Phosphines, as nucleophiles

Phosphines, as nucleophiles, add to many unsaturated substrates giving metal-lated ylides. Scheme 17 collects some representative examples of the addition of phosphines to carbyne complexes, giving (57) [132], to allenylidenes (58) [133], a-alkenyls (59) [134], or a-alkynyls (60) [135]. Moreover, reaction of phosphines with 7i-alkenes [136] and 71-aIkynes (61)-(64) [137-140] have also been reported. It is not possible to explain in depth each reaction, but the variety of resulting products provides an adequate perspective about the synthetic possibihties of this type of reactions. 

High enantiomeric excess in organocatalytic desymmetrization of meso-diols using chiral phosphines as nucleophilic catalysts was achieved for the first time by Vedejs et al. (Scheme 13.21) [36a], In this approach selectivity factors up to 5.5 were achieved when the C2-symmetric phospholane 42a was employed (application of chiral phosphines in the kinetic resolution of racemic secondary alcohols is discussed in Section 12.1). A later study compared the performance of the phos-pholanes 42b-d with that of the phosphabicyclooctanes 43a-c in the desymmetrization of meso-hydrobenzoin (Scheme 13.21) [36b], Improved enantioselectivity was observed for phospholanes 42b-d (86% for 42c) but reactions were usually slow. Currently the bicyclic compound 43a seems to be the best compromise between catalyst accessibility, reactivity, and enantioselectivity - the monobenzoate of hydrobenzoin has been obtained with a yield of 97% and up to 94% ee [36b]. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Fundamentally, the high nucleophilicity of stable carbenes, coupled with the tendency to increase the coordination number at the carbenic carbon, renders their chemical behavior very similar to that of electron-rich phosphines. As such, they have aroused considerable interest as ligands in p-, cl-, and / -block chemistry. Earlier reviews (7a,b) have covered some aspects of the main group chemistry of stable nucleophilic carbenes however, there has been considerable recent activity in this field, and thus a comprehensive, up-to-date review was considered desirable. 

Vinylsilane to copper transmetallation has entered the literature,93 93a,93b and a system suitable for catalytic asymmetric addition of vinylsilanes to aldehydes was developed (Scheme 24).94 A copper(l) fluoride or alkoxide is necessary to initiate transmetallation, and the work employs a copper(ll) fluoride salt as a pre-catalyst, presumably reduced in situ by excess phosphine ligand. The use of a bis-phosphine was found crucial for reactivity of the vinylcopper species, which ordinarily would not be regarded as good nucleophiles for addition to aldehydes. The highly tailored 5,5 -bis(di(3,5-di-tert-butyl-4-methoxyphenyl)phosphino-4,4 -bis(benzodioxolyl) (DTBM-SEGPHOS) (see Scheme 24) was found to provide the best results, and the use of alkoxysilanes is required. Functional group tolerance has not been adequately addressed, but the method does appear encouraging as a way to activate vinylsilanes for use as nucleophiles. 

According to the latter approach, reducing sugars 128 were reacted with triethylammonium dimethyl boranophosphate in the presence of bis(2-oxo-3-oxazolidinyl)phosphinic chloride as condensing reagent, 3-nitro- 1,2,4-triazole as nucleophilic catalyst and A,A-diisopropyl-A-ethyl-amine to provide boranophosphate triester derivatives 129 as anomeric... 

The borane adducts of phosphines having hydrogen, methyl or methylene groups adjacent to the phosphoms can be easily deprotonated by strong bases and the resulting anions react with various nucleophiles affording borane-protected tertiaiy phosphines as air stable, crystalline materials [23], Quantitative deprotection of the phosphoms can be achieved by treatment with morpholine at 110 °C followed by evaporation to dryness. Dissolution of the solid residue and addition of THF results in precipitation of the products such as -among others-19. 

A different approach to synthesize nonstabilized ylide complexes is the reaction of halomethyl-metallic precursors with the corresponding nucleophile EZ . This method is quite general and usually occurs in very mild reaction conditions. Platinum, rhodium, iron, and palladium complexes (21)-(25) (Scheme 8) have been prepared, using phosphines [79-83], amines [84], or sulfides [85] as nucleophiles. Some of the most representative examples are shown in Scheme 8. 

By contrast, the use of phosphines as catalysts is a more recent phenomenon and the development of chiral phosphines has been less well explored, possibly also because of synthetic difficulties associated with developing chiral nucleophilic phosphorus-containing scaffolds. 

