Tetrakis(triphenylphosphine)palladium(0)1

Pd(PPh3)4

[14221-01-3]  · C72H60P4Pd  · Tetrakis(triphenylphosphine)palladium(0)  · (MW 1155.62)

(catalyzes carbon-carbon bond formation of organometallics with a wide variety of electrophiles;2 in combination with other reagents, catalyzes the reduction of a variety of functional groups;3 catalyzes carbon-metal (Sn, Si) bond formation;4 catalyzes deprotection of the allyloxycarbonyl group5)

Physical Data: mp has been reported to vary between 100-116 °C (dec) and is not a good indication of purity.

Solubility: insol saturated hydrocarbons; moderately sol many other organic solvents including CHCl3, DME, THF, DMF, PhMe, benzene.

Form Supplied in: yellow, crystalline solid from various sources. The quality of batches from the same source have been noted to be highly variable and can dramatically alter the expected reactivity.

Preparative Methods: readily prepared by the reduction of PdCl2(Ph3P)26 with Hydrazine or by the reaction of Tris(dibenzylideneacetone)dipalladium with Triphenylphosphine.7

Handling, Storage, and Precautions: is air and light sensitive and should be stored in an inert atmosphere in the absence of light. It can be handled for short periods quickly in the air but best results are achieved by handling in a glove box or glove bag under argon or nitrogen.

Direct Carbon-Carbon Bond Formation.

One of the most attractive features of Pd(Ph3P)4 is its ability to catalyze carbon-carbon bond formation under mild conditions by the cross-coupling of organometallic (typically organoaluminum,2e -boron,2f -copper, -magnesium, -tin,2b-d or -zinc2e reagents) and unsaturated electrophilic partners (halides or sulfonates such as trifluoromethanesulfonates2d (triflates)). Although Pd(Ph3P)4 is the catalyst of choice in many of these reactions, numerous other Pd0 and PdII catalysts have been used successfully.

Symmetrical or unsymmetrical biaryls are efficiently produced by the Pd(Ph3P)4 catalyzed cross-coupling of aryl halides or aryl triflates (I, Br > OTf in terms of rate of reaction8a) with a variety of metalated aromatics such as arylboronic acids,8 arylstannanes,9 aryl Grignards10 and arylzincs11 (eqs 1 and 2). Reactions employing ArB(OH)2 are carried out in aqueous base (2M Na2CO3 or K3PO4) while the remainder are conducted under anhydrous conditions. A recent report documents the reaction of ArB(OR)2 with ArBr under nonaqueous conditions in the presence of Thallium(I) Carbonate.8c Reactions employing ArOTf and ArSnR3 as coupling partners require greater than stoichiometric amounts of Lithium Chloride.9a,b Acceleration of the reaction rate has been noted in the coupling of ArSnMe3 and either ArOTf or ArBr/I by the addition of catalytic Copper(I) Bromide9c or stoichiometric Silver(I) Oxide,9f respectively. In many cases, one or both of the aromatic species can be heteroaromatic such as pyridine, furan, thiophene, quinoline, oxazole, thiazole, or indole.8e,9f,g,11 Symmetrical biaryls have been prepared in excellent yields by the Pd(Ph3P)4-catalyzed homocoupling of ArBr/I under phase transfer conditions.12

In a similar manner, Pd(Ph3P)4 catalyzes the cross-coupling of metalated alkenes, such as vinylaluminum reagents,13 vinylboronates or -boronic acids,8d,14 vinylstannanes,15 vinylsilanes,16 vinylzincs or -zirconates,17 vinylcuprates18 or -copper reagents19 and vinyl Grignards20 with vinyl halides (I, Br), triflates, or phosphates to form 1,3-dienes (eq 3). Vinylallenes,17f dienyl sulfides,14h and dienyl ethers17d have also been prepared using this strategy. In most instances the dienes are formed with retention of double bond geometry in both reacting partners.14g However, the formation of (E,Z)- and (Z,Z)-diene combinations has been documented to suffer from poor reaction yields or scrambling of alkene geometry in some cases (eq 4).14a,b,18-20 A dramatic rate enhancement has been noted in the coupling of vinyl iodides with vinylboronic acids by replacing the aqueous bases that are normally used (NaOEt or NaOH) with Thallium(I) Hydroxide14f,i or Thallium(I) Carbonate.21 LiCl15a,c is required when vinyl triflates are used in coupling reactions with vinylstannanes. Intramolecular versions of the vinylstannane-vinyl triflate coupling have been reported22 and the necessity of adding LiCl in these reactions has been debated.22a 1,3-Dienes have been prepared via the Pd(Ph3P)4-catalyzed reaction between allylic alcohols and aldehydes in the presence of Phenyl Isocyanate and Tri-n-butylphosphine (eq 5).23 (E/E):(E/Z) ratios range from 1:1 to 4:1.

Similar cross-coupling procedures have been used to prepare styrenes by the reaction of metalated aromatics with vinyl halides/triflates11d,24 or, conversely, metalated alkenes with aromatic halides/triflates9b,16,25 in the presence of Pd(Ph3P)4 (eq 6). Typically, ArCl are poor substrates in Pd(PPh3)4-catalyzed coupling reactions. However, by forming the chromium tricarbonyl complex of the aryl chloride, a facile coupling reaction with vinylstannanes can be achieved (eq 7).26

Enynes and arenynes are available from the Pd(Ph3P)4-catalyzed coupling of metalated alkynes (Mg,20 Al,13,27 Zn,17f,28 Sn15a,b,29) with vinyl or aryl halides, triflates or phosphates (eq 8). Alternatively, 1-haloalkynes and metalated alkenes (B14c or Zn11a,17a) can be utilized in similar procedures.

