Asymmetric Organocatalytic Stepwise [2+2] Entry to Tetra‐Substituted Heterodimeric and Homochiral Cyclobutanes

Abstract

An asymmetric synthesis of tetra-substituted cyclobutanes involving an organocatalytic, stepwise [2+2]-cycloaddition is described. The secondary-amine-catalyzed method allows for the hetero-dimerization of two different cinnamic-acid-derived sub-units, opening a novel one-step assembly to densely functionalized, head-to-tail coupled dimeric cyclobutanes in high enantiomeric excess. A series of selective synthetic interconversions in these sensitive cycloadducts is also described.

Synthesis of Nitrogen‐Containing Goniothalamin Analogues with Higher Cytotoxic Activity and Selectivity against Cancer Cells

“…There were af ew cases, however,i nw hich the substrates were inactive or unstable when heated at 110 8C( Figure 3). Unsurprisingly,s uccinimide (25), thiourea (26), and imidazole (27)w eren ot active in the presence of Pd 2 (dba) 3 and ligand L 1 (Scheme 5).…”

“…The synthesis of m ‐aminogoniothalamin ( 7 ) started from known aldehyde 9 , which was prepared in this study from m ‐nitrobenzoic acid (see Supporting Information). Compound 9 was used to prepare homoallylic alcohol 10 in the presence of allyltributylstannane.…”

DualPhos: a versatile, chemoselective reagent for two-carbon aldehyde to latent ( E )-alkenal homologation and application in the total synthesis of phomolide G

“…The intermediate latent alkenals may be cleaved immediately, revealing synthetically useful α,β-unsaturated aldehydes, or may be carried through a wide range of synthetic transformations intact. The robust nature of these latent alkenals contrasts sharply with dialkyl- and cyclic acetals obtained using standard reagents such as 4 and 5 [57,58], and permits a multitude of chemoselective transformations demonstrated in a new synthesis of the natural product macrolactone phomolide G. Further developments on the use of DualPhos and applications of the readily available alkenals in organocatalytic cascade sequences [59,60] are under active investigation in our laboratories.…”

Stereoretention in styrene heterodimerisation promoted by one-electron oxidants

“…Since the rst report of photochemical [2 + 2] cycloaddition accessing a 4-membered carbocycle by Liebermann in 1877, 6 the construction of 4membered cyclobutyl rings from photo-cycloaddition of alkenes has become arguably the most employed technique for cyclobutanation. [7][8][9][10][11][12] Cyclobutanation can now also be readily achieved via organocatalysis, [13][14][15] organometallic catalysis, 7,[16][17][18] as well as electrocatalysis [19][20][21][22] (Scheme 1). Until recently when the synthesis of substituted cyclobutanes could be realised via selective C-H functionalisation of unsubstituted cyclobutanes, [23][24][25][26] formal [2 + 2] cycloaddition remained the main strategy for the synthesis of complex, tetra-substituted cyclobutyl rings.…”