1,n‐Glycols as Dialdehyde Equivalents in Iridium‐Catalyzed Enantioselective Carbonyl Allylation and Iterative Two‐Directional Assembly of 1,3‐Polyols

Abstract

Nature's vast collection of polyketide natural products comprises thousands of compounds incorporating polyacetate derived 1,3-diol or higher 1,3-polyol substructures. While numerous protocols for the synthesis of these ubiquitous structural motifs have been advanced,[1] the iterative allylmetallation of aldehydes has found exceptionally broad use.

Evaluation of Chromane-Based Bryostatin Analogues Prepared via Hydrogen-Mediated C–C Bond Formation: Potency Does Not Confer Bryostatin-like Biology

“…18 The resulting C 2 -symmetric diol 3 is converted to the mono -TBS ether 4 . Deprotonation of 4 using sodium hydride followed by addition of the alkoxide to tert -butyl 3-bromo-2-fluorobenzoate delivers the S N Ar product 5 .…”

Direct Generation of Triketide Stereopolyads via Merged Redox-Construction Events: Total Synthesis of (+)-Zincophorin Methyl Ester

“…Indeed, as borne out in total syntheses of roxaticin, 7a bryostatin 7, 7b trienomycins A and F, 7c cyanolide A, 7d and 6-deoxyerythronolide B, 7e application of these methods have availed a “step-function increase” in efficiency – in each case, the synthetic route was significantly more concise than in any prior approach. 4b These studies brought to light an especially powerful protocol for the direct assembly of acetate- or propionate-based triketide stereopolyads 2a or 2b involving the bidirectional enantioselective double allylation 8a or anti -crotylation 8b of 1,3-diols 1a or 1b , respectively (eq. 1).…”

“…Key C-C bond formations include Breit’s method for the stereospecific substitution of α-hydroxy ester triflates with Grignard reagents to create the C22 stereocenter, 15 stereoselective Wittig olefination, 17 which defines the geometry of the trisubstituted olefin, and direct redox-triggered anti -crotylation of allylic alcohol 5 to form the C18-C19 stereodiad. 18 The synthesis of Fragment B takes advantage of the two-directional double anti -crotylation of 2-methyl-1,3-propane diol 1b to form adduct 2b , 7e,8b which directly establishes the triketide stereopolyad spanning C6-C10. Cross-metathesis is used to introduce the C12-C13 carbon atoms of allyl alcohol 8 , and hydroformylation is used to forge the C3-C4 bond of Fragment B .…”

“…7e,8b Iodoetherification defines the chirotopic nonstereogenic center of diol 2b at C8, and serves to differentiate the terminal olefin moieties. The pseudo - C -symmetric diol 2b is produced as a single enantiomer due to Horeau’s principle, 21 that is, the minor enantiomer of the intervening mono-adduct is converted to the pseudo - meso -diastereomer.…”

C(21)−C(40) of Tetrafibricin via Metal Catalysis: Beyond Stoichiometric Chiral Reagents, Auxiliaries, and Premetalated Nucleophiles

“…4 Tetrafibricin is a fibrinogen receptor inhibitor that embodies a unique array of functionality, including alternating 1,3-diol and 1,5-ene-diol substructures, a tetraenoic acid moiety and a primary amine. 5 Although biosynthetically related to oxo-polyene macrolide antibiotics such as lienomycin, 6 tetrafibricin lacks a macrocyclic structure and is inactive against Bacillus subtilis and Escherichia coli .…”