The
first systematic study of simple nitronate nucleophiles in
iridium-catalyzed allylic alkylation is described. Using a tol-BINAP-modified
π-allyliridium C,O-benzoate
catalyst, α,α-disubstituted nitronates substitute racemic
branched alkyl-substituted allylic acetates, thus providing entry
to β-stereogenic α-quaternary primary amines. DFT calculations
reveal early transition states that render the reaction less sensitive
to steric effects and distinct trans-effects of diastereomeric chiral-at-iridium
π-allyl complexes that facilitate formation of congested tertiary–quaternary
C–C bonds.
Cyclometallated iridium-PhanePhos complexes generated in situ from [Ir(cod)Cl] 2 and (R)-PhanePhos catalyze 2-propanol-mediated reductive couplings of 2-substituted dienes with oxetanone and Nacyl-azetidinones to form branched homoallylic oxetanols and azetidinols with excellent control of regio-and enantioselectivity without CÀ C cleavage of the strained ring via enantiotopic π-facial selection of transient allyliridium nucleophiles. This work represents the first systematic study of enantioselective additions to symmetric ketones.
The first use of 1,4-pentadiene and 1,5-hexadiene as
allylmetal
pronucleophiles in regio-, anti-diastereo-, and enantioselective
carbonyl addition from alcohol proelectrophiles is described. As corroborated
by deuterium labeling experiments, primary alcohol dehydrogenation
delivers a ruthenium hydride that affects alkene isomerization to
furnish a conjugated diene, followed by transfer hydrogenative carbonyl
addition. Hydrometalation appears to be assisted by the formation
of a fluxional olefin-chelated homoallylic alkylruthenium complex II, which exists in equilibrium with its pentacoordinate η1 form to enable β-hydride elimination. This effect confers
remarkable chemoselectivity: while 1,4-pentadiene and 1,5-hexadiene
are competent pronucleophiles, higher 1,n-dienes
are not, and the olefinic functional groups of the products remain
intact under conditions in which the 1,4- and 1,5-dienes isomerize.
A survey of halide counterions reveals iodide-bound ruthenium-JOSIPHOS
catalysts are uniquely effective in these processes. This method was
used to prepare a previously reported C1–C7 substructure of
(−)-pironetin in 4 vs 12 steps.
Cyclometallated iridium-PhanePhos complexes generated in situ from [Ir(cod)Cl] 2 and (R)-PhanePhos catalyze 2-propanol-mediated reductive couplings of 2-substituted dienes with oxetanone and Nacyl-azetidinones to form branched homoallylic oxetanols and azetidinols with excellent control of regio-and enantioselectivity without CÀ C cleavage of the strained ring via enantiotopic π-facial selection of transient allyliridium nucleophiles. This work represents the first systematic study of enantioselective additions to symmetric ketones.
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