3 Organometallic chemistry Part (ii) Transition metals in organic synthesis—stoichiometric applications Guy C. Lloyd-Jones School of Chemistry University of Bristol Cantock’s Close Bristol UK BS8 1TS 1 Introduction A selection of useful or unusual transition metal mediated reactions from the chemical literature of 1998 are reviewed below. Some reactions also involve transition metal catalysis in addition to the stoichiometric transition metal component. In all cases the reactions are organised by the transition metal group of the stoichiometric component with further subdivisions by reaction class or intermediates. 2 Applications Scandium ytterbium and the lanthanides Stoichiometric applications of these metals are scarce. However the dehydrogenative coupling of aromatic aldimines has been reported to occur on treatment with Yb metal and then an aromatic aldehyde as a hydrogen acceptor.Thus for example treatment of aldimine 1 with Yb and then 1-naphthaldehyde a.orded dimine 2 in 81% yield (Scheme 1). Titanium zirconium and hafnium Ole.nation. Ole.nations involving dithioacetal desulfurisation by titanocene reagents has been reviewed. Metallocenes. Zirconacyclopentadiene intermediates formed by reaction of zirconocene with acetylenes continue to be of interest. For example they may be crosscoupled with 3-iodopropenoates to a.ord cyclopentadienylacetate derivatives. Alternatively the two C—Zr bonds can be selectively cleaved by halogenating agents such as NCS NBS or I to a.ord 1,4-dihalogeno-1,3-dienes in good yield. Furthermore reaction with 2-iodothiophene in the presence of CuCl and DMPU furnishes thienyl dienes. The intriguing cyclophane 4 in which each pyridine is anti (X-ray crystallography) was prepared by reaction of zirconocene with bisacetylene 3 (Scheme 2).The 117 Annu. Rep. Prog. Chem. Sect. B 1999 95 117—136 Ph N Ph i ii N Ph Ph Ph H N Ph 1 2 Scheme 1 Reagents (i) Yb; (ii) 1-naphthaldehyde. Cp Zr 2 TMS TMS TMS N N N i N N N TMS N TMS N Cp2Zr TMS TMS ZrCp2 TMS 3 4 Scheme 2 Reagents (i) Cp2Zr. i n-Hex ZrCp2 n-Hex Cl O N O Cl N 5 6 7 Scheme 3 Reagents (i) Ni(0) cat. dezirconated cyclophane (prepared by reaction with acetic acid) is much less rigid in solution according to comparative NMR experiments. Vinyl zirconocenes e.g.5 react smoothly with chloromethyl heteroaromatics e.g. 6 in the presence of Ni(0) to a.ord E-allylated heteroaromatics e.g. 7 in good yield (Scheme 3). 2-Bromophosphinines 8 react with zirconocene to a.ord 2-(phosphininyl)bromozirconocenes 9. These may then be transmetallated to Ni(0) resulting in dimerisation (to give 10) and subsequent decomplexation by addition of hexachloroethane a.ords 2,2-biphosphinine ligands 11 (Scheme 4). Azazirconocycles are the key intermediates in an e.cient process for meta-functionalisation of phenols protected with an ortho-lithiating group (Scheme 5). Thus lithiation of 12 followed by zirconocene addition and subsequent insertion of nitrile (RCN) a.ords 13 which on acidic hydrolysis gives 14. Diastereoselective synthesis of substituted dihydrofurans is facilitated by insertion of ketones into azazirconocycle 16 (prepared from cinnamaldehyde 15) and subsequent oxidative dezirconation then acidic cyclisation/dehydration to give 17 (98% de) (Scheme 6). Tricyclic compounds e.g.19 the skeleton of dolastane diterpenes can be constructed by elaboration of bicyclic zirconocenes 18 prepared by reaction of dibutylzirconocene with 1,6- or 1,7-dienes. 