Practical Enantioselective Synthesis of β-Substituted-β-amino Esters

Abstract

[reaction: see text] A practical, large-scale synthesis of a beta-amino ester 1 was developed. A chiral imine derived from (S)-phenylglycinol and 3-trimethylsilylpropanal was coupled with the Reformatsky reagent 3 with high diastereoselectivity (de > 98%) to give (SS)-4a as the major isomer. The amino alcohol residue of the coupling product 4 was oxidatively cleaved with sodium periodate in the presence of methylamine. An unusual selective oxidative cleavage of the (SS)-isomer was observed and the imine 6 was obtained with ee > 99% while the (RS)-4b isomer was not cleaved. Reaction with p-toluenesulfonic acid monohydrate allowed for the hydrolysis of the imine and the isolation of the amine as its salt. The title compound 1 was then obtained by transesterification, desilylation, and hydrochloride salt formation in a one-pot process. The method was successfully applied toward the synthesis of a wide variety of beta-amino esters.

A Catalyst‐free Addition Reaction of Zinc Amide Enolates to N‐Sulfonyl Imines

“…To expand the scope of this strategy, recent studies are heavily focused on the asymmetrical approach of the imino‐Reformatsky reaction. Regarding this subject, several attempts have been undertaken using various reaction systems as follows: diethylzinc, diethylzinc/H 2 O, dimethylzinc/Ni(0), Zn/sonication, Zn/dibromoethane, and diethylzinc/Rh(cat.) .…”

Five-membered oxaza heterocyclic compounds on the basis of epoxides and aziridines

“…Nucleophilic addition of anion 198 to Schiff base 199 was assumed to be the key step in the [3 + 2]-cycloaddition process (Scheme 112). The use of Schiff bases and epoxides separately in syntheses of heterocycles, in particular heterocyclization of 3-hydroxy-substituted and other Schiff bases, is considered below [228][229][230][231][232][233]. Sharma A complementary ambiphilic pairing strategy was applied to study reactions of epoxy compounds having CH 2 OCH 2 Ph, CH 2 OPh, (CH 2 ) 2 CH=CH 2 , and other groups with arene-and alkenesulfonamides 214 [237] under microwave irradiation.…”

Silicon- and germanium-substituted propynals as ambident electrophiles for the design of new heterocycles and polyfunctional acetylenes

“…The presence of silicon and germanium heteroatoms at the triple bond of a propynal stabilizes the molecule of the aldehyde and the forming adducts, while subsequent demetallation under mild conditions can result in analogs with the terminal triple bond. This advantage of trialkylsilylpropynals is used in the synthesis of natural cytostatics -forboxazoles, 11 inhibitor of thrombocite aggregation -xemilofibane, 12 as well as siliconacetylenic porphyrines, 13 butadiynyl polyconjugated porphyrin ensembles, 14 which are pro spective for the synthesis of materials used as sensors, reading devices, transformers of photochemical energy. 15 Synthetic potential of substituted propynals and their element containing analogs also includes efficient methods for the synthesis of chiral homoallylic amines and amino acids, 16 propargylamines as precursors of azomethine ylides, 17 dithianes, 18 diazepines, 19 1,3 enynes by the Horner-Emmons reaction, 20 α,β unsaturated esters (as a result of the carbene induced stereoselective esterifica tion of alkynylaldehydes), 21 epoxy diynes, the key frag ments of neocarcinostatine (highly efficient antibacterial and antitumor agent 22 ), hydroxy containing triynes, 23 car bonyl containing enynes, which cyclize into α vinyl furans.…”