Enynes and arenynes can also be prepared by the Pd(Ph3P)4-catalyzed reaction between vinyl halides (I, Br, or Cl) and 1-alkynes in the presence of Copper(I) Iodide and an amine base such as RNH2 (R = Bu, Pr), Et2NH, or Et3N.30 A modified procedure employing aqueous base under phase transfer conditions has also been described (eq 9).31 The arenyne products derived from such coupling reactions provide ready access to substituted indoles (eq 10).29c,30d

Pd(Ph3P)4 catalyzes the coupling of simple alkyl metals and vinyl halides (Br, I) or triflates to form substituted alkenes (eq 11). Alkylboron,32 alkyl Grignard,20,33 alkylzinc,34 and alkylaluminum13 reagents have been particularly useful in this regard. A variety of functional groups on either reacting partner are tolerated and the reaction proceeds with retention of alkene geometry (usually >98%), providing stereochemically pure, highly substituted alkenes. For example, allylsilanes (eq 12)35 and vinylcyclopropanes (eq 13)36 have been prepared employing Trimethylsilylmethylmagnesium Chloride and cyclopropylzinc chloride, respectively, as the organometallic partner.

Ketones are obtained by the Pd(Ph3P)4-catalyzed coupling of acid chlorides with organometallic reagents (eq 14). Organozinc37 and organocopper38 reagents have been used most successfully, while other reports document the utility of R4Pb (R = Bu, Et),39 R4Sn (R = Me, Bu, Ph),40 and R2Hg (R = Et, Ph)41 reagents in this reaction. For those cases in which the organometallic reagent is alkenic, complete retention of alkene geometry is observed (see eq 14). In addition, the formation of tertiary alcohols is not observed under the conditions employed. A modified procedure that substitutes alkyl chloroformates for acid chlorides leads to an efficient preparation of esters (eq 15).37b,38 In a related reaction, Pd(Ph3P)4 catalyzes the coupling reaction between substituted aryl- or alkylsulfonyl chlorides and vinyl- or allylstannanes, providing a general route to sulfones (eq 16).42

The Pd(Ph3P)4-catalyzed reaction of various allylic electrophiles with carbon-based nucleophiles is a very useful method for the formation of C-C bonds under relatively mild conditions (eq 17) and has been extensively reviewed elsewhere.2a,43 The most commonly used electrophilic substrates for Pd(Ph3P)4-catalyzed allylic substitution reactions are allylic esters, carbonates, phosphates, carbamates, halides, sulfones, and epoxides. More recently, allylic alcohols themselves have been demonstrated to be useful substrates.44 Commonly employed nucleophiles include soft stabilized carbanions such as malonate and, to a lesser extent, a variety of organometallic reagents (Al, Grignards, Sn, Zn, Zr). A few selected examples begin to illustrate the scope of this reaction in terms of the general patterns of reactivity with respect to regioselectivity (eqs 18 and 19) and stereoselectivity (eqs 17 and 18). It should be noted that a variety of other Pd catalysts (including Palladium(II) Acetate-1,2-Bis(diphenylphosphino)ethane and Bis(dibenzylideneacetone)palladium(0)) have been shown to be useful in these alkylations. In addition, certain nitrogen-, sulfur-, and oxygen-based reagents are suitable nucleophilic substrates. The utility of some of these latter reagents are covered in subsequent sections.

Aldehydes and a-bromo ketones or esters are efficiently coupled in an aldol reaction in the presence of Diethylaluminum Chloride-Tri-n-butylstannyllithium (or Tin(II) Chloride) and catalytic Pd(Ph3P)4, providing b-hydroxy ketones or esters (eq 20).45

Carbonylative Carbon-Carbon Bond Formation.

A general, mild (50 °C), and high yielding conversion of halides and triflates into aldehydes via Pd(Ph3P)4-catalyzed carbonylation (1-3 atm CO) in the presence of Tri-n-butylstannane has been described (eq 21).46 The range of usable substrates is extensive and includes ArI, benzyl and allyl halides, and vinyl iodides and triflates. The reaction has been extended to include ArBr by carrying out the carbonylation at 80 °C under pressure (50 atm CO), using poly(methylhydrosiloxane) (PMHS) instead of tin hydride.47

Pd(Ph3P)4 catalyzes the carbonylation of benzyl48a and vinyl48b bromides under phase transfer conditions in the presence of hydroxide to form the corresponding carboxylic acids. A wide variety of substitution is tolerated and the products are formed in moderate to excellent yield at room temperature and at normal pressure (1 atm CO). Extension of the reaction to the formation of esters from aryl, alkyl, and vinyl bromides has been described.49 These transformations usually require a co-catalyst system of Pd(Ph3P)4 and [(1,5-cyclohexadiene)RhCl]2 in the presence of either M(OR)4 (M = Ti, Zr) or M(OR)3 (M = B, Al) (eq 22).

Vinyl triflates serve as substrates for Pd(Ph3P)4-catalyzed carbonylation and have been converted into the corresponding esters50 or ketones15c,51 (eq 23).

Aromatic and Vinyl Nitriles.

Aromatic halides (Br, I) have been converted into nitriles in excellent yields by Pd(Ph3P)4 catalysis in the presence of Sodium Cyanide/Alumina,52 Potassium Cyanide,53 or Cyanotrimethylsilane54 (eq 24). While the latter two procedures require the use of ArI as substrates, a more extensive range of substituents are tolerated than the alternative method employing ArBr. A Pd(Ph3P)4-catalyzed extrusion of CO from aromatic and heteroaromatic acyl cyanides (readily available from cyanohydrins) at 120 °C provides aryl nitriles in excellent yields (eq 25).55

Similarly, vinyl halides (Br, Cl) provide vinyl nitriles upon treatment with Pd(Ph3P)4/Potassium Cyanide/18-Crown-6.56

Carbon-Heteroatom (N, S, O, Sn, Si, Se, P) Bond Formation.

