Horner-wadsworth-emmons reaction: Use of lithium chloride and an amine for base-sensitive compounds

A mild olefination procedure, utilizing LiCl and an amine, has been developed for use with base-sensitive aldehydes and phosphonates.     

Reaction of arylsulfonylhydrazones of aldehydes with alpha-magnesio sulfones. A novel olefin synthesis

Reactions of representative tosylhydrazones of aldehydes and ketones with alpha-metalated sulfones were examined in order to develop a practical olefination method. Treatment of aldehyde tosylhydrazone 2 with an excess of alpha-lithiated methyl phenyl or dimethyl sulfones yielded 3a. The reaction of 2 with sterically unhindered lithiated alkyl sulfones gave mixtures of the respective olefination products 3b-d along with the Shapiro fragmentation product 4. Sterically hindered lithiated sulfones afforded Shapiro products exclusively. In contrast, aldehyde tosylhydrazones 2 or 6 in reactions with a variety of alpha-magnesio primary or secondary alkyl sulfones gave olefination products 3a-j and 7a-c in high yields (Tables 1 and 2). beta-Branched alkyl sulfones afforded predominantly (E)-alkenes, whereas unhindered primary sulfones gave mixtures of (E)- and (Z)-alkenes with low selectivity. Reaction of the 2,4,6-triisopropylbenzenesulfonylhydrazone (trisylhydrazone) of cyclodecanone 11c with alpha-magnesio methyl phenyl sulfone afforded the methylidene derivative 12a contaminated with the Shapiro product 13. Tosylhydrazone 2 resisted reaction with i-PrMgCl and gave only a small amount of the addition product in reaction with Bu(2)Mg. Some mechanistic aspects of the reaction of tosylhydrazones with organomagnesium compounds are discussed.     

3,5-bis(trifluoromethyl)phenyl sulfones in the direct Julia-Kocienski olefination

3,5-bis(trifluoromethyl)phenyl (BTFP) sulfones 7 have been employed in the Julia-Kocienski olefination reaction with carbonyl compounds. Sulfones 7 are readily prepared in high yields (64-97%) from commercially available 3,5-bis(trifluoromethyl)thiophenol through an alkylation/oxidation two-step sequence. The stability of metalated BTFP sulfones has been studied and compared with heteroaryl benzothiazol-2-yl (BT), 1-phenyl-1H-tetrazol-5-yl (PT), and 1-tert-butyl-1H-tetrazol-5-yl (TBT) sulfones 9-11 under different reaction conditions. The Julia-Kocienski olefination between alkyl BTFP sulfones 7 and a wide variety of aldehydes affords the corresponding 1,2-disubstituted alkenes and dienes in good yields and stereoselectivities. This one-pot protocol can be performed using KOH at room temperature or the phosphazene bases P2-Et and P4-t-Bu at -78 degrees C or rt and has been successfully used in a high-yielding and stereoselective synthesis of various methoxylated stilbenes such as trimethylated resveratrol. These new reaction conditions for the Julia-Kocienski olefination reaction have been also studied with BT, PT, and TBT sulfones, giving poorer results. Methylenation of aliphatic and aromatic aldehydes, ketones, and 1,2-dicarbonyl compounds is carried out through the modified Julia olefination using BTFP methyl sulfone 7d to give terminal alkenes and dienes. Mechanistic studies of the olefination reaction between benzyl BTFP sulfone 7a and aromatic aldehydes performed by KOH-induced Smiles rearrangement of stereodefined syn- and anti-beta-hydroxyalkyl BTFP sulfones indicate that the stereocontrol of the reaction is determined in the elimination step.     

Stereoselective synthesis of hydroxy stilbenoids and styrenes by atom-efficient olefination with thiophthalides

The synthesis of stilbenoids and styryl carboxylic acids is accomplished with high E-stereoselectivity by olefination of aldehydes with thiophthalides under basic conditions. The olefination is highly atom-efficient as it only loses elemental sulfur during the reaction. This olefination, in conjunction with retro Kolbe-Schmitt reaction, allows facile synthesis of E-hydroxystilbenoids with minimal employment of protecting groups. This study also discloses two important findings: formation of i) 4-methylsulfanyl isocoumarins and ii) an 2-arylindenone.     

Homogeneous silicone modified primary amine-Brønsted acid salt catalyzed aldol reaction: unexpected synergistic effect of polysiloxane with remarkable improvement of efficiency and stereoselectivity

We have developed a new strategy to improve the stereoselectivity in enamine catalysis by the introduction of super-hydrophobic long-chain silicone/polysiloxane as support/functional group for a model aldol reaction. The homogeneous direct aldol reaction of cyclic ketones with different aromatic aldehydes catalyzed by polysiloxane-derived primary amines has been reported with high yields, good diastereoselectivity, and up to 99% ee.     

