Diastereoselective nickel-catalyzed reductive couplings of aminoaldehydes and alkynylsilanes: application to the synthesis of d-erythro-sphingosine

Abstract

A strategy for the nickel-catalyzed reductive coupling of α-aminoaldehydes with silyl alkynes has been developed. The process proceeds with exceptional regiocontrol and diastereoselectivity. A variety of protected serinal derivatives were examined, and Garner aldehyde afforded the highest chemical yields of an easily deprotected coupling product. Use of a C-15 alkyne allowed a direct and efficient synthesis of D-erythro-sphingosine. With this silyl alkyne of interest, coupling reactions were most efficient when trace water was employed with THF as solvent. Using this procedure, D-erythro-sphingosine was prepared by a short sequence, wherein the alkene stereochemistry, C-3 stereocenter, and the C-3-C-4 carbon-carbon bond were all efficiently installed by the key nickel-catalyzed coupling process.

Metallacycle-mediated cross-coupling in natural product synthesis

“…111 Here, the authors employed their N -heterocyclic carbene-modified Ni-catalyzed process to couple Garner aldehyde 65 to TMS-alkyne 66 (Figure 27B). Overall, they achieved C3–C4 bond-formation with exquisite levels of regio- and stereocontrol en route to 67 .…”

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

“…Montgomery studied the nickel-catalyzed reductive additions of α-aminoaldehydes with silylalkynes ( Scheme 20 ) [ 76 ]. The reduction of TMS-alkyne 53 was performed with a trialkylsilane and a Ni(COD) 2 catalyst ligated with an in situ formed N-heterocyclic carbene.…”

Total Synthesis of 3-<i>epi</i>-Juruenolide C

“…Next, we attempted to perform the cross metathesis of the internal akene 6 with terminal alkene 7, which was prepared using the Wittig reaction of the known aldehyde 8 13) with triphenylphosphonium methylide (Chart 2, method A) or using the Kumada coupling 14) of commercially available 1-bromo-3,4-(methylenedioxy) benzene (9) with 7-octenylmagnesium bromide (Chart 2, method B). With both the alkenes 6 and 7 in hand, the cross metathesis between 6 and 7 was performed under optimized conditions (6 : 7 = 1 : 1, 40°C in Highlighted Paper selected by Editor-in-Chief 15,16) in the presence of 10 mol% Hoveyda-Grubbs second generation catalyst affording desired (E)-alkene 10 in 65% yield with excellent selectivity along with recovered 6 (20%).…”