Sequence‐Dependent Stereodivergent Allylic Alkylation/Fluorination of Acyclic Ketones

Abstract

The stereodivergent iridium‐catalyzed allylic alkylation and fluorination of acyclic ketones is described. α‐Pyridyl‐α‐fluoroketones with vicinal tertiary and quaternary stereocenters were obtained in moderate to excellent yields and stereoselectivities. Distinct from known stereodivergent synthesis, for which two different chiral catalysts are required in general, herein we report a sequence‐dependent stereodivergent synthesis. With only a single chiral Ir catalyst, all four possible stereoisomers of the products were prepared from the same starting materials by simply adjusting the sequence of asymmetric allylic alkylation and fluorination and varying the absolute configuration of the Ir catalyst.

Data-driven catalyst optimization for stereodivergent asymmetric synthesis of α-allyl carboxylic acids by iridium/boron hybrid catalysis

“…1a). Following this pioneering work, stereodivergent Ir-catalyzed allylic substitutions with prochiral enolates derived from ketones [21][22][23] , esters [24][25][26][27][28][29] and amides 30 were reported. As a target reaction of our data-driven catalyst optimization, we chose the catalytic asymmetric migratory -C-allylation of allyl esters 1 to afford -allyl carboxylic acids 2, using a combination of a chiral Ir complex catalyst [31][32][33] and a chiral boron (B) complex catalyst 34 (Fig.…”

“…Despite recent significant progress, previous stereodivergent -C-allylation of carbonyl compounds was limited to reactions affording aryl-substituted products (R 3 = Ar in Fig. 1a ) [20][21][22][23][24][25][26][27][28][29][30] . Indeed, when Carreira's conditions were applied to an aliphatic allylic alcohol (R 3 = Pr), desired β-aliphatic-substituted product was not obtained at all (see Supplementary Information section 9).…”

Stereodivergent entry to β-branched β-trifluoromethyl α-amino acid derivatives by sequential catalytic asymmetric reactions

“…With this background in mind, we envisioned an original stereodivergent 11 entry to β-branched AAs grounded on the dynamic stereoselective ring-opening of enantioselectively reduced Erlenmeyer–Plöchl azlactones ( Scheme 1(c) ). In contrast with catalytic hydrogenation, this formal hydrogenation of the azlactone olefin (a DHAA derivative) fixes the configurations of the two hydrogenated centres in different steps, lending itself to stereodivergency.…”

Stereodivergent catalytic asymmetric allylic alkylation (AAA)

“…More recently, You and co-workers have disclosed a distinct method for an overall diastereo-and enantiodivergent AAA between allylic carbonates and a-(2pyridyl) ketones, by coupling the catalytic C-C bond formation with a stoichiometric C-F bond formation using N-fluorobenzenesulfonimide (NFSI; Fig. 1d) [14]. Here, a sequence-dependent strategy has been developed: the use of a single-chiral Ir(I) complex, derived from phosphoramidite ligand (R,R)-5 [or (S,S)-5], in the presence of Brønsted bases -LiO t Bu (stoichiometric) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD, catalytic)-for the C-C bond formation; coupled with the use of Li-N(SiMe3)2 for the C-F bond formation.…”