Synthesis of Spirocyclic C‐Arylglycosides and ‐Ribosides by Ruthenium‐Catalyzed Cycloaddition

Spirocyclic C‐arylglycosides were synthesized from the appropriately protected δ‐gluconolactones. Addition of lithium acetylide followed by glycosylation with 3‐(trimethylsilyl)propargyl alcohol converted the δ‐gluconolactones into silylated diynes. After desilylation, subsequent ruthenium‐catalyzed cycloaddition of the resultant diynes with alkynes or chloroacetonitrile gave spirocyclic C‐arylglycosides in good yields and selectivity. This strategy was also extended to the synthesis of spirocyclic C‐arylribosides from the known γ‐ribonolactone derivative. Moreover, silver‐catalyzed iodination of the sugar diynes followed by ruthenium‐catalyzed cycloaddition with acetylene delivered spirocyclic C‐iodophenylglycosides and ‐ribosides, which were subjected to palladium‐catalyzed C? C bond‐forming reactions and copper‐catalyzed coupling with nitrogen heterocycles to lead to various derivatives.     

1,3‐Dipolar Cycloaddition of Nitrones with Electron‐rich Alkenes Catalyzed by Yb(OTf)3

1,3‐Dipolar cycloaddition of nitrones with ethyl vinyl ether or 2,3‐dihydrofuran proceeds smoothly in the presence of a catalytic amount (10 mol%) of ytterbium triflate to afford isoxazolidines and dicyclic isoxazolidine respectively with good yields and high stereoselectivity.     

Alkenyl Arenes as Dipolarophiles in Catalytic Asymmetric 1,3‐Dipolar Cycloaddition Reactions of Azomethine Ylides

The use of alkenyl arenes as dipolarophiles in the catalytic asymmetric 1,3‐dipolar cycloaddition of azomethine ylides is reported. Under appropriate reaction conditions with a Cu^I or Ag^I catalyst either the exo or the endo adduct was obtained with high stereoselectivity. This process provides efficient access to highly enantiomerically enriched 4‐aryl proline derivatives. The observed results are compatible with the blockage of one prochiral face of the 1,3‐dipole, as well as with the efficient transmission of electrophilicity towards the terminal carbon atom of the dipolarophile. This polarization results in a change from a concerted to a stepwise mechanism.     

Enantioselective Intramolecular [2+2] Photocycloaddition Reactions of 4‐Substituted Coumarins Catalyzed by a Chiral Lewis Acid

Eight coumarins, which carry a terminal alkene tethered by a CH₂XCH₂ group to their 4‐position (X=CH₂, CMe₂, O, S, NBoc, NZ, NTs, NBn), were synthesized in overall yields of 51–80 %. Starting materials for the syntheses were either commercially available 4‐hydroxycoumarin or 4‐formylcoumarin. The intramolecular [2+2] photocycloaddition of these coumarins gave diastereoselectively products with a tetracyclic 3,3a,4,4a‐tetrahydro‐1H‐cyclopenta[2,3]cyclobuta[1,2‐c]chromen‐5(2H)‐one skeleton. Direct irradiation at λ=300 nm in dichloromethane (c=10 mM ) led to product formation in good yields for most substrates, presumably via a singlet excited state intermediate. Due to the low coumarin absorption at λ >350 nm the photocycloaddition was slow upon irradiation at λ=366 nm. Addition of a chiral oxazaborolidine‐based Lewis acid (50 mol %) increased the reaction rate at λ=366 nm and induced a significant enantioselectivity in the [2+2] photocycloaddition. Six out of eight coumarin substrates (X=CH₂, CMe₂, O, NBoc, NZ, NTs) gave the respective products in yields of 72–96 % and with 74–90 % enantiomeric excess (ee) upon irradiation in dichloromethane (c=20 mM ) at ?75 °C. The Lewis acid presumably acts by coordination to the coumarin carbonyl oxygen atom, which leads to a bathochromic shift (redshift) of the UV absorption and which increases the singlet state lifetime. A second electrostatic interaction of the hydrogen atom at C3 with the oxygen atom of the oxazaborolidine is likely.     

Synthesis of Spirocyclic and Tricyclic Isoxazoline via 1,3‐Dipolar Cycloaddition Reactions

1,3‐Dipolar cycloadditions of the bicyclic monoterpenes (S)‐(?)‐camphene ( 1 ), (R)‐(+)‐a‐pinene ( 2 ), and (S)‐(?)‐b‐pinene ( 3 ) with aryl and heteroaryl nitrile oxides afforded new spirocyclic and tricyclic isoxazoline derivatives 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 whose biological activities were evaluated in bioassay studies.     

Asymmetric “Acetylenic” [3+2] Cycloaddition of Nitrones Catalyzed by Cationic Chiral PdII Lewis Acid

Highly enantioselective [3+2] cycloaddition of ynones and nitrones has been developed. Very bulky ligand, DTBM‐SEGPHOS, was used for an effective asymmetric induction over distal reaction centers on the linear ynone dipolarophile and for prevention of Pd^II catalyst deactivation by coordination of the nitrones. The reaction has wide scope of substrates in both ynones and nitrones.     

Stereoselective Ag‐Catalyzed 1,3‐Dipolar Cycloaddition of Activated Trifluoromethyl‐Substituted Azomethine Ylides

A silver‐catalyzed 1,3‐dipolar cycloaddition of fluorinated azomethine ylides and activated olefins is reported. The reaction offers a straightforward and atom‐economical procedure for the preparation of fluorinated pyrrolidines. Broad scope and high levels of diastereoselectivity have been achieved simply by using AgOAc/PPh₃ as the catalyst system. The high efficiency of the cycloaddition relies on the presence of a metal‐coordinating group on the imine moiety, such as an ester or heteroaryl group. The asymmetric version of the cycloaddition has been developed by using Taniaphos as a chiral ligand.     

Lewis Acid Catalyzed Cascade Reactions of 1,6‐Diynes and 1,6‐Enynes with Vinylidenecyclopropanes

Cascade reactions : Lewis acid catalyzed cascade reactions of 1,6‐diynes and 1,6‐enynes with arylvinylidenecyclopropanes produce polycyclic compounds and isopropylidene‐3,3‐diarylcyclobut‐1‐enylmethyl derivatives (see scheme) in good to high yields along with a PtCl₂‐catalyzed cyclization and a Cu(OAc)₂ ? H₂O‐catalyzed Eglinton coupling reaction.

     

Lewis Acid Catalyzed Selective Reactions of Donor–Acceptor Cyclopropanes with 2‐Naphthols

Lewis acid‐catalyzed reactions of 2‐substituted cyclopropane 1,1‐dicarboxylates with 2‐naphthols is reported. The reaction exhibits tunable selectivity depending on the nature of Lewis acid employed and proceed as a dearomatization/rearomatization sequence. With Bi(OTf)₃ as the Lewis acid, a highly selective dehydrative [3+2] cyclopentannulation takes place leading to the formation of naphthalene‐fused cyclopentanes. Interestingly, engaging Sc(OTf)₃ as the Lewis acid, a Friedel–Crafts‐type addition of 2‐naphthols to cyclopropanes takes place, thus affording functionalized 2‐naphthols. Both reactions furnished the target products in high regioselectivity and moderate to high yields.