118 Annu. Rep. Prog. Chem. Sect. B 1999 95 117—136 R2 R2 R3 R1 R3 R1 i P Br P Cp2(Br)Zr 9 8 ii R2 R2 R3 R3 R1 R1 R1 R1 R2 R2 P iii P P Ni PPh2 P R3 R3 Ph2P 11 10 Scheme 4 Reagents (i) Cp Zr; (ii) Ni(dppe)Cl; (iii) CCl. O O O O O O Zr(Cp)2 i ii iii iv N O R R 12 14 Scheme 5 Reagents (i) t-BuLi ; (ii) Cp Zr(i-Bu)Cl; (iii) RCN; (iv) HCl (aq).13 O Ar O iii iv v vi i ii N Zr Ph Ph Ph (¡Ó) 16 15 17 Scheme 6 Reagents (i) o-anisidine; (ii) Cp Zr; (iii) t-BuCOMe; (iv) pyr-N-oxide; (v) HCl THF; (vi) PPTS. H H O ZrCp2 HO n R H H O 20 19 18 The titanium() complex Cp TiPh promotes the reductive cyclisation of of - and -cyano ketones and also -ketoesters to give -hydroxy cycloalkanones e.g. 20 in good yield. Vinyl halides e.g. 21 are converted to allylic Ti() reagents on reaction 119 Annu. Rep. Prog. Chem. Sect. B 1999 95 117¡X136i ii Ph Cl OH Ph Ph 22 Scheme 7 Reagents (i) Cp TiCl and Me Al; (ii) PhCHO. with a reagent prepared from Cp TiCl and Me Al (toluene 3 days). The resultant Ti-allyl species react with carbonyl compounds.For example homoallylic alcohol 22 21 was prepared in 50% yield (Scheme 7). Miscellaneous. Reaction of vinyl zirconium species with phenyl iodanes a.ords vinyl iodonium salts which can be coupled with Grignard reagents in the presence of Cu(.) to a.ord E-1,2-disubstituted alkenes. The process occurs with retention of con.guration throughout the various steps. Lewis acids. TiCl strongly chelates -keto sulfones and allows their erythroselective reduction to -hydroxysulfones by pyridine—borane complex in non-coordinating solvent (CH Cl ) at low temperature. Vanadium niobium and tantalum Vanadium(.)-mediated deoxygenation and subsequent aldehyde elimination allows smooth conversion of -.uoro-,-dihydroxy acids 23 (and esters) to -.uorinated- ,-unsaturated acids 24 (and esters) with high selectivity for the Z isomer (Scheme 8). Chromium molybdenum and tungsten Carbene complexes.Fischer carbene complexes particularly of Cr continue to be of great interest and diverse application. For example MeC(OMe)——Cr(CO) reacts with keto-enynes such as 25 to a.ord aceto-furan derivatives e.g. 26 (Scheme 9). Similar processes with enediynes a.ord benzannulated products via Moore cyclisation. Chiral oxazolidinone bearing ene-carbamates 27 undergo diastereoselective photochemical reaction with a chromium ethoxycarbene complex to a.ord cyclobutanones e.g. 28 (RH) in high de (Scheme 10). By varying the R group in 27 the reaction can also be performed to generate -stannyl cyclobutanones (RBu Sn).The 2-alkoxycyclobutanones can be further elaborated by ring opening -bromination Baeyer—Villiger oxidation and photolysis in the presence of acetic acid to generate 2-acetoxy-5-alkoxytetrahydrofurans. Fischer carbenes undergo [3 2] cycloaddition with nitrilimines to produce -pyrazolinones. For example reaction of Nphenyl benzonitrilimine (generated in situ) with carbene 29 (Rmenthyl) a.ords 30 with high regio- and moderate diastereoselectivity. Intramolecular Friedel—Crafts type acylation reactions of Cr-carbene complexes are also possible. Thus treatment of 31 with ZnCl gave 32 in 67% yield (Scheme 11). A novel entry to the pyrimidine skeleton is provided by the reaction of ureas with alkynyl alkoxyWand Cr carbenes.120 Annu. Rep. Prog. Chem. Sect. B 1999 95 117—136 OH OH CO2R i R R R F F CO2 R 23 Scheme 8 Reagents (i) VOCl 24 PhCl heat. R2 R2 O i O O R1 R1 25 26 Scheme 9 Reagents (i) MeC(OMe)——Cr(CO) . O O O R R i O O N N OEt Ph Ph Ph Ph 27 Scheme 10 Reagents (i) MeC(OEt)——Cr(CO) 28 h. OR OR Ph (OC)5Cr (OC)5Cr N Ph Ph Ph N 30 29 For example carbene complex 33 reacts with dimethylurea to a.ord alkylidenyl