Organocatalytic trans Phosphinoboration of Internal Alkynes

We report the first trans phosphinoboration of internal alkynes. With an organophosphine catalyst, alkynoate esters and the phosphinoboronate Ph₂P‐Bpin are efficiently converted into the corresponding trans‐α‐phosphino‐β‐boryl acrylate products in moderate to good yield with high regio‐ and Z‐selectivity. This reaction operates under mild conditions and demonstrates good atom economy, requiring only a modest excess of the phosphinoboronate. X‐ray crystallography experiments allowed structural assignment of the unprecedented and densely functionalized (Z)‐α‐phosphino‐β‐boryl acrylate products.     

Phosphinoboration of Diazobenzene: Intramolecular FLP Synthon for PN2B-Derived Heterocycles

Phosphinoboration of diazobenzene with Ph₂PBR′₂ cleanly affords products of the form Ph₂P(PhNNPh)BR′₂ ( 2 : R′₂=catechol, cat; 4 : R′₂=phenanthrenediol, quin) and shows evidence of Ph₂P(PhNNPh)Bpin 7 (pin: pinacol). The mechanism of these reactions was probed computationally and shown to proceed via intermediates involving a diazobenzene-adduct of the boron center of the PB reagent. The resulting PNNB species 2 and 4 are shown to be frustrated Lewis pairs (FLPs). Despite the presence of weakly Lewis acidic boron centers, these species react with diazobenzene. Additionally, the FLP reactivity of 2 was further probed with 4-phenyl-1,2,4-triazole-3,5-dione, 1,10-phenanthroline-5,6-dione, and benzyl azide to give unique five-, six-, and eight-membered heterocyclic rings. Thus, phosphinoboration provides a new avenue to FLPs in which donor and acceptor sites are linked by nitrogen atoms.     

Tuning Catalysts to Tune the Products: Phosphine‐Catalyzed Aza‐Michael Addition Reaction of Hydrazones with Allenoates

A new tunable phosphine‐catalyzed aza‐Michael β‐addition reaction between allenoates and various hydrazones has been developed. These reactions are most‐efficiently promoted by a catalytic amount of phosphine catalysts. These atom‐economical reactions are operationally simple and their corresponding adducts can been achieved in high yields and high selectivity under mild reaction conditions. Further studies revealed that different phosphine catalyst can produce different adducts from the same starting materials.     

Double Phosphinoboration of CO2: A Facile Route to Diphospha-Ureas

The reactions of CO₂ with a series of phosphinoboranes, including R₂PBpin (R=Ph, tBu; pin=pinacol), R₂PBMes₂ (R=Ph, tBu; Mes=2,4,6-Me₃-C₆H₂), and R₂PBcat (R=Ph, tBu, Mes; cat=catechol) are described. Although R₂PBpin and R₂PBMes₂ afford products of the form R₂PCO₂Bpin (R=Ph 1 , tBu 4 ) and R₂PCO₂BMes₂ (R=Ph 2 , tBu 3 ), respectively, R₂PBcat lead to further reaction affording the diphospha-ureas, (R₂P)₂CO (R=Ph 5 , tBu 6 , Mes 7 ), together with O(Bcat)₂. Computational studies provide insight into the mechanism, revealing an intermediate derived from double phosphinoboration of CO₂.     

Heterogeneous versus Homogeneous Copper(II) Catalysis in Enantioselective Conjugate‐Addition Reactions of Boron in Water

We have developed Cu^II‐catalyzed enantioselective conjugate‐addition reactions of boron to α,β‐unsaturated carbonyl compounds and α,β,γ,δ‐unsaturated carbonyl compounds in water. In contrast to the previously reported Cu^I catalysis that required organic solvents, chiral Cu^II catalysis was found to proceed efficiently in water. Three catalyst systems have been exploited: cat. 1: Cu(OH)₂ with chiral ligand L1 ; cat. 2: Cu(OH)₂ and acetic acid with ligand L1 ; and cat. 3: Cu(OAc)₂ with ligand L1 . Whereas cat. 1 is a heterogeneous system, cat. 2 and cat. 3 are homogeneous systems. We tested 27 α,β‐unsaturated carbonyl compounds and an α,β‐unsaturated nitrile compound, including acyclic and cyclic α,β‐unsaturated ketones, acyclic and cyclic β,β‐disubstituted enones, acyclic and cyclic α,β‐unsaturated esters (including their β,β‐disubstituted forms), and acyclic α,β‐unsaturated amides (including their β,β‐disubstituted forms). We found that cat. 2 and cat. 3 showed high yields and enantioselectivities for almost all substrates. Notably, no catalysts that can tolerate all of these substrates with high yields and high enantioselectivities have been reported for the conjugate addition of boron. Heterogeneous cat. 1 also gave high yields and enantioselectivities with some substrates and also gave the highest TOF (43 200 h^?1) for an asymmetric conjugate‐addition reaction of boron. In addition, the catalyst systems were also applicable to the conjugate addition of boron to α,β,γ,δ‐unsaturated carbonyl compounds, although such reactions have previously been very limited in the literature, even in organic solvents. 1,4‐Addition products were obtained in high yields and enantioselectivities in the reactions of acyclic α,β,γ,δ‐unsaturated carbonyl compounds with diboron 2 by using cat. 1, cat. 2, or cat. 3. On the other hand, in the reactions of cyclic α,β,γ,δ‐unsaturated carbonyl compounds with compound 2 , whereas 1,4‐addition products were exclusively obtained by using cat. 2 or cat. 3, 1,6‐addition products were exclusively produced by using cat. 1. Similar unique reactivities and selectivities were also shown in the reactions of cyclic trienones. Finally, the reaction mechanisms of these unique conjugate‐addition reactions in water were investigated and we propose stereochemical models that are supported by X‐ray crystallography and MS (ESI) analysis. Although the role of water has not been completely revealed, water is expected to be effective in the activation of a borylcopper(II) intermediate and a protonation event subsequent to the nucleophilic addition step, thereby leading to overwhelmingly high catalytic turnover.     

