A one-pot selective synthesis of N-Boc protected secondary amines: tandem direct reductive amination/N-Boc protection

Abstract

A one-pot tandem direct reductive amination of aldehydes with primary amines resulting in N-Boc secondary amines using a (Boc)2O/sodium triacetoxyborohydride (STAB) system is reported. The tandem procedure is efficient, selective, and versatile, giving excellent yields of N-Boc protected secondary amines even in those cases where the products are prone to intramolecular lactamization

Mild deprotection of the N-tert-butyloxycarbonyl (N-Boc) group using oxalyl chloride

“…Ellipsoid plots were drawn using SHELXTL-XP. 5 The structures, deposited in the Cambridge Structural Database, 6 were checked for missed symmetry, twinning, and overall quality with PLATON, 7 an Rtensor, 8 and nally validated using CheckCIF.…”

“…[3][4][5] Boc fullls this requirement of a 'good' protecting group, and is preferred in amino protection because of its stability to nucleophilic reagents, hydrogenolysis and base hydrolysis. 6,7 The Boc-masking group is installed by reacting the amino-substrate with di-tert-butyl dicarbonate under basic conditions, [8][9][10] or solvent free conditions. [11][12][13] Traditional approaches for N-Boc deprotection relies largely on TFA-induced cleavage.…”

Active Esters as Pseudostoppers for Slippage Synthesis of [2]Pseudorotaxane Building Blocks: A Straightforward Route to Multi‐Interlocked Molecular Machines

“…The carboxylic acid compound 2 could be readily obtained from commercially available tert ‐butylbenzaldehyde in a two‐step sequence. The tandem reductive amination/ N ‐Boc protection of the tert ‐butylbenzaldehyde was achieved in 66 % overall yield by following a method derived from a procedure reported by Petukhov and Neelarapu . The intermediate imine was obtained by mixing tert ‐butylbenzaldehyde and methyl‐6‐aminohexanoate at reflux in toluene by using a Dean–Stark apparatus; this intermediate was directly used in the next reaction without any purification.…”

Weinreb Amide as Secondary Station for the Dibenzo‐24‐crown‐8 in a Molecular Shuttle

“…The targeted Weinreb amide‐containing [2]rotaxane molecular shuttle 6 / 7 was synthesized according to a multi‐step sequence, from the commercially available p‐tert ‐butylbenzaldehyde and 3‐aminopropane‐1,2‐diol (Scheme ). The reductive amination using sodium triacetoxyborohydride (STAB) as the reducing agent and the subsequent one pot N ‐carbamoylation of the intermediary secondary amine using Boc 2 O were carried out in the conditions of Petukhov and afforded the pure corresponding diol 1 in a 59 % overall yield. The vicinal diol 1 was then easily cleaved through Malaprade oxidation using a polymer‐supported ammonium periodate that was anteriorly prepared from the commercial hydroxide form Amberlyst A26.…”