Lewis Acid‐Catalyzed [3+2] Cycloaddition of Donor‐Acceptor Cyclopropanes and Enamines: Enantioselective Synthesis of Nitrogen‐Functionalized Cyclopentane Derivatives

A straightforward and efficient method for the synthesis of nitrogen‐functionalized cyclopentane derivatives via [3+2] cycloaddition of enamines with donor‐acceptor cyclopropanes in the presence of catalytic amounts of various Lewis acids at room temperature has been developed; furthermore, the corresponding β‐amino acid was synthesized by monodecarboxylation and hydrogenolysis. An enantioenriched synthesis of nitrogen‐functionalized cyclopentane derivatives through dynamic kinetic asymmetric transformation of racemic donor‐acceptor cyclopropanes has also been achieved employing a copper complex [Cu(OTf)₂‐ L1 ] as the catalyst affording an enantiomeric ratio up to 8:1.

     

Enantiomerically Pure Cyclopropane Building Blocks: Synthesis and Transformations of 2‐Iodocyclopropylboronic Esters

Enantiomerically pure 2‐iodocyclopropylboronic esters 6 and 8 have been synthesized from the readily available allylic alcohol 2 via an oxidation‐radical decarboxylation sequence. These unique building blocks have been demonstrated to be versatile intermediates for a consecutive Suzuki‐coupling with aryl‐, heteroaryl‐, alkenyl‐, and cyclopropylboron derivatives (1 example each).     

Suzuki–Miyaura Cross‐Coupling of 2‐Nitroarenediazonium Tetrafluoroborates: Synthesis of Unsymmetrical 2‐Nitrobiphenyls and Highly Functionalized Carbazoles

The Suzuki–Miyaura cross‐coupling of 2‐nitrodiazonium tetrafluoroborate salts with substituted boronic acids is an effective and efficient means of preparing highly functionalized 2‐nitrobiphenyls in modest to excellent yield under extremely mild reaction conditions. Cross‐coupling of 2‐nitrodiazonium tetrafluoroborate salts with ortho‐methoxy‐ and benzyloxyphenylboronic acids was also demonstrated leading to the ortho‐ortho‐2‐nitrobiphenyls. Reductive cyclization of the 2‐nitrobiphenyl products allows for the overall three‐step synthesis of uniquely substituted carbazoles from readily available 2‐nitroanilines. The methodology was further highlighted by the short total synthesis of the carbazole alkaloids clausine V, N, C, and glycoborine.     

Stereoselective Cascade Reactions of Donor–Acceptor Cyclopropanes with m‐N,N‐Dialkylaminophenyl α,β‐Unsaturated Carbonyls: Diastereoselective Synthesis of cis‐ and trans‐Tetralins

The ytterbium(III) triflate [Yb(OTf)₃]‐catalyzed diastereoselective cascade reaction of m‐N,N‐dimethylaminophenyl α,β‐unsaturated carbonyls with cyclopropane 1,1‐diesters under mild reaction conditions afforded highly substituted cis‐ and trans‐tetralins. The reaction of m‐N,N‐dimethylaminophenyl α,β‐unsaturated ketones with cyclopropane 1,1‐diesters provided tetralins with a trans orientation of the 1,4‐substitutents on the cyclohexyl ring; cis‐tetralins were obtained from m‐N,N‐dimethylaminophenyl substituted methylidenemalonates with high diastereoselectivities.

     

Direct Aza‐Darzens Aziridination of N‐Tosylimines with 2‐Bromomalonates for the Synthesis of Highly Functionalized Donor‐Acceptor Aziridines

An approach to highly functionalized donor‐acceptor aziridines by the aziridination of N‐tosylimines and 2‐bromomalonates in the presence of sodium hydride under mild conditions has been developed. The high‐yielding reaction has a relatively broad scope and can be easily scaled up to the gram level.     

