Chemo‐ and Regioselective Rhodium(I)‐Catalyzed [2+2+2] Cycloaddition of Allenynes with Alkynes

A highly chemo‐ and regioselective partially intramolecular rhodium(I)‐catalyzed [2+2+2] cycloaddition of allenynes with alkynes is described. A range of diverse polysubstituted benzene derivatives could be synthesized in good to excellent yields, in which the allenynes served as synthetic equivalent to the diynes. A high regioselectivity could be observed when allenynes were treated with unsymmetrical alkynes.     

Rhodium‐Catalyzed Asymmetric Synthesis of Silicon‐Stereogenic Dibenzosiloles by Enantioselective [2+2+2] Cycloaddition

A rhodium‐catalyzed asymmetric synthesis of silicon‐stereogenic dibenzosiloles has been developed through a [2+2+2] cycloaddition of silicon‐containing prochiral triynes with internal alkynes. High yields and enantioselectivities have been achieved by employing an axially chiral monophosphine ligand, and the present catalysis is also applicable to the asymmetric synthesis of a germanium‐stereogenic dibenzogermole. Preliminary studies on the optical properties of these compounds are also described.     

Catalytic Asymmetric Synthesis of Cyclopentyl β‐Amino Esters by [3+2] Cycloaddition of Enecarbamates with Electrophilic Metalloenolcarbene Intermediates

Chiral cyclopentyl β‐amino esters are formed catalytically by [3+2] cycloaddition reactions of enecarbamates with electrophilic metalloenolcarbenes in high yield with up to 98 % ee and excellent diastereocontrol. Use of β‐silyl‐substituted enoldiazoacetates with a chiral dirhodium catalyst and trans‐β‐arylvinylcarbamates are optimal for this transformation, which occurs with hydrogen‐bond association between the vinylcarbamate and the intermediate metalloenolcarbene. Reductive conversion of the protected amino esters forms highly functionalized cyclopentyl β‐amino acids and 3‐aminocyclopentanones.     

Stereospecific and Stereoselective Rhodium(I)‐Catalyzed Intramolecular [2+2+2] Cycloaddition of Allene‐Ene‐Ynes: Construction of Bicyclo[4.1.0]heptenes

Treatment of the allene‐ene‐yne substrates with [{RhCl(CO)₂}₂] effected the intramolecular [2+2+2]‐type ring‐closing reaction to produce various of tri‐ and tetracyclic derivatives containing a cyclopropane ring. The reaction is highly stereoselective as well as stereospecific with good to excellent yields.     

Synthesis of Tricyclic Fused 3‐Aminopyridines through Intramolecular CoI‐Catalyzed [2+2+2] Cycloaddition between Ynamides,Nitriles, and Alkynes

Three‐ring circus : An expedient route to tricyclic fused 2‐trimethylsilyl‐3‐aminopyridines exhibiting unprecedented skeletons is described. The key step is a very efficient cobalt‐catalyzed [2+2+2] cycloaddition of a polyunsaturated compound displaying an ynamide, an alkyne, and a nitrile functionality (see picture).

     

Rhodium‐Catalyzed Intramolecular [5+2] Cycloaddition of Inverted 3‐Acyloxy‐1,4‐enyne and Alkyne: Experimental and Theoretical Studies

By switching the position of the alkene and alkyne, a new type of 3‐acyloxy‐1,4‐enyne (ACE) five‐carbon building block was developed for Rh‐catalyzed intramolecular [5+2] cycloaddition. An electron‐withdrawing acyl group on the alkyne termini of the ACE was essential for a regioselective 1,2‐acyloxy migration. This new method provided bicyclic [5.3.0]decatrienes that are different from previous methods because of the positions of the alkenes and the acyloxy group. Multiple mechanistic pathways become possible for this new [5+2] cycloaddition and they are investigated by computational studies.     

Rhodium(I)‐Catalyzed Intramolecular Carbonylative [2+2+1] Cycloaddition of Bis(allene)s: Bicyclo[6.3.0]undecadienones and Bicyclo[5.3.0]decadienones

No templates needed : The title reaction makes it easy to construct the bicyclo[6.3.0]undecadienone framework in high yields (see scheme). A template effect is not required to achieve this ring‐closing reaction efficiently. The present method can be applied to the construction of bicyclo[5.3.0] and bicyclo[4.3.0] ring systems. Ts=p‐toluenesulfonyl.

     

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.     

Ruthenium‐Catalyzed [2+2+2] Cycloaddition of 1,6‐Enynes and Unactivated Alkynes: Access to Ring‐Fused Cyclohexadienes

The [2+2+2] intermolecular carbocyclization reactions between 1,6‐enynes and alkynes catalyzed by [RuCl(cod)(Cp*)] (cod=1,5‐cyclooctadiene, Cp*=pentamethylcyclopentadienyl) are reported to provide bicyclohexa‐1,3‐dienes. The presented reaction conditions are compatible with internal and terminal alkynes and the chemo‐ and regioselectivity issues are controlled by the presence of substituents at the propargyl carbon center of the alkyne(s) partner(s).     

Total Synthesis of Indolizidine Alkaloid (−)‐209D: Overriding Substrate Bias in the Asymmetric Rhodium‐Catalyzed [2+2+2] Cycloaddition

CO! You had me at hello : The use of chiral biphenyl‐based phosphoramidite ligands on rhodium provides an efficient [2+2+2] cycloaddition between terminal alkyl alkynes and alkenyl isocyanates (see scheme). The cycloaddition proceeds through a CO migration pathway, and facilitates a rapid four‐step asymmetric synthesis of indolizidine (?)‐209D.

     

[2+2] Photocycloaddition of 3‐Alkenyloxy‐2‐cycloalkenones: Enantioselective Lewis Acid Catalysis and Ring Expansion

By application of substoichiometric amounts (50 mol %) of a chiral Lewis acid, the intramolecular [2+2] photocycloaddition of the title compounds was achieved with high enantioselectivity (up to 94 % ee). Upon cleavage of the cyclobutane ring the resulting tricyclic products underwent ring‐expansion reactions under acidic conditions and formed anellated seven‐ or eight‐membered‐ring systems without racemization. The ring expansion could be combined with a diastereoselective reduction (triethylsilane) or allylation (allyltrimethylsilane) upon BF₃ catalysis (48–87 % yield).     

Metal‐Free Synthesis of Highly Substituted Pyridines by Formal [2+2+2] Cycloaddition under Mild Conditions

The synthesis of pyridines through direct intermolecular cycloaddition of alkynes and nitriles is a contemporary challenge in organic synthesis. A Brønsted acid mediated formal [2+2+2] cycloaddition of heteroalkynes and nitriles was developed that proceeds under mild conditions. This constitutes a modular approach to highly substituted pyridine cores.