Primary and secondary amines (but not ammonia) undergo reaction with allylic acetates,57 halides,58 phosphates,59 and nitro compounds60 in the presence of Pd(Ph3P)4 to provide the corresponding allylic amines (eq 26). A variety of ammonia equivalents have been demonstrated to be useful in this Pd(Ph3P)4-catalyzed alkylation, including 4,4Ž-dimethoxybenzhydrylamine,57c NaNHTs,58 and NaN361 (eq 26). Both allylic phosphates and chlorides react faster than the corresponding acetates58,59a and (Z)-alkenes are isomerized to the (E)-isomers.57a,59a The use of primary amines as nucleophiles in the synthesis of secondary allyl amines is sometimes problematic since the amine that is formed undergoes further alkylation to form the tertiary amine. Thus hydroxylamines have been shown to be useful primary amine equivalents (eq 27) since the reaction products are easily reduced to secondary amines.59b

Allyl sulfones can be obtained by the Pd(Ph3P)4-catalyzed reaction of allylic acetates62 and allylic nitro compounds63,64 with NaSO2Ar (eq 28). Pd(Ph3P)4 also catalyzes the addition of HOAc to vinyl epoxides, providing a facile entry into 1,4-hydroxy acetates.65

Aryl halides (Br, I) have been converted in good yields into the corresponding arylstannanes or -silanes by treatment with R6Sn2 (R = Bu, Me)4,66 or Hexamethyldisilane,67 respectively, in the presence of catalytic Pd(Ph3P)4 (eq 29). Aryl9a,b and vinyl15b,68 triflates produce aryl- and vinylstannanes under similar conditions, provided Hexamethyldistannane and LiCl are used as co-reactants. In some cases, the presence of additional Ph3P has been observed to improve yields.68 By using the (Ph3Sn)2Zn-TMEDA complex, vinyl halides can also be converted into vinylstannanes.69

Acyltrimethylstannanes can be prepared in moderate yields by the treatment of acid chlorides with Me6Sn2 and catalytic Pd(Ph3P)4 in refluxing THF.70c However, Pd(Ph3P)2Cl2 is a superior catalyst for this transformation when using sterically bulky or electron-poor acyl halides.

Pd(Ph3P)4 catalyzes the addition of R6Sn2,70 R6Si2,71 Ph2S2, and Diphenyl Diselenide72 across the triple bond of 1-alkynes to provide the respective (Z)-1,2-addition products (eq 30). The (Z)-distannanes can be partially isomerized to the (E)-isomers by photolysis.70 The reaction cannot be extended to include internal alkynes containing alkyl substituents, but allenes do undergo 1,2-addition of disilane73 and ditin.74 In a similar fashion, Pd(PPh3)4 catalyzes the regio- and stereospecific addition of R3Sn-SiR3 to 1-alkynes, the (Z)-1-silyl-2-stannylalkene isomers being the sole products (eq 30).75

a,b-Acetylenic esters react with R6Sn2 in the presence of Pd(Ph3P)4 at room temperature to provide only the (Z)-2,3-distannylalkenoates (eq 31).76 When heated to 75-95 °C, clean isomerization to the (E)-isomers is observed. The corresponding amides are also useful substrates but provide either the (E)-isomers directly or (E/Z)-distannane mixtures.76 Surprisingly, under similar reaction conditions, a,b-alkynic aldehydes and ketones form (Z)-b-stannyl enals and enones in excellent yields (eq 32).77

The Pd(Ph3P)4-catalyzed hydrostannylation of 1-alkynes with R3SnH provides mixtures of vinylstannane regio- and stereoisomers, the ratios depending upon the nature of the alkyne substituents and the R group of the tin reagent.78 In general, when using alkyl-substituted 1-alkynes, Triphenylstannane provides (E)-1-stannylalkenes78a as the major products, while 2-stannylalkenes are obtained predominantly with (Bu3Sn)2Zn78c (eq 33). The Pd(Ph3P)4 mediated cis addition of R3Sn-H across symmetrical internal alkynes has also been demonstrated to be generally high yielding.78b The hydrostannylation of a,b-unsaturated nitriles with Bu3SnH/Pd(Ph3P)4 is regioselective, providing a-stannyl nitriles as the sole products.79

The Pd(Ph3P)4-mediated preparation of allyl- and benzylstannanes has been achieved by treatment of allylic acetates with Et2AlSnBu380 or by reacting benzyl halides (Br, Cl) with R6Sn2.66c In a similar fashion, allyl- and benzylsilanes are prepared by the Pd(Ph3P)4-catalyzed reaction of R6Si2 with allylic halides81 and benzyl halides,4 respectively. Allylstannanes have also been prepared by the addition of Bu3SnH to 1,3-dienes in the presence of Pd(Ph3P)4 (eq 34).82

Dialkyl aryl- and vinylphosphonates (RPO(ORŽ)2) are readily prepared in excellent yields by the reaction of aryl or vinyl bromides, respectively, with dialkyl phosphite (HPO(ORŽ)2) in the presence of catalytic Pd(Ph3P)4 and Et3N.83 In a related process, unsymmetrical alkyl diarylphosphinates (ArPhPO(OR)) are obtained in good yields, regardless of aromatic substitution, by the Pd(Ph3P)4-catalyzed coupling reaction between aryl bromides and alkyl benzenephosphonites (HPhPO(OR)).84

Oxidation Reactions.

a-Bromo ketones are dehydrobrominated to produce enones in low to good yields, especially when the products are phenolic, by treatment with stoichiometric Pd(Ph3P)4 in hot benzene.85 Primary and secondary alcohols are oxidized in the presence of PhBr, base (NaH or K2CO3) and Pd(Ph3P)4 as catalyst to the corresponding aldehydes or ketones.86 The practical advantages of these methods to alternative strategies have yet to be demonstrated.

Reduction Reactions.

At elevated temperatures (100-110 °C), ArBr and ArI are reduced to ArH in the presence of catalytic Pd(Ph3P)4 and reducing agents such as HCO2Na (eq 35),3,87 NaOMe,88 and PMHS/Bu3N.3 Aldehydes, ketones, esters, acids, and nitro substituents are unaffected. ArCl are poor substrates unless the aromatic nucleus is substituted with NO2.88 ArOTf are reduced in poorer yield under similar conditions; Pd(OAc)2 and Pd(Ph3P)2Cl2 are superior catalysts with these substrates.89 A limited number of examples of the Pd(PPh3)4-catalyzed reduction of vinyl bromides and triflates to alkenes in the presence of HCO2Na3 and Bu3SnH,15a,b respectively, have been described.

