12 Organometallic Chemistry Part (i) The Transition Elements By M. BOCHMANN and R. A. HEAD ICI New Science Group The Heath Runcorn Cheshire WA7 4QE M. D. JOHNSON Department of Chemistry University College London 20Gordon Street London WClH OAJ 1 Introduction The publication of the new Journal ‘Organometallics’ and of the nine volume ‘Comprehensive Organometallic Chemistry” were major events of 1982. Other books recently published include ‘Organotransition Metal Chemistry Applications to Organic Synthesis’,2 ‘Catalytic Aspects of Metal Phosphine Com~lexes’,~ the first volume of a new series on Inorganic and Organometallic Reaction mechanism^,^ which includes a chapter on the reactions of organochromium(II1) compounds and ‘Me tal-catalysed Oxidations’.’ The text of Hoffman’s Nobel lecture on Building Bridges between Inorganic and Organic Chemistry6 and a broad-ranging survey of Electron Transfer Catalysis7 provide perceptive views of a spectrum of organometallic chemistry whereas two reviews on the Fischer Tropsch Synthesis,8 and reviews on the Co-ordination Chemistry of Acetonitrile,’ the Co-ordination Chemistry of Metal Alkynyl Com- plexes,” Organometallic Intramolecular Co-ordination Compounds having a Cyclo- pentadienyl Donor Ligand l1 Organometallic Intramolecular T-Olefin Co-ordina- tion Compounds l2 and Palladium and Nickel Catalysed Cross Coupling Reac- tion~,~~ provide more specific coverage of earlier work.In addition two reviews by ‘Comprehensive Orgariometallic Chemistry’ ed. E.Abel F. G. A. Stone and G. Wilkinson Pergamon Press 9 vols 1982. ‘Organotransition Metal Chemistry Applications to Organic Synthesis’ S. G. Davies Pergamon Press 1982. ‘Catalytic Aspects of Metal Phosphine Complexes’ ed. E. C. Alyea and D. W. Meck Am. Chem. Soc. Adv. Chem. Ser. 1982,196. J. H. Espenson in ‘Advances in Inorganic and Bioinorganic Reaction Mechanisms’ ed. A. G. Sykes Academic Press 1982,1,2. ‘Metal-Catalysed Oxidation of Organic Compounds’ ed. R. A. Sheldon and J. K. Kochi Academic Press 1981. R. Hoffmann Angew. Chem. Int. Ed. Engl. 1982 21,711. M. Chanon and M. L. Tobe Angew. Chem. Znt. Ed. Engl. 1982,21 1. W. A. Herrman Angew. Chem. Int. Ed. Engl. 1982 21 117; C. K. Rofer-De Poorter Chem. Rev. 1981,81,447. S. J. Bryan P. G.Huggett K. Wade J. A. Daniels and J. R. Jennings Coord. Chem. Rev. 1982,44 149. lo R.Nast Coord. Chem. Rev. 1982,47,89. “ I. Omae Coord. Chem. Rev. 1982 42,31. l2 I. Omae Angew. Chem. Int. Ed. Engl. 1982,21 899. l3 E. Negishi Acc. Chem. Res. 1982 15 240. 240 M. Bochrnann R. A. Head andM. D. Johnson Halpern14 illustrate extended aspects of the topic discussed in the next section of this report and a survey of the use of transition metals in organic ~ynthesis,'~ covers the year 1980. 2 Free-radical Processes An increasing number of organometallic reactions hitherto believed to be heterolyt- ic or concerted are now being shown to proceed at least under some conditions by free-radical pathways. In a key study pertinent to the question of carbon-metal bond homolysis the enthalpies of dissociation of some carbon-cobalt bonds have been determined from equilibrium and kinetic data.l6 For l-phenyl-ethylbis(dimethylglyoximato)pyridinecobalt(III)complexes the enthalpy of dissoci- ation [corresponding to that for equation (3)] deduced from the temperature dependence of the measured equilibrium constant for reaction (l),and from PhCH(CH3)Co(dmgH),L + PhCH=CH2 + $H2 + c~(dmgH)~L (1) PhCH=CH2 + iH2 + PhCHCH3 (2) PhCH(CH3)Co(dmgH)2L + PhCHCH3 + Co(dmgH)*L (3) estimates of the enthalpy change of reaction (2),varies from 76 to 88 W mol-' for L = 4-cyanopyridine and L = 4-aminopyridine respectively.It remains to be seen what influence the solvent may have on these values. The kinetics of decomposition of (1 L = aq) in aqueous acid under non-equilibrium conditions which gives a mixture of styrene and dimers of the 1-phenylethyl radical suggest that both products are formed as a result of the homolysis shown in equation (3); in the latter case followed by free-radical dimerization in the former by abstraction of a hydrogen atom from the 2-carbon of the organic radical by the paramagnetic metal complex [equation (4);R' = Ph R2 = H M = C~(dmgH)~aq].'