Oxazaborolidinium Ion-Catalyzed Cyclopropanation of α-Substituted Acroleins: Enantioselective Synthesis of Cyclopropanes Bearing Two Chiral Quaternary Centers

Abstract

A catalytic synthetic route to highly functionalized chiral cyclopropane derivatives was developed by Michael-initiated cyclopropanation of α-substituted acroleins with aryl- and alkyl diazoacetates. In the presence of chiral (S)-oxazaborolidinium cation 1b as a catalyst, the reaction proceeded in high yield (up to 93%) with high to excellent diastereoselectivity (up to 98% de) and enantioselectivity (up to 95% ee).

Second generation modifiers of colistin resistance show enhanced activity and lower inherent toxicity

“…15 The homologated ester, 3 underwent diazotransfer reaction, accomplished by reaction with para -acetamidobenzenesulfonyl azide ( p -ABSA) in the presence of DBU, to yield diazoketone 4 . 16 Analog diversity was then introduced via a Ru-catalyzed N-H insertion reaction. 17 Conversion of the ester to the N -methoxy- N -methylamide (Weinreb amide) proceeded without the need for protection of the newly installed amine.…”

Catalytic Enantioselective Synthesis of 2,5‐Dihydrooxepines

“…Thec oordination mode of the acrolein to catalyst 3d is the same as that previously observed for enantioselective cyclopropanation reactions. [7] After asymmetric cyclopropanation between the a-bromoacrolein and avinyldiazo compound, the resulting cyclopropane 1 shows cis geometry between the aldehyde and olefin groups.T he intermediate cyclopropane cis-FVC 1 is immediately converted into cis-(2S,5R)-2,5-dihydrooxepine as the major enantiomer for 2t.T he absolute configuration of cis-(2S,5R)-6-bromo-2,5-dimethyl-2,5-dihydrooxepine (2t; Table 3, entry 9) supports the rearrangement proceeding in aconcerted manner via boat-like transition state 4,asseveral DFT calculations have reported. [6c, 14] Further chemical transformations of the resulting optically active 6-bromo-2,5-dihydrooxepine are illustrated in Scheme 2.…”

“…Theo bserved stereochemistry for the enantioselective formation of 2,5-dihydrooxepine with COBI catalyst 3d can be rationalized on the basis of the transition-state model shown in Figure 3. [7] After asymmetric cyclopropanation between the a-bromoacrolein and avinyldiazo compound, the resulting cyclopropane 1 shows cis geometry between the aldehyde and olefin groups.T he intermediate cyclopropane cis-FVC 1 is immediately converted into cis-(2S,5R)-2,5-dihydrooxepine as the major enantiomer for 2t.T he absolute configuration of cis-(2S,5R)-6-bromo-2,5-dimethyl-2,5-dihydrooxepine (2t; Table 3, entry 9) supports the rearrangement proceeding in aconcerted manner via boat-like transition state 4,asseveral DFT calculations have reported. [7] After asymmetric cyclopropanation between the a-bromoacrolein and avinyldiazo compound, the resulting cyclopropane 1 shows cis geometry between the aldehyde and olefin groups.T he intermediate cyclopropane cis-FVC 1 is immediately converted into cis-(2S,5R)-2,5-dihydrooxepine as the major enantiomer for 2t.T he absolute configuration of cis-(2S,5R)-6-bromo-2,5-dimethyl-2,5-dihydrooxepine (2t; Table 3, entry 9) supports the rearrangement proceeding in aconcerted manner via boat-like transition state 4,asseveral DFT calculations have reported.…”

“…[4c] Indeed, using this approach for the formation of oxepine derivatives is discouraged due to the multiple steps required to prepare chiral cis-1-formyl-2-vinylcyclopropanes (FVCs) for such arearrangement reactions. [6] Recently,o ur group has reported highly enantioselective catalytic Michael addition initiated cyclopropanations [7] using diazoesters as ylides with the chiral oxazaborolidinium ion [8] (COBI) as aL ewis acid catalyst. We envisioned that the reaction of substituted acroleins with vinyldiazoester would generate chiral cis-1-formyl-2-vinylcyclopropanes (FVCs; 1), which are ideally substituted for subsequent retro-Claisen rearrangement to provide highly functionalized 2,5-dihydrooxepines (2;Scheme 1).…”

Palladium-catalysed formation of vicinal all-carbon quaternary centres via propargylation

“…1a). For a selection of such efforts, see refs 8, 9, 10, 11. So far, the commonly notable approach is the allylic substitution reaction with an issue of regioselectivity, which is obviously still in its early stage in terms of the scope (equation (3), Fig.…”