Cyclic vinylogous triflate hemiacetals as new surrogates for alkynyl aldehydes

Cyclic vinylogous triflate hemiacetals can serve as ‘synthetic equivalents’ for alkynyl aldehydes: treatment of a vinylogous triflate hemiacetal with excess amounts of Grignard reagents produces acyclic alkynyl alcohols in good to high yields. This transformation likely involves the Grob-type C-C bond cleaving fragmentation to form the alkynyl aldehyde in situ. Subsequent nucleophilic attack of the Grignard reagent furnishes secondary alkynols. Vinylogous triflate hemiacetals are easily prepared by DIBALH reduction of vinylogous acyl triflates, which are derived from cyclic 1,3-diketones.     

Claisen-type condensation of vinylogous acyl triflates

[reaction: see text] The Claisen-type condensation reaction of cyclic vinylogous carboxylic acid triflates with lithium enolates and their analogues produces acyclic alkynes bearing a 1,3-diketone-type moiety. The present transformation is proposed to proceed via a 1,2-addition of the enolate to the vinylogous acyl triflate, followed by fragmentation of the aldolate intermediate.     

Generation of medium-ring cycloalkynes by ring expansion of vinylogous acyl triflates

Reductive cyclization of aryl and vinyl iodides tethered to vinylogous acyl triflates (VATs) induces a ring-expanding fragmentation to provide cyclic alkynyl ketones, including strained nine-membered cycloalkynes, in fair to excellent yield. The tandem cyclization/C-C bond-cleavage is initiated under carefully optimized conditions by halogen-metal exchange in the presence of carbonyl and vinyl triflate functionality. A modified protocol for alkylation of 1,3-cyclohexanedione is described for preparing the relevant VAT substrates.     

An open-and-shut strategy: preparation of benzo-fused indanes by ring-opening of a vinylogous acyl triflate and metal-catalyzed Asao-Yamamoto benzannulation

A two-step strategy for the synthesis of benzo-fused indanes is outlined herein. The strategy draws on two independent methodologies: the tandem addition/fragmentation of vinylogous acyl triflates (VATs) and the intramolecular benzannulation of o-alkynylphenyl ketones. Reduction of this strategy to practice involves the use of aryltriazenes as masked aryl iodides; a synthetic equivalent of 2-iodophenyllithium is featured. Benzo-fused indanes are prepared efficiently and in high yield.     

Aminophosphinidene derivatives

Abstract

Elimination and fragmentation reactions lead to carbene analogous iminophosphanes which undergo 2 + 1 addition as well as insertion reactions. Secondary aminophosphanes and amino substituted three-membered phosphorus rings are phosphinidene transfer reagents and therefore valuable building units for cyclic and acyclic compounds. Synthetic routes to amino substituted diphosphenes and their reaction behaviour are reported.     

Ready Access to Fluorinated Phosphonate Mimics of Secondary Phosphates. Synthesis of the (alpha,alpha-Difluoroalkyl)phosphonate Analogues of L-Phosphoserine, L-Phosphoallothreonine, and L-Phosphothreonine

In addition to the previously recorded reactions of diethyl lithio(difluoromethyl)phosphonate (8) with primary triflates and aldehydes, we report here that 8 reacts with functionalized, but unactivated, methyl esters to give efficient acyl substitution. Thus, 8 reacts cleanly (-78 degrees C, THF) with the following methyl esters (product, yield): methyl (S)-isopropylideneglycerate (14, 99%), methyl (S)-3-O-(tert-butyldimethylsilyl)-2 -O-tetrahydropyranylglycerate (16, 85%), and the Garner ester derived from D-serine (15, 77%). Expeditious treatment of the resultant alpha,alpha-difluoro-beta-keto phosphonates with hydride or Grignard reagents followed by alcohol deoxygenation provides a general method for the synthesis of (alpha,alpha-difluoroalkyl)phosphonate analogues of secondary phosphates. For tertiary alcohols, Dolan-MacMillan deoxygenation conditions are employed. The requisite methyl oxalate esters are obtained by an improved procedure wherein the lithium alkoxide of the hindered tertiary alcohol is irreversibly generated at low temperature and then condensed with methyl oxalyl chloride. Relative stereochemistry is assigned via conversion of the Garner ester derived Boc-amino alcohols to the corresponding cyclic, six-membered phosphonate esters and examination of their (1)H NMR spectra. The relevant vicinal coupling constants are extracted from these spectra by performing double quantum-filtered phase-sensitive COSY experiments. This new (difluoromethylene)phosphonate anion-methyl ester condensation, Grignard (hydride) addition, deoxygenation sequence has been applied to the synthesis of (alpha,alpha-difluoroalkyl)phosphonate analogues of L-phosphoserine (>/=96% ee) and L-phosphoallothreonine (93% ee) from D-serine and of L-phosphothreonine (91% ee) from L-glycerate, respectively.     

