Addition reaction of spiro orthoesters with electrophiles: A model reaction for the development of novel polyaddition accompanying ring-opening isomerization

The addition reaction of spiro orthoesters (SOEs) with electrophiles accompanying ring-opening isomerization was investigated as a model reaction for polyaddition of bifunctional SOEs with bifunctional electrophiles. Among several electrophiles such as carboxylic acids and carboxylic anhydrides, acid halides showed particularly high reactivities to SOEs. An equimolar reaction of SOEs with acid chlorides took place selectively, leading to the corresponding 1 : 1 adducts. SOEs with seven-membered cyclic ether rings—1,4,6-trioxaspiro[5.6]undecane derivatives—showed higher reactivities than SOEs with six- and five-membered cyclic ether rings. The reaction accompanied zero shrinkage in volume. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 4502–4509, 1999     

Synthesis of thiophosphoramidates in water: click chemistry for phosphates

An aqueous method for the preparation of N,S-dialkyl thiophosphoramidates is reported. Thiophosphorylation of alkylamines was performed using SPCl(3) in aqueous reaction media, and the resulting thiophosphoramidate-S-anions were S-alkylated with soft electrophiles. Ranges of amines and electrophiles were explored.     

Regioselection in the reaction of α-silyloxyallyl carbanions with electrrophiles

Regioselection in the reaction of α-silyloxyallyl carbanion with electrophiles has been found to change with the nature of leaving groups in the electrophiles.     

Iridium‐Catalyzed Regio‐ and Enantioselective Allylic Substitution of Trisubstituted Allylic Electrophiles

The first Ir‐catalyzed enantioselective allylation of trisubstituted allylic electrophiles has been developed. Through modification of the leaving group of allylic electrophiles, we found that trisubstituted allylic phosphates are suitable electrophiles for asymmetric allylation. The reaction of allylic phosphates with enol silanes derived from dioxinones gave allylated products in good yields with high enantioselectivities.     

α-methoxyallyl sulfides as a novel homoenolate dianion equivalent

α-Methoxyallyl sulfides 1 proved to serve a novel homoenolate dianion equivalent. Introduction of two electrophiles into 1 was realized by successive regiospecific reaction of an allylic moiety with electrophiles intervened by an acid-catalyzed thioallylic rearrangement. Facile desulfurization of the products under mild conditions afforded a variety of (α,β- unsaturated carbonyl compounds and 2,3,4-trisubstituted furans.     

Chemoselective synthesis of highly substituted 1,2-allenyl ketones, furans, and 2-alkynyl ketones from reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and electrophiles

A homo-Michael addition reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and the subsequent reaction with electrophiles such as PhSeBr, NFSI and NCS is reported. Based on the nature of electrophiles, this reaction may afford highly substituted 1,2-allenyl ketones or furans (E(+) = PhSe(+)) and 2-alkynyl ketones (E(+) = F(+), Cl(+), active halides) as the final products, respectively.     

On the nature of organoindium intermediates: the formation of readily isolable difluoropropargylindium reagents and their regioselectivity towards electrophilic substitutions

The structure and reactivity of intermediate propargylindium complexes have been investigated. Their reaction with electrophiles produced a difluoroalkyne or -allene, depending on the nature of the electrophiles. A mechanism based on the Curtin-Hammett principle was invoked to explain this phenomenon. A newly proposed mechanism on the formation of indium(III) complexes, through the intermediacy of indium(I) species, could help to explain the reaction of indium with 1,1,1-difluorobromo-2-alkynes in the presence of aldehydes.     

Domino rhodium(I)-catalysed reactions for the efficient synthesis of substituted benzofurans and indoles

Rhodium(I) catalysts promote the transformation of o-alkynyl phenols and anilines to the corresponding benzo[b]furans and indoles. The reaction is postulated to proceed via a transient 3-rhodium heterocycle intermediate, which can be trapped with suitable electrophiles to give poly-substituted heterocycles. In the case of mono-substituted electron-withdrawn electrophiles, excellent yield and selectivity for conjugate addition versus Heck-Mizoroki reaction can be achieved. In the case of 2-alkynyl pyridine electrophiles, novel 2-(benzofuran-3-yl)vinylpyridines are formed.     

An efficient method for the phosphonation of C=X compounds

Reaction of trialkyl phosphites with C=X electrophiles (aldehydes, ketones, ketophosphonates, aldimines, ketimines, isocyanates, isothiocyanates, and activated olefins) in the presence of amines and anilines hydrohalides was studied. We found that pyridine hydrohalides effectively activate the reaction of tralkyl phosphites with various C=X electrophiles: aldehydes, ketones, ketophosphonates, aldimines, ketimines, isocyanates, isothiocyanates, and activated olefins. Particularly high activity showed pyridine hydroiodide. This reaction is a convenient method of synthesis of hydroxyphosphonates, aminophosphonates, carbamoylphosphonates, carbamoylthiophosphonates, and methylenebisphosphonates.     

Highly selective 5-substitution of 3-methylthiophene via directed lithiation

Lithiation of 3-methylthiophene with lithium 2,2,6,6-tetra-methylpiperidide (LiTMP) is highly selective at the 5-position, and reaction with a range of electrophiles gives high yields of the corresponding 2,4-disubstituted thiophenes, even when unhindered electrophiles are used.     

Soluble polymer supported synthesis of alpha-amino acid derivatives

A Schiff base activated glycine supported on a soluble polymer (poly(ethylene glycol) (PEG)) was readily alkylated with a wide variety of electrophiles in the presence of a carbonate base in acetonitrile. The presence of the polymer provided a phase-transfer catalysis environment which accelerated the reaction. Effects of various carbonate bases and leaving groups have been also studied. Completion of the PEG-supported reaction was obtained without using a large excess of reagents or an extra phase-transfer catalyst, even in the case of unreactive or hindered electrophiles. After cleavage from the polymer, alpha-amino esters are obtained in good yields.     

