Stereoselective Alkylation of Imines and its Application towards the Synthesis of β‐Lactams

Abstract

S)-4-Isopropyl-1-[(R)-1-phenylethyl]imidazolidin-2one was evaluated as ac hiral auxiliary for asymmetrica cetate and propionate Mannich-type reactions,b yg eneration of the titanium enolates, affording excellent yields and ste-reoselectivities. The application of the auxiliary was exemplified in the stereoselective synthesis of the b-lactam antihyperlipidemic drug ezetimibe.

Concerted Enantioselective [2+2] Cycloaddition Reaction of Imines Mediated by a Magnesium Catalyst

“…The β-lactam 6 was then transformed to a medium-ring amine 8 by employing the tandem copper-catalyzed C–N bond formation-ring-expansion process, as reported by Buchwald and co-workers (Scheme A) . A similar operation from ent - 3i produced β-lactam 9 , and further coupling with p -fluoro-iodobenzene easily led to compound 10 , which is the key intermediate of the lipid-lowering agent Ezetimibe 11 (Scheme B) …”

“…14 A similar operation from ent-3i produced β-lactam 9, and further coupling with pfluoro-iodobenzene easily led to compound 10, which is the key intermediate of the lipid-lowering agent Ezetimibe 11 (Scheme 5B). 15 Moreover, by linking with the azide compound 12, triazole 13 was conveniently obtained from 4l without erosion of enantiopurity (Scheme 5C). The direct deprotection process was also realized using tBuONa with similar methods, and the tautomeric intermediates were further protected to generate products 14a and 14b.…”

A Telescoped Continuous Flow Enantioselective Process to Access Chiral Intermediates of Atomoxetine, Dapoxetine, Duloxetine and Ezetimibe

“…7 While asymmetric catalytic methods are more atom-efficient and produce less waste, the high cost of chiral ligands and organocatalysts often makes the of use chiral auxiliaries the preferred option. 2,3,8 In order to maximize the efficiency of existing catalytic enantioselective transformations, there has been a growing interest in the development of recyclable catalysts during the last decade. 9 In particular, chiral phosphoric acids (CPAs) have seen widespread adoption due to their versatility.…”

A Telescoped Continuous Flow Enantioselective Process for Accessing Intermediates of 1-Aryl-1,3-diols as Chiral Building Blocks

“…Several synthetic routes have been developed to access optically active 1-aryl-1,3-diols using enantioselective reactions , and, most interestingly, organocatalysis . While asymmetric catalytic methods are more atom-efficient and produce less waste, the high cost of chiral ligands and organocatalysts often makes chiral auxiliaries the preferred option. ,, To maximize the efficiency of existing catalytic enantioselective transformations, there has been a growing interest in the development of recyclable catalysts during the past decade . In particular, chiral phosphoric acids (CPAs) have seen widespread adoption due to their versatility .…”

“…1-Aryl-1,3-diols 1 are important synthetic building blocks for the pharmaceutical industry. 1 They are key intermediates in the synthesis of numerous drugs, including ezetimibe (treatment of high blood cholesterol), 2 dapoxetine (premature ejaculation), 3 atomoxetine (attention deficit hyperactivity disorder), 4 and duloxetine (major depressive and anxiety disorders) 5 ( Figure 1 ).…”