Garner aldehyde

What is Garner aldehyde?

In 1984, Garner reported the synthesis of the Garner aldehyde, also known as 1,1-dimethylethyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate or N-Boc D-serinal acetonide, which is now commercially available. This compound is a versatile synthon widely used in organic synthesis due to its chemical and optical stability, high enantiopurity, and multifunctionality.

Garner aldehyde - 1,1-dimethylethyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate - N-Boc D-serinal acetonide
Garner aldehyde

The 4-formyl group in the Garner aldehyde can participate in most reactions that occur on regular aldehydes, such as the aldol reaction and Wittig reaction, introducing the contiguous amino-hydroxy functionality found in many natural products. The Garner aldehyde can be prepared in multigram quantities without partial racemization, but it has been reported to epimerize under Wittig reaction conditions when BuLi is used as the base. To enhance its stability under acidic conditions, the Garner aldehyde is protected by Cbz instead of Boc.

Garner aldehyde - general reaction scheme
Use of Garner aldehyde in a reaction

The Garner aldehyde can be used to prepare olefins in either the Z– or E-configuration, and allylation with allylindium reagent gives a diastereoselective product in anti-form. It has been applied in the synthesis of glycosyl amino acids, sphingosines, piperidine, and the proteasome inhibitor TMC-95A. The corresponding ester of the Garner aldehyde is called the Garner ester.

References

Garner, P. Stereocontrolled addition to a penaldic acid equivalent: an asymmetric of threo-β-hydroxy-L-glutamic acid. Tetrahedron Letters, 25(51), 5855-5858 (1984)
DOI: 10.1016/S0040-4039(01)81703-2

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