Highly efficient and selective olefination of acyl phosphonates with ethyl diazoacetate catalyzed by a cobalt(II) porphyrin complex

The cobalt(II) porphyrin complex (CoTPP) was found to be an efficient catalyst for the Wittig type olefination of acyl phosphonates with ethyl diazoacetate (EDA) in the presence of triphenylphosphine (Ph₃P). By using this one pot methodology under mild conditions, densely functionalized vinyl phosphonates were obtained in high yields and high E/Z selectivities in relatively short reaction times. A rather broad substrate spectrum and steric influence on the reaction rate were observed.     

Modified Julia fluoroolefination: selective preparation of fluoroalkenoates

The modified Julia olefination reaction has been applied to develop a stereoselective synthesis of fluoroalkenoate derivatives from a fluorobenzothiazolyl sulfone and aldehydes or a ketone. The olefination reaction can be achieved by using a variety of bases. DBU and DBU in the presence of MgBr2 were found to be the most efficient systems to prepare either (Z)- or (E)-alkenoates in moderate to excellent stereoselectivity.     

Microwave-assisted, regioselective, Petasis olefination of unsymmetrical oxalates. Formation of pyruvate-based enol ethers and enamines

The Petasis olefination of unsymmetrical oxalates and oxalate monoesters/monoamides (tert-BuO₂CC(O)X, where X = OR, NR₂) is highly regioselective and provides pyruvate-based enol ether and enamine derivatives. The olefination step occurs under conventional thermal conditions, but is dramatically improved--shorter reaction times and higher yields--when promoted by microwave irradiation.     

Iridium as a general catalyst for the decarbonylative addition of aldehydes to alkynes

A general catalytic system for the decarbonylative addition reaction of aldehydes with alkynes is developed by using an iridium catalyst system. Both aromatic and aliphatic aldehydes reacted with terminal alkynes efficiently to give the corresponding olefination products in high yields and up to 11:1 E/Z selectivity.     

Curtin-Hammett paradigm for stereocontrol in organocatalysis by diarylprolinol ether catalysts

Detailed mechanistic study of two reactions catalyzed by diarylprolinol ether catalysts, the conjugate addition of aldehydes to nitro-olefins and the α-chlorination of aldehydes, leads to the proposal that the stereochemical outcome in these cases is not determined by the transition state of the step in which the stereogenic center is formed from enamine attack on the electrophile but instead is correlated with the relative stability and reactivity of diastereomeric intermediates downstream in the catalytic cycle. This combination of kinetic and thermodynamic factors illustrates a remarkable Curtin-Hammett scenario that can result in either an enhancement or an erosion of the selectivity that would be predicted by the transition state for enamine attack on the electrophile. Evidence is offered to suggest that this concept may represent a general phenomenon for pyrrolidine-based catalysts lacking an acidic directing proton. Implications for catalyst and reaction design are discussed.     

New mixed phosphonate esters by transesterification of pinacol phosphonates and their use in aldehyde and ketone coupling reactions with nonstabilized phosphonates

Alkylpinacol phosphonates were prepared by rhodium-catalyzed olefin hydrophosphorylation, and attempted alpha-deprotonation of the pinacol derived alkyl phosphonates resulted in ring cleavage. The propensity of the alkylpinacol phosphonates to undergo ring opening was exploited to prepare phosphonic acid monomethyl esters in high yield by transesterification in acidulated methanol. Esterification and alkylation with aldehydes or ketones gave beta-hydroxy mixed phosphonate esters. tert-Butyl and benzylic phosphonate ester protective groups were introduced to improve the efficiency and functional group compatibility of beta-hydroxy phosphonate saponification. The beta-hydroxy phosphonic acid monomethyl esters were dehydrated with diisopropylcarbodiimide, which gave oxaphosphetane intermediates that collapse to an olefin. The overall reaction sequence complements the arsenal of Horner-Wadsworth-Emmons-type coupling reactions.     

Reactivity of aldehydes with semi-stabilised arsonium ylide anions: synthesis of terminal (e)-1,3-dienes

A study of the reactivity of semi-stabilised arsonium ylide anions in olefination reactions is presented. The different ylide anions were generated by the addition of nBuLi to various arsonium halide derivatives: [Ph(2)As(R)R'](+)X(-), where R and R' are methyl, allyl, prenyl or benzyl groups. By using diallyldiphenylarsonium bromide (R=R'=allyl) an olefination protocol was optimised allowing the efficient transformation of aliphatic aldehydes into terminal 1,3-dienes with a high selectivity for the E isomer (E/Z ratios ranging from 90:10 to 97:3). The olefination reactions of aldehydes with dissymmetric arsonium halides (R not equal R') are very chemoselective; with arsonium ylide anions the benzyl moiety is more reactive than the allyl moiety which is much more reactive than prenyl and methyl groups. Based on the experimental results, a mechanism is proposed for the reaction.     

