Petasis vs. Strecker Amino Acid Synthesis: Convergence, Divergence and Opportunities in Organic Synthesis

Abstract

α-Amino acids find widespread applications in various areas of life and physical sciences. Their syntheses are carried out by a multitude of protocols, of which Petasis and Strecker reactions have emerged as the most straightforward and most widely used. Both reactions are three-component reactions using the same starting materials, except the nucleophilic species. The differences and similarities between these two important reactions are highlighted in this review.

Keywords: Petasis; Strecker; amino acids; biomolecules; multicomponent reactions; peptides.

Figure 1

Examples of bioactive amino acids prepared by the Strecker synthesis. Purple colour shows the amino nitrile functions obtained as a result of a direct Strecker reaction.

Scheme 1

General Petasis and Strecker amino acid synthesis.

Scheme 2

General mechanism of the Strecker amino acid synthesis.

Scheme 3

Synthesis of radiolabelled [¹¹C]sarcosine.

Scheme 4

Green synthesis of α-amino nitriles in the presence of potassium ferrocyanide and its mechanism.

Scheme 5

Mechanochemical Strecker synthesis of α-aminonitriles using K₃[Fe(CN)₆].

Scheme 6

Oxidative cyanation of a tertiary amine.

Scheme 7

Mechanism for the α-cyanation of tertiary amines with K₃[Fe(CN)₆]/O₂. −•= radical anion, +• = radical cation.

Scheme 8

Resolution of chiral amino acids by subtilisin.

Scheme 9

Asymmetric Strecker synthesis of (S)-alanine from a chiral amine.

Scheme 10

Chiral induction by tert-butylsulfinyl ketimines.

Scheme 11

Asymmetric hydrocyanation of imines.

Scheme 12

Proposed mechanism for the asymmetric hydrocyanation of imines.

Scheme 13

Asymmetric Strecker synthesis mediated by Kobayashi’s catalyst.

Scheme 14

Two-step one-pot asymmetric Strecker reaction.

Scheme 15

Spontaneous resolution of racemic α-amino nitriles.

Scheme 16

Resolution of racemic 2-chlorophenyl glycine followed by (S)-clopidogrel synthesis.

Scheme 17

Synthesis of allyl amine by Petasis reaction.

Scheme 18

Mechanism of the Petasis amino acid synthesis.

Scheme 19

Cu(I)-catalysed Petasis synthesis of Ethyl glycinates.

Scheme 20

Mechanism of Cu(I)-catalysed Patasis reaction of ethyl glyoxylate with amines and boronic acids.

Scheme 21

Synthesis of α-propargyl and/or α-allenyl α-amino acids.

Scheme 22

Synthesis of azulenylglycine derivatives by Petasis reaction.

Scheme 23

Petasis amino acid synthesis in water.

Scheme 24

Synthesis of γ-unsaturated amino esters by Petasis reaction followed by Suzuki coupling.

Scheme 25

Catalytic asymmetric amino acid synthesis.

Scheme 26

Petasis reaction followed by ring-closure metathesis. * signifies an asymmetric center.

Scheme 27

Synthesis of (+)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid. * indicates that this substituent is chiral and its stereochemistry is specified in the definition of R*.