pyrimidine 34. Oxidative decomplexation a.ords the pyrimidinedione 35 (Scheme 12). Hydrostannylation and hydrosilylation of Cr-carbenes bearing an imidazolidinone chiral auxiliary proceed with high diastereoselectivity. Thus carbene 36 reacts with Ph SiH to a.ord 37 (96% de) (Scheme 13).The corresponding stannanes may be transmetallated and then alkylated. -Complexes. Enantiomerically pure substituted benzaldehyde—Cr(CO) derivatives e.g. 38 undergo samarium(..) diiodide mediated pinacol type coupling to produce after oxidative decomplexation with I solely the threo diols 39 as single enantiomers (Scheme 14). Apparently in the ketyl intermediates C—C rotation is restricted su.ciently such that no stereomutation occurs during coupling. Enantiomerically pure complex 40 underwent diastereoselective Suzuki coupling with 121 Annu. Rep. Prog. Chem. Sect. B 1999 95 117—136 O Cr(CO)5 i O O MeO 32 31 MeO h CO. OEt O N O ii (OC)5W N N Ph Ph Ph 35 33 34 Scheme 12 Reagents (i) N,N-dimethylurea; (ii) CAN.OC SiPh3 O CO Cr O i OC Ph N Ph N Scheme 11 Reagents (i) ZnCl (OC)5W N O i CO N N Ph Ph 37 36 Scheme 13 Reagents (i) Ph SiH. O OH i ii H (OC)3Cr 38 39 THF; (ii) I . OH Scheme 14 Reagents (i) SmI boronic acid 41 giving 42 as a key step in the synthesis of atropisomerically pure O,O-dimethylkorupensamine A 43 (Scheme 15). The Cr(CO) -complex of anisole has been employed in a short enantioselective synthesis of ( )-ptilocaulin 44 with the key initial step being an asymmetric deprotonation—trimethylsilylation sequence. The bis-lithium amide base 45 was found to be highly e.ective in the enantioselective deprotonation of 1,3-dihydroisobenzothiophene chromium tricarbonyl complexes. Enantiomerically pure axially chiral Cr(CO) -complex generated from 5,6-dimethoxy- 1-tetralone was employed in an asymmetric total synthesis of putative helioporin D.The study allowed a revision of the structure of the natural product. A range of terpenoid-based chiral auxiliaries have been tested for diastereoselective induction in nucleophilic attack of alkoxyarene chromium tricarbonyl complexes. 2-Phenylisoborneol was found to be highly e.ective with de’s approaching 92%. The coordination of the Cr(CO) fragment to polycyclic aromatics (typically phenanthrene or anthracene) allows highly regioselective deprotonation—methylation. Aerobic oxidation 122 Annu.Rep. Prog. Chem. Sect. B 1999 95 117—136 Br O OMe OBn O MeO + Cr(CO)3 OMe B(OH)2 41 40 i OBn OMe OH OMe O O MeO MeO NH Cr(CO)3 OMe OMe 42 43 Scheme 15 Reagents (i) cat. Pd(0) Na CO . NH2 Li Ph NH HN H N Ph N Ph Ph Li H 45 44 decomplexes the products a.ording ring-methylated products in high yield. An ingeneous heterocycle construction sequence is facilitated by conjugate addition of salicylaldehyde to the Cr(CO) -complex of aryl allenyl phosphonates e.g. 46. On heating the resultant vinyl phosphonate 47 undergoes an intramolecular Horner—Wadsworth—Emmons ole.nation to give chromium-complexed heterocycle 48 in 87% yield (Scheme 16). The Do� tz benzannulation reaction of Cr(CO) —carbene complexes with hexyne has been employed for the generation of polycyclic arenes.For example 49 is converted into 50 in 62% yield (Scheme 17). A remarkable sequence involving [6 4] cycloaddition to Cr(0) complex 51 followed by oxidation a.ords the cycloadduct 52. Introduction of a bridgehead hydroxy group (via addition of Davis oxaziridine reagent to the enolate) then Tsuchihashi pinacol rearrangement a.ords the bicyclo[4.3.2]undecane structure 53 (Scheme 18). 