[1+1+1] Cyclotrimerization for the Synthesis of Cyclopropanes

The synthesis of small rings by functionalization of C(sp³)?H bonds remains a great challenge. We report for the first time a copper‐catalyzed [1+1+1] cyclotrimerization of acetophenone derivatives under mild reaction conditions. The reaction has a broad scope for the stereoselective synthesis of cyclopropanes by trimerization of acetophenone. The developed transformation is based on an extraordinary copper‐catalyzed cascade process that allows saturated carbocycles to be obtained for the first time by cyclotrimerization through functionalization of C(sp³)?H bonds. The cascade of sixfold C(sp³)?H bond functionalization allows the synthesis of cyclopropanes in a highly stereoselective approach.     

Highly Stereocontrolled Cyclopropanation by the 1,3-Elimination of a Bis(tributylstannyl)propanol Derivative

The highly stereoselective ring closure of gamma-hydroxystannyl derivative was realized. The aldol reaction of methyl bis(tributylstannyl)propionate (2) with aldehyde 5 proceeds stereoselectively to give (gamma-hydroxypropyl)stannane 6, and the cyclopropanation reaction of aldol product 6 proceeds smoothly in a highly stereoselective manner presumably via a W-shape transition state. The stannyl group on the cyclopropane ring can be converted into various electrophiles with a retention of configuration. As a result, various stereocontrolled 1,2,3-trisubstituted cyclopropanes can be obtained in high yields.     

Preparation of chiral cyclopropanes with a carbohydrate fragment from levoglucosenone

Levoglucosenone (a chiral α,β-unsaturated ketone derivative of cellulose) underwent stereoselective cyclopropanation with sulfonium ylides to form chiral trisubstituted cyclopropanes annulated with the carbohydrate moiety in high yields.     

Alkyne-based, highly stereo- and regioselective synthesis of stereodefined functionalized vinyl tellurides.

(Z)-beta-Aryltellurovinylphosphonates and (Z)-beta-aryltellurovinyl sulfones were synthesized via the highly stereoselective anti-hydrotelluration of 1-alkynylphosphonates and 1-alkynyl sulfones. The configurations of these compounds were characterized via 1H NMR spectra or NOESY experiments and by X-ray diffraction analysis; (E)-beta-aryltellurovinyl sulfones were obtained with the reaction of sodium aryltellurate with (E)-2-iodovinyl sulfones to confirm the stereochemistry of the above anti-hydrotelluration. When the tandem reaction of alkynes with diaryl ditellurides and sodium arylsulfinates was carried out in AcOH/H2O (4/1), the corresponding (E)-beta-aryltellurovinyl sulfones were obtained in one step in good yields. This reaction is highly regio- and stereoselective and proceeds by using arylsulfinate as the sulfonyl radical precursor and diaryl ditellurides as free radical acceptors. (E)-1-Iodo-2-aryltelluroalkenes can be obtained by the anti-addition of ArTeI with terminal alkynes in THF. The stereochemistry of compound 17b was also determined by X-ray diffraction analysis.     

Rhodium(I)-catalyzed addition of arylboronic acids to (benzyl-/arylsulfonyl)acetonitriles: efficient synthesis of (Z)-β-sulfonylvinylamines and β-keto sulfones

An efficient rhodium(I)-catalyzed addition of arylboronic acids to (benzyl-/arylsulfonyl)acetonitrile is described. Novel β-sulfonylvinylamine products are formed in a stereoselective fashion (Z-alkene). Upon hydrolysis, useful β-keto sulfones are obtained with a broad scope of aryl and sulfonyl substituents.     

A new entry to enantiopure polysubstituted cyclopropanes: stereoselective denitrogenation of sulfinylpyrazolines under Yb(OTf)3 catalysis

[Structure: see text] Chemoselective and completely stereoselective denitrogenation of optically pure pyrazolines, derived from 3-sulfinylfuran-2(5H)-ones, into cyclopropanes can be achieved under substoichiometric Yb(OTf)3 catalysis. Reactions evolve in almost quantitative yields with complete retention of the configuration at both carbons flanking the nitrogen atoms. The resulting enantiomerically pure polysubstituted cyclopropanes, containing up to five substituens, can be desulfinylated with Ra-Ni providing polysubstituted cyclopropanecarboxylic acid derivatives.     