Aminohydroxyphosphine ligand for the copper-catalyzed enantioselective conjugate addition of organozinc reagents

An alanine-derived aminohydroxyphosphine ligand was developed for copper-catalyzed asymmetric conjugate addition of organozinc reagents to alpha,beta-unsaturated carbonyl compounds. This new tridentate ligand induces consistently high enantioselectivity in reactions of a variety of acyclic substrates. Theoretical mechanistic analysis suggests that the C-C bond formation takes place through a highly ordered transition state by the coordination of the phosphorus and nitrogen atoms to the copper(III) and zinc(II) atoms, respectively, and of the oxygen anion to both the metal centers.     

Palladium-catalyzed cross-coupling reaction of bis(pinacolato)diboron with vinyl triflates β-substituted by a carbonyl group: efficient synthesis of β-boryl-α,β-unsaturated carbonyl compounds and their synthetic utility

Cross-coupling reaction of bis(pinacolato)diboron with β-(trifluoromethanesulfonyloxy)-α,β-unsaturated carbonyl compounds was carried out in the presence of PdCl₂(PPh₃)₂-2PPh₃ (3 mol%) and KOPh in toluene or K₂CO₃ in dioxane for the synthesis of cyclic and acyclic β-boryl-α,β-unsaturated esters, amides, and ketones in high yields. The vinylboronates thus obtained readily participated in carboncarbon bond formation such as cross-coupling with vinyl triflates and 1,4-addition to α,β-unsaturated ketones.     

钯催化带有酮或醛的芳基三氟甲磺酸酯与胺或酰胺的取代反应

各种含有酮或醛的芳基三氟甲磺酸酯在催化量的钯和膦配体的存在下与胺或酰胺发生取代反应。BINAP为配体对仲胺效果最好,MOP-型配体对伯胺和少量仲胺效果较好,Xantphos 对伯酰胺和环状仲酰胺效果好。脂肪族的仲酰胺作为亲核试剂没有得到好的结果。     

Ring opening/fragmentation of dihydropyrones for the synthesis of homopropargyl alcohols

Ring-opening/C-C bond cleavage reactions induced by nucleophilic addition of methyl Grignard to 5,6-dihydro-2-pyrone (DHP) triflates 1 furnish homopropargyl alcohols (1 --> 2) stereospecifically with respect to the stereochemistry of 1. Carbonyl extrusion from DHP triflates provides a unified and operationally simple strategy for preparing chiral homopropargyl alcohols.     

Photoredox-Catalyzed Giese Reactions: Decarboxylative Additions to Cyclic Vinylogous Amides and Esters

An effective strategy has been developed for the photoredox-catalyzed decarboxylative addition of cyclic amino acids to both vinylogous amides and esters leading to uniquely substituted heterocycles. The additions take place exclusively trans to the substituent present on the dihydropyridone ring affording stereochemical control about the new carbon-carbon bond. These reactions are operationally simplistic and afford the desired products in good to excellent isolated yields.     

Reactions of Methylphenylvinylsulfonium Tetrafluoroborate with Ketone Enolates

The reactions of methylphenylvinylsulfonium tetrafluoroborate (1) with the lithium enolates of 1,3-dicarbonyl compounds, acyclic ketones and cyclic ketones have been studied. Cyclopropanes and cyclic ethers are obtained. The reaction mechanisms are also discussed.     

Benzylic aroylation of toluenes with unactivated tertiary benzamides promoted by directed ortho-lithiation

The deprotonative functionalization of toluenes, for their weak acidity, generally needs strong bases, thus leading to the requirement of harsh conditions and the generation of by-products. Direct nucleophilic acyl substitution reaction of amides with organometallic reagents could provide an ideal solution for ketone synthesis. However, the inert amides and highly reactive organometallic reagents bring great challenges for an efficient and selective synthetic approach. Herein, we reported an lithium diisopropylamide(LDA)-promoted benzylic aroylation of toluenes with unactivated tertiary benzamides, providing a direct and efficient synthesis of various aryl benzyl ketones. This process features a kinetic deprotonative functionalization of toluenes with a readily available base LDA. Mechanism studies revealed that the directed ortho-lithiation of the tertiary benzamide with LDA promoted the benzylic kinetic deprotonation of toluene and triggered the nucleophilic acyl substitution reaction with the amide.     

Synthesis and Reactions of Enediynes and Enyne-Allenes

The thermal cycloaromatization reactions of (Z)-3-hexene-1,5-diynes (enediynes) and (Z)-1,2,4-heptatrien-6-ynes (enyne-allenes) provide easy entries to a variety of carbon biradicals. Several new synthetic routes to these highly unsaturated compounds were developed by using multifunctional reagents properly substituted with combinations of boron, silicon, and tin appendages. Condensation of γ-(trialkylsilyl)allenylboranes 1 and 2 with conjugated acetylenic and allenic aldehydes followed by the elimination step of the Peterson olefination reaction furnished enediynes and enyne-allenes with high geometric purity. Convenient procedures for the synthesis of enediynes and enyne-allenes were also developed by using alkenylboronic ester 28 and the trimethyltin-substituted alkenylboranes 34 for cross-coupling reactions. On heating, acyclic enyne-allene 22 underwent a sequence of intramolecular transformations through biradical intermediates to form 26 , providing a new example of a one-step 0 → ABCD ring construction of the tetracyclic-steroidal skeleton.     

New Perspectives in Thiazole Chemistry

Abstract

Carbon-carbon bond forming reactions at C-2 of the thiazole ring have been carried using two strategies, one involving the addition of organometallic reagents (lithium carbanions of esters, Grignard salts, silyl enol ethers, silyl ketene acetals, silylazoles) to N-acylthiazolium salts; the other involving the addition of carbon electrophiles (ketenes, acyl chlorides, anhydrides, aldehydes) to N-acylthiazolium ylides generated in situ. The reactions have been applied to 1,3-thiazole and 2-trimethylsilyl-1,3-thiazole, the latter being more reactive than the former toward electrophiles. This methodology constitutes a new entry to a variety of functionalized thiazoles and thiazolines which are potential building blocks for the synthesis of natural compounds and analogues of biologically active molecules (penems, arylpropionic acids). Some ring transformations of thiazoles induced by carbon-sulfur bond cleavage are also described. The fundamental role played by the sulfur atom of the thiazole ring in the observed reactions is pointed out and briefly discussed.     

Development of diversified methods for chemical modification of the 5,6-double bond of uracil derivatives depending on active methylene compounds

The reaction of 5-halogenouracil and uridine derivatives 1 and 7 with active methylene compounds under basic conditions produced diverse and selective C-C bond formation products by virtue of the nature of the carbanions. Three different types of reactions such as the regioselective C-C bond formation at the 5- and 6-positions of uracil and uridine derivatives (products 2, 5, 8, 17, 20 and 21), and the formation of fused heterocycle derivatives 2,4-diazabicyclo[4.1.0]heptane (15) and 2,4-diazabicyclo-[4.1.0]nonane (16) via dual C-C bond formations at both the 5- and 6-positions were due to the different active methylene compounds used as reagents.     

Stereoselective Synthesis of Enamides through Palladium-Catalyzed Oxidative Amidation of Conjugated Olefins with 2-Pyridones

A palladium-catalyzed oxidative amidation of conjugated olefin with 2-pyridone is described. A series of E-Enamides were synthesized in a highly stereocontrolled manner. The reaction also accommodates other cyclic and acyclic amides. Z-Enamides were predominantly prepared for primary amides probably due to the presence of an intramolecular hydrogen bond. Gram-scale synthesis of enamide and the following oxidative annulation with diphenylacetylene demonstrates the synthetic utility of this reaction.     

Ring–Opening of a Carbohydrate Triflate to form an Acyclic Alkene

ABSTRACT

The ease with which carbohydrate trifluoromethanesulfonates (triflates) undergo substitution reactions with a wide variety of nucleophiles¹ has allowed these compounds to play an increasingly important role in synthetic carbohydrate chemistry.² The exceptional reactivity of triflates also creates an opportunity for unusual reactions to occur;³ for example, triflyl group migration⁴ and internal displacement by very weak nucleophiles⁵ both have been observed. Also, carbohydrate triflates have been used as alkylating agents in oligosaccharide synthesis.⁶ In this communication a new triflate reaction is described. This new process is one in which departure of the triflyloxy group is accompanied by ring opening to give an acyclic alkene.     

Lewis base activation of Lewis acids. Vinylogous aldol addition reactions of conjugated N,O-silyl ketene acetals to aldehydes

N,O-Silyl dienyl ketene acetals derived from unsaturated morpholine amides have been developed as highly useful reagents for vinylogous aldol addition reactions. In the presence of SiCl4 and the catalytic action of chiral phosphoramide (R,R)-3, N,O-silyl dienyl ketene acetal 8 undergoes high-yielding and highly site-selective addition to a wide variety of aldehydes with excellent enantioselectivity. Of particular note is the high yields and selectivities obtained from aliphatic aldehydes. Low catalyst loadings (2-5 mol %) can be employed. The morpholine amide serves as a useful precursor for further synthetic manipulation.     

Reactivite des organomagnesiens vis-a-vis de composes acetyleniques en presence du complexe de nickel (PPh3)2NiCl2

In the presence of dichlorobis(triphenylphosphine) nickel, acetylenic compounds undergo stereospecific or stereoselective syn addition of non recuding Grignard reagent. With reducing Grignard reagents, addition and reduction reactions are observed. These reactions yield vinylic organomagnesium compounds. A catalytic process is proposed to explain the experimental results.