~ The thermo- chemistry of equation (4)is such that its endothermic reverse path may be a R'R2CCH3 + M + R'R2C=CH2 + MH (4) key step in the reaction of metal hydrides with olefins.Thus a strong CIDNP effect observed in the proton n.m.r. spectrum of the 1,l-diphenylethane formed on reduction of 1,l-diphenylethene with HCO(CO)~ has been ascribed to non-equili- brium spin states generated as a result of sequential hydrogen-atom transfers from the metal hydride to the olefin and to the 1,l-diphenylethyl radical.18 Similarly a kinetic analysis of the reaction of HMn(C0)4P(OMe)3 with PhCH,Mn(CO),P(OMe) coupled with earlier data has been interpreted in terms of homolysis of the carbon-metal bond followed by a hydrogen-atom transfer from the metal hydride to a benzyl radical." l4 J.Halpern Acc. Chem. Res. 1982,15 238; 332. L. S. Hegedus J. Organomet. Chem. 1982 237,231. 16 F. T. T. Ng G. L. Rempel and J. Halpern J. Am. Chem. Soc. 1982,104,621; M. J. Nappa R. Santi S. P. Diefenbach and J. Halpern ibid. 619. H. B. Gjerde and J. H. Espenson Organometallics 1982,1 435.T. E. Nalesnik and M. Orchin Organometallics 1982,1 222; c.f. J. Organomet. Chem. 1981 222 25. l9 T.-T. Tsou M. Loots and J. Halpern J. Am. Chem. SOC., 1982,104 623. Organometallic Chemistry -Part (i) The Transition Elements 241 The first kinetic study of the attack of an organic radical on saturated carbon in solution has been made. The radical Me2COH formed by the unimolecular homolysis of the complex (2) undergoes a bimolecular attack at the a-benzylic carbon of benzylbis(dimethylglyoximato)aquocobalt(rII)in aqueous acid to give the compound Me2C(OH)Cr(H20)52' $ Me2COH + CI-(H~O)~~' (5) (2) Me2COH + PhCH2Co(dmgH)2L $ Me2C(OH)CH2Ph+ Co(dmgH)zL (6) (3) (4) (3)and the bis(dimethylglyoximato)aquocobalt(II)complex (4),with rate coefficients of 7 x lo6and 1.9 x lo7dm3 mol-' s-l respectively.20 Bimolecular rate coefficients for the abstraction of a halogen atom from some polyhalogenomethanes by Re(CO), Mn(CO)5 and c~(dmgH)~L have also been determined [equation (7)].21*22 The formation of trichloromethyl radicals by equation (7) [M = C~(dmgH)~py] in the presence of hex-5-enylbis(dimethylglyoximato)pyridinecobalt(111)leads ci3cx+ M + CI~C + MX (7) as part of a sequence of chain-propagating steps to the radical (5) [M = C~(dmgH)~py] which undergoes an intramolecular homolytic displacement at the saturated a-carbon with the formation of trichloroethylcyclopentane; the first example of a homolytic attack of a remote organic radical on the a-carbon of an alkyl chain.23 -M CI3C Scheme 1 Cobaloxime(I1) complexes have also been used as catalysts in the reaction of halogenoethyl ethers of the type (6) with borohydride ion in methan01.~~ Electron transfer from a regenerable cobaloxime(1) species to the organic halide allows the formation of the radical (7) which after cyclization abstracts a hydrogen atom from the reagent to give a 3-methyleneoxolane.Oxidation with Cr03 then provides a route to a-methylene-y- butyrolactones. Free-radical reactions frequently occur as a consequence of one- and two-electron oxidations. Thus though the iron(I1) complex R2FeL2 (R = Me Et Pr" Bun,etc.) undergoes thermal decomposition by a p-elimination path leading to alkane and 'O R. C. McHatton J. H. Espenson and A.Bakac J. Am. Chem. Soc. 1982,104,3531. W. K. Meckstroth. R. T. Walters W. L. Waltz A. Wojcicki and L. M. Dorfman 1.Am. Chem. Soc. 1982,104 1802. '' J. H. Espenson and M. S. McDowell Organometallics 1982 1 1514. 23 P. Bougeard A. Bury C. J. Cooksey M. D. Johnson J. M. Hungerford and G. M. Lampman J. Am. Chem. Soc. 1982,104,5230. 24 M. Okabe M. Abe and M. Tada J. Org. Chem. 1982,47 1775. M. Bochmann R. A. Head andM. D. Johnson Scheme 2 alkene the corresponding iron(II1) complex reversibly formed by electrochemical oxidation undergoes homolysis of the carbon-iron bond (Scheme 3). The corre- sponding iron(1v) complex formed also by chemical oxidation with Fe(phen),,' undergoes a very rapid yet efficient apparently electrocyclic coupling of the two alkyl ligands.For example the tetramethyleneiron(1v) complex [R = (CH,)J decomposes rapidly to give a high yield of cyclobutane whereas the corresponding tetramethylene diradical would have given mostly ethene .25 Alkyl radicals formed in such processes are also capable of attacking other ligands such as the phenanthro- line ligand in Fe(~hen),~+ site-specifically.26 [R2FeL2] A R(-H) + [RFe(H)L,] + RH + [FeL,] 1-e-[R2FeL2]+ -R + [RFeL2]+ 1-e-[R2FeL2I2+ -R2 + [FeL2I2+ Scheme 3 Another process that proceeds by a one-electron oxidation is apparent hydride transfer from an a-carbon of an alkylmetal c~mplex.