Chiral Bronsted acid-catalyzed allylboration of aldehydes.
ABSTRACT: The catalytic enantioselective allylation of aldehydes is a long-standing problem of considerable interest to the chemical community. We disclose a new high-yielding and highly enantioselective chiral Brønsted acid-catalyzed allylboration of aldehydes. The reaction is shown to be highly general, with a broad substrate scope that covers aryl, heteroaryl, alpha,beta-unsaturated, and aliphatic aldehydes. The reaction conditions are also shown to be effective for the catalytic enantioselective crotylation of aldehydes. We believe that the high reactivity of the allylboronate is due to protonation of the boronate oxygen by the chiral phosphoric acid catalyst.
Project description:We report a straightforward and efficient Pd/enamine catalytic procedure for the direct asymmetric ?-allylation of branched aldehydes. The use of simple chiral amines and easily prepared achiral or racemic phosphoric acids, together with a suitable Pd-source resulted in a highly active and enantioselective catalyst system for the allylation of various ?-branched aldehydes with different allylic alcohols. The reported procedure could provide an easy access to both product antipodes. Furthermore, two possible orthogonal derivatizations of the enantioenriched aldehydes were performed without any decrease in enantioselectivity.
Project description:The catalytic asymmetric allylboration of cyclic imines with ?,?-disubstituted allylboronic acids provides products with adjacent stereocenters in high yield and stereoselectivity. Various electrophiles, including 3,4-dihydroisoquinolines and indoles, were prenylated in a fully stereodivergent fashion by switching the E/Z geometry of the allylboronate and/or the enantiomer of the BINOL catalyst. 3-Methylindole provided products with three adjacent stereocenters with high stereoselectivity in one synthetic operation.
Project description:Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration of acyl imines. The reaction requires 15 mol % (S)-3,3'-Ph2-BINOL as the catalyst and allyldiisopropoxyborane as the nucleophile. The reaction products are obtained in good yields (75-94%) and high enantiomeric ratios (95:5-99.5:0.5) for aromatic and aliphatic imines. High diastereoselectivities (diastereomeric ratio > 98:2) and enantioselectivities (enantiomeric ratio > 98:2) are obtained in the reactions of acyl imines with crotyldiisopropoxyboranes. This asymmetric transformation is directly applied to the synthesis of Maraviroc, the selective CCR5 antagonist with potent activity against HIV-1 infection. Mechanistic investigations of the allylboration reaction including IR, NMR, and mass spectrometry studies indicate that acyclic boronates are activated by chiral diols via exchange of one of the boronate alkoxy groups with activation of the acyl imine via hydrogen bonding.
Project description:Catalytic enantioselective allyl-allyl cross-coupling of a borylated allylboronate reagent gives versatile borylated chiral 1,5-hexadienes. These compounds may be manipulated in a number of useful ways to give functionalized chiral building blocks for asymmetric synthesis.
Project description:5-Substituted-2-furan methanols 1a-c are subject to enantioselective carbonyl allylation, crotylation and tert-prenylation upon exposure to allyl acetate, alpha-methyl allyl acetate, or 1,1-dimethylallene in the presence of an ortho-cyclometalated iridium catalyst modified by (R)-Cl,MeO-BIPHEP, (R)-C3-TUNEPHOS, and (R)-C3-SEGPHOS, respectively. In the presence of 2-propanol, but under otherwise identical conditions, the corresponding substituted furfurals 2a-c are converted to identical products of allylation, crotylation, and tert-prenylation. Optically enriched products of carbonyl allylation, crotylation, and reverse prenylation 3b, 4b, and 5b were subjected to Achmatowicz rearrangement to furnish the corresponding gamma-hydroxy-beta-pyrones 6a-c, respectively, with negligible erosion of enantiomeric excess.
Project description:Delta-methyl-substituted homoallylic alcohols 2 were prepared in 71-88% yield, E:Z >30:1 and 93% to >95% ee via BF(3).Et(2)O-promoted allylboration with alpha-Me-allylboronate 1. The origin of high (E)-selectivity is proposed.
Project description:We report the first catalytic enantioselective conjugate addition of allyl groups to α,β-unsaturated aldehydes. The chemistry exploits the visible-light-excitation of chiral iminium ions to activate allyl silanes towards the formation of allylic radicals, which are then intercepted stereoselectively. The underlying radical mechanism of this process overcomes the poor regio- and chemoselectivity that traditionally affects the conjugate allylation of enals proceeding via polar pathways. We also demonstrate how this organocatalytic strategy could selectively install a valuable prenyl fragment at the β-carbon of enals.
Project description:A highly enantioselective synthesis of (E)-delta-stannyl homoallylic alcohols 4 via aldehyde allylboration reactions of the double-chiral allylborane reagent 2a is reported. Allylborane 2a was generated from the hydroboration of commercially available allenylstannane 1 with ((d)Ipc)(2)BH at -40 to -20 degrees C followed by a kinetically controlled and highly diastereoselective 1,3-boratropic shift in intermediate 3a.
Project description:Allylic gem-dichlorides are shown to be efficient substrates for catalytic asymmetric allylboration of alkynes. The method employs a chiral NHC-Cu catalyst capable of generating in a single step chiral skipped dienes bearing a Z-alkenyl chloride, a trisubstituted E-alkenyl boronate and a bis-allylic stereocenter with excellent levels of chemo-, regio- enantio- and diastereoselectivity. This high degree of functionalization makes these products versatile building blocks as illustrated with the synthesis of several optically active compounds. DFT calculations support the key presence of a metal cation bridge ligand-substrate interaction and account for the stereoselectivity outcome.
Project description:The enantioselective crotylation of aldehydes with 1,2-diaminochlorocrotylsilane reagents is effectively catalyzed by Sc(OTf)(3). The one significant limitation on the utility of these reagents--substrate scope--has thus been addressed. The net result is the most comprehensive and highly practical method for enantioselective aldehyde crotylation yet advanced.