situ generated metal hydride species based on Mg, Rh, Zn, La, and Th were found to promote 1,2‐hydroboration of pyridines– while 1,4‐selectivity was observed via an ionic outer‐sphere pathway catalysed by Lewis or Brønsted acids –. Despite these recent advances in the dearomative hydroboration of N ‐heteroarenes, to our best knowledge, no catalytic procedures have been revealed thus far for the sp 3 C−B bond‐forming hydroboration of N ‐heteroaromatics …”

“…Indeed, our group recently reported the B(C 6 F 5 ) 3catalyzed silylative reduction of pyridines, quinolines, and α,β-unsaturated nitriles and imines to afford C (sp 3 )À Si moiety-containing products (Scheme 1b). [7] Herein we report a B(C 6 F 5 ) 3 -catalyzed double hydroboration of quinolines to give rise to β-borylated tetrahydroquinolines (Scheme 1d). [6] For example, in situ generated metal hydride species based on Mg, Rh, Zn, La, and Th were found to promote 1,2-hydroboration of pyridines [6a-f] while 1,4-selectivity was observed via an ionic outersphere pathway catalysed by Lewis or Brønsted acids.…”

“…[6g-m] Despite these recent advances in the dearomative hydroboration of N-heteroarenes, to our best knowledge, no catalytic procedures have been revealed thus far for the sp 3 CÀ B bond-forming hydroboration of N-heteroaromatics. [7] Herein we report a B(C 6 F 5 ) 3 -catalyzed double hydroboration of quinolines to give rise to β-borylated tetrahydroquinolines (Scheme 1d). It represents the first catalyst system toward consecutive borylative reduction of quinolines.…”

“…[10] The initially formed 1,3-bis-borylated tetrahydroquinolines were converted to the 3-hydroxytetrahydroquinolines upon the one-pot oxidation with sodium perborate tetrahydrate. Quinolines with alkyl, aryl, or halide groups at the C5 to C8 positions were found to display minimal impact on the formation of the desired β-borylated products (2)(3)(4)(5)(6)(7)(8)(9)(10). An ethereal sp 2 CÀ O bond (aryloxy group) was tolerated under the present reductive conditions to give the product 11 in 79% yield.…”

The Therapeutic Strategies for SLE by Targeting Anti-dsDNA Antibodies

“…The peptides' small molecular property has advantages in high-throughput and standardized synthesis technology. A practical, simplified synthetic method has been attempted to achieve rapid and cheap synthesis [106]. FISLE-412 was well tolerated and had no toxicity nor immunogenicity [105].…”