A chiral relay auxiliary for the synthesis of homochiral α-amino acids

Evolution of a Synthetic Strategy for the Variecolortides

“…We reasoned that the Boc protecting groups might not survive the deprotection conditions and, therefore, switched to the more stable PMB ( p ‐methoxybenzyl) protecting group. Thus, 15 was doubly alkylated to give the corresponding bis(PMB) derivative,10 which could be desilylated by using ammonium fluoride in methanol. With the desired alcohol 18 in hand, we next screened a variety of different oxidation conditions, again with no success.…”

The Asymmetric Synthesis of (2R,3R)- and (2R,3S)-3-Methyl-aspartates via an Enantiodiscrimination Strategy

“…The configuration of the newly formed stereogenic centre at C 3 of 4a was assigned as R according to extensive literature precedent since it is known that alkylation of enolate 2 with electrophiles affords trans-alkylated products in high d.e. 4 Furthermore, comparison of the sign and value of the specific rotation of the unreacted electrophile recovered from the reaction of enolate 2 and 1.5 equivalents of ethyl 2-bromopropionate 3a {recovered yield 16%, [a] 23 D = -11.1, (c 1.1 in CHCl 3 )}, with the specific rotation previously described for homochiral ethyl (R)-(+)-2-bromo-propionate 3a {[a] 23 D +32.4, (c 3.9 in CHCl 3 )}, 7 revealed that it was enantiomerically enriched in the S-enantiomer. While the 34% e.e.…”

“…4 Given the high facial selectivity observed in the alkylation of the enolate derived from 1 with a wide range of haloalkyl electrophiles, we wished to investigate whether enolate 2 had the capacity to resolve racemic electrophiles such as a-bromo-propionate esters 3a-c. 5 Thus, treatment of enolate 2 with ten equivalents of racemic ethyl 2-bromopropionate 3a in THF at -78 °C afforded a 94.5: 5.5 mixture of diastereoisomers 4a and 5a, 6 which after chromatographic purification (1:1 ether:hexane) gave ethyl (3R,6S,2'R) -2'-[N,N'-bis-p-methoxybenzyl-6-iso-propylpiperazine-2-5-dion-3-yl]propionoate 4a {[a] 23 D = -13.1, (c 1.0 in CHCl 3 )}, and ethyl (3R,6S,2'S) -2'-[N,N'-bis-p-methoxybenzyl-6-isopropylpiperazine-2-5-dion-3-yl]propionoate The stereochemistry of the major diastereoisomer 4a was assigned as (3R,6S,2'R) according to the following arguments. The configuration of the newly formed stereogenic centre at C 3 of 4a was assigned as R according to extensive literature precedent since it is known that alkylation of enolate 2 with electrophiles affords trans-alkylated products in high d.e.…”

Ceric ammonium nitrate oxidation of N-(p-methoxybenzyl)lactams: competing formation of N-(hydroxymethyl)δ-lactams

“…Nevertheless, the most widely used method for deprotection involves the oxidative cleavage of the N-PMB moiety using ceric ammonium nitrate (CAN). [2][3][4][5][6][7][8][9][10][11][13][14][15][16][17][19][20][21]23,32,33 Factors such as the mild reaction conditions that are generally tolerant towards many different functional groups, the experimental simplicity, and the relatively low cost of CAN make this a method of choice.…”

“…The p-methoxybenzyl (PMB) group is often used for the N-protection 1 of amides, lactams and aza-heterocycles in the synthesis of natural [2][3][4][5][6][7][8][9][10][11][12] and non-natural products [13][14][15][16][17][18][19][20][21][22][23] because of its ease of removal. Many methods, such as Lewis 24 and Brönsted acid 18,22,[25][26][27] -mediated hydrolysis, benzylic anion oxidation, 12,28,29 catalytic hydrogenation, 30 and persulfate-mediated oxidative cleavage, 31 have been employed for the removal of the N-PMB group.…”