Pd(Ph3P)4 catalyzes the reductive displacement of a variety of allylic substituents with hydride transfer reagents. Allylic acetates are reduced to simple alkenes in the presence of Sodium Cyanoborohydride,90 PMHS,91 Samarium(II) Iodide/i-PrOH,92 or Bu3SnH93 (eq 36). Bu3SnH/Pd(Ph3P)4 also reduces allylic amines93 and thiocarbamates.94 All of these reductive procedures are accompanied by positional and/or geometrical isomerization of the alkene to an extent dependent upon the substrate structure. Interestingly, the Pd(Ph3P)4-catalyzed reduction of allylic sulfones with Sodium Borohydride is high yielding with no double bond positional isomerization observed.95 By using a more bulky reducing agent, Lithium Triethylborohydride, a range of allylic groups, such as methyl, phenyl, and silyl ethers, sulfides, sulfones, selenides, and chlorides, are reduced to alkenes in the presence of Pd(Ph3P)4 and excess Ph3P with little or no loss of alkene regio- or stereochemistry (eq 37).96 An interesting Pd(Ph3P)4-catalyzed reduction of allylic acetates, tosylates, and chlorides to the corresponding alkenes has been described that uses n-BuZnCl as the hydride source.97 This procedure proceeds with high levels of regio- and stereospecificity, but the scope has yet to be explored.

Acid chlorides98 and acyl selenides99 are efficiently reduced in the presence of Bu3SnH under Pd(Ph3P)4 catalysis to provide the corresponding aldehydes in good to excellent yields without the formation of ester or alcohol byproducts (eq 38). A wide variety of substrate substituents, such as alkenes, nitriles, bromides, and nitro groups, are tolerated.

The conjugate reduction of a,b-unsaturated ketones and aldehydes to the saturated analogs can be accomplished in the presence of Pd(Ph3P)4 and hydride transfer reagents such as Bu3SnH100 or mixed systems of Bu3SnH/HOAc or Bu3SnH/ZnCl2.79 A potentially more versatile, general, and selective reduction procedure involves a three-component system of Pd(Ph3P)4/Ph2SiH2/ZnCl2 (eq 39).101 a,b-Unsaturated esters and nitriles are untouched using this latter method.

a-Bromo ketones are reductively debrominated to the parent ketones in the presence of Pd(Ph3P)4 and Ph2SiH2/K2CO3 at room temperature.102 However, Hexacarbonylmolybdenum appears to be a superior catalyst for this conversion. Reductive debromination of a-bromo ketones, acids, and nitriles can also be accomplished by Pd(Ph3P)4 catalysis using PMHS/Bn3N,87b HCO2Na,87b or Me6Si2103 as hydrogen donors but under much more drastic conditions (110-170 °C).

Removal of Allyloxycarbonyl (Aloc) and Allyl Protecting Groups.

The allyloxycarbonyl protecting group5 has been used extensively for the protection of a variety of alcohols104 and amines,105 including the amines of nucleotide bases,106 N-terminal amines of amino acids and peptides,107 and amino sugars.108 Pd(Ph3P)4 mediates the high yielding removal of the Aloc group in the presence of nucleophilic allyl scavengers (eq 40) such as Bu3SnH, 2-ethylhexanoic acid, dimedone, malonate, Ammonium Formate, N-Hydroxysuccinimide, and various amines including Morpholine and Pyrrolidine. The deprotections are effected at or below room temperature, often in the presence of excess Ph3P. The mild conditions used in these procedures leave most of the common N or O protecting groups intact, including Boc, TBDMS, MMT, DMT, and carbonates.

The Pd(Ph3P)4-catalyzed removal of the O-allyl protecting group has been described for a number of systems.5 For example, allyl esters are efficiently cleaved to the parent acid in chemically sensitive systems such as penicillins105,109 and glycopeptides.110 The internucleotide phosphate linkage, protected as the allyl phospho(III)triester, remains intact upon deprotection under Pd(Ph3P)4 catalysis.111 Allyl ethers that protect the anomeric hydroxy in carbohydrates (mono- and disaccharides) are efficiently removed under Pd(Ph3P)4 catalysis in hot (80 °C) HOAc.112

Rearrangements, Isomerizations and Eliminations.

Pd(Ph3P)4 catalyzes several [3,3]-sigmatropic rearrangements including those of O-allyl phosphoro- and phosphonothionates to the corresponding S-allyl thiolates (eq 41)113 and allylic N-phenylformimidates to N-allyl-N-phenylformamides (eq 42).114 The 3-aza-Cope rearrangement of N-allylenamines to g,d-unsaturated imines (eq 43)115 and a Claisen rearrangement but with no allyl inversion116 have also been described. In general, these Pd(Ph3P)4-catalyzed rearrangements provide compounds that are either not accessible via thermal reactions or are produced only under much more forcing reaction conditions. For those cases in which the allyl moiety contains substituents that may lead to regioisomers upon rearrangement, the less substituted isomer is usually favoured113,115 (see eq 41), although exceptions are known.114

Pd(Ph3P)4 catalyzes stereoselective, intramolecular metallo-ene reactions of acetoxydienes in HOAc, efficiently generating a range of cyclic 1,4-dienes (eq 44).117 The reactions proceed in good to excellent yields and have been extended to include the preparation of pyrrolidines, piperidines, and tetrahydrofurans by incorporating N and O atoms into the bridge that tethers the reactive alkenes.

The isomerization of allylic acetates is a useful method for allylic oxygen interconversion. Although these reactions are typically carried out in the presence of PdII catalysts such as Pd(OAc)2, Pd(Ph3P)4 has proven to be useful in the 1,3-rearrangement of a-cyanoallylic acetates to g-acetoxy-a,b-unsaturated nitriles (eq 45).118 These compounds are conveniently transformed into furans.