A novel enantioselective alkylation and its application to the synthesis of an anticancer agent

A novel enantioselective alkylation of double benzylic substrates with secondary electrophiles is reported. A simple norephedrine-based chiral ligand was synthesized that gives alkylation product in 95% yield and 95% ee. A unique water effect on the enantioselectivity was unveiled. Good to excellent ee values were obtained with a number of double benzylic substrates and secondary electrophiles. This novel reaction has been applied to the synthesis of a promising anticancer agent.     

Palladium-Catalyzed Catellani Reaction with 1,1-Bis[(pinacolato)boryl]methane as the Nucleophilic Component

We report herein the application of 1,1-bis[(pinacolato)boryl]methane as a new type of terminating reagent to realize three-component coupling reaction with aryl iodide and different electrophiles. A series of ortho-disubstituted benzylboronates can be synthesized and the ortho-substituent can be varied by using bromoacetic esters or O-benzoyl hydroxylamine as electrophiles with slightly modified reaction conditions. The reaction shows good functional group tolerance and the obtained benzyl boronate products can be easily transformed to various synthetically useful compounds.     

Selective monolithiation of dibromobiaryls using microflow systems

Selective monolithiation of dibromobiaryls, such as 2,2'-dibromobiphenyl, 4,4'-dibromobiphenyl, 2,7-dibromo-9,9-dioctylfluorene, 2,2'-dibromo-1,1'-binaphthyl, and 5,5'-dibromo-2,2'-bithiophene, with 1 equiv of n-butyllithium followed by the reaction with electrophiles was achieved using a microflow system by virtue of fast micromixing and precise temperature control. Sequential introduction of two different electrophiles based on this method was also achieved using a microflow system composed of four micromixers and four microtube reactors.     

Controllable highly stereoselective reaction of in situ generated magnesium dienolate intermediates with different electrophiles

In this paper, we have described an efficient controllable stereoselective alpha-acylation and -allylation reaction of the magnesium dienolate intermediates generated in situ from the Fe(III)-catalyzed reaction between 2,3-allenoates and Grignard reagents with different electrophiles to afford 2-acylated or allylated 3( Z)- or ( E)-alkenoates depending on the nature of the electrophiles and reaction conditions. The distinct stereoselectivity may be caused by the isomerization of metallic Z-1,3-dienoate to E-1,3-dienoate via the intermediacy of anti-allylic MgCl and syn-metallic species.     

Pd-P(t-Bu)(3)-catalyzed consecutive cross-coupling of p-phenylenedizinc compound with two different electrophiles leading to unsymmetrically 1,4-disubstituted benzenes

Pd-P(t-Bu)3 was found to be a chemoselective catalyst for the reaction of p-phenylenedizinc compound with equimolar amounts of carbon electrophiles to afford the single cross-coupling products in good yields, effectively suppressing the formation of double cross-coupling products. The subsequent additions of other electrophiles to the resulting solutions caused the second cross-coupling of the incipient products to take place, achieving a novel and efficient one-pot synthesis of unsymmetrically 1,4-disubstituted benzenes. The origin of the observed high chemoselectivity was speculated.     

Carbocupration-functionalization of arynes: rapid access to variably ortho-substituted ((E)-3-phenylprop-1-enyl)silanes

A consecutive three-component coupling reaction involving a lithium di[3-(prop-1-enyltrimethylsilyl)]cuprate, variably substituted ortho-arynes, and a selection of common electrophiles is described. The method affords readily functionalized homobenzylic vinylsilanes with exceptional E-diastereoselectivity and allows for in situ incorporation of carbon- or heteroatom-based electrophiles into the arene.     

Synthesis of 4-hydroxy-3-triftuoromethylpyrazoles

Trifluoroacetaldehyde hydrazones are condensed with glyoxals to give 4-hydroxy-3-trifluoromethylpyrazoles, the reaction offering a novel route to 4-hydroxypyrazoles carrying trifluoromethyl group. The 4-hydroxyl group was easily converted to its derivatives by the reaction with various electrophiles.     

Site-selective iodine-magnesium exchange reaction of 1,4-diiodo-1,3-alkadienes by an organomagnesium ate complex,and its application to synthesis of polysubstituted styrenes and phenols

When 1,4-diiodo-1,3-alkadienes were treated with i-PrBu2MgLi, highly site-selective iodine-magnesium exchange reaction took place to afford, after the reaction with electrophiles, a variety of 1-iodo-1,3-alkadiene derivatives. Synthetic utility of the reaction was demonstrated by an efficient preparation of polysubstituted styrenes and phenols.     

A computational approach towards predicting π-facial selectivity in sterically unbiased olefins: an evaluation of the relative importance of electrostatic and orbital effects

Computational studies are presented to show that electrostatic interactions significantly impact the stereochemical outcome in electrophilic addition to a number of sterically unbiased alkenes. Transition states have been located for the reaction of different electrophiles with all the sterically unbiased alkenes studied here and the calculations effectively include interactions involving the σ and σ^∗ orbitals of the newly formed bond. Electrostatic interaction between the substrates and electrophiles was modelled by removing the electrophiles from the transition state geometry and placing the calculated charge at a distance from a selected atom as observed in TS structures. Electrostatic interactions between the electrophiles and the substrate seem to effectively determine the face selectivities in the systems studied and our model calculations indicate that it may not be important to invoke Cieplak type orbital interactions to rationalize the observed face selectivities. The face selectivities predicted for these alkenes and electrophiles with DFT B3LYP/6-31G^∗ and ab initio MP2/6-31G^∗ levels are generally in good agreement.