Synthesis of Chiral, Enantiopure Allylic Amines by the Julia Olefination of α-Amino Esters

Fabio Benedetti; Federico Berti; Lidia Fanfoni; Michele Garbo; Giorgia Regini; Fulvia Felluga

doi:10.3390/molecules21060805

Synthesis of Chiral, Enantiopure Allylic Amines by the Julia Olefination of α-Amino Esters

Molecules ◽

10.3390/molecules21060805 ◽

2016 ◽

Vol 21 (6) ◽

pp. 805

Author(s):

Fabio Benedetti ◽

Federico Berti ◽

Lidia Fanfoni ◽

Michele Garbo ◽

Giorgia Regini ◽

...

Keyword(s):

Allylic Amines ◽

Amino Esters ◽

Julia Olefination

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ChemInform Abstract: One-Pot Synthesis of Enantiomerically Pure N-Protected Allylic Amines from N-Protected α-Amino Esters.

ChemInform ◽

10.1002/chin.201636056 ◽

2016 ◽

Vol 47 (36) ◽

Author(s):

Gaston Silveira-Dorta ◽

Sergio J Alvarez-Mendez ◽

Victor S Martin ◽

Jose M Padron

Keyword(s):

Allylic Amines ◽

One Pot ◽

Enantiomerically Pure ◽

Amino Esters ◽

One Pot Synthesis

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One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.12.94 ◽

2016 ◽

Vol 12 ◽

pp. 957-962 ◽

Cited By ~ 1

Author(s):

Gastón Silveira-Dorta ◽

Sergio J Álvarez-Méndez ◽

Víctor S Martín ◽

José M Padrón

Keyword(s):

Amino Acids ◽

Allylic Amines ◽

One Pot ◽

Enantiomerically Pure ◽

Amino Esters ◽

One Pot Synthesis ◽

Sequential Reduction ◽

Natural Amino Acids ◽

Hydroxy Groups

An improved protocol for the synthesis of enantiomerically pure allylic amines is reported. N-Protected α-amino esters derived from natural amino acids were submitted to a one-pot tandem reduction–olefination process. The sequential reduction with DIBAL-H at −78 °C and subsequent in situ addition of organophosphorus reagents yielded the corresponding allylic amines without the need to isolate the intermediate aldehyde. This circumvents the problem of instability of the aldehydes. The method tolerates well both Wittig and Horner–Wadsworth–Emmons organophosphorus reagents. A better Z-(dia)stereoselectivity was observed when compared to the previous one-pot method. The (dia)stereoselectivity of the process was affected neither by the reaction solvent nor by the amount of DIBAL-H employed. The method is compatible with the presence of free hydroxy groups as shown with serine and threonine derivatives.

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Understanding the Role of Protic Ionic Liquids (PILs) in Reactive Systems: Rational Selection of PILs for the Design of Green Synthesis Strategies for Allylic Amines and β‐Amino Esters

ChemPlusChem ◽

10.1002/cplu.201900318 ◽

2019 ◽

Vol 84 (7) ◽

pp. 919-926

Author(s):

María V. Bravo ◽

José L. Fernández ◽

Claudia G. Adam ◽

Claudia D. Della Rosa

Keyword(s):

Ionic Liquids ◽

Green Synthesis ◽

Reactive Systems ◽

Rational Selection ◽

Protic Ionic Liquids ◽

Allylic Amines ◽

Amino Esters ◽

Selection Of

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Exogenous Directing Group Free, Ligand-Enabled gamma-C(sp3)–H Arylation of Free Primary Aliphatic Amines and α-Amino Esters

10.26434/chemrxiv.11301017 ◽

2019 ◽

Author(s):

Yongzheng Ding ◽

Shuai Fan ◽

Xiaoxi Chen ◽

yuzhen gao ◽

Gang Li

Keyword(s):

Amino Acids ◽

Large Scale ◽

Free Ligand ◽

Aliphatic Amines ◽

Rapid Synthesis ◽

Amino Esters ◽

Directing Group ◽

Large Scale Synthesis ◽

Primary Aliphatic Amines

A Pdᴵᴵ-catalyzed, ligand-enabled gamma-C(sp3)–H arylation of free primary aliphatic amines and amino esters without using an exogenous directing group is reported. This reaction is compatible with unhindered free aliphatic amines, and it is also be applicable to the rapid synthesis of biologically and synthetically valuable unnatural α-amino acids. Large scale synthesis is also feasible using this method.<br>

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Synthetic and Mechanistic Studies of a Versatile Heteroaryl Thioether Directing Group for Pd(II) Catalysis

10.26434/chemrxiv.7927166.v1 ◽

2019 ◽

Author(s):

Andrew Romine ◽

Kin Yang ◽

Malkanthi Karunananda ◽

Jason Chen ◽

Keary Engle

Keyword(s):

Mechanistic Studies ◽

Salvianolic Acid ◽

Wide Range ◽

Computational Data ◽

Synthetic Utility ◽

Directing Group ◽

High Yields ◽

Julia Olefination ◽

Reaction Progress Kinetic Analysis

A weakly coordinating monodentate heteroaryl thioether directing group has been developed for use in Pd(II) catalysis to orchestrate key elementary steps in the catalytic cycle that require conformational flexibility in a manner that is difficult to accomplish with traditional strongly coordinating directing groups. This benzothiazole thioether, (BT)S, directing group can be used to promote oxidative Heck reactivity of internal alkenes providing a wide range of products in moderate to high yields. To demonstrate the broad applicability of this directing group, arene C–H olefination was also successfully developed. Reaction progress kinetic analysis provides insights into the role of the directing group in each reaction, which is supplemented with computational data for the oxidative Heck reaction. Furthermore, this (BT)S directing group can be transformed into a number of synthetically useful functional groups, including a sulfone for Julia olefination, allowing it to serve as a “masked olefin” directing group in synthetic planning. In order to demonstrate this synthetic utility, natural products (+)-salvianolic acid A and salvianolic acid F are formally synthesized using the (BT)S directed C–H olefination as the key step.

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