Several 1,3-diene syntheses involving elimination reactions that are catalyzed by Pd(Ph3P)4 have been reported. The first involves the Et3N mediated elimination of HOAc from allylic acetates in refluxing THF.119 A complementary procedure involves the Pd(Ph3P)4 catalyzed decarboxylative elimination of b-acetoxycarboxylic acids (eq 46).120 The substrates are easily prepared by the condensation of enals and carboxylate enolates; irrespective of the diastereomeric mixture, (E)-alkenes are formed in a highly stereocontrolled manner. The geometry of the double bond present in the enal precursor remains unaffected in the elimination and the reaction is applicable to the formation of 1,3-cyclohexadienes.

Monoepoxides of simple cyclic 1,3-dienes are smoothly converted in good yield to b,g-unsaturated ketones in the presence of Pd(Ph3P)4 catalyst (eq 47).121 Other vinyl epoxides, such as those in open chains or in cyclic systems in which the double bond is not in the ring, are converted under similar conditions into dienols.

A mixture of Pd(Ph3P)4/dppe catalyzes the transformation of a,b-epoxy ketones, readily available via several methods, into b-diketones (eq 48).122 The reaction is applicable to both cyclic and acyclic compounds, although epoxy ketones bearing an a-alkyl group are poor substrates.

Related Reagents.

Diphenylsilane-Tetrakis(triphenylphosphine)palladium(0)-Zinc Chloride.