In order to accelerate these types of reactions, Che et al. applied microwave conditions, a variety of phosphine gold(I) complexes as catalysts and carboxamides as nucleophiles, in both intra- and inter-molecular transformations [66]. 

Non-activated aryl bromides (but not fluorides) can be used as substrates for palla-dium(0)-catalyzed aromatic nucleophilic substitutions with aliphatic or aromatic amines. These reactions require sodium alcoholates or cesium carbonate as a base, and sterically demanding phosphines as ligands. Moreover, high reaction temperatures are often necessary to achieve complete conversion (Entries 7 and 8, Table 10.4 Experimental Procedure 10.1). Unfortunately, the choice of substituents on the amine... 

Ring-opening reactions of phosphetanes (phosphetanium salts) are known to be promoted by nucleophiles. The reaction profile has been analyzed by theoretical calculations (HF/6-31+G(d)) <2001JOC915> and compared with those of a phosphirane and an acyclic phosphine as shown (Equations 2-4). The activation energy (/. /,) for the reaction of a four-membered ring is twice as high as that for a three-membered ring, whereas exothermicities (AE0) of both reactions are almost identical. 

Palladium-catalyzed nucleophilic substitutions of activated allylic alcohols have been investigated using a bicyclic phosphine as the chiral element. Reactions have been reported with racemic acyclic allylic acetates <1999TL7791> and cycloalkenyl carbonates <2001TL1297> using the phosphine 203, with good to excellent enantiomeric excesses. 

Compared to diazonium salts, diazo compounds are generally much less reactive towards nucleophiles than towards electrophiles. As a result of this azo coupling reactions of diazo compounds are the exception rather than the rule. Electron withdrawing substituents on the diazo carbon increase the reactivity towards nucleophiles. Consequently the ability to undergo azo coupling reactions increases from diazomethane to diazocarbonyl- and 2-diazo-l, 3-dicarbonyl compounds. Among the earliest reactions known were those with cyanide and sulfite ions Tertiary phosphines, as opposed to amines, can form stable addition complexes with diazoalkanes probably due to the ability of phosphorus to stabilize the betaine with its empty d orbitals (6). 

In the simplest of these, jS-enaminones are synthesized (equation 129) by the addition of amines to 1,3-diketones or /3-ketoesters. The reaction has been apphed to the Friedlander synthesis of quinolines by condensation of the enaminone and other carbonyl present in the substrate. Substituted pyrroles in equation (130) can be obtained as well when a propargyl group is present, by addition of the enaminone to the triple bond. Alcohols, thiols, and secondary phosphines have been also tested as nucleophiles with good results. A particularly interesting case is found in the condensation of indoles with 1,3-diketones to give substituted indol derivatives in equation (131). ... 

It is worth mentioning the synthesis of cyclic a-methylene carbamates, which were also produced via Markovnikov intramolecular nucleophilic addition of O-car-bamates, generated in situ from a propargylic amine and CO2, in the presence of Ru(cod) (cot)/phosphine as catalyst precursor (cod cyclooctadiene cot cycloocta-triene) (Scheme 8.23) [75]. 

White phosphorus also reacts with carbon nucleophiles in ether or tetrahydrofuran to give dark red solutions believed to be complex organophosphides (Rauhut and Semsel). Hydrolysis of a mixture obtained from reactions of white phosphorus with organolithium and organomagnesium compounds gives the primary phosphine as the major product, with small amounts of secondary and tertiary phosphines being formed under some conditions. 

Substitution of CO by phosphines 145 The Dotz reaction 149 Rearrangement reactions with loss of CO 151 Photochemical reactions 153 Reactions at the carbene carbon 158 General features 158 Amine nucleophiles 159 Phospine and phosphite nucleophiles 167 Alcohols and alkoxide ion nucleophiles 171 Thiol and thiolate ion nucleophiles 179 Intramolecular nucleophilic reactions 191 Hydroxide ion and water as nucleophiles 194 Insertion reactions initiated by nucleophilic attack Acid-base reactions at the a-carbon 207 General features and methods 207 Kinetic and thermodynamic acidities 209 Effect of structure on pKa values 210 Intrinsic rate constants for proton transfer 219 Thermodynamic acidities in organic solvents 223 Hydrolysis of ionizable carbene complexes 228 Acknowledgments 232 References 233... 

Nucleophilic catalytic reactions are usually addition and substitution reactions. A diverse array of Lewis bases (e.g., tertiary phosphines, tertiary amines, pyridines, and imidazoles) have been shown to serve as nucleophilic catalysts. Nucleophilic reactions typically occur at C=X and activated C=C multiple bonds. In a general form for a reaction... 

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