Stereocontrolled Synthesis of Polypropionate Fragments based on a Building Block Assembly Strategy using Lithiation‐Borylation Methodologies

Abstract

Polypropionates are important structural motifs in nature and are commonly made by iterative aldol or crotylation methodologies. Herein, an alternative strategy is presented in which stereochemically predefined building blocks, bearing appropriate functionality, are coupled together using a lithiation-borylation methodology with complete stereocontrol. The building blocks comprise lithiated carbamates acting as donors, and boronic esters acting as acceptors. The acceptor building blocks contain β-hydroxyl groups masked as silyl groups to avoid elimination of the boronate intermediates. Subsequent oxidation of both the boron and silyl moieties can then deliver an array of polypropionate fragments with full stereochemical control, including the synthetically challenging anti-anti isomers.

Synthesis and Configuration of a p‐Aminoacetophenonic Acid Isolated from Endophyte of the Mangrove Plant Kandel candel

“…The synthesis of (2 R ,4 R )‐ 1 is shown in Scheme . The commercially available ( S )‐Roche ester 4 was protected with TBSCl and reduced with DIBAL‐H to afford 5 according to the literature. Alcohol 5 was then subjected to Swern oxidation to give aldehyde 6 , which was directly used without any purification in the subsequent Evans[6a], [6b] aldol condensation with 7 to furnish the known[6b] aldol 8 .…”

Enantioselective Construction of Tertiary Boronic Esters by Conjunctive Cross‐Coupling

“…[6b] It should be noted that enantioselectivity can be modestly improved, although reactivity is diminished for some substrates,b yc onducting the reaction at room temperature (substrate 20). [14] However,aneffective solution was found in the use of compound 35 where the silyl group serves as am asked hydroxyl group. Lastly,i ts hould be noted that at risubstituted alkenylboron substrate did not deliver conjunctive coupling products with the current catalytic conditions.…”

“…Forr easons that we have not determined, b-oxygenation was not tolerated in the migrating group,possibly due to b-elimination of the resulting "ate" complex. [14] However,aneffective solution was found in the use of compound 35 where the silyl group serves as am asked hydroxyl group. [15] Conjunctive coupling followed by am odified Tamao-Fleming oxidation [16] furnished 37, ak nown precursor [17] to 38.A lso as depicted in Figure 1, the analgesic agent 41 was easily assembled by conjunctive coupling followed by amination [18] and conversion of the intermediate amine group to an isocyanate (40); intramolecular substitution [19] furnished the isoquinolone 41.…”

Ring‐Opening Lithiation–Borylation of 2‐Trifluoromethyl Oxirane: A Route to Versatile Tertiary Trifluoromethyl Boronic Esters

“…Analysis of the mixture revealed an 8:92 mixture of the desired boronic ester 3a and borinic ester 4a, the latter originating from 1,2-migration of one of the pinacol oxygen atoms (O-migration). Theu nusually strong preference for contra-thermodynamic O-migration over C-migration [15] provided one of many surprises at how the CF 3 group profoundly changes reactivity.A sthe reactivity of boronates can be strongly dependent on solvent, [16] we performed aT HF!toluene solvent exchange after formation of the boronate,w ith subsequent addition of TESOTf at À102 8 8C.…”