Novel Approach to the Synthesis of Phosphorus Sulfur Organic Compounds and Their Metal Complexes

Abstract

The reaction of elemental phosphorus (P_{ti 4}) and sulfur with protonodonor reagents (alcohols, phenols, and thiols) has been studied in the presence of amines and complexes based on trialkyltrithiophosphites and transition metal halides. A novel approach to the synthesis of phosphorus sulfur organic compounds has been proposed on the basis of these reactions.     

A Simple Procedure for Preparing Annulated p-Benzoquinones. Improved Synthesis of 1,4-Dihydro-1,4-methanonaphthalene-5,8-dione

A simple and efficient two-step, one-pot synthesis of substituted 1,4-dihydro-1,4-methanonaphthalene-5,8-diones is reported. This synthesis, which utilizes readily available starting materials and inexpensive reagents, can be used to prepare 1a-1c in 70–90% overall yield. This procedure was extended successfully to prepare a more highly complex annulated p-benzoquinone i.e., 8.     

Polystyrene‐Supported (Catecholato)oxorhenium Complexes: Catalysts for Alcohol Oxidation with DMSO and for Deoxygenation of Epoxides to Alkenes with Triphenylphosphine

Polymer‐supported catalysts offer practical advantages for organic synthesis, such as improved product isolation, ease of catalyst recycling, and compatibility with parallel solution‐phase techniques. We have developed the (carboxypolystyrene‐catecholato)rhenium catalyst 2 derived from tyramine (=4‐(2‐aminoethyl)phenol), which is effective for alcohol oxidation with dimethylsulfoxide (DMSO) and for epoxide deoxygenation with triphenylphosphine. The supported [Re(catecholato)]catalyst 2 is air‐ and moisture‐stable and can be recovered and used repeatedly without decreasing activity. The procedures work with non‐halogenated solvents (toluene). DMSO for Re‐catalyzed alcohol oxidation is inexpensive and safer for transport and storage than commonly used peroxide reagents. The oxidation procedure was best suited for aliphatic alcohols, and the mild conditions were compatible with unprotected functional groups, such as those of alkenes, phenols, nitro compounds, and ketones (see Tables 1 and 2). Selective oxidation of secondary alcohols in the presence of primary alcohols was possible, and with longer reaction time, primary alcohols were converted to aldehydes without overoxidation. Epoxides (oxirans) were catalytically deoxygenated to alkenes with this catalyst and Ph₃P (see Table 3). Alkyloxiranes were converted to the alkenes with retention of configuration, while partial isomerization was observed in the deoxygenation of cis‐stilbene oxide ( cis‐1,2‐diphenyloxirane). These studies indicate that supported [Re(catecholato)] complexes are effective catalysts for O‐atom‐transfer reactions, and are well suited for applications in organic synthesis.     

Facile Preparation of Benzylic Iodides Under Solvent‐Free Conditions Using Microwave Irradiation

Abstract

Benzylic alcohols are rapidly converted to the corresponding benzylic iodides using combination of p‐toluenesulfonic acid (PTSA) and potassium iodide under solvent‐free microwave irradiation conditions.     

A Rapid and Convenient Synthesis of Homoallylic Alcohols by the Barbier‐Grignard Reaction

Abstract

The use of the Barbier‐Grignard reaction, where premixed allyl bromide and the carbonyl compound are added to magnesium in ether, is reported for the synthesis of homoallylic alcohols. This reaction provides good to excellent yields of most homoallylic alcohols with minimal formation of Wurtz coupling products.     

Metal‐Free I2‐Catalyzed Highly Selective Dehydrogenative Coupling of Alcohols and Cyclohexenones

The I₂ catalyzed highly selective oxidative condensation of cyclohexenones and alcohols for the synthesis of aryl alkyl ethers has been described. DMSO is employed as the mild terminal oxidant. This novel methodology offers a metal‐free reaction condition, operational simplicity and broad substrate scope to afford valuable products from inexpensive reagents. Various meta‐substituted aromatic ethers which are hardly synthesized from the reported methods requiring meta‐substituted phenols, are efficiently prepared by the present protocol.     

Selective organic synthesis through generation and reactivity control of hyper‐coordinate metal species

This paper is a review of my 40 years of research at Kyoto, Sagamihara, and Yokohama, all based on the generation of hyper‐coordinate metal species such as ate complexes and pentacoordinate silicates. The topics are: (i) carbenoid reagents for carbon–carbon bond‐forming reactions, (ii) nucleophilic substitution at acetal carbons using aluminate reagents, (iii) preparation of magnesium enolates and its reaction with nitriles, (iv) Cr(II) reagents for reduction of organic halides and highly selective carbon–carbon bond formation, (v) organic synthesis with organosilion reagents/fluoride ions, (vi) cross‐coupling reaction of organosilicon compounds, and (vii) silicon‐based conjugate addition to α,β‐unsaturated carbonyl acceptors. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 337–350; 2008: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20162     