1. (a) Heck, R. F. Palladium Reagents in Organic Syntheses; Academic: London, 1985. (b) Tsuji, J. Organic Synthesis with Palladium Compounds; Springer: Berlin, 1980.
2. (a) Frost, C. G.; Howarth, J.; Williams, J. M. J. TA 1991, 3, 1089. (b) Stille, J. K. PAC 1985, 57, 1771. (c) Stille, J. K. AG(E) 1986, 25, 508. (d) Scott, W. J.; Stille, J. K. ACR 1988, 21, 47. (e) Negishi, E. ACR 1982, 15, 340. (f) Suzuki, A. PAC 1985, 57, 1749. (g) Beletskaya, I. P. JOM 1983, 250, 551. (h) Mitchell, T. N. JOM 1986, 304, 1.
3. Pri-Bar, I.; Buchman, O. JOC 1986, 51, 734.
4. Azarian, D.; Dua, S. S.; Eaborn, C.; Walton, D. R. M. JOM 1976, 117, C55.
5. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991.
6. Coulson, D. Inorg. Synth 1972, 13, 121.
7. Ito, T.; Hasegawa, S.; Takahashi, Y.; Ishii, Y. JOM 1974, 73, 401.
8. (a) Fu, J.; Snieckus, V. TL 1990, 31, 1665. (b) Miyaura, N.; Yanagi, T.; Suzuki, A. SC 1981, 11, 513. (c) Sato, M.; Miyaura, N.; Suzuki, A. CL 1989, 1405. (d) Takayuki, O.; Miyaura, N.; Suzuki, A. JOC 1993, 58, 2201. (e) Sharp, M. J.; Snieckus, V. TL 1985, 26, 5997. (f) Sharp, M. J.; Cheng, W.; Snieckus, V. TL 1987, 28, 5093. (g) Miller, R. B.; Dugar, S. OM 1984, 3, 1261. (h) Thompson, W. J.; Gaudino, J. JOC 1984, 49, 5237. (i) Huth, A.; Beetz, I.; Schumann, I. T 1989, 45, 6679.
9. (a) Echavarren, A. M.; Stille, J. K. JACS 1987, 109, 5478. (b) Echavarren, A. M.; Stille, J. K. JACS 1988, 110, 4051. (c) Gómez-Bengoa, E.; Echavarren, A. M. JOC 1991, 56, 3497. (d) Dondoni, A.; Fantin, G.; Fogagnolo, M.; Medici, A.; Pedrini, P. S 1987, 693. (e) Clough, J. M.; Mann, I. S.; Widdowson, D. A. TL 1987, 28, 2645. (f) Malm, J.; Björk, P.; Gronowitz, S.; Hörnfeldt, A.-B. TL 1992, 33, 2199. (g) Achab, S.; Guyot, M.; Potier, P. TL 1993, 34, 2127.
10. Widdowson, D. A.; Zhang, Y.-Z. T 1986, 42, 2111.
11. (a) Negishi, E.; Luo, F.-T.; Frisbee, R.; Matsushita, H. H 1982, 18, 117. (b) Negishi, E.; Takahashi, T.; King, A. O. OS 1988, 66, 67. (c) Roth, G. P.; Fuller, C. E. JOC 1991, 56, 3493. (d) Arcadi, A.; Burini, A.; Cacchi, S.; Delmastro, M.; Marinelli, F.; Pietroni, B. SL 1990, 47. (e) Pelter, A.; Rowlands, M.; Clements, G. S 1987, 51. (f) Pelter, A.; Rowlands, M.; Jenkins, I. H. TL 1987, 28, 5213.
12. Torii, S.; Tanaka, H.; Morisaki, K. TL 1985, 26, 1655.
13. Takai, K.; Sato, M.; Oshima, K.; Nozaki, H. BCJ 1984, 57, 108.
14. (a) Miyaura, N.; Yamada, K.; Suzuki, A. TL 1979, 3437. (b) Miyaura, N.; Suginome, H.; Suzuki, A. TL 1981, 22, 127. (c) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. JACS 1985, 107, 972. (d) Miyaura, N.; Satoh, M.; Suzuki, A. TL 1986, 27, 3745. (e) Satoh, M.; Miyaura, N.; Suzuki, A. CL 1986, 1329. (f) Uenishi, J.; Beau, J.-M.; Armstrong, R. W.; Kishi, Y. JACS 1987, 109, 4756. (g) Miyaura, N.; Suginome, H.; Suzuki, A. T 1983, 39, 3271. (h) Ishiyama, T.; Miyaura, N.; Suzuki, A. CL 1987, 25. (i) Roush, W. R.; Moriarty, K. J.; Brown, B. B. TL 1990, 31, 6509.
15. (a) Scott, W. J.; Crisp, G. T.; Stille, J. K. JACS 1984, 106, 4630. (b) Scott, W. J.; Stille, J. K. JACS 1986, 108, 3033. (c) Scott, W. J.; Crisp, G. T.; Stille, J. K. OS 1990, 68, 116. (d) Stille, J. K.; Groh, B. L. JACS 1987, 109, 813.
16. Hatanaka, Y.; Hiyama, T. TL 1990, 31, 2719.
17. (a) Negishi, E.; Okukado, N.; King, A. O.; Van Horn, D. E.; Spiegel, B. I. JACS 1978, 100, 2254. (b) Negishi, E.; Takahashi, T.; Baba, S. OS 1988, 66, 60. (c) Negishi, E.; Luo, F.-T. JOC 1983, 48, 1562. (d) Negishi, E.; Takahashi, T.; Baba, S.; Van Horn, D. E.; Okukado, N. JACS 1987, 109, 2393. (e) Okukado, N.; Van Horn, D. E.; Klima, W. L.; Negishi, E. TL 1978, 1027. (f) Ruitenberg, K.; Kleijn, H.; Elsevier, C. J.; Meijer, J.; Vermeer, P. TL 1981, 22, 1451.
18. (a) Jabri, N.; Alexakis, A.; Normant, J. F. TL 1981, 22, 959. (b) Jabri, N.; Alexakis, A.; Normant, J. F. BSF(2) 1983, 321.
19. (a) Jabri, N.; Alexakis, A.; Normant, J. F. TL 1982, 23, 1589. (b) Jabri, N.; Alexakis, A.; Normant, J. F. BSF(2) 1983, 332.
20. Dang, H. P.; Linstrumelle, G. TL 1978, 191.
21. Hoshino, Y.; Miyaura, N.; Suzuki, A. BCJ 1988, 61, 3008.
22. (a) Piers, E.; Friesen, R. W.; Keay, B. A. CC 1985, 809. (b) Stille, J. K.; Tanaka, M. JACS 1987, 109, 3785.
23. Okukado, N.; Uchikawa, O.; Nakamura, Y. CL 1988, 1449.
24. (a) Miller, R. B.; Al-Hassan, M. JOC 1985, 50, 2121. (b) McCague, R. TL 1987, 28, 701.
25. (a) McKean, D. R.; Parrinello, G.; Renaldo, A. F.; Stille, J. K. JOC 1987, 52, 422. (b) Miyaura, N.; Suzuki, A. CC 1979, 866. (c) Miyaura, N.; Maeda, K.; Suginome, H.; Suzuki, A. JOC 1982, 47, 2117.
26. Scott, W. J. CC 1987, 1755.
27. (a) Takai, K.; Oshima, K.; Nozaki, H. TL 1980, 21, 2531. (b) Sato, M.; Takai, K.; Oshima, K.; Nozaki, H. TL 1981, 22, 1609.
