Transesterifications with 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene/Lithium Bromide (DBU/LiBr) – Also Applicable to Cleavage of Peptides from Resins in Merrifleld Syntheses

Abstract

(2 1. V. 9 1)A mixture of the amidine base 1,8-diazabicyclo[5,4.0]undec-7-ene (DBU) and LiBr (preferably 0.5 and 5 equiv., resp.) turns out to be a highly efficient catalyst (at 0-25O) for saponifications (in THF/H20) and transesterifications (in ROH). The scope and limitations of the method are determined using ca. two dozens of different ester/alcohol combinations (Schemes 2 and 3 ) . The investigation is focused on peptides as substrates. Under carefully controlled conditions, no epimerization occurs with N-Boc-and N-Z-protected peptide esters, when methyl, ethyl, isopropyl, or ally1 esters are the products, as shown for peptides containing up to six amino acids, with Ala, Leu, MeLeu, Asp(OEt), or Tyr at the C-terminus (Scheme 3 and Tables 1 and 2). Hydrolytic and transesterifying detachments of Boc-Leu-Ala-Gly-Val-OR and Boc-Leu-Ala-Gly-Phe-OR (R = H, Me) from PAM and Wang resins (1-8 h at 0-25", 2 equiv. of DBU, 5 equiv. of LiBr) can be achieved by this method without epimerization of the C-terminal stereogenic center; a comparison with other methods (HF, Ti(OR),) is given (Schemes 4 and 5 ) . Possible protecting-group strategies involving the DBU/LiBr method are discussed (Table 3 ) . Extensive experimental details are given.In the course of our work on olefinations 'A la Horner-Emmons-Wadsworth' [l] with the phosphonate [2] and the highly efficient base system DBU')/LiBr [3] shown in Scheme 1, we noticed that traces of moisture led to rapid hydrolysis of the phosphonate ester at room temperature. Since such esters are normally not readily hydrolyzed, we embarked on a systematic investigation to test, whether saponifications and transesterifications could be generally effected under these conditions.There are numerous methods of achieving transesterifications and ester hydrolyses4) under acidic and basic conditions, with ester-cleaving enzymes'), with titanate@), with ion-exchange resins [8], with KF/crown ether [9], and with distannoxane [lo] to mention

Directed Evolution by Using Iterative Saturation Mutagenesis Based on Multiresidue Sites

“…Because we were in the advantageous situation of having catalysts that favored opposite enantiomers, we used a catalyst of each stereochemical preference and N ‐Boc aspartic acid benzyl ester to establish a three‐point calibration curve. The curve relates CD signal intensity at 270 nm to the ee of the alcohols derived from our product lactones via methanolysis (Figure 3b; Table 1, entries 1 , 7 , and 12 ) 12. The y‐intercept of the calibration curve corresponded to approximately a 4% error in ee (Figure 3b, from the expected value of 0 for racemic), which is clearly useable for a rapid screening method.…”

A Synergistic Combinatorial and Chiroptical Study of Peptide Catalysts for Asymmetric Baeyer–Villiger Oxidation

“…The curve relates CD signal intensity at 270 nm to the ee of the alcohols derived from our product lactones via methanolysis (Figure 3b; Table 1, entries 1 , 7 , and 12 ). [12] The y-intercept of the calibration curve corresponded to approximately a 4% error in ee (Figure 3b, from the expected value of 0 for racemic), which is clearly useable for a rapid screening method. In addition, we observed equivalent performance of the CD-assay when compared to HPLC for the remaining 9 combinatorial hits (Figure 3c, black trend line).…”

“…The dried residue was then ring opened (we note that other common lactone-opening methods led to full or partial epimerization of the C2 stereocenter, confounding the analysis of our data.). According to a modification of the procedure of Seebach, [12] a solution in CH 3 OH of 0.1 M DBU (1,8-Diazabicyclo[5.4.0]undec-7-ene) and 1.0 M LiBr was prepared in a volumetric flask. An aliquot of this solution was added to lactone sample to afford a reaction mixture that was 0.2 M in lactone (1.0 equiv.…”

Direct access to functional (Meth)acrylate copolymers through transesterification with lithium alkoxides

“…As just one illustrative example, it is used as the key reaction step for the production of biodiesel . To optimize and increase the efficiency of transesterification reactions a variety of suitable catalysts, ranging from organic and inorganic bases, to Lewis acids, and N ‐heterocyclic carbenes, have been developed . For polymer chemists, transesterification is a useful tool for the synthesis of polyesters, for example, poly(ethylene terephthalate) through transesterification of dimethyl terephthalate with ethylene glycol or for reactive compatibilization of polymer blends by the in‐situ formation of copolymers in the presence of transesterification catalysts …”