The 9-Phenyl-9-fluorenyl Group for Nitrogen Protection in Enantiospecific Synthesis

Abstract

One of the biggest challenges in asymmetric synthesis is to prevent racemization of enantiopure starting materials. However, at least some of the enantiopurity is lost in most of the existing reactions used in synthetic organic chemistry. This translates into unnecessary material losses. Naturally enantiopure proteinogenic amino acids that can be transformed into many useful intermediates in drug syntheses, for example, are especially vulnerable to this. The phenylfluoren-9-yl (Pf) group, a relatively rarely used protecting group, has proven to be able to prevent racemization in α-amino compounds. This review article showcases the use of Pf-protected amino acid derivatives in enantiospecific synthesis.

Structures, Lewis Acidities, Electrophilicities, and Protecting Group Abilities of Phenylfluorenylium and Tritylium Ions

“…The “tunable protecting‐group strategy” proposed by Surprenant and Lubell can now be rationalized on a quantitative basis. When transforming the bromine atom of a para ‐bromophenylfluorenyl protecting group (same E f value as 2 e considering that σ p =0.23 for Br and Cl), into a R 2 N substituent via a nucleophilic substitution, the electrofugality of the fluorenyl protecting group increases by a factor>10 6 ( E f of 2 e (−4.92) and 2 a (>1.0) in Table ) .…”

Harmicine, a Tetracyclic Tetrahydro-β-Carboline: From the First Synthetic Precedent to Isolation from Natural Sources to Target-Oriented Synthesis (Review)*

“…The problem using amino acids as a chiral pool starting material stems from the inherent ability of α-amino aldehydes, ketones, esters, and amides to racemize (or epimerize) under the reaction conditions. As a solution, the 9-phenylfluoren-9-yl (Pf) protecting group strategy was developed as an alternative to the previously employed, acid-labile trityl group [85,86]. There are other means to prevent racemization in said substrates, but those methods typically require the use of double nitrogen protecting groups (for representative examples, see [87]).…”

Chirospecific synthesis: Catalysis and chiral pool hand in hand

“…However, the synthetic methodology is still far from perfect; no one general approach can be inferred for all similar substrates. We have recently embarked on a more detailed investigation of the effect of the nitrogen protecting group to protect the stereogenic center against epimerization, and we have reason to believe that a sterically bulky 9-phenyl-9-fluorenyl group can give a more general solution to this problem [27][28][29][30][31]. However, these investigations are only in their infancy, and detailed reports of their success will be the topic of future disclosures.…”