28. (a) King, A. O.; Okukado, N.; Negishi, E. CC 1977, 683. (b) King, A. O.; Negishi, E. JOC 1978, 43, 358. (c) Negishi, E.; Okukado, N.; Lovich, S. F.; Luo, F.-T. JOC 1984, 49, 2629. (d) Carpita, A.; Rossi, R. TL 1986, 27, 4351. (e) Chen, Q.-Y.; He, Y.-B. TL 1987, 28, 2387.
29. (a) Castedo, L.; Mouriño, A.; Sarandeses, L. A. TL 1986, 27, 1523. (b) Stille, J. K.; Simpson, J. H. JACS 1987, 109, 2138. (c) Rudisill, D. E.; Stille, J. K. JOC 1989, 54, 5856.
30. (a) Ratovelomanana, V.; Linstrumelle, G. TL 1981, 22, 315. (b) Ratovelomanana, V.; Linstrumelle, G. SC 1981, 11, 917. (c) Jeffery-Luong, T.; Linstrumelle, G. S 1983, 32. (d) Arcadi, A.; Cacchi, S.; Marinelli, F. TL 1989, 30, 2581. (e) Scott, W. J.; Peña, M. R.; Swärd, K.; Stoessel, S. J.; Stille, J. K. JOC 1985, 50, 2302. (f) Mandai, T.; Nakata, T.; Murayama, H.; Yamaoki, H.; Ogawa, M.; Kawada, M.; Tsuji, J. TL 1990, 31, 7179.
31. Rossi, R.; Carpita, A.; Quirici, M. G.; Gaudenzi, M. L. T 1982, 38, 631.
32. Hoshino, Y.; Ishiyama, T.; Miyaura, N.; Suzuki, A. TL 1988, 29, 3983.
33. (a) Murahashi, S.-I.; Yamamura, M.; Yanagisawa, K.; Mita, N.; Kondo, K. JOC 1979, 44, 2408. (b) Huynh, C.; Linstrumelle, G. TL 1979, 1073.
34. (a) Negishi, E.; Valente, L. F.; Kobayashi, M. JACS 1980, 102, 3298. (b) Negishi, E.; Zhang, Y.; Cederbaum, F. E.; Webb, M. B. JOC 1986, 51, 4080. (c) Tamaru, Y.; Ochiai, H.; Nakamura, T.; Yoshida, Z. TL 1986, 27, 955.
35. Negishi, E.; Luo, F.-T.; Rand, C. L. TL 1982, 23, 27.
36. Piers, E.; Jean, M.; Marrs, P. S. TL 1987, 28, 5075.
37. (a) Sato, T.; Itoh, T.; Fujisawa, T. CL 1982, 1559. (b) Negishi, E.; Bagheri, V.; Chatterjee, S.; Luo, F.-T., Miller, J. A.; Stoll, A. T. TL 1983, 24, 5181. (c) Tamaru, Y.; Ochiai, H.; Nakamura, T.; Yoshida, Z. OS 1989, 67, 98.
38. Jabri, N.; Alexakis, A.; Normant, J. F. T 1986, 42, 1369.
39. Yamada, J.; Yamamoto, Y. CC 1987, 1302.
40. Kosugi, M.; Shimizu, Y.; Migita, T. CL 1977, 1423.
41. Takagi, K.; Okamoto, T.; Sakakibara, Y.; Ohno, A.; Oka, S.; Hayama, N. CL 1975, 951.
42. Labadie, S. S. JOC 1989, 54, 2496.
43. (a) Trost, B. M. AG(E) 1989, 28, 1173. (b) Tsuji, J.; Minami, I. ACR 1987, 20, 140. (c) Trost, B. M. ACR 1980, 13, 385. (d) Trost, B. M. T 1977, 33, 2615.
44. Starý, I.; Stará, I. G.; Kocovský, P. TL 1993, 34, 179.
45. Matsubara, S.; Tsuboniwa, N.; Morizawa, Y.; Oshima, K.; Nozaki, H. BCJ 1984, 57, 3242.
46. (a) Baillargeon, V. P.; Stille, J. K. JACS 1983, 105, 7175. (b) Baillargeon, V. P.; Stille, J. K. JACS 1986, 108, 452.
47. Pri-Bar, I.; Buchman, O. JOC 1984, 49, 4009.
48. (a) Alper, H.; Hashem, K.; Heveling, J. OM 1982, 1, 775. (b) Galamb, V.; Alper, H. TL 1983, 24, 2965.
49. (a) Woell, J. B.; Fergusson, S. B.; Alper, H. JOC 1985, 50, 2134. (b) Hashem, K. E.; Woell, J. B.; Alper, H. TL 1984, 25, 4879. (c) Alper, H.; Antebi, S.; Woell, J. B. AG(E) 1984, 23, 732.
50. Hashimoto, H.; Furuichi, K.; Miwa, T. CC 1987, 1002.
51. Crisp, G. T.; Scott, W. J.; Stille, J. K. JACS 1984, 106, 7500.
52. Dalton, J. R.; Regen, S. L. JOC 1979, 44, 4443.
53. Sekiya, A.; Ishikawa, N. CL 1975, 277.
54. Chatani, N.; Hanafusa, T. JOC 1986, 51, 4714.
55. Murahashi, S.-I.; Naota, T.; Nakajima, N. JOC 1986, 51, 898.
56. Yamamura, K.; Murahashi, S.-I. TL 1977, 4429.
57. (a) Genêt, J. P.; Balabane, M.; Bäckvall, J. E.; Nyström, J. E. TL 1983, 24, 2745. (b) Nyström, J. E.; Rein, T.; Bäckvall, J. E. OS 1989, 67, 105. (c) Trost, B. M.; Keinan, E. JOC 1979, 44, 3451.
58. Byström, S. E.; Aslanian, R.; Bäckvall, J. E. TL 1985, 26, 1749.
59. (a) Tanigawa, Y.; Nishimura, K.; Kawasaki, A.; Murahashi, S.-I. TL 1982, 23, 5549. (b) Murahashi, S.-I.; Imada, Y.; Taniguchi, Y.; Kodera, Y. TL 1988, 29, 2973.
60. Tamura, R.; Hegedus, L. S. JACS 1982, 104, 3727.
61. Murahashi, S.-I.; Tanigawa, Y.; Imada, Y.; Taniguchi, Y. TL 1986, 27, 227.
62. Inomata, K.; Yamamoto, T.; Kotake, H. CL 1981, 1357.
63. (a) Tamura, R.; Hayashi, K.; Kakihana, M.; Tsuji, M.; Oda, D. TL 1985, 26, 851. (b) Ono, N.; Hamamoto, I.; Yanai, T.; Kaji, A. CC 1985, 523.
64. Tamura, R.; Hayashi, K.; Kakihana, M.; Tsuji, M.; Oda, D. CL 1985, 229.
65. Deardorff, D. R.; Myles, D. C. OS 1989, 67, 114.
66. (a) Kosugi, M.; Shimizu, K.; Ohtani, A.; Migita, T. CL 1981, 829. (b) Kosugi, M.; Ohya, T.; Migita, T. BCJ 1983, 56, 3855. (c) Azizian, H.; Eaborn, C.; Pidcock, A. JOM 1981, 215, 49.
67. (a) Matsumoto, H.; Nagashima, S.; Yoshihiro, K.; Nagai, Y. JOM 1975, 85, C1. (b) Matsumoto, H.; Yoshihiro, K.; Nagashima, S.; Watanabe, H.; Nagai, Y. JOM 1977, 128, 409.
68. Wulff, W. D.; Peterson, G. A.; Bauta, W. E.; Chan, K.-S.; Faron, K. L.; Gilbertson, S. R.; Kaesler, R. W.; Yang, D. C.; Murray, C. K. JOC 1986, 51, 277.
