Cu-Catalyzed Enantioselective Borylative Desymmetrization of 1-Vinyl Cyclobutanols and Axial-to-Point Chirality Transfer in a Diastereoconvergent/Stereoretentive Allylation Scenery.

Cu-catalyzed asymmetric allylic borylation of 3,3'-disubstituted 1-vinylcyclobutan-1-ols renders axially chiral allylborane systems, with high asymmetric induction for both enantiomers, by precise selection of the cis or trans substrate. The enantioenriched alkylidenecyclobutanes served as chiral platform to prove the conceptually challenging transference of the axial-to-point chirality through two new stereocenters and one pseudoasymmetric carbon generated via diastereoconvergent allylation of aldehydes, without enantioselective erosion.

Role of curvature in acridone for 1 O2 oxidation of a natural product homoallylic alcohol: A novel iso-hydroperoxide intermediate.

A density functional theoretical (DFT) study is presented, implicating a 1 O2 oxidation process to reach a dihydrobenzofuran from the reaction of the natural homoallylic alcohol, glycocitrine. Our results predict an interconversion between glycocitrine and an iso-hydroperoxide intermediate [R(H)O+ -O- ] that provides a key path in the chemistry which then follows. Formations of allylic hydroperoxides are unlikely from a 1 O2 'ene' reaction. Instead, the dihydrobenzofuran arises by 1 O2 oxidation facilitated by a 16° curvature of the glycocitrine ring imposed by a pyramidal N-methyl group. This curvature facilitates the formation of the iso-hydroperoxide, which is analogous to the iso species CH2 I+ -I- and CHI2 + -I- formed by UV photolysis of CH2 I2 and CHI3 . The iso-hydroperoxide is also structurally reminiscent of carbonyl oxides (R2 C=O+ -O- ) formed in the reaction of carbenes and oxygen. Our DFT results point to intermolecular process, in which the iso-hydroperoxide's fate relates to O-transfer and H2 O dehydration reactions for new insight into the biosynthesis of dihydrobenzofuran natural products.

Copper-Catalyzed Enantioselective and Regiodivergent Allylation of Ketones with Allenylsilanes.

We report herein a regiodivergent and enantioselective allyl addition to ketones with allenylsilanes through copper catalysis. With the combination of CuOAc, a Josiphos-type bidentate phosphine ligand and PhSiH3 , allyl addition to a variety of ketones furnishes branched products in excellent enantioselectivities. The regioselectivity is completely reversed by employing the P-stereogenic ligand BenzP*, affording the linear products with excellent enantioselectivities and good Z-selectivities. The linear Z-product could be converted to E-product via a catalytic geometric isomerization of the Z-alkene group. The silyl group in the products could provide a handle for downstream elaboration.

Transition-Metal-Free Unusual Oxidative Cleavage of Homoallylic Alcohol and Its Application in the Upcycling of Terpene to Value-Added Chemicals.

A NaOtBu-O2 -mediated oxidative dehomologation of homoallylic alcohols into structurally different carboxylic acids through direct oxidative cleavage of either the C(sp2 )-C(sp2 ) or C(sp3 )-C(sp3 ) bond utilizing enolate chemistry was demonstrated. Furthermore, under transition-metal-free conditions, this protocol has been applied to convert terpene as biomass feedstock into value-added chemicals.

Iridium-Catalyzed 1,3-Rearrangement of Allylic Alcohols.

The allylic alcohol structural motif is prevalent in many important molecules and valuable building blocks. The rearrangement reaction is one of the most important transformations, however there are only a few reports for the 1,3-rearrangement of allylic alcohols. Herein, a 1,3-rearrangement of allylic alcohols catalyzed by an Ir(III) dihydride complex is described. This reaction could provide the corresponding less accessible allylic alcohols regio- and stereoselectively from readily available E/Z mixtures of the substrates. Furthermore, a tandem alkene isomerization followed by 1,3-rearrangement of homoallylic alcohols was also realized. In addition, this rearrangement reaction could be used to synthesize the natural product Navenone B. Mechanistic investigation indicated that the reaction pathway involved a π-allyl-Ir(V) intermediate and that the dihydride in the iridium catalyst acts as a hydrogen switch to modulate the valence of the iridium center.

KOtBu-catalysed α-homoallylic alkylation of acyclic amides with 1-aryl-1,3-dienes.

Herein, we report a KOtBu-catalysed α-homoallylic alkylation of acyclic amides with 1-aryl-1,3-dienes. With this transition metal-free and atom-economic protocol, a series of α-homoallylic alkylated acyclic amides were synthesized in good to excellent yields. This transformation is proposed to proceed through a cation-π interaction-based C-C bond formation from the in situ-generated potassium enolate with the diene unit.

Stereochemical Control via Chirality Pairing: Stereodivergent Syntheses of Enantioenriched Homoallylic Alcohols.