Selective reduction of organic compounds with Al-acetoxy- and Al-trifluoroacetoxydiisobutylalane

The new MPV-type reagents, Al-acetoxydiisobutylalane (DIBAOAc) and Al-trifluoroacetoxydiisobutylalane (DIBAO₂CCF₃), have been prepared and their reducing characteristics in the reduction of selected organic compounds containing representative functional groups have been examined in order to find out a new reducing system with unique applicability in organic synthesis. In general, the reactivity of DIBAO₂CCF₃ appears to be much stronger than that of DIBAOAc, presumably due to the acidity increase by the electron-withdrawing fluorine-substituent. Both reagents reduce aldehydes and ketones relatively slowly, but show an excellent selectivity in 1,2-reduction of α,β-unsaturated carbonyl compounds to produce the corresponding allylic alcohols in an absolutely 100% purity. In addition, the reagents achieve the regioselective cleavage of phenyl- or alkyl-substituted epoxides to the less substituted alcohols in an excellent selectivity. Moreover, both reagents show interesting features in the stereoreduction of cyclic ketones. However, these reagents show a very low or/and no reactivity toward most organic functional groups other than carbonyl and epoxy function.     

Synthesis of α,α‐Difluoromethylene Alkynes by Palladium‐Catalyzed gem‐Difluoropropargylation of Aryl and Alkenyl Boron Reagents

gem‐Difluoropropargyl bromides are versatile intermediates in organic synthesis, but have rarely been employed in transition‐metal‐catalyzed cross‐coupling reactions. The first palladium‐catalyzed gem‐difluoropropargylation of organoboron reagents with gem‐difluoropropargyl bromides is now reported. The reaction proceeds under mild reaction conditions with high regioselectivity; it features a broad substrate scope and excellent functional‐group compatibility and thus provides an attractive approach for the synthesis of complex fluorinated molecules, in particular for drug discovery and development.     

Isolation and Synthesis of Dibenzocyclooctadiene Lignans: (±)‐Schizandrin and Its Analogues

Simple isolation of (±)‐schizandrin (1) and preparation of its analogues (6–8) via acylation of (±)‐schizandrin (1) are described. The key strategy in the synthesis involves the catalytic acylation reaction of 1 with several acylating reagents.     

Solid‐Phase Synthesis of N‐Aryl‐N′‐Carboalkoxy Guanidines by the Mitsunobu Reaction of Fmoc‐Guanidines

Abstract

A new method for the solid‐phase synthesis of N‐aryl‐N′‐carboalkoxy guanidines is described. Aromatic amines were reacted with Fmoc‐isothiocyanate to provide Fmoc‐thioureas, which were coupled with Rink amide resin to provide the corresponding resin‐bound Fmoc‐guanidines. Subsequent Mitsunobu alkylation with a variety of alcohols delivered N‐aryl‐N′ carboalkoxy guanidines in good to high purity after resin cleavage.     

Application of the PMC Protecting Group in the Efficient Synthesis of 4,4‐Disubstituted Piperidines

Abstract

An efficient synthesis of the 4,4‐disubstituted piperidine scaffold 1 was accomplished by treating the PMC N‐protected α,β‐unsaturated ethyl cyanoacetate 9 with various Grignard reagents (R₁MgX). Subsequent heating at 190°C in a strong base provided carboxylic acids 12–20b in good yield. The PMC group was easily removed at room temperature with 33% HBr in acetic acid.     

Green synthesis of new pyrimido[4,5‐d]pyrimidine derivatives using 7‐aminonaphthalene‐1,3‐disulfonic acid‐functionalized magnetic Fe3O4@SiO2 nanoparticles as catalyst

We, herein, describe a novel, simple, efficient and one‐pot multi‐component procedure for the synthesis of substituted pyrimido[4,5‐d]pyrimidines via reaction of N,N‐dimethyl‐6‐amino uracil, isothiocyanate and aromatic aldehydes promoted by 7‐aminonaphthalene‐1,3‐disulfonic acid (ANDSA)‐functionalized magnetic Fe₃O₄@SiO₂ in water as solvent and without using any other harmful organic reagents. Compared with other reactions, using these organic–inorganic hybrid heterogeneous catalysts can help us to achieve a green procedure, high catalytic activity, easy recovery with an external magnetic field, and short reaction times.     

Access to chiral α-bromo and α-H-substituted tertiary allylic alcohols via copper(I) catalyzed 1,2-addition of Grignard reagents to enones

The catalytic asymmetric synthesis of tertiary alcohols by the addition of organometallic reagents to ketones is of central importance in organic chemistry. The resulting quaternary stereocentres are difficult to prepare selectively by other means despite their widespread occurrence in natural products and pharmaceuticals. Here we report on a new methodology which allows access to both α-bromo-substituted and α-H-substituted allylic tertiary alcohols with excellent yields, and enantioselectivities of up to 98% using the copper(I)-catalysed 1,2-addition of Grignard reagents to enones. As an example, the methodology is applied in the synthesis of a chiral dihydrofuran.     

