Memory of chirality effects in aldol cyclisations of 1-(3-oxobutyryl) derivatives of l-4-oxaproline and l-proline isopropyl esters

Asymmetric Total Synthesis of (+)‐Neooxazolomycin Using a Chirality‐Transfer Strategy

“…[13] In turn, it was envisioned that 7 could be traced College of Pharmacy,S eoul NationalUniversity 1G wanak-ro, Gwanak-gu,S eoul 08826 (Korea) E-mail:pennkim@snu.ac.kr back to the known b-keto acid 8 [9c] and d-serine.I ft he principles of "memory of chirality" (MOC) and "dynamic kinetic resolution" (DKR) were applied to the aldol reaction of 7, [14] as in our previous total synthesis of (À)-penibruguieramine starting from l-proline, [11a] the asymmetric synthesis of 3 could be achieved from d-serine without the aid of external chiral influences.Ifsuccessful, this approach would complete the total synthesis of the natural product with high chiral economy and might also have implications in the biosynthesis of the oxazolomycin family of natural products. We planned to conduct an intramolecular aldol reaction of the oxaproline derivative 7 to construct the lactam ring of 6 and to install the three contiguous stereocenters.T his type of aldol reaction has been proposed as ap lausible step in the biosynthetic pathway towards oxazolomycins.…”

Enantioselective Rearrangement of Proline Sulfonamides: An Easy Entry to Enantiomerically Pure α‐Aryl Quaternary Prolines

“…Deprotonation of the less crowded conformer of the substrate 1 a, in which the arylsulfonyl group is far from the tert-butyl ester, gives the non-racemic enolate A. [9] This intermediate, through a Re-face attack, evolves into a chiral spiro-Meisenheimer complex B that, in turn, undergoes the stereoselective S À C a migration of the aryl group, with an overall con- www.chemeurj.org figuration retention. Compounds 1 b-e-due to the rigidity of the proline ring and the presence of aryl groups that generate similar or increased steric hindrance-are expected to rearrange through the same stereochemical pathway.…”

Biomimetic Total Synthesis of (−)‐Penibruguieramine A Using Memory of Chirality and Dynamic Kinetic Resolution

“…Thepresence of an acidic proton at the C2 stereocenter of substrate 3 allows for easy epimerization under basic conditions.T he conformer 3-I is energetically more favored than 3-II due to minimized 1,3-allylic strain, [10,17] and the deprotonation reaction at the proline a position on conformer 3-I generates an axially chiral enolate 5.This transient enolate can be converted back into 3 by protonation with complete configuration retention at the C8 position. Thepresence of an acidic proton at the C2 stereocenter of substrate 3 allows for easy epimerization under basic conditions.T he conformer 3-I is energetically more favored than 3-II due to minimized 1,3-allylic strain, [10,17] and the deprotonation reaction at the proline a position on conformer 3-I generates an axially chiral enolate 5.This transient enolate can be converted back into 3 by protonation with complete configuration retention at the C8 position.…”

“…[3] We anticipated the successful outcome of this reaction after considering the study reported by Stoodley et al demonstrating the use of MOC in an aldol reaction of simpler proline derivatives. [10] In that report, although the diastereoselectivity and yield were low,acertain degree of configuration retention was obtained at the chiral center of the proline moiety.…”