123 Annu. Rep. Prog. Chem. Sect. B 1999 95 117—136 EtO O EtO P H EtO i ii P(O) EtO . O O O Cr(CO)3 Cr(CO)3 Cr(CO)3 48 46 47 Scheme 16 Reagents (i) o-(OH)-PhCHO NaH; (ii) THF re.ux. OMe MeO OMe MeO i ii Cr(CO)5 TBDMSO Cr(CO)3 49 50 Scheme 17 Reagents (i) hex-1-yne; (ii) TBDMSCl Et N.O O iv v vi vii i ii iii H H Cr(CO)3 53 51 52 Scheme 18 Reagents (i) 1-acetoxybuta-1,3-diene; (ii) K CO ; (iii) Swern; (iv) KHMDS Davis reagent; (v) NaBH CeCl ; (vi) MsCl; (vii) Et AlCl. Miscellaneous. DMAP- and bpy-chlorochromates e.ect oxidative decomplexation of THP ethers to their corresponding carbonyl compounds in good yield. A short synthesis of ()-mitsugashiwalactone 54 has been developed utilising -tungsten alkynol chemistry. O H O H 54 Manganese technetium and rhenium Of these metals only manganese appears in mainstream organic synthetic applications. 124 Annu. Rep. Prog. Chem. Sect. B 1999 95 117—136 Mn(CO)4 TMS ii i Ph N Ph N Ph N N N Ph Ph NH Ph 56 57 Scheme 19 Reagents (i) PhCH Mn(CO) ; (ii) TMS-acetylene.Organomanganese -compounds. Arylhydrazones undergo ortho-manganation in reasonable yields. Thus treatment of 55 with BnMn(CO) a.ords 56. Furthermore subsequent addition of alkynes leads to indenyl hydrazines e.g. 57 (Scheme 19). Allylation of aryl aldehydes by allyl chloride is readily e.ected in water by use of Mn metal in the presence of catalytic Cu (neitherMn nor Cu alone is e.ective). Interestingly aryl aldehydes react chemoselectively in the presence of aliphatic aldehydes and pinacol coupling is induced by acidic conditions. 55 Manganese ‘ate’ complexes. Treatment of 1,3-dihalopropene (halogenCl or Br) with n-Bu MnLi generates a butylated-allyl manganese complex which can be further reacted with electrophiles e.g.benzaldehyde. Iron ruthenium and osmium -Complexes. The reactivity and in particular the regioselectivity of attack of the Fe(CO) complex of cyclohepta-2,4-diene-1,6-dione (58) by nucleophiles and electrophiles has been explored. As part of the investigation 58 was converted to hinokitiol 59. Sequential addition of a cuprate Ac O and CO to iron-complex 60 O O O HO Fe(CO)3 58 59 a.ords azadiene complex 61. Meta-acyl aniline derivatives 62 are readily prepared from these by treatment withK CO (Scheme 20). Similar procedures can be used to generate meta-acyl alkyl benzene derivatives. Sodium triacetoxyborohydride e.ects decomplexation of -allyltricarbonyl iron lactone complexes.The resulting acyclic diols are obtained in reasonable yield and with high stereoselectivity (96% de). Intramolecular photothermal cyclisations of Fe—diene -complexes bearing a pendent alkene proceed in moderate yields. For example Fe-complex 63 is converted to pyrrolidinone 64 (in 12% yield) (Scheme 21). The reaction is hampered by isomerisation —in this case to give 65. The intramolecular cycloaddition (formally a Diels—Alder addition) of a diene tethered to a cyclobutadiene Fe-complex (66) gives tricyclic cyclobutene compound 67 (Scheme 22). A range of analogous reactions are also reported. Usage of the planar chirality of ferrocenes is a growing area. However 125 Annu. Rep.Prog. Chem. Sect. B 1999 95 117—136 Cu Li ; (ii) Ac O—CO; (iii) K CO . Ph Ph N N Ph H Ph 3Fe (OC)3Fe (OC)3Fe O O 65 63 64 Scheme 21 Reagents (i) hv. i (OC)3Fe O Scheme 20 Reagents (i) R Ph i N Ph (OC) O O 67 66 Scheme 22 Reagents (i) heat CAN. O H O CHO i ii N Fe Fe O 69 68 iii iv O O H R O HO v N R Fe H2N O (+ 68) 71 70 Scheme 23 Reagents (i) Na (S)-alaninate; (ii) Me COCl; (iii) LDA; (iv) RBr; (v) Amberlyst-15. 