Very Simple One-Step Synthesis of Vinylphosphonates and Enamine Phosphonates by Direct Addition of Organolithium Reagents to 1-Alkynylphosphonates

Abstract

Direct addition of organolithium to 1-alkynylphosphonates (1) afforded vinylphosphonates and enamine phosphonates (2) in good to excellent yields. The reaction was carried out in dry THF at low temperature and proved to be completely stereoselective (syn addition). Alkyl, aryl, and haloalkyl groups were attached to the alkynyl entity, so the resulting vinylphosphonates contained various functional groups. The stereochemistry of the products as well as mechanism of the reaction were determined based on ¹H and ¹³C NMR. The synthesis of enamine phosphonates in the absence of complicated, highly expensive organometallic catalysis has not been previously reported.     

β-Olefination of 2-alkynoates leading to trisubstituted 1,3-dienes

A phosphine-mediated olefination of 2-alkynoates with aldehydes forming 1,3-dienes with high E-selectivity and up to 88% yield is described. Reaction conditions are optimized and reactions are demonstrated for various aryl, alkyl, and alkenyl aldehydes and for ethyl 2-alkynoates with different substituents in the δ-position. Proof of concept is shown for the generation of a β,γ-unsaturated lactone by intramolecular olefination, and furthermore the use of the generated 1,3-dienes in the Diels-Alder reaction has been demonstrated.     

叔膦参与下联烯酸酯与醛的反应

联烯酸酯是近年来研究较多的一类重要的缺电子联烯,具有丰富的化学反应.本文着重总结了近年来在叔膦参与下(催化或化学计量方式)联烯酸酯与醛的新反应,包括2,3-丁二烯酸酯与醛的成环反应、γ-取代联烯酸酯与醛的[3+2]环加成反应和烯化反应、α-取代联烯酸酯与醛的Vinylogous Wittig反应以及环丙烷化反应,并从反应机理的角度,探讨了联烯酸酯与亲电试剂活化烯、亚胺和醛在反应性上的差异.在这些重要的化学转化中,叔膦的特殊性质如亲核性与夺氧能力起了关键的作用.     

Convenient procedure of Horner-Wadsworth-Emmons olefination for the synthesis of simple and functionalized α,β-unsaturated nitriles

A mild and practical procedure of Horner-Wadsworth-Emmons olefination promoted by lithium hydroxide and α-cyano phosphonates has been set up for the synthesis of α,β-unsaturated nitriles. The reaction conditions are tolerated by functionalized ketones and the exclusive formation of E-γ-hydroxy α,β-unsaturated nitriles has been observed.     

Mechanistic investigation of the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes

The mechanism for the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes with electrophilic halogenation reagents has been investigated by using experimental and computational methods. These studies have led us to propose a mechanism for the reaction that proceeds through an initial N-chlorination of the chiral catalyst-substrate complex, followed by a 1,3-sigmatropic shift of the chlorine atom to the enamine carbon atom. The suggested reaction course is different from previously proposed mechanisms for organocatalytic enamine reactions, in which the carbon-electrophile bond is formed directly. Furthermore, the rate-determining step in the overall reaction was determined and the presence of nonlinear effects was probed.     

Catalytic olefination of carbonyl compounds. Effect of the structure of the carbonyl compound on the reaction

The mechanism of the novel reaction of catalytic olefination of carbonyl compounds was studied. The reaction involves the transformation of hydrazones of aromatic aldehydes and ketones into the corresponding dichloroalkenes and symmetrical azines by the treatment with carbon tetrachloride in the presence of CuCl as a catalyst. The stability of intermediate diazoalkanes is the main factor determining the direction of the reaction. In the case of sufficiently stable diazoalkanes, other products can be formed under the reaction conditions along with the products of catalytic olefination.     

A Green Synthesis of 1-Aminoalkyl Phosphonates Under Microwave Irradiation without Any Catalysts and Solvent

The synthesis of 1-aminoalkyl phosphonates has been developed during past 20 years. 1-Aminoalkyl phosphonates have received much attentions as an important substrate in the synthesis of phosphonopeptides. It is reported that 1-aminoalkyl phosphonates can be used as enzyme inhibitors, antibiotics and pharmacological agents, herbicides and haptens of catalytic antibolies. Many papers mention that synthesis of 1-aminoalkyl phosphonates is convenient by using a base or an acid as a catalyst. For example, Lewis acids such as SnCl2, SnCl4, ZnCl2, MgBr2, INCl3 or acids alumia can be used as a catalyst in this reaction. It is found that the product can be obtained from a mixture of aldehydes, amine and dithyl phosphite under microwave irradiation in yields of 80%～95%.     

A facile and highly efficient route to alpha-amino phosphonates via three-component reactions catalyzed by Mg(ClO4)2 or molecular iodine

Three-component reactions of aldehydes, amines, and diethyl phosphite catalyzed by Mg(ClO4)2 or molecular iodine afforded the corresponding alpha-amino phosphonates in excellent yields under mild reaction conditions.