Molecular versatility : Unusual reactivities such as hydrolysis, nucleophilic aromatic substitution, and addition reactions of human orotidine‐5′‐monophosphate decarboxylase are explained by crystal structures and involve a nucleophilic lysine residue that normally is expected to act solely as a general base (RP=phosphoribosyl, R=CO2H, CN, acetyl, N3, I; R′=OH, SH, acetyl, hydroxymethyl).
Double protection : Efficient Fmoc‐based solid‐phase synthesis (SPPS) of sulfotyrosine (sY) peptides is achieved by incorporating the sY residue(s) as a dichlorovinyl‐protected (DCV) sulfodiester(s) and using 2‐methylpiperidine for Fmoc removal. After removal of the other protecting groups, the DCV group could be cleaved by mild hydrogenolysis giving the sY peptides in good yield.
The quaternary king : Azithromycin ( 1 ), which has improved pharmacological profiles compared with erythromycins, was the target of an enantioselective synthesis. All the stereogenic quaternary carbon centers were elaborated by a desymmetrization of 2‐substituted glycerols using a chiral imine/CuCl2 catalyst.
Piecing it together : The first total synthesis of naturally occurring diterpene pallavicinolide A was achieved. Notable features are highlighted by three key biomimetic transformations: a base‐promoted Grob fragmentation, a singlet oxygen oxidation, and an intramolecular Diels–Alder cycloaddition.
Chiral oxazaborolidines can be activated by N‐protonation using strong protic acids or by N‐coordination with AlBr3 to form very strong chiral Lewis acids. The resulting chiral boron electrophiles (see structure) are powerful chiral catalysts that effectively promote [4+2], [3+2], and [2+2]‐cycloaddition reactions with high enantioselectivity.
Division of labour : The rapid enzyme inactivation in the electroenzymatic synthesis of chiral alcohols has been the main obstacle for synthetic applications during the last two decades. The reasons for this inactivation have now been elucidated. The development of a water‐soluble polymeric mediator and the spatial separation of enzyme and mediator led to the first stable process and significantly improved catalyst utilisations (see picture).
Pinches like a crab : The utilization of guanidines as catalysts has been growing at a steady pace. They possess high pKa values and activate through dual hydrogen‐bonding modes of activation. This Focus Review highlights the development of chiral guanidine catalysts in asymmetric organic transformations.
No hurdle is too high : The regioselectivity and stereoselectivity of the halohydroxylation of non‐activated allenes are controlled by a remote sulfinyl group through anchimeric assistance (see scheme). The resulting halohydrines are excellent chiral targets for the preparation of optically pure propargylic alcohols and Baylis–Hillman‐type products.
Meeting the challenge : The zinc/amino alcohol catalyzed enantioselective addition of terminal alkynes to aldehydes is effective with both phenylacetylene and methyl propiolate, leading to chiral secondary propargyl alcohols with very high enantioselectivity (see scheme).
