Practical, Scalable, High-Throughput Approaches to η³-Pyranyl and η³-Pyridinyl Organometallic Enantiomeric Scaffolds Using the Achmatowicz Reaction

Abstract

A unified strategy for the high-throughput synthesis of multigram quantities of the eta(3)-oxopyranyl- and eta(3)-oxopyridinylmolybdenum complexes TpMo(CO)(2)(eta(3)-oxopyranyl) and TpMo(CO)(2)(eta(3)-oxopyridinyl) is described (Tp = hydridotrispyrazolylborato). The strategy uses the oxa- and aza-Achmatowicz reaction for the preparation of these organometallic enantiomeric scaffolds, in both racemic and high enantiopurity versions.

Chemoenzymatic Approach to Optically Active 4‐Hydroxy‐5‐alkylcyclopent‐2‐en‐1‐one Derivatives: An Application of a Combined Circular Dichroism Spectroscopy and DFT Calculations to Assignment of Absolute Configuration

“…The carbinol (±)‐ 3a (Scheme ) was prepared by NaBH 4 – MeOH reduction of 2‐acylfuran following the reported procedure . For the preparation of carbinols (±)‐ 3b and (±)‐ 3c with purity over 99%, some modifications of the reported procedures proved necessary: (±)‐ 3b was prepared in reaction of isopropylmagnesium bromide and furfural in diethyl ether at –78°C [at higher temperatures (2‐furyl)methanol was formed as a by‐product], (±)‐ 3c was obtained by coupling of 2‐lithiofuran with pivalic chloride followed by NaBH 4 reduction of the intermediate 2‐furyl tert ‐butyl ketone.…”

Organometallic Enantiomeric Scaffolding: General Access to 2-Substituted Oxa- and Azabicyclo[3.2.1]octenes via a Brønsted Acid Catalyzed [5 + 2] Cycloaddition Reaction

“…1 Short, scalable, and practicable methods of synthesis of high enantiopurity scaffolds TpMo(CO) 2 (3-oxopyranyl) 1 and TpMo(CO) 2 (3-oxopyridinyl) 2 have been developed, 2 and from these simple scaffolds a diverse array of biologically relevant heterocyclic core structures can be obtained in an enantiocontrolled fashion ( Figure 1). [3][4][5][6][7][8][9][10][11][12][13][14][15] The synthetic elaboration of the 3-oxopyranyl and -pyridinyl complexes 1 and 2 often proceeds via the 5-substituted η 3 -pyranyl and -pyridinyl scaffolds 5 and 6 shown in Figure 2.…”

Organometallic Enantiomeric Scaffolding: A Strategy for the Enantiocontrolled Construction of Regio- and Stereodivergent Trisubstituted Piperidines from a Common Precursor

“…Rather than beginning with a substituent-specific scaffold, the new strategy relies on the N -protected 5-oxo-η 3 -dihydropyridinyl scaffold 2 , a general enantiomeric platform (Scheme 3) that is easily prepared using an aza-Achamatowicz tactic. 9 …”