We report herein the development of stereodivergent syntheses of enantioenriched homoallylic alcohols using chiral nonracemic α-CH2 Bpin-substituted crotylboronate. Chiral phosphoric acid (S)-A-catalyzed asymmetric allyl addition with the reagent gave Z-anti-homoallylic alcohols with excellent enantioselectivities and Z-selectivities. When the enantiomeric acid catalyst (R)-A was utilized, the stereoselectivity was completely reversed and E-anti-homoallylic alcohols were obtained with high E-selectivities and excellent enantioselectivities. By pairing the chirality of the boron reagent with the catalyst, two complementary stereoisomers of chiral homoallylic alcohols can be obtained selectively from the same boron reagent. DFT computational studies were conducted to probe the origins of the observed stereoselectivity. These reactions generate highly enantioenriched homoallylic alcohol products that are valuable for rapid construction of polyketide structural frameworks.

Intermolecular C-H Activation at the Allylic/Benzylic and Homoallylic/Homobenzylic Positions of Cyclic Hydrocarbons by a Stable Divalent Silicon Species.

Direct activation of inert C(sp3 )-H bonds by main group element species is yet a formidable challenge. Herein, the dehydrogenation of cyclohexene and 1,2,3,4-tetrahydronaphthalene through the allylic/benzylic and homoallylic/homobenzylic C-H bond activation by cyclic (alkyl)(amino)silylene 1 in neat conditions is reported to yield the corresponding aromatic compounds. As for the reaction of cyclohexene, allylsilane 3 and 7-silanorbornene 4 were also observed, which could be interpreted as a direct dehydrogenative silylation reaction of monoalkenes at the allylic positions. Experimental and computational studies suggest that the dehydrogenation of cyclohexene at the homoallylic position was accomplished by a combination of silylene 1 and radical intermediates such as hydrosilyl radical INT1 or cyclohexenyl radical H, which are generated in the initial step of the reaction.

Regio- and Enantioselective Synthesis of Trifluoromethyl-Substituted Homoallylic α-Tertiary NH2 -Amines by Reactions Facilitated by a Threonine-Based Boron-Containing Catalyst.

A method for catalytic regio- and enantioselective synthesis of trifluoromethyl-substituted and aryl-, heteroaryl-, alkenyl-, and alkynyl-substituted homoallylic α-tertiary NH2 -amines is introduced. Easy-to-synthesize and robust N-silyl ketimines are converted to NH-ketimines in situ, which then react with a Z-allyl boronate. Transformations are promoted by a readily accessible l-threonine-derived aminophenol-based boryl catalyst, affording the desired products in up to 91 % yield, >98:2 α:γ selectivity, >98:2 Z:E selectivity, and >99:1 enantiomeric ratio. A commercially available aminophenol may be used, and allyl boronates, which may contain an alkyl-, a chloro-, or a bromo-substituted Z-alkene, can either be purchased or prepared by catalytic stereoretentive cross-metathesis. What is more, Z-trisubstituted allyl boronates may be used. Various chemo-, regio-, and diastereoselective transformations of the α-tertiary homoallylic NH2 -amine products highlight the utility of the approach; this includes diastereo- and regioselective epoxide formation/trichloroacetic acid cleavage to generate differentiated diol derivatives.

Diastereo- and Enantioselective Synthesis of (E)-δ-Boryl-Substituted anti-Homoallylic Alcohols in Two Steps from Terminal Alkynes.

We report the highly diastereo- and enantioselective preparation of (E)-δ-boryl-substituted anti-homoallylic alcohols in two steps from terminal alkynes. This method consists of a cobalt(II)-catalyzed 1,1-diboration reaction of terminal alkynes with B2 pin2 and a palladium(I)-mediated asymmetric allylation reaction of the resulting 1,1-di(boryl)alk-1-enes with aldehydes in the presence of a chiral phosphoric acid. Propyne, which is produced as the byproduct during petroleum refining, could be used as the starting material to construct homoallylic alcohols that are otherwise difficult to synthesize with high stereocontrol.

Indium-Mediated Allylation of Carbonyl Compounds in Ionic Liquids: Effect of Salts in Ionic Liquids.

The In-mediated allylation of carbonyl compounds can be performed in various types of solvents including ionic liquids. However, we have found that in [bmim][BF4] (where bmim = 1-butyl-3-methylimidazolium), the In-mediated coupling of crotyl bromide with benzaldehyde gives a complex mixture, and some additives, such as halides and amines, are crucial for the successful conversion to the corresponding γ-adduct. Instead, the addition of alcohols or water promotes the formation of the α-adduct. An asymmetric induction with up to 62% enantiomeric excess (ee) was observed employing cinchonidine as an additive in a binary solvent consisting of an ionic liquid and dichloromethane.

γ-, Diastereo-, and Enantioselective Addition of MEMO-Substituted Allylboron Compounds to Aldimines Catalyzed by Organoboron-Ammonium Complexes.

