Organocatalyzed, enantioselective synthesis of bicyclo-[2.2.2]-octanes containing benzylic, all-carbon quaternary centers

Proline aryl sulfonamide-catalyzed, multi-component couplings have been developed for accessing densely functionalized [2.2.2] bicyclic ketones containing up to four contiguous chiral centers including an all-carbon benzylic quaternary center in high enantio- and diastereoselectivity. Application to the bicyclic core of the recently isolated alkaloid kopsonoline is illustrated.     

Catalytic enantioselective 1,2-diboration of 1,3-dienes: versatile reagents for stereoselective allylation

More with boron: The development of catalytic enantioselective 1,2-diboration of 1,3-dienes enables a new strategy for enantioselective carbonyl allylation reactions (see scheme). These reactions occur with outstanding levels of stereoselection and can be applied to both monosubstituted and 1,1-disubstituted dienes. The carbonyl allylation reactions provide enantiomerically enriched functionalized homoallylic alcohol products.     

Catalytic enantioselective aryl transfer: asymmetric addition of boronic acids to aldehydes using pyrrolidinylmethanols as ligands

Pyrrolidinylmethanols, easily accessible from readily available (S)-proline, were applied in zinc-catalyzed addition of arylboronic acids to aromatic aldehydes; the reaction was found to proceed in excellent yields and high enantioselectivities (up to 98% ee).     

Asymmetric synthesis of all-carbon quaternary spirocycles via a catalytic enantioselective allylic alkylation strategy

Rapid access to enantioenriched spirocycles possessing a 1,4-dicarbonyl moiety spanning an all-carbon quaternary stereogenic spirocenter was achieved using a masked bromomethyl vinyl ketone reagent. The developed protocol entails an enantioselective palladium-catalyzed allylic alkylation reaction followed by a one-pot unmasking/RCM sequence that provides access to the spirocyclic compounds in good yields and selectivities.     

Catalytic enantioselective synthesis of quaternary all-carbon stereogenic centers. Preparation of alpha,alpha'-disubstituted beta,gamma-unsaturated esters through Cu-catalyzed asymmetric allylic alkylations

[reaction: see text] Peptide-based chiral ligands, readily prepared from commercially available materials, are used to promote Cu-catalyzed asymmetric allylic alkylations of alpha,beta-unsaturated esters bearing a gamma-phosphate with various alkylzinc reagents. These transformations lead to the formation of alpha,alpha'-dialkyl-beta,gamma-unsaturated esters in high yields as well as high regio- (re) and enantioselectivities (ee).     

Highly diastereo- and enantioselective construction of phthalide-oxindole hybrids bearing vicinal quaternary chiral centers via an organocatalytic allylic alkylation

A diastereo- and enantioselective synthesis of phthalide-oxindole hybrids including congested adjacent quaternary chiral centers was demonstrated through a Lewis base catalyzed asymmetric allylic alkylation reaction of Morita–Baylis–Hillman carbonates of isatins and 3-cyanophthalides. The various hybrid molecules with two valuable pharmacophores-combined frameworks can be obtained in good to high diastereo- and enantioselectivities.     

亚甲胺叶立德参与的不对称1,3-偶极环加成构建含连续季碳中心的螺四氢吡咯衍生物

Cu(I)催化的亚甲胺叶立德和亚环丙基乙酸乙酯参与的不对称endo-1,3-偶极环加成反应,高效构建了多官能化、含有多个连续季碳中心的5-氮杂-[2,4]庚烷化合物.此反应具有广泛的底物适用性,α-取代的和α-非取代的亚甲胺叶立德和亚环丙基乙酸乙酯都能很好的参与反应,并以很高的产率、优秀的非对映选择性(95:5–98:2 d.r)和对映选择性(87%–98%ee)生成相应的在2,3,4位上含有连续季碳中心的螺四氢吡咯化合物.     

Palladium-catalyzed desulfinylative C-C allylation of Grignard reagents and enolates using allylsulfonyl chlorides and esters

2-Methylprop-2-ene-, prop-2-ene-, 1-methylprop-2-ene-, and (E)-but-2-enesulfonyl chlorides have been used as electrophilic partners in desulfinylative palladium-catalyzed C-C coupling with Grignard reagents and sodium salts of dimethyl malonate and methyl acetoacetate. Neopentyl alk-2-ene sulfonates can also be used as electrophilic partners in desulfinylative allylic arylations and allylic alkylations. The regioselectivity of the allylic arylation and alkylation depends on the nature of the catalyst. With PdCl₂(PhCN)₂, (E)-crotyl derivatives are formed in high regioselectivity using either 1-methylprop-2-ene- or (E)-but-2-enesulfonyl chloride.     

Efficient and scalable arylation of bicyclic lactones to form quaternary centers using conventional and microwave radiation

Easily accessible bicyclic lactones were efficiently arylated under modified Hartwig and Buchwald conditions to form quaternary aryl centers with complete cis selectivity. This series is notable in that unreactive substrates, including sterically-demanding ortho-substituted aromatic compounds, enjoyed significant rate acceleration under microwave radiation. Additionally, it was noted that the reactions could be accomplished under standard anaerobic conditions and on multi-gram scale.