Condensation Oligomers with Sequence Control but without Coupling Reagents and Protecting Groups via Asymmetric Hydroformylation and Hydroacyloxylation

Abstract

A novel strategy, free of coupling reagents and protection/deprotection steps, for the synthesis of oligo(2-hydroxyacid)s containing up to four monomer units with atom economy, sequence specificity, and control of stereocenter configuration is described. The strategy comprises an iterative application of the sequence asymmetric hydroformylation/oxidation/alkyne hydroacyloxylation that features catalytic, atom-economical C-C and C-O bond forming reactions. Asymmetric hydroformylation with Rh-bisdiazaphospholane catalyst introduces each stereocenter with high enantio- (ca. 93% e.e.), diastereo- (up to 25:1 d.r.), and regioselectivity (>50:1) at low catalyst loadings and mild pressures. The side chain in each monomer is tailored by choosing from a variety of readily available alkynes.

Recent Progress in the Design of Monodisperse, Sequence-Defined Macromolecules

“…Foarta and Landis reported an interesting approach towards sequence‐defined oligoesters with stereocontrol . Therefore, three reactions, namely asymmetric hydroformylation (AHF), oxidation and alkyne hydroacyloxylation, were performed iteratively.…”

“…Foarta and Landis reported an interesting approach towards sequencedefined oligoesters with stereocon trol. [48] Therefore, three reactions, namely asymmetric hydroformylation (AHF), oxidation and alkyne hydroa cyloxylation, were performed iteratively. Starting from acetic acid, the ruthenium catalyzed alkyne hydroacy loxylation was performed, whereby the corresponding (Z)enolester was obtained and a sidechain was intro duced by the alkynecompound.…”

“…Meier et al [14] 100 mg (5) oligo-amide high (SEC traces) 4.5 (15%) 3 Meier et al [13,46] 2.4 g (10) oligo-ester high (SEC traces) 10 (44%) 4 Hibi, Ouchi and Sawamoto [47] 66 mg (3) oligo-acrylate not clear (only MALDI spectrum) 3 (74%) 5 Foarta and Landis [48] 120 mg (4) oligo(2-hydroxy acid)…”

Metal-Catalyzed Intra- and Intermolecular Addition of Carboxylic Acids to Alkynes in Aqueous Media: A Review

“…Intra-and intermolecular processes are covered, The intermolecular addition of carboxylic acids to alkynes also presents enormous interest since the reaction products, i.e., enol esters (C or D in Scheme 2), are versatile building blocks in organic synthesis and material science. For example, to name just a few of their myriad applications, they are widely employed as mild acylating reagents [12,13], as monomers in diverse polymerization reactions [14][15][16], as substrates in asymmetric hydrogenation for the generation of enantioenriched alcohols [17][18][19], or as starting materials for different cross-coupling processes [20][21][22]. As for the cycloisomerization of alkynoic acids, a huge number of catalytic systems involving late transition metals have been described, with those based on ruthenium playing a prominent role [1][2][3][4][5].…”

The intermolecular hydro-oxycarbonylation of internal alkynes: current state of the art

“…Enol ester derivatives represent a relevant class of compounds widely used as mild acylating reagents, [1][2][3][4] as monomers for the production of diverse types of polymers and copolymers, [5][6][7][8] and as starting materials in a large variety of reactions, including asymmetric hydrogenation, [9][10][11][12] cycloaddition, [13][14][15][16] cyclization, [17][18][19][20] hydroformylation, [21][22][23] cross-coupling, [24][25][26][27] Michael addition, [28][29][30][31] aldol-type, [32][33][34] Mannich-type 35 and amide bond-forming processes, 36 to name a few. The enol ester motif is also found in a number of natural products with relevant biological properties.…”