The first catalytic, broadly applicable, efficient, γ-, diastereo-, and enantioselective method for addition of O-substituted allyl-B(pin) compounds to phosphinoylimines (MEM=methoxyethoxymethyl, pin=pinacolato) is presented. The identity of the most effective catalyst and the optimal protecting group for the organoboron reagent were determined by consideration of the steric and electronic requirements at different stages of the catalytic cycle, namely, the generation of the chiral allylboronate, the subsequent 1,3-borotropic shift, and the addition step. Aryl-, heteroaryl-, alkenyl- and alkyl-substituted vicinal phosphinoylamido MEM-ethers were thus accessed in 57-92 % yield, 89:11 to >98:2 γ:α selectivity, 76:24-97:3 diastereomeric ratio, and 90:10-99:1 enantiomeric ratio. The method is scalable, and the phosphinoyl and MEM groups may be removed selectively or simultaneously. Utility is highlighted by enantioselective synthesis of an NK-1 receptor antagonist.

Reductive Carbocyclization of Homoallylic Alcohols to syn-Cyclobutanes by a Boron-Catalyzed Dual Ring-Closing Pathway.

The organoborane-catalyzed reductive carbocyclization of homoallylic alcohols has been developed by using hydrosilanes as reducing reagents to provide a range of 1,2-disubstituted arylcyclobutanes. The reaction proceeds in a cis-selective manner with high efficiency under mild conditions. Mechanistic studies, including deuterium scrambling and Hammett studies, and DFT calculations, suggest a dual ring-closing pathway.

Enantioselective Synthesis of (E)-δ-Boryl-Substituted anti-Homoallylic Alcohols Using Palladium and a Chiral Phosphoric Acid.

(E)-δ-Boryl-substituted anti-homoallylic alcohols are synthesized in a highly diastereo- and enantioselective manner from 1,1-di(boryl)alk-3-enes and aldehydes. Mechanistically, the reaction consists of 1) palladium-catalyzed double-bond transposition of the 1,1-di(boryl)alk-3-enes to 1,1-di(boryl)alk-2-enes, 2) chiral phosphoric acid catalyzed allylation of aldehydes, and 3) palladium-catalyzed geometrical isomerization from the Z to E isomer. As a result, the configurations of two chiral centers and one double bond are all controlled with high selectivity in a single reaction vessel.

Synthesis of Carbonates from Alcohols and CO2.

Alcohols are ubiquitous compounds in nature that offer modular building blocks for synthetic chemistry. Here we discuss the most recent development of different classes of alcohols and their coupling chemistry with carbon dioxide as to afford linear and cyclic carbonates, the challenges associated with their formation, and the potential of this chemistry to revive a waste carbon feed stock.

Practical and Broadly Applicable Catalytic Enantioselective Additions of Allyl-B(pin) Compounds to Ketones and α-Ketoesters.

A set of broadly applicable methods for efficient catalytic additions of easy-to-handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic α-ketoesters was developed. Accordingly, a large array of tertiary alcohols can be obtained in 60 to >98 % yield and up to 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of the small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh3 ) results in much higher enantioselectivity. With α-ketoesters, on the other hand, not only does the opposite hold true, since Me substitution leads to substantially higher enantioselectivity, but the sense of the selectivity is reversed as well.

A One-Pot Tandem Strategy in Catalytic Asymmetric Vinylogous Aldol Reaction of Homoallylic Alcohols.

Reported is a rationally-designed one-pot sequential strategy that allows homoallylic alcohols to be employed in a catalytic, asymmetric, direct vinylogous aldol reaction with a series of activated acyclic ketones, including trifluoromethyl ketones, γ-ketoesters, and α-keto phosphonates, in high yields (up to 95%) with excellent regio- and enantio-selectivity (up to 99% ee). This modular combination, including Jones oxidation and asymmetric organocatalysis, has satisfactory compatibility and reliability even at a 20 mmol scale, albeit without intermediary purification.

Stereodivergent Synthesis of Functionalized Tetrahydropyrans Accelerated by Mechanism-Based Allylboration and Bioinspired Oxa-Michael Cyclization.

A stereodivergent strategy enabled by bioinspired oxa-Michael cyclization was developed for the synthesis of functionalized tetrahydropyrans on the basis of the inherent symmetry in 1,3-diols, the symmetries of which were tunable by stereoselective hydroboration of an allene with a variety of alkylborane reagents and subsequent allylation of an aldehyde. The mechanism-based utilization of monoalkyl borane in the hydroboration and allylation cascade is unprecedented.

Lewis Acid Catalyzed Borotropic Shifts in the Design of Diastereo- and Enantioselective γ-Additions of Allylboron Moieties to Aldimines.

Catalytic allylboron additions to aldimines are presented for which small amounts of Zn(OMe)2 serve as the co-catalyst to accelerate allyl exchange and 1,3-borotropic shift processes. Low-yielding and moderately α- and diastereoselective reactions are thus turned into highly efficient γ-, diastereo-, and enantioselective transformations that exhibit considerable scope.