Palladacycle Catalyzed Asymmetric PH Addition of Diarylphosphines to N‐Enoyl Phthalimides

The first asymmetric phospha‐Michael addition of diarylphosphines to N‐enoyl phthalimides has been developed in the presence of a chiral palladacycle catalyst. A library of free chiral tertiary phosphine adducts were directly obtained with excellent yields and enantioselectivities. Products can be subsequently functionalized to afford β‐phosphinoamides, the direct preparation of which from cinnamides has been notoriously challenging.     

Copper‐Catalyzed Enantioselective β‐Boration of Acyclic Enones

Josi or Mandy? Asymmetric conjugate addition of diboron to acyclic enones catalyzed by copper affords chiral organoboronates that possess a boronate group at the β stereocenter with excellent chemical yields and enantioselectivities (see scheme). This method accommodates the structural variation of acyclic enones and provides access to highly functionalized chiral organoboronates in one step.

     

Me‐bipam for Enantioselective Ruthenium(II)‐Catalyzed Arylation of Aldehydes with Arylboronic Acids

Ligand design by‐pam : A ruthenium‐catalyzed asymmetric arylation of aldehydes with arylboronic acids has been developed, giving chiral diarylmethanols in good yields. The use of a chiral bidentate phosphoramidite ligand ((R,R)‐Me‐bipam) led to excellent enantioselectivities.

     

Visible-Light-Promoted Reaction of N-Hydroxyphthalimide Esters with Vinyl Boronic Pinacol Ester

A novel and easy-to-execute light-driven protocol for the preparation of alkyl boronic acid pinacol esters from vinyl boronate using N-hydroxyphthalimide esters as the potential precursor is described. In this photochemical protocol, the N-hydroxyphthalimide ester's fragmentation generates C-centered radicals, which undergo a radical Michael addition to vinyl boronic pinacol ester furnishing the desired products. A good substrate scope having various functionalities is presented and good to high yields are obtained.     

Rhodium‐Catalyzed Formation of Stereocontrolled Trisubstituted Alkenes from Baylis–Hillman Adducts

Efficient and general conditions for the formation of stereodefined trisubstituted alkenes by using the rhodium‐catalyzed reaction of unactivated Baylis–Hillman adducts with either organoboronic acids or potassium trifluoro(organo)borates are reported (see scheme).

     

Enantioselective Synthesis of Allylboronates and Allylic Alcohols by Copper‐Catalyzed 1,6‐Boration

Chiral secondary allylboronates are obtained in high enantioselectivities and 1,6:1,4 ratios by the copper‐catalyzed 1,6‐boration of electron‐deficient dienes with bis(pinacolato)diboron (B₂(pin)₂). The reactions proceed efficiently using catalyst loadings as low as 0.0049 mol %. The allylboronates may be oxidized to the allylic alcohols, and can be used in stereoselective aldehyde allylborations. This process was applied to a concise synthesis of atorvastatin, in which the key 1,6‐boration was performed using only a 0.02 mol % catalyst loading.     

Regio- and stereospecific addition of phosphines to cyanoacetylenes

Primary and secondary phosphines add regio- and stereospecifically to phenylcyanoacetylene and 4-hydroxy-4-methylpent-2-ynenitrile under mild conditions to form corresponding functionalized secondary and tertiary phosphines of Z-configuration in 70-91% yield. According to ESR and UV data, the addition of primary phosphines to phenylcyanoacetylene involves a single electron transfer process.     

Rhodium‐Catalyzed Cascade Reaction of 1,6‐Enynes Involving Addition,Cyclization, and β‐Oxygen Elimination

The reaction of arylboronic acids with 1,6‐enynes that contain an allylic ether moiety is catalyzed by a rhodium(I) complex to produce cyclopentanes with a tetrasubstituted exo olefin and a pendant vinyl group. The reaction is initiated by the regioselective addition of an arylrhodium(I) species to the carbon–carbon triple bond of the 1,6‐enyne. The resulting alkenylrhodium(I) compound subsequently undergoes intramolecular carborhodation of the allylic double bond in a 5‐exo‐trig mode. β Elimination of the methoxy group affords the cyclization product and the catalytically active methoxorhodium(I) species. The use of alkyl Grignard reagents instead of arylboronic acids as organometallic nucleophiles was also examined.     

Novel Polycarbonate Copolymer as Organocatalyst for Aldol and Michael Reaction

A new polymeric organocatalyst is prepared by free radical copolymerization of allyl diglycol carbonate (ADC) and Boc-protected allyl prolinate and evaluated as a chiral catalyst for aldol and Michael reaction.