Remarkable switch of regioselectivity in epoxide ring opening of 3-benzyl-7-oxa-3-azabicyclo[4.1.0]heptane with amines: practical synthesis of trans-4-amino-3-hydroxypiperidines and trans-3-amino-4-hydroxypiperidines

Direct α‐Acylation of Thioesters With Carbonylimidazolides Toward α‐Substituted Malonate Monothioates and Weinreb‐Type Monoamides

“…[16][17]. This sharp difference highlights the crucial involvement of the lithium ion, likely due to its Lewis acid activity in activating the carbonyl group [49][50][51][52][53][54][55][56][57]. Although LDA also contains a lithium ion, it afforded no desired product (entry 18).…”

Direct α‐Acylation of Thioesters With Carbonylimidazolides Toward α‐Substituted Malonate Monothioates and Weinreb‐Type Monoamides

“…[16][17]. This sharp difference highlights the crucial involvement of the lithium ion, likely due to its Lewis acid activity in activating the carbonyl group [49][50][51][52][53][54][55][56][57]. Although LDA also contains a lithium ion, it afforded no desired product (entry 18).…”

Fragtory: Pharmacophore-Focused Design, Synthesis, and Evaluation of an sp3-Enriched Fragment Library

“…In the case of the pyrrolidine-based fragment 1 , the bromo-pyridine moiety is pointing toward the solvent and did not contribute constructively to ligand binding (other than by shape complementarity). Still, this compound class attracted our attention, since it was derived from a tailored in-house set of fragments and thus came with already established synthesis procedures, held a number of potential handles for chemical modification, showed a clearly defined electron density in the crystal structure, and also displayed a yet unexplored and unprecedented chemotype . Furthermore, the sp 3 -rich scaffold not only exhibits multiple exit vectors and functional groups contributing to a beneficial polarity but the ligand was also found in proximity of the catalytic dyad and thus, depending on the substitution pattern, might replace the conserved water and thereby open up a potential optimization route toward improved compound affinity.…”

Regio - and stereoselective synthesis of the iminosugars – 4-substituted 1-benzylpiperidine-3,5-diols

“…There is a general consensus that this outcome of the nucleophilic ring opening is promoted by the bidentate coordination of epoxide 7a organized to produce only 4-substituted regioisomer. [19][20][21][22][23] Such coordination activates the epoxide ring for the nucleophilic attack and shifts the conformational equilibrium (originally in favor the anti-conformer A by ~1.6 kcal/mol 17 ) entirely towards the lithium complex of syn-conformer B, producing only 4-substituted regioisomer upon the epoxide cleavage.…”

Direct α‐Acylation of Thioesters With Carbonylimidazolides Toward α‐Substituted Malonate Monothioates and Weinreb‐Type Monoamides

“…[16][17]. This sharp difference highlights the crucial involvement of the lithium ion, likely due to its Lewis acid activity in activating the carbonyl group [49][50][51][52][53][54][55][56][57]. Although LDA also contains a lithium ion, it afforded no desired product (entry 18).…”

Fragtory: Pharmacophore-Focused Design, Synthesis, and Evaluation of an sp3-Enriched Fragment Library

“…In the case of the pyrrolidine-based fragment 1 , the bromo-pyridine moiety is pointing toward the solvent and did not contribute constructively to ligand binding (other than by shape complementarity). Still, this compound class attracted our attention, since it was derived from a tailored in-house set of fragments and thus came with already established synthesis procedures, held a number of potential handles for chemical modification, showed a clearly defined electron density in the crystal structure, and also displayed a yet unexplored and unprecedented chemotype . Furthermore, the sp 3 -rich scaffold not only exhibits multiple exit vectors and functional groups contributing to a beneficial polarity but the ligand was also found in proximity of the catalytic dyad and thus, depending on the substitution pattern, might replace the conserved water and thereby open up a potential optimization route toward improved compound affinity.…”

Regio - and stereoselective synthesis of the iminosugars – 4-substituted 1-benzylpiperidine-3,5-diols

“…There is a general consensus that this outcome of the nucleophilic ring opening is promoted by the bidentate coordination of epoxide 7a organized to produce only 4-substituted regioisomer. [19][20][21][22][23] Such coordination activates the epoxide ring for the nucleophilic attack and shifts the conformational equilibrium (originally in favor the anti-conformer A by ~1.6 kcal/mol 17 ) entirely towards the lithium complex of syn-conformer B, producing only 4-substituted regioisomer upon the epoxide cleavage.…”

Direct α‐Acylation of Thioesters With Carbonylimidazolides Toward α‐Substituted Malonate Monothioates and Weinreb‐Type Monoamides

“…[16][17]. This sharp difference highlights the crucial involvement of the lithium ion, likely due to its Lewis acid activity in activating the carbonyl group [49][50][51][52][53][54][55][56][57]. Although LDA also contains a lithium ion, it afforded no desired product (entry 18).…”

Fragtory: Pharmacophore-Focused Design, Synthesis, and Evaluation of an sp3-Enriched Fragment Library

“…In the case of the pyrrolidine-based fragment 1 , the bromo-pyridine moiety is pointing toward the solvent and did not contribute constructively to ligand binding (other than by shape complementarity). Still, this compound class attracted our attention, since it was derived from a tailored in-house set of fragments and thus came with already established synthesis procedures, held a number of potential handles for chemical modification, showed a clearly defined electron density in the crystal structure, and also displayed a yet unexplored and unprecedented chemotype . Furthermore, the sp 3 -rich scaffold not only exhibits multiple exit vectors and functional groups contributing to a beneficial polarity but the ligand was also found in proximity of the catalytic dyad and thus, depending on the substitution pattern, might replace the conserved water and thereby open up a potential optimization route toward improved compound affinity.…”

Regio - and stereoselective synthesis of the iminosugars – 4-substituted 1-benzylpiperidine-3,5-diols

“…There is a general consensus that this outcome of the nucleophilic ring opening is promoted by the bidentate coordination of epoxide 7a organized to produce only 4-substituted regioisomer. [19][20][21][22][23] Such coordination activates the epoxide ring for the nucleophilic attack and shifts the conformational equilibrium (originally in favor the anti-conformer A by ~1.6 kcal/mol 17 ) entirely towards the lithium complex of syn-conformer B, producing only 4-substituted regioisomer upon the epoxide cleavage.…”