General Papers ARKIVOC 2005 (xiv) 20-28
During our investigation towards the synthesis of celogenitins,18 we tried to perform Suzuki coupling reaction at C-2 position of tryptophan derivative 1a with imidazole in the presence of Cs2CO3 and catalytic amount of palladium reagent in acetonitrile at 70 oC. It is worthy to mention that, under various conditions of employing different palladium reagent, we could able to isolate only the Boc-deprotected product 1b (Scheme 1).
Imidazole
OMe
OMe
NHBoc
N Br N CH3CN, 70 oC
(Boc)2O Cs2CO3 O
Boc N Br
H
1b
1a
Scheme 1
We report herein a new and mild method for the deprotection of Boc-group from amino compounds under basic conditions, using Cs2CO3 and imidazole system, from di-tbutyldiimidodicarbonate as well as nitrogen atom conjugated to a carbonyl or aromatic system.
Results and Discussion
To explore the scope and limitations, we investigated a series of Boc-protected amino compounds with different protecting groups and functionalities, which are shown in Table 1. Although it is known that cleavage of the protecting groups in methyl N-Boc-a-amino esters gave the corresponding N-Boc-amino acids without racemization19 under basic condition, in our case, we were worried about such a possibility in the presence of an additional Boc group. To investigate this, we submitted compound 2, 3, and 4 to above basic conditions to cleave the Boc group. We found that the optical rotation of the product obtained changed with time, showing clearly that epimerization has occurred. Furthermore, chiral HPLC analysis of 2b showed two peaks confirming the epimerization during the reaction.20 In light of this result, we decided to convert the acid into its benzyl esters. To ensure the enantiomeric purity of such a product (8b), we again submitted for the chiral HPLC which showed single peak at the corresponding retention time and in addition, the rotation clearly confirmed no detectable racemization. With the retention of optical purity on amino acids, we applied the above method to other Boc-protected compounds. Boc-group attached to nitrogen atoms part of an aromatic system or in conjugation with a carbonyl group was removed in high yields. Simple aliphatic mono-Boc compounds were unaffected under above reaction conditions. In entry 12a, where the nitrogen functionality is protected by Boc as well as Cbz group, we found that only Boc group was selectively cleaved from the nitrogen and Cbz group was untouched affording the product 12b in 82% yield.
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