Microwave‐Accelerated Coupling‐Isomerization Reaction (MACIR) – A General Coupling‐Isomerization Synthesis of 1,3‐Diarylprop‐2‐en‐1‐ones

The microwave‐accelerated coupling‐isomerization reaction (MACIR) of (hetero)aryl halides and propargyl alcohols represents a general Pd/Cu and base‐catalyzed process for the synthesis of 3‐arylprop‐2‐en‐1‐ones in good yields.     

Palladium‐Catalyzed Synthesis of (Z)‐3‐Arylthioacrylic Acids and Thiochromenones

The three‐component reaction of aryl halides, sodium sulfide pentahydrate (Na₂S⋅5 H₂O), and propiolic acid in the presence of 2.5% bis(triphenylphosphine)palladium chloride [Pd(PPh₃)₂Cl₂], 5% 1,4‐bis(diphenylphosphino)butane (dppb) and 2 equivalents of 1,8‐diazabicycloundec‐7‐ene (DBU) produces stereoselectively (Z)‐3‐arylthioacrylic acids in good yields. A study of the reaction pathway suggested that the C S bond formation between aryl halides and Na₂S⋅5 H₂O proceeded first, and the resulting intermediate reacted with propiolic acid to produce the desired product. In addition, when the resulting product was treated with acid, the respective thiochromenones were formed in good yields.     

Synthesis of 2‐Aminobenzothiazoles via Copper(I)‐Catalyzed Cross‐Coupling with Part‐Per‐Million Catalyst Loadings

An efficient protocol has been developed for the preparation of 2‐aminobenzothiazoles via a copper(I)‐catalyzed tandem reaction of 2‐iodoanilines with isothiocyanates at very low catalyst loadings [typically 50 ppm of copper(I) iodide (CuI)]. A variety of 2‐iodoanilines could be cross‐coupled with isothiocyanates, affording 2‐aminobenzothiazoles in moderate to good yields (49–93%) under the given conditions. The turnover number (TON) of this reaction reaches 67,000 and the reaction could be scaled up, at least, to the gram‐scale.     

A General Synthesis of α‐Trifluoromethylstyrenes through Palladium‐Catalyzed Cross‐Couplings with 1,1,1‐Trifluoroacetone Tosylhydrazone

1,1,1‐Trifluoroacetone tosylhydrazone is presented as a very convenient substrate for the palladium‐catalyzed cross‐coupling with aryl halides. Under the proper reaction conditions, 3,3,3‐trifluoromethylstyrenes – very valuable trifluoromethylated synthetic intermediates – are obtained with high yields. The reaction features a very wide scope, as the presence of most functional groups is tolerated. Moreover, the reaction has been extended to substituted trifluoromethylstyrenes by employing substituted tosylhydrazones derived from other trifluoromethyl ketones.

     

Synthesis and characterization of degradable copoly(ester–amide)s: Poly(trans‐4‐hydroxy‐L‐proline‐co‐ε‐caprolactam)

Novel copolyesteramides were synthesized by reacting trans‐4‐hydroxy‐N‐benzyloxycarbonyl‐L ‐proline (N‐CBz‐Hpr) with ε‐caprolactam (CLM) in the presence of stannous octoate [Sn(II) Oct.] as a catalyst. Various techniques, including ¹H‐NMR, IR, DSC, and viscosity, were used to elucidate structural characteristics and thermal properties of the resulting copolymers. Data showed that the optimal reaction condition for the synthesis of the copolymers was obtained by using 3 wt % Sn(II) Oct. at 170°C for 24 h. The DSC analysis demonstrated amorphous structure for most of the copolymers. The glass‐transition temperature of the copolymers shifts to a higher temperature with increasing Hpr/CLM molar ratio. In vitro degradation of these poly(N‐CBz‐Hpr‐co‐CLM)s was evaluated by weight loss measurements. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1615–1621, 2002     

