A Mild and Selective Method for the Hydrolysis of Esters with Trimethyltin Hydroxide

Abstract

The mild and selective hydrolysis of esters can often be crucial in the sequence toward a target molecule and is, therefore, an important objective in contemporary organic synthesis. Although several methods exist to accomplish this task in certain cases, a mild, generally applicable protocol remains absent. Frequent problems encountered include the concurrent hydrolysis of other ester groups present within the molecule under scrutiny, epimerization of stereocenters, and elimination reactions induced by the often basic conditions employed. Herein we report a new and selective method for the hydrolysis of esters under extremely mild conditions that avoid such side reactions and lead to high yields of the corresponding carboxylic acids.It was during our campaign toward thiostrepton, [1] a highly complex thiopeptide antibiotic, that we had the opportunity to search for such a method. Our sensitive intermediates proved too fragile to tolerate standard ester hydrolysis conditions. We finally came upon Me 3 SnOH, which had been previously employed by Mascaretti and co-workers [2] to cleave phenacyl ester anchored amino acids and peptides from a polystyrene resin and to hydrolyze methyl and isopropyl phenylacetate to give the corresponding acids in high yield. To our knowledge, these are the only examples in which Me 3 SnOH has been previously used to carry out hydrolytic ruptures of esters.[3] As shown in Table 1, this reagent proved extremely useful to us in attaining the highyielding and selective hydrolysis of methyl esters within the sensitive substrates 1-4, which were encountered en route to thiostrepton. These remarkable results prompted a secondphase investigation in which we attempted to determine systematically the generality and scope of this protocol, which involved heating the substrate with 1-10 equivalents of[*] Prof.

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

“…[4][5][6][7] Besides tediously efficient or racemizing procedures using CaCl 2 , or AlCl 3 /DMA, [8] organotins seem to be the most reliable reagents. [4] So, trimethyltin hydroxide (TMTOH), initially explored by O. Mascaretti et al, [9] and further applieda taspecific point in at otal synthesis reaction, [10] was describedt oc leave ethyl/ methyl estersw ithout affecting the Fmoc PG in good yields with occasional slight epimerization.I nF moc-free syntheses, ethyl,i sopropyl, or allyl estersw ere partially susceptible to deprotection in the presence of TMTOH,w hereas Boc and Alloc remained stable. In am ore general way,awide range of mild methodsu sing Lewisa cids to remove PGs were advanced to overcome basic racemizing conditions, side reactions inherent to strong acidolytic deprotections, catalytic hydrogenolysis, or even palladium-catalyzed PG cleavages.…”

Application of aluminum triiodide in organic synthesis

“…9 Such kind of non-hydrolytic cleavage of esters features the advantage of avoiding strong acidic or basic conditions and is suitable for substrates containing sensitive functional groups. The transformation can be accessed alternatively with trimethyltin hydroxide, 10 lithium iodide, 11 lithium 1-propanethiolate, 12 lithium bromide, 13 and trimethylsilyl iodide (TMSI). 14 …”

Synthesis of Mono and Bis[60]fullerene‐Based Dicationic Peptoids

“…Therefore, the previously unknown diacid 41 was synthesised from the reported bis-adduct 40, [17a] by using trimethyltin hydroxide [23] at 80 °C or borontribromide at -10 °C to room temperature -the former conditions resulted in a better yield of 65% compared to the latter of 50% (Scheme 4). As expected, attempts to synthesise [60]fullerene bis peptoid 42 using diacid 41 and peptide 13 under the standard coupling conditions used previously in this study failed, due to poor solubility.…”