126 Annu. Rep. Prog. Chem. Sect. B 1999 95 117—136 in the following example all of the chirality is central. Condensation of ferrocenecarbaldehyde 68 with (S)-alanine and then addition of pivaloyl chloride generates 69 in 98% de.This can be deprotonated with LDA and then alkylated by addition of RBr with complete retention of relative con.guration to a.ord 70. Hydrolysis a.ords a range of -alkyl--methyl amino acids 71 in very high enantiomeric excess (Scheme 23). The (-naphthalene)(-COD)Ru(0) complex 72 cleanly cyclotrimerises Ru 72 alkynes with loss of the naphthalene fragment to a.ord the corresponding (- arene)(-COD) complex. The -arene complexes of anisole with dicationic osmium pentammine have proved to be interesting substrates for a range of selective reactions that eventually generate functionalised cyclohexanones. For example reaction of complex 73 with CH (OEt) generates the electrophilic complex 74 which can then be reacted with silyl enol ethers to a.ord 75 (Scheme 24). Alternatively OEt CO2Me OEt MeO Me+O MeO [Os(NH3)5]2+ [Os(NH3)5]2+ [Os(NH3)5]2+ 73 75 Scheme 24 Reagents (i) CH (OEt) ; (ii) (CH ) C——C(OMe)(OTMS).74 HO O H iii iv MeO MeO [Os(NH i ii 3)5]2+ Me+O [Os(NH3)5]2+ 77 76 78 SO H; (ii) MVK; (iii) DMA; (iv) [Bu N][B(CN)H ]. i ii [Os(NH3)5]2+ Scheme 25 Reagents (i) CF tri.ic acid mediated reaction of 76 with methyl vinyl ketone instead of CH (OEt) forms 77 (Scheme 25). This may then undergo dimethylacetamide promoted deprotonation of the vinylogous methyl group resuing in cyclisation by attack of the ketone carbonyl and subsequent regioselective reduction with cyanoborohydride to a.ord a decalin type complex 78 with high stereoselectivity. Similarly naphthalene Os(..)-complexes can be dearomatised by sequential electrophile—nucleophile 1,4- additions. 127 Annu.Rep. Prog. Chem. Sect. B 1999 95 117—136 R R i ii R R O O 80 79 Scheme 26 Reagents (i) Fe(CO) NaBH AcOH; (ii) CuCl ·H O. HO O i ii H H H H 82 83 Scheme 27 Reagents (i) Co (CO) ; (ii) DME re.ux. Miscellaneous. Iron hydride reagents generated in situ can be used in conjunction with a Cu(..) oxidant to e.ect a one-pot conversion of alkynes to cyclobutenediones and ,-unsaturated carboxylic acids. The reagent [HFe (CO) ][Na] is highly selective for formation of cyclobutenediones.For example R-alkynes 79 are converted to cyclobutenediones 80 in 60—73% yields (Scheme 26). The nucleophilic metallate [Cp(CO )FeM] (MNa or K) adds cleanly to aldehydes (RCHO) and capture of the resultant alkoxy anion by TMS chloride a.ords (-siloxyalkyl)iron Cp complexes 81 in moderate to good yield. R Me3Si Fe Cp O OC CO 81 Cobalt rhodium and iridium Despite important catalytic reactions of Rh and Ir only Co appears in mainstream stoichiometric applications. -Complexes. The diastereoselective Nicholas reaction has been used in the construction of functionalised benzopyrans. High yielding decomplexation of Co—alkyne complexes is e.ected by excess (ca. 10 equiv.) ethylenediamine in THF e.g. diphenylacetylene was decomplexed from Co (CO) in 98% yield in 10 minutes. Acetylenic cyclopropanols rearrange to cyclopentenones with high stereoselectivity on heating after complexation with Co (CO) .For example 82 gave 83 in 86% yield (Scheme 27). Tetrahydrofurans tetrahydropyrans and oxepanes are formed by 128 Annu. Rep. Prog. Chem. Sect. B 1999 95 117—136 O O O O Co O H O O O 84 85 Ar i ii Ar Nu Pt PPh3 Pt PPh3 PPh3 PPh3 87 86 88 Scheme 28 Reagents (i) ArH (e.g. C H NMe ); (ii) [Nu] (e.g. NaCH(SO Ph) . cyclisation of -cationic dihydroxycobaloximes. The ready complexation and removal of Co (CO) to the alkynes of the