69. Nonaka, T.; Okuda, Y.; Matsubara, S.; Oshima, K.; Utimoto, K.; Nozaki, H. JOC 1986, 51, 4716.
70. (a) Mitchell, T. N.; Amamria, A.; Killing, H.; Rutschow, D. JOM 1983, 241, C45. (b) Mitchell, T. N.; Amamria, A.; Killing, H.; Rutschow, D. JOM 1986, 304, 257. (c) Mitchell, T. N.; Kwetkat, K. JOM 1992, 439, 127.
71. Watanabe, H.; Kobayashi, M.; Saito, M.; Nagai, Y. JOM 1981, 216, 149.
72. Kuniyasu, H.; Ogawa, A.; Miyazaki, S.-I.; Ryu, I.; Kambe, N.; Sonoda, N. JACS 1991, 113, 9796.
73. Watanabe, H.; Saito, M.; Sutou, N.; Kishimoto, K.; Inose, J.; Nagai, Y. JOM 1982, 225, 343.
74. Killing, H.; Mitchell, T. N. OM 1984, 3, 1318.
75. (a) Chenard, B. L.; Laganis, E. D.; Davidson, F.; RajanBabu, T. V. JOC 1985, 50, 3666. (b) Chenard, B. L.; Van Zyl, C. M. JOC 1986, 51, 3561. (c) Mitchell, T. N.; Killing, H.; Dicke, R.; Wickenkamp, R. CC 1985, 354. (d) Mitchell, T. N.; Wickenkamp, R.; Amamria, A.; Dicke, R.; Schneider, U. JOC 1987, 52, 4868.
76. Piers, E.; Skerlj, R. T. CC 1986, 626.
77. Piers, E.; Tillyer, R. D. JCS(P1) 1989, 2124.
78. (a) Ichinose, Y.; Oda, H.; Oshima, K.; Utimoto, K. BCJ 1987, 60, 3468. (b) Miyake, H.; Yamamura, K. CL 1989, 981. (c) Matsubara, S.; Hibino, J.-I.; Morizawa, Y.; Oshima, K.; Nozaki, H. JOM 1985, 285, 163.
79. Four, P.; Guibe, F. TL 1982, 23, 1825.
80. Trost, B. M.; Herndon, J. W. JACS 1984, 106, 6835.
81. Matsumoto, H.; Yako, T.; Nagashima, S.; Motegi, T.; Nagai, Y. JOM 1978, 148, 97.
82. Miyake, H.; Yamamura, K. CL 1992, 507.
83. (a) Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T. TL 1980, 21, 3595. (b) Hirao, T.; Masunaga, T.; Yamada, N.; Ohshiro, Y.; Agawa, T. BCJ 1982, 55, 909.
84. Xu, Y.; Li, Z.; Xia, J.; Guo, H.; Huang, Y. S 1983, 377.
85. Townsend, J. M.; Reingold, I. D.; Kendall, M. C. R.; Spencer, T. A. JOC 1975, 40, 2976.
86. Tamaru, Y.; Yamada, Y.; Inoue, K.; Yamamoto, Y.; Yoshida, Z. JOC 1983, 48, 1286.
87. Helquist, P. TL 1978, 1913.
88. Zask, A.; Helquist, P. JOC 1978, 43, 1619.
89. (a) Chen, Q.-Y.; He, Y.-B.; Yang, Z.-Y. CC 1986, 1452. (b) Peterson, G. A.; Kunng, F.-A.; McCallum, J. S.; Wulff, W. D. TL 1987, 28, 1381.
90. Hutchins, R. O.; Learn, K.; Fulton, R. P. TL 1980, 21, 27.
91. Keinan, E.; Greenspoon, N. JOC 1983, 48, 3545.
92. Tabuchi, T.; Inanaga, J.; Yamaguchi, M. TL 1986, 27, 601.
93. Keinan, E.; Greenspoon, N. TL 1982, 23, 241.
94. Yamamoto, Y.; Hori, A.; Hutchinson, C. R. JACS 1985, 107, 2471.
95. Kotake, H.; Yamamoto, T.; Kinoshita, H. CL 1982, 1331.
96. Hutchins, R, O.; Learn, K. JOC 1982, 47, 4380.
97. Matsushita, H.; Negishi, E. JOC 1982, 47, 4161.
98. (a) Guibe, F.; Four, P.; Riviere, H. CC 1980, 432. (b) Four, P.; Guibe, F. JOC 1981, 46, 4439.
99. Kuniyasu, H.; Ogawa, A.; Higaki, K.; Sonoda, N. OM 1992, 11, 3937.
100. Keinan, E.; Gleize, P. A. TL 1982, 23, 477.
101. (a) Keinan, E.; Greenspoon, N. TL 1985, 26, 1353. (b) Keinan, E.; Greenspoon, N. JACS 1986, 108, 7314.
102. Perez, D.; Greenspoon, N.; Keinan, E. JOC 1987, 52, 5570.
103. Urata, H.; Suzuki, H.; Moro-Oka, Y.; Ikawa, T. JOM 1982, 234, 367.
104. Guibe, F.; Saint M'Leux, Y. TL 1981, 22, 3591.
105. Jeffrey, P. D.; McCombie, S. W. JOC 1982, 47, 587.
106. Hayakawa, Y.; Kato, H.; Uchiyama, M.; Kajino, H.; Noyori, R. JOC 1986, 51, 2400.
107. (a) Kunz, H.; Unverzagt, C. AG(E) 1984, 23, 436. (b) Kinoshita, H.; Inomata, K.; Kameda, T.; Kotake, H. CL 1985, 515.
108. Boullanger, P.; Descotes, G. TL 1986, 27, 2599.
109. Deziel, R. TL 1987, 28, 4371.
110. (a) Kunz, H.; Waldmann, H. AG(E) 1984, 23, 71. (b) Kunz, H.; Waldmann, H. HCA 1985, 68, 618. (c) Friedrich-Bochnitschek, S.; Waldmann, H.; Kunz, H. JOC 1989, 54, 751.
111. Hayakawa, Y.; Uchiyama, M.; Kato, H.; Noyori, R. TL 1985, 26, 6505.
112. Nakayama, K.; Uoto, K.; Higashi, K.; Soga, T.; Kusama, T. CPB 1992, 40, 1718.
113. (a) Tamaru, Y.; Yoshida, Z.; Yamada, Y.; Mukai, K.; Yoshioka, H. JOC 1983, 48, 1293. (b) Yamada, Y.; Mukai, K.; Yoshioka, H.; Tamaru, Y.; Yoshida, Z. TL 1979, 5015.
114. Ikariya, T.; Ishikawa, Y.; Hirai, K.; Yoshikawa, S. CL 1982, 1815.
115. Murahashi, S.-I.; Makabe, Y.; Kunita, K. JOC 1988, 53, 4489.
116. Trost, B. M.; Runge, T. A.; Jungheim, L. N. JACS 1980, 102, 2840.
117. Oppolzer, W. AG(E) 1989, 28, 38.
118. Mandai, T.; Hashio, S.; Goto, J.; Kawada, M. TL 1981, 22, 2187.
119. Trost, B. M.; Verhoeven, T. R.; Fortunak, J. M. TL 1979, 2301.
120. Trost, B. M.; Fortunak, J. M. JACS 1980, 102, 2843.
121. Suzuki, M.; Oda, Y.; Noyori, R. JACS 1979, 101, 1623.
122. Suzuki, M.; Watanabe, A.; Noyori, R. JACS 1980, 102, 2095.

Richard W. Friesen

Merck Frosst Centre for Therapeutic Research, Quebec, Canada



Copyright © 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.