Construction of stereodefined 1,1,2,2-tetrasubstituted cyclopropanes by acid catalyzed reaction of aryldiazoacetates and alpha-substituted acroleins

Michael-initiated ring closure of aryldiazoacetates and alpha-substituted acroleins under acid catalysis offers a unique opportunity for the stereoselective formation of various tetrasubstituted cyclopropanes.     

Asymmetric synthesis of 4-ethoxy-1-p-tolylsulfonyl-3,6-dioxabicyclo[3.1.0]hexan-2-ones

Optically pure sulfinylfuranones undergo oxidation at sulfur followed by a totally stereoselective epoxidation at the electron deficient double bond by treatment with MCPBA at room temperature to afford, in good yields, enantiomerically pure 4-ethoxy-5-alkyl-1-p-tolylsulfonyl-3,6-dioxabicyclo[3.1.0]hexan-2-ones. These epoxyfuranones are obtained along with cyclopropanefuranones by reaction of 4-ethoxy-6-p-tolylsulfinylfuro[3,4-c]pyrazolin-6-ones with MPCBA. In both cases, the formation of the sulfonyl epoxylactones takes place by oxidation of the sulfonylfuran-2(5H)-one resulting from the starting materials. This reaction is completely stereoselective (controlled by the configuration of C-5 of furanone) and results from the nucleophilic attack of the peroxycarboxylate generated by interaction of the reagent with weak basic centres at the substrates.     

Organocatalytic enantioselective cascade Michael-alkylation reactions: synthesis of chiral cyclopropanes and investigation of unexpected organocatalyzed stereoselective ring opening of cyclopropanes

The development of efficient methods for the facile construction of important molecular architectures is a central goal in organic synthesis. An unprecedented organocatalytic asymmetric cascade Michael-alkylation reaction of alpha,beta-unsaturated aldehydes with bromomalonates has been developed. The process, efficiently catalyzed by chiral diphenylprolinol TMS ether in the presence of base 2,6-lutidine, serves as a powerful approach to the preparation of synthetically and biologically important cyclopropanes in high levels of enantio- and diastereoselectivities. Remarkably, the power of the cascade process is fueled by its high efficiency of the production of two new C-C bonds, two new stereogenic centers, and one quaternary carbon center in one single operation, which otherwise is difficult to achieve by traditional strategies. Moreover, the beauty of the cascade process is further underscored by the nature of the product formation depending on the reaction conditions. With the alternation of base from 2,6-lutidine (1.1 equiv), which is effective for the cyclopropanations, to NaOAc (4.0 equiv), the spontaneous ring-opening of cyclopropanes takes place to lead to stereoselective (E) alpha-substituted malonate alpha,beta-unsaturated aldehydes. A possible reaction mechanism, which involves a Michael-alkylation-retro-Michael pathway, is proposed and verified by experimental studies. This investigation represents the first example of an organocatalyst-promoted ring opening of the cyclopropanes, whereas such reactions have been intensively explored by Lewis acid-based catalysis.     

Directing the Activation of Donor–Acceptor Cyclopropanes Towards Stereoselective 1,3‐Dipolar Cycloaddition Reactions by Brønsted Base Catalysis

The first stereoselective organocatalyzed [3+2] cycloaddition reaction of donor‐acceptor cyclopropanes is presented. It is demonstrated that by applying an optically active bifunctional Brønsted base catalyst, racemic di‐cyano cyclopropylketones can be activated to undergo a stereoselective 1,3‐dipolar reaction with mono‐ and polysubstituted nitroolefins. The reaction affords functionalized cyclopentanes with three consecutive stereocenters in high yield and stereoselectivity. Based on the stereochemical outcome, a mechanism in which the organocatalyst activates both the donor‐acceptor cyclopropane and nitroolefin is proposed. Finally, chemoselective transformations of the cycloaddition products are demonstrated.     

Highly regio- and stereoselective synthesis of polysubstituted cyclopropane compounds via the Pd(0)-catalyzed coupling-cyclization reaction of 2-(2',3'-allenyl)malonates with organic halides

A new method for highly regio- and stereoselective synthesis of polysubstituted cyclopropane compounds via the Pd(0)-catalyzed coupling-cyclization reaction of 2-(2',3'-allenyl)malonates with organic halides is described. In these reactions, the starting materials are easily available and the operation is convenient. The ratios of trans-isomer/cis-vinylic cyclopropanes are up to 98:2.     