Highly (≥98%) Stereo‐ and Regioselective Trisubstituted Alkene Synthesis of Wide Applicability via 1‐Halo‐1‐alkyne Hydro‐ boration–Tandem Negishi–Suzuki Coupling or Organoborate Migratory Insertion

(Z)‐1‐Halo‐1‐alkenylboranes ( 7 ), preparable in 80–90% yields as ≥98% isomerically pure compounds via hydroboration of 1‐halo‐1‐alkynes, have been converted to a wide range of trisubstituted alkenes via three different routes in the tail‐to‐head ( T ‐to‐ H ) direction, i.e., (i) palladium‐catalyzed Negishi–Suzuki tandem alkenylation, (ii) treatment with organolithium or Grignard reagents to generate α‐bromo‐1‐alkenylboronate complexes that can undergo migratory insertion of a carbon group (R²) to form (E)‐alkenylboranes with inversion of alkene configuration (≥98% inversion), followed by fluoride‐promoted Suzuki alkenylation, and (iii) Negishi coupling to generate (Z)‐alkenylboranes in ≥98% retention of configuration, followed by treatment with organolithium or Grignard reagents to produce trisubstituted alkenes with reversed stereo configurations. The synthetic utility of the present methodology has been demonstrated in the highly selective synthesis of the side chain of scyphostatin in 28% yield over nine steps in the longest linear sequence from allyl alcohol. Thus, this new tandem protocol has been emerged as the most widely applicable and highly selective route to trisubstituted alkenes including those that are otherwise difficult to prepare.     

Copper‐Catalyzed Domino SN2′/Coupling Reaction: A Versatile and Facile Synthesis of Cyclic Compounds from Baylis–Hillman Acetates

A variety of substituted quinoline/pyridine, thiochromene and naphthalene derivatives, which might be of biological and medicinal value, were synthesized by copper‐catalyzed domino S_N2′/coupling, S_N2′/deacylation/coupling and S_N2′/coupling/elimination reactions. The method provides a general and convenient approach to the synthesis of various substituted cyclic compounds from the corresponding Baylis–Hillman (B‐H) acetates and N‐/S‐/C‐nucleophiles.     

Multiple Oxidative Dehydrogenative Functionalization of Arylacetaldehydes Using Molecular Oxygen as Oxidant Leading to 2‐Oxo‐acetamidines

A novel copper‐catalyzed, multiple oxidative dehydrogenative functionalization of arylacetaldehydes leading to 2‐oxo‐acetamidine compounds has been developed. This transformation is highly efficient with dissociation of six hydrogens including two sp³ C H and one sp² C H bond activations. This method not only provides an efficient approach to 2‐oxo‐acetamidine compounds, but also offers a valuable mechanistic insight into this novel copper catalysis.     

Synthesis of 2,4‐ and 2,5‐Disubstituted Oxazoles via Metal‐ Catalyzed Cross‐Coupling Reactions

The rapid synthesis of 2,4‐ and 2,5‐disubstituted oxazoles via metal‐catalyzed cross‐coupling reactions is reported. The 4‐ or 5‐position of the corresponding 4‐ or 5‐halogenated 2‐butylthiooxazoles was successfully functionalized via Suzuki–Miyaura, Sonogashira and Stille cross‐coupling reactions. The 2‐position of the 2‐butylthiooxazoles obtained was further coupled to various organozinc reagents through palladium‐ or nickel‐mediated cross‐coupling reactions.     

