Lewis Acid-Mediated Selective Removal of N-tert-Butoxycarbonyl Protective Group (t-Boc)

Abstract

A simple and efficient method for the selective cleavage of N -Boc protective groups from amines employing Lewis acid aluminum chloride, is described. The scope of this procedure is explored for the deprotection of a variety of amines including amino acid derivatives.

MgI2‐Mediated Chemoselective Cleavage of Protecting Groups: An Alternative to Conventional Deprotection Methodologies

“…Then, mild non-transition-metal-assisted deprotections ystems of the most usual PGs of amines (trityl, [11,12] Z, [13][14][15] Boc [14,[16][17][18] )o rcarboxylic acids [19] (tert-butyl, [18,[20][21][22][23] benzyl [24][25][26][27][28] esters) were reported,b esides al ow effectivem ethod for allyl ester, [27] and none for the alloc PGs. [29] Here, we reasoned that Lewis acids in aproticm edium needed to be explored in am ore systematic way for their chemoselective potential, amino-acids being indeeda ni deal model of functional group diversity and for racemizations tudies.D uring our campaign to find selectivec onditions to cleave ethyl esters while preserving the Fmoc group, we discovered the impressivep otentialo f MgI 2 ,e nlarginga fterwards the scopet of acile chemoselective cleavages of various standardsP Gs or PS-resins( Figure 1).…”

Total Synthesis of Halipeptin A: A Potent Antiinflammatory Cyclic Depsipeptide

“…The Boc protecting group was exchanged for a Fmoc group, and subsequent exposure to DAST15 afforded the methylthiazoline 20 (Scheme ). Removal of the allyl protecting group from 20 by a Pd 0 ‐catalyzed reaction16 gave the corresponding acid, which was coupled with the amine liberated from 16 17 in the presence of BEP18 as an activating agent to deliver the dipeptide part 21 . Partial racemization at Cα of the L ‐alanine residue still occurred, even under the very mild conditions, and two isomers (3:1) were determined by 1 H NMR spectroscopy.…”

Protection Reactions

“…Lewis Acids Nonprotic acids such as AlCl 3 , BF 3 ÁOEt 2 [108,109], montmorillonite (acidic clay), celite, silica gel, and ion-exchange resins like Amberlyst 15 can also be used for deblocking the Boc group [110]. The last example can be used for simultaneous deprotection and purification of Boc-protected peptides.…”