crown ether macrocyclic diyne 84 provide a general method for the modulation of the properties of the macrocycle.For example acting as a protecting group and blocking catenane formation by RCM with N,N- bis(hex-5-enyl)pyromellitic diimide. A sequential [4 2] then [2 2] cyclisation was employed in the construction of the AB taxane ring system utilising a Cp—Co template to generate 85. SparteineN-oxide has been used as a chiral promoter in the Pauson—Khand reaction of various alkynes with norbornene. Low to moderate ee’s were observed in the resultant cyclopentenones the highest being 33%. Nickel palladium and platinum The bulk of applications of Ni Pd and Pt involve catalytic quantities. Furthermore stoichiometric applications of Pd and Pt obviously su.er the issue of the high cost. However the regioselective addition of the C—H bonds of pyrrole indole and electronrich benzene derivatives to the central carbon of a cationic propargyl (prop-2-ynyl) complex of Pt 86 to a.ord a -allyl complex e.g.87 has been reported (Scheme 28). A mechanism involving platinacyclobutane intermediates is suggested. Subsequent addition of stabilised carbanion nucleophiles to 87 a.ords 88 the product of overall aryl vinylation of propargyl derivatives. Insertion of elemental sulfur into the Ar—Ni bond of 89 allows preparation of thiolate 90 (Scheme 29). 129 Annu. Rep. Prog. Chem. Sect. B 1999 95 117—136 S N i N Ni Ni N N 90 89 OH O O i ii O Ph O Ph Ph Ph Me Me 92 91 93 Scheme 30 Reagents (i) MeLi—CuI Et O; (ii) PhCHO Et AlCl.Scheme 29 Reagents (i) S . O Cu(Me)Li O O O O i ii iii ii n-Bu TBDMSO n-Bu 94 95 ent-95 Scheme 31 Reagents (i) [n-Bu Cu(CN)Li ]; (ii) DBU; (iii) [n-BuCu(CN)Li]. Copper silver and gold Organocuprates. Moderate to good menthyl induced diastereoselectivity is observed in a three component synthesis of what are in essence Baylis—Hillman type adducts. For example addition of lithium dimethylcuprate to the menthyl ester of phenylpropiolic acid 91 a.ords intermediate vinyl cuprate 92 (Scheme 30). This is trapped with benzaldehyde (with Et AlCl as a Lewis acid accelerant) to a.ord 93 as an E/Z mixture and in 88 and 70% de respectively. The reaction of 98% ee TBDMSprotected hydroxycyclohexenone 94 with ‘higher order’ and ‘lower order’ cyano cuprates takes startlingly di.erent courses in terms of diastereoselectivity.Subsequent DBU-mediated elimination of the conjugate addition product allows the preparation of both enantiomers of cyclohexenone 95 in 97% ee (Scheme 31). The reaction proceeds analogously with a range of other cuprates and ketones. Miscellaneous. Silver(.) salts e.ect the oxidation of tertiary amines in toluene —water mixtures. A radical chain mechanism is proposed. A combination of silver tri.ate and phenyl chloroformate mediates the coupling of alk-1-ynylsilanes with quinoline derivatives to a.ord the corresponding alk-1-ynyl-1,2-dihydroquinoline derivative in good yield. Copper(..) salts promote highly e.cient O-arylation of phenols by aryl boronic acids at ambient temperatures.This has a great advantage in 130 Annu. Rep. Prog. Chem. Sect. B 1999 95 117—136 the arylation of phenolic amino acids since the process is racemisation-free. Cu() salts also promote the N-arylation of N¡XH containing compounds in the presence of triethylamine again by aryl boronic acids. Zinc cadmium and mercury O OP Addition of organomercury organozinc and organocadmium reagents to elec- trophiles. The asymmetric addition of dialkylzinc to aldehydes catalysed by e.g. amino alcohols is fast becoming a rather