Superbase-promoted rearrangement of oxiranes to cyclopropanes

Aryl- and alkenyl substituted oxiranes, when submitted to treatment with superbasic reagents, undergo a highly regio- and stereoselective rearrangement leading to cyclopropylmethanol derivatives. The process can also be applied to mono- and dihydroxy substituted substrates thus leading to polyhydroxylated cyclopropanes.     

Stereospecific 1,3‐Aminobromination of Donor–Acceptor Cyclopropanes

Sn(OTf)₂‐catalyzed 1,3‐aminobromination of donor–acceptor cyclopropanes with various sulfonyl amides or electron‐poor anilines and N ‐bromosuccinimide is reported. These experimentally straightforward reactions occurred with complete regio‐ and stereospecificity (for anilines) to give γ‐aminated α‐brominated malonic diesters in good to excellent yields (up to 98 %). These compounds served as valuable substrates for subsequent reactions to provide substituted azetidines and γ‐lactams in high yields.     

Synthesis and trimethylaluminum additions on gamma-hydroxy-delta-sulfinyl and sulfonyl enoates

[reaction: see text] The stereoselective synthesis of epimeric (R)- and (S)-gamma-hydroxy-delta-p-tolylsulfinyl (or sulfonyl) enoates is reported. Reaction with AlMe3 occurred exclusively at the ester group allowing a clean and high-yielding access to enantiopure 1,4-diols bearing a tertiary carbinol.     

Stereoselective synthesis of beta-substituted beta-amino sulfones and sulfonamides via addition of sulfonyl anions to chiral N-sulfinyl imines

[reaction: see text] A highly stereoselective synthesis of beta-amino sulfones and sulfonamides via addition of sulfonyl anions to chiral N-sulfinyl imines is described. The addition reaction proceeds in good yield (75-99%) and stereoselectivity.     

Asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones via bifunctional thiourea-mediated intramolecular cyclization

A novel asymmetric preparation of optically enriched 2-aryl-2,3-dihydroquinolin-4(1H)-ones has been developed. By installing a sulfonyl group on the nitrogen of the anilines and an ester function on the unsaturated ketones, an intramolecular organocatalytic cyclization took place readily in a stereoselective manner, resulting in the formation of dihydroquinolones with high enantioselectivity.     

A syn‐Selective Aza‐Aldol Reaction of Boron Aza‐Enolates Generated from N‐Sulfonyl‐1,2,3‐Triazoles and 9‐BBN‐H

A syn‐selective aza‐aldol reaction of boron aza‐enolates, generated from N‐sulfonyl‐1,2,3‐triazoles and 9‐BBN‐H, is reported. It provides a sequential one‐pot procedure for the stereoselective construction of 1,3‐amino alcohols, having contiguous stereocenters, starting from terminal alkynes.     

A Mild and Rapid Synthesis of (Z)‐β‐Sulfonyl Enoates from Sodium Sulfinates and Propargyl Esters

Water‐promoted sulfonylation of propargyl esters leading to highly regioselective and stereoselective formation of (Z)‐β‐sulfonyl enoates in excellent yields, by a simple, mild, rapid and environmentally benign reaction procedure is reported.     

Mechanism‐Driven Elaboration of an Enantioselective Bromocyclopropanation Reaction of Allylic Alcohols

A stereoselective bromocyclopropanation of allylic alcohols using dibromomethylzinc bromide is described. Spectroscopic studies to monitor the formation of transient intermediates not only led to the development of a more‐atom‐economical halocyclopropanation reaction, but also highlighted the unique role of ether additives in the process. The desired bromo‐substituted cyclopropanes were isolated in high yields and excellent diastereo‐ as well as enantioselectivities using readily available reagents.     

Polarity inversion of donor-acceptor cyclopropanes: disubstituted δ-lactones via enantioselective iridium catalysis

The coupling of carbonyl electrophiles at the donor position of donor-acceptor cyclopropanes is described, representing an inversion of polarity with respect to conventional reactivity modes displayed by these reagents. Specifically, upon exposure of donor-acceptor cyclopropanes to alcohols in the presence of a cyclometalated iridium catalyst modified by (S)-BINAP, catalytic C-C coupling occurs, providing enantiomerically enriched products of carbonyl allylation. Identical products are obtained upon isopropanol-mediated transfer hydrogenation of donor-acceptor cyclopropanes in the presence of aldehydes. The reaction products are directly transformed to cis-4,5-disubstituted δ-lactones.