Natural Occurrence, Syntheses, and Applications of Cyclopropyl-Group-Containing α-Amino Acids. 2. 3,4- and 4,5-Methanoamino Acids

Synthesis of Methylene‐ and Alkylidenecyclopropane Derivatives

“…For example, only very recently, excellent enantioselectivities as high as 95% ee were reported by Buono et al for the reaction between norbornene derivatives and terminal alkynes in the presence of a chiral palladium catalyst. In the same time, comparable enantioselectivities (up to 90% ee) were reported by Gregg et al for the reaction of monosubstituted allenes with methyl aryldi-A C H T U N G T R E N N U N G azoacetates mediated by the chiral rhodium catalyst, Rh 2 A C H T U N G T R E N N U N G (S-DOSP) 4 . In addition, several novel [2,3]-sigmatropic rearrangements of cyclopropenecarbinols and derivatives, along with Pd-catalyzed nucleophilic substitutions of cyclopropylvinyltosylates have proved their efficiency.…”

“…Since this preliminary result, there have been few reports on the degree of enantioselectivity that might be feasible given the wide array of available chiral catalysts. Among recent examples, Gregg et al reported high enantioselectivities of up to 90% ee for the reaction of a series of monosubstituted allenes with methyl aryldiazoacetates mediated by the rhodium tetraprolinate catalyst, Rh 2 A C H T U N G T R E N N U N G (S-DOSP) 4 . [18] In this study, monosubstituted alkyl-and arylallene substrates provided the corresponding methylenecyclopropanes 2a-d in 54-76% yield under standard conditions, while yields for 1,1-disubstituted allenes were generally significantly lower (30-33% for 2e-f), as shown in Scheme 3.…”

“…There is also a growing interest in small carbocycles from the related fields of medicinal and biological chemistry. [4] Therefore, while the cyclopropane ring is a highly strained entity, it is nonetheless found in a wide variety of naturally occurring compounds including terpenes, pheromones, fatty acid metabolites and unusual amino acids. [5] Cyclopropane subunits also occur in many natural products of primary and secondary metabolism.…”

Function-Oriented Biosynthesis of β-Lactone Proteasome Inhibitors in Salinispora tropica

“…To complement the commercially available pool of proteinogenic and non-proteinogenic amino acids, three additional substrates were synthesized. Racemic 3-cyclopropylalanine and 3-cyclobutylalanine were prepared by alkylation of diethyl formamidomalonate with (bromomethyl)cyclopropane and (bromomethyl)cyclobutane, respectively 21. 3- R , S -Cyclopent-2-enyl- d,l -alanine was synthesized in a Strecker-type reaction from 2-cyclopent-2-enyl-1-acetaldehyde,22 readily available by reduction/oxidation of 2-cyclopent-2-enyl-1-acetic acid 23…”

Methyl 2‐(Benzyloxycarbonylamino)‐2‐cyclopropylideneacetate: A Versatile Building Block for Cyclopropyl‐Containing Amino Acids

“…[1][2][3] Several such amino acids have been made accessible [4,5] from our previously developed alkyl 2-chloro-2-cyclopropylideneacetates 1-R. [6,7] Although this type of multifunctional building block may be quite convenient, especially for the preparation of β-functionalized amino acids, a more convergent access to cyclopropyl-containing α-amino acids ought to be achievable from modified 2-cyclopropylideneacetates of type 2 already containing a protected amino group adjacent to the carboxylic acid functionality. Here we report a convenient preparation of methyl (2-benzyloxycarbonylamino)cyclopropylideneacetate (2) (Scheme 1) and some of its versatile transformations.…”