A New Strategy to Prepare Poly(2‐methyl‐2‐oxazoline)‐Based Antifouling Coatings: Using UV‐Crosslinked Copolymer Anchors

A series of the copolymer, poly(styrene‐random‐glycidyl methacrylate) (P(St‐r‐GMA)), is synthesized by free radical polymerization, and characterized by ¹H NMR spectroscopy and gel permeation chromatography. The various substrates are then modified by P(St‐r‐GMA) under ultraviolet (UV) irradiation. Subsequently, the poly(2‐methyl‐2‐oxazoline) (PMOXA) based coatings are prepared by anchoring amino‐terminated PMOXA onto the P(St‐r‐GMA) modified surfaces through the reaction between the amino group of PMOXA and epoxy group of P(St‐r‐GMA). The results of ellipsometry, X‐ray photoelectron spectroscopy, atomic force microscopy, and water contact angle reveal that PMOXA‐based coatings can be prepared successfully on the substrates through UV‐crosslinked P(St‐r‐GMA) as anchoring coatings. Besides, the PMOXA‐based coatings display not only a superior antifouling property but long‐term stability as well. Furthermore, the location of the coating formed on the substrate can be well controlled through selecting the site of UV irradiation, which can be utilized for the selectivity of protein adsorption (or resistance) on special devices.     

Highly trans‐1,4‐specific polymerization of 1,3‐butadiene catalyzed by [2,6‐bis{(4S)‐ (−)‐isopropyl‐2‐oxazolin‐2‐yl}pyridine] chromium complex activated with modified methylaluminoxane

Chromium complexes with N,N,N‐tridentate ligands, LCrCl₃ (L = 2,6‐bis{(4S)‐(?)‐isopropyl‐2‐oxazolin‐2‐yl}pyridine ( 1 ), 2,2′:6′,2″‐terpyridine ( 2 ), and 4,4′,4″‐tri‐tert‐butyl‐2,2′:6′,2″‐terpyridine ( 3 )), were prepared. The structures of 1 and 2 were determined by X‐ray crystallography. Upon activation with modified methylaluminoxane (MMAO), 1 catalyzed the polymerization of 1,3‐butadiene, while 2 and 3 was inactive. The obtained poly(1,3‐butadiene) obtained with 1 ‐MMAO was found to have completely trans‐1,4 structure. The 1 ‐MMAO system also showed catalytic activity for the polymerization of isoprene to give polyisoprene with trans‐1,4 (68%) and cis‐1,4 (32%) structure. Copyright © 2011 Society of Chemical Industry     

Mild and Functional Group Tolerant Method for Tandem Palladium‐Catalyzed Carbocyclization–Coupling of ε‐Acetylenic β‐Ketoesters with Aryl Bromides and Chlorides

We report a new protocol for the annulative difunctionalization of acetylenes via tandem carbocyclization–coupling of ε‐acetylenic β‐ketoesters with aryl and heteroaryl bromides and chlorides catalyzed by the palladium species derived from an air‐ and moisture‐stable palladacyclic precatalyst. In the tandem process, the palladium complex combines appropriate carbophilic Lewis acidity and redox activity to catalyze two mechanistically distinct reactions ‐ nucleophilic addition of the enolate to unactivated alkyne, followed by C C coupling. We found that a broad range of electronically varied aryl and heteroaryl bromides and chlorides underwent this reaction with various ε‐acetylenic β‐ketoesters, providing corresponding substituted vinylidenecyclopentanes in high yield with excellent functional group tolerance.

     

Synthesis and characterization of novel block copolymer from trans‐4‐hydroxy‐L‐proline and poly(ethylene glycol)

A series of novel ABA‐type block copolymers were synthesized by polymerization of trans‐4‐hydroxy‐L ‐proline (HyP) in the presence of various molecular weight poly(ethylene glycol)s (PEGs), a bifunctional OH‐terminated PEG using stannous octoate as catalyst. The optimal reaction conditions for the synthesis of the copolymers were obtained with 5 wt % stannous octoate at 140°C under vacuum (20 mmHg) for 24 h. The synthesized copolymers were characterized by IR spectroohotometry, proton nuclear magnetic resonance, differential scanning calorimetry, and Ubbelohde viscometer. The glass transition temperature (T_g) of the copolymers shifted to significantly higher temperature with increasing the number average degree of polymerization and HyP/PEO molar ratio. In contrast, the melting temperature (T_m) decreased with increasing the HyP/PEO molar ratio. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 1581–1587, 2001