overworked reaction. However the addition of dimethylzinc to benzaldehyde catalysed by 2S-3-exo-(dimethylamino)isoborneol (DAIB) displays non-linear asymmetric phenomena and this has been studied in a quantitative kinetic sense in great detail by Noyori et al.Addition of dialkylzincs to ketones is promoted by the stoichiometric addition of Ti() isopropoxide. When the reaction is performed in the presence of catalytic amounts of camphor sulfonamide derivatives asymmetric induction is observed (up to 89% ee). The asymmetric addition (up to 92% ee) of dialkylzincs to imines is eected by stoichiometric addition of an azanorbornylmethanol type ligand. The ligand can easily be recovered and recycled. Acyclic congurationally-dened mixed dialkylzinc reagents can be prepared from trisubstituted alkenes by hydroboration (Et BH) then transmetallation (i-Pr Zn). Ph Ph Ph O O P N OO O O Ph Ph 97 96 98 Perfect anti selectivity is reported for the S2 and S2 type addition of dialkylzinc reagents to vinyl oxiranes catalysed by Cu().By use of the Feringa type 2,2-binaphthyl phosphorus amidite ligand 96 ecient kinetic resolution (allowing90% ee) is observed for the reaction of cyclic ,-unsaturated epoxides e.g. 97. Taddol derived phosphite ligand 98 is highly eective for the conjugate Cu-catalysed addition of diethylzinc to a range of enones. For example reaction of cyclohexenone in the presence of 0.5mol% Cu and 1mol% 98 aorded (S)-3-ethylcyclohexanone in 96% ee and 95% yield. Binaphthoxy phosphorus amidite ligands are also successful. A remarkable ee enhancement through the use of molecular sieves has been reported for the analogous reactions involving Taddol-phosphorus amidite ligands. Houk and Goldfuss have performed informative PM3 calculations of the transition states for enantioselective chiral -amino alcohol catalysed addition of EtZn to benzaldehyde.Highly enantioenriched propargylic mesylates 99 are smoothly converted to chiral non-racemic allenyl zinc reagents (100) on reaction with excess EtZn and 5mol% Pd(0). Reagents 100 may then be reacted with aldehydes (e.g. cyclohexanecarbaldehyde) to aord the anti adduct 101 in 90¡X95%ee (Scheme 32).UVlight induces 131 Annu. Rep. Prog. Chem. Sect. B 1999 95 117¡X136Scheme 32 Reagents (i) cat. Pd(0) Et Zn; (ii) c-CH-CHO. CO2Et Br Br ZnI I ii i ii CO2Me I IZn 106 103 102 CO2Et CO2Me 104 105 Scheme 33 Reagents (i) Zn powder; (ii) cat. Pd(PPh). catalyses the tandem coupling of Me selective phenylation of naphtho-1,4-quinones at the 2-position by reaction with diphenylmercury in acetonitrile. Readily prepared 2-bromophenylzinc() (103) can be used as the equivalent of an ortho cationic anionic reagent.Thus reaction of 2-iodobromobenzene 102 with zinc and then methyl 3-iodobenzoate 104 followed by ethyl 4-(iodozinc)benzoate 105 in the presence of Pd(0) catalyst aords terphenyl 106 (Scheme 33). Ni(acac) Zn with allyl- X¡XHC¡X ¡X¡XCR to aord predominantly allyl¡XCH¡X¡XC(R)Me (where allyl and R are trans). Organocadmium reagents (primary alkyl secondary alkyl and aryl) add selectively to just one of the carbonyl carbons of quinone derivatives¡Xallowing the selective synthesis of quinols. Zinc carbenoids. Enantiomerically pure trans-diaminocyclohexane bis-sulfonamide ligands are known to eect catalytic asymmetric cyclopropanation of cinnamyl alcohol by Et Zn ZnI and Zn(CHI). A solution state (NMR) and solid state (X-ray crystallography) study of the reaction and model systems has now identied kinetically active intermediates.Allylic stereocentres can induce diastereoselectivity in the EtZn mediated cyclopropanation of allylic alcohols. Remote aryl substituents can reverse the diastereoselectivity¡Xpossibly through -complexation. Theoretical studies on the Simmons¡XSmith cyclopropanation reaction of zinc carbenoids with olens reveal methylene transfer versus carbometallation as two possible pathways. Experimentally only the methylene transfer mechanism is observed¡Xhowever both processes can compete eectively with lithium carbenoids. Modication of Simmons¡XSmith reagents by reaction with enantiomerically pure chiral alcohols ROH aords reagents of the type ROZnCHI which eect cylopropanation of prochiral alkenes with modest enantioselectivity.For example E-PhCH¡X¡XCHMe was cyclopropanated in 51% ee. A three-component palladium-catalysed coupling of biszincio-methylenes and methylmethynes with propargyl and allylic electrophiles has 132 Annu. Rep. Prog. Chem. Sect. B 1999 95 117¡X136i ii iii iv Cl 107 108 Scheme 34 Reagents (i) CH CH(ZnI) ; (ii) cat. Pd(0)—tri-(3,5-(CF ) -phenyl)phosphine; (iii) CuCN; (iv) allyl bromide. i ii iii Br Zn Br 113 112 114 Scheme 35 Reagents (i) 2 BuLi; (ii) ZnCl ·OEt ; (iii) CuCl . H O O H i ii O O N N N N MeO MeO O O O O 115 116 Scheme 36 Reagents (i) Bu Sn-allyl; (ii) 2 eq. ZnCl ·OEt . been reported. Thus Pd-catalysed reaction of cinnamyl chloride 107 with CH CH(ZnI) followed by transmetallation (CuCN) then trapping with allyl bromide a.orded 1,6-diene 108 in 66% yield (Scheme 34). Lewis acids.Zinc(..) bromide is a useful Lewis acid for the formal [2 2] cycloaddition of selenosilyl alkenes with activated ethylene compounds. Highly enantioselective mercury cation induced cyclisation of allylic-homoallylic diol 109 reversibly gives 110 (which can be trapped by addition of Et B—LiBH ). This has been employed in a total synthesis of ( )-furanomycin 111. Miscellaneous. Biphenylene 114 and derivatives can be prepared in moderate to good yields via intramolecular coupling of zincacyclopentadiene 113 generated by lithiation then ZnCl -transmetallation of 2,2-dibromobiphenyl 112 (Scheme 35). Based on studies involving inhibition by galvinoxyl ZnCl ·OEt functions both as 133 Annu.Rep. Prog. Chem. Sect. B 1999 95 117—136 Ph i ii D Ph D 117 118 Scheme 37 Reagents (i) Et Zn 10mol% Ti(); (ii) DO. N N i ii iii OMe OMe O O 119 120 Scheme 38 Reagents (i) LDA; (ii) ZnBr; (iii) HO. radical initiator and chelating agent in the tin-based allylation of 115 to aord 116 with 86% de (Scheme 36). A T i()-catalyst prepared in situ from 10mol% Ti(i-PrO)Cl and 20 mol% EtMgBr allows carbozincation of enynes by Et Zn. For example enyne 117 is smoothly converted after deuterative work-up to 118 (Scheme 37). Functionalised pyrrolidines are readily prepared by diastereoselective intramolecular amino-zinc-enolate carbometallation.Thus for example lithiation of 119 followed by addition of ZnBr and then hydrolysis gave 120 in 70% yield (Scheme 38). Sequential oxymercuration¡Xreduction (Hg(OAc) then NaBH) eects conversion of mono- di- and tri-saccharide glycals into their corresponding 2-deoxy sugars. The process is mild and non-acidic thereby allowing the use of acid-labile groups such as silyl ethers. A combination of diethylzinc and air (CAUTION!) is eective as an initiator in tin hydride mediated radical reactions of organic halides. Activated zinc on a polymeric support can be prepared by addition of ZnCl solutions to polymeric supported alkali metals (prepared by evaporation of liquid ammonia solutions). 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