~' For example the formation of the hydridoethene complex (1 1) in the reaction of the dimethyltungsten complex (8) with the trityl cation takes place uia a one-electron transfer to give the tungsten(v) complex (9) which has been characterized at -78 "C,and thence via the carbene complex (10).That the oxidative path favours a-hydrogen abstraction is evident from several related reactions including the fact that the corresponding complex with R = Et does not undergo hydrogen abstraction from the ethyl Iigand but from the methyl ligand with the formation of the hydridopropene complex (12). Electron-transfer processes probably account for the formation of free radicals in the reactions between 2-benzophenonezirconocene with alkyl halides.28 Thus 25 W. Lau J. C. Hoffman and J. K. Kochi Organomefaflics,1982,1 155. 26. K. L. Rollick and J. K. Kochi J. Org. Chem. 1982 47,435.27 J. C. Hayes and N. J. Cooper J. Am. Chem. SOC. 1982,104,5570. 28 G. Erker and F. Rosenfeldt J. Organornet. Chern. 1982 224 29; Tetrahedron 1982 38 1285. Organometallic Chemistry -part (i) The Transition Elements Scheme 4 in the reaction with 2-bromo-2-methylhept-6-ene(13) the cyclic product (14) is formed in 75% yield indicative of the formation of the 2-methylhept-6-en-2-yl radical as an intermediate (Scheme 5). Me Me Cp2Zrqph + LMe + Br Ph M2' + (13) Br (14) 75% Scheme 5 3 Oxidation The oxidation of 1-alkenyl ethers and amines to their corresponding a-ketoesters and amides (15) is achieved in good isolated yields using iodosylbenzene and a ruthenium compound such as RuC~~(PP~~)~ as ~atalyst.~' Reaction (8) proceeds very,smoothly at 25 "C where no further oxidation of the product is found.Using the same catalyst and molecular oxygen (1atm. 25 "C) 3,5-di-t-butylcatechol is converted to a mixture of the muconic acid anhydride (16)and the 2H-pyran-2-one 0 C" x C,HSIO (15)(X= OR',NR'z) (8) R-c-C-x RuCI,(Ph,P) 'R / \c/II 0 29 P. Muller and J. Godoy Tetrahedron Lett. 1982 23 366. M. Bochmann R. A. Head and M. D. Johnson (17) as shown in Scheme 6.30Experiments using 1802 have confirmed that in both (16) and (17) it is only the exocyclic oxygen that is derived from molecular oxygen. 26% 0 -'Ru' 02 OH Scheme 6 A key step in the total synthesis of 14a-methyl-19-nortesterone (20) is the stereoselective epoxidation of (18) to (19).By conventional techniques only poor yields of the required stereoisomer are obtained but this problem has now been overcome by the use of the Sharpless reagent Mo(CO)~-BU'O~H.~~ At 80 "C (19) is produced in ca. 80% selectivity with near-quantitative conversion of (18) (Scheme 7). H H & & Me Mo(CO), Bu'O~H \ Me0 \ Me0 Me Me Reagents i BF,-Et,O 0-5 "C; ii Na-Pr'OH 100 "C; iii Li-NH, -60 "C;iv 1N-HCl 60 "C Scheme 7 3" M. Matsumoto and K. Kuroda J. Am. Chem. SOC.,1982,104 1433. 31 M. B. Groen and F. J. Zeelen Tetrahedron Lett. 1982 23,3611. Organometallic Chemistry -Part (i) The Transition Elements 245 Regioselective control over the oxidation of internal alkenes is highly desirable but difficult to achieve.It has now been found that palladium-catalysed oxidation of ally1 and homoallyl ethers or acetates gives predominantly p-alkoxy [reaction (9)] and -acetoxy ketones [reaction (lo)] re~pectively.~~ Palladium is introduced as PdCl with either CuCl or p-benzoquinone and high yields of these synthetically valuable products are obtained under very mild conditions (50 "C,1atm. 02). 4 Carbonylation Palladium-catalysed ring closure in the presence of CO has found an interesting application in the conversion of (21) into the anthramycin precursor The reaction (Scheme 8) proceeds under mild conditions (5 atm. CO 110 "C) with 27% isolated yield. R2> R2 Me&A P~(OAC)~-P~~P+ CO-Bun3N -, ._* CI Br N H OR' OR' 0 Anthramycin Scheme 8 A range of aromatic acid anhydrides can be prepared using a one-step synthesis directly from the aromatic compound with CO [reaction (ll)].34 Not only do the benzenoid aromatics C6H5X (X =H Me OMe C1) and naphthalene undergo the 32 J.Tsuji H. Nagashima and K. Hori Tetrahedron Lett. 1982 23 2679; H. Nagashima K. Sakai and J. Tsuji Chem. Lett. 1982 859. 33 M. Ishikura M. Mori M. Terashima and Y. Ban J. Chem. SOC.,Chem. Commun. 1982 741. 34 Y. Fujiwara I. Kawata