The Economic Synthesis of Pyridinium Fluorochromate(VI), C5H5NH[CrO3F] (PFC), and Solvent‐Free Oxidation of Organic Substrates with PFC

Abstract

A 1:1:1 stoichiometric reaction among CrO₃, aqueous HF and pyridine affords orange crystalline pyridinium fluorochromate(VI), C₅H₅NH[CrO₃F] (PFC), in 99.2% isolated yield. The reagent under solvent‐free conditions readily converts benzylic, secondary, and allylic alcohols to the corresponding carbonyls and selectively oxidizes secondary alcohols in the presence of primary alcohols, polycyclic hydrocarbons to cyclic ketones, benzoin to benzil, PPh₃ to O?PPh₃, methylphenyl sulfide to sulfoxide, cyclohexanone oxime to cyclohexanone, an allylic Δ⁵‐steroid to the corresponding α,β‐unsaturated ketone and deprotects dioxolanes and dithiolanes to aldehydes; the economic synthesis of PFC, its ease of reaction without solvent, versatility, and high isolated yields of the products are the significant features of the protocol.     

Organoallylaluminum reagents promote easy access to trihalomethyl triazolyl homoallylic alcohols analogous to rufinamide

The results of allylation reactions employing allylaluminum reagents are described for 5-substituted (2,6-difluorobenzyl)-4-trifluoro(chloro)acetyl-1H-1,2,3-triazoles (1), in which the 5-substituents are H, Me, and Ph. The allylating reagents were generated in situ by the catalytic insertion of aluminum into allyl and crotyl bromides (2), in order to furnish a new series of twelve trihalomethyl triazolyl homoallylic alcohols (3) at yields of up to 94%. The excellent reactivity of these organoallyl reagents is highlighted as an economical alternative to the indium-mediated reactions to produce homoallylic alcohols, which are important building blocks in organic synthesis.     

Direct Borylation of Primary C?H Bonds in Functionalized Molecules by Palladium Catalysis

Organoborane compounds are among the most commonly employed intermediates in organic synthesis and serve as crucial precursors to alcohols, amines, and various functionalized molecules. A simple palladium‐based system catalyzes the conversion of primary C(sp³) H bonds in functionalized complex organic molecules into alkyl boronate esters. Amino acids, amino alcohols, alkyl amines, and a series of bioactive molecules can be functionalized with the use of readily available and removable directing groups in the presence of commercially available additives, simple ligands, and oxygen (O₂) as the terminal oxidant. This approach represents an economic and environmentally friendly method that could find broad applications.     

Remote induction of stereoselective 1,2-addition of aryl Grignard reagents to β-sulfinyl enones

Optically active tert-allylic alcohols constitute important and often challenging targets in organic synthesis. In this work, we employed a β-sulfinyl moiety as a remote chiral auxiliary to effect asymmetric 1,2-addition of aryl Grignard reagents to enones to form a variety of optically active tert-allylic alcohols. The absolute configuration of a representative alcohol product was determined by X-ray crystallography.     

New Chemical Transformations Involving SO2F2-Mediated Alcohol Activation

Sulfuryl fluoride is a gas produced on a multi-ton scale for its use as a fumigant. In the last decades, it has gained interest in organic synthesis as a reagent with unique properties in terms of stability and reactivity when compared to other sulfur-based reagents. Sulfuryl fluoride has not only been used for sulfur-fluoride exchange (SuFEx) chemistry but also encountered applications in classic organic synthesis as an efficient activator of both alcohols and phenols, forming a triflate surrogate, namely a fluorosulfonate. A long-standing industrial collaboration in our research group drove our work on the sulfuryl fluoride-mediated transformations that will be highlighted below. We will first describe recent works on metal-catalyzed transformations from aryl fluorosulfonates while emphasizing the one-pot processes from phenol derivatives. In a second section, nucleophilic substitution reactions on polyfluoroalkyl alcohols will be discussed and the value of polyfluoroalkyl fluorosulfonates in comparison to alternative triflate and halide reagents will be brought to light.     

Facile and Efficient Method for the Prins Reactions of Styrenes and Homoallyl Alcohols to 1,3‐Dioxanes and 4‐Tetrahydropyranols Using Bismuth(III) Triflate

Abstract

Bismuth(III) triflate has been found to be an efficient catalyst for the Prins reactions of styrenes and homoallyl alcohols, the reaction proceeds rapidly and affords the corresponding 1,3‐dioxanes and tetrahydropyran‐4‐ol in good yields. Scope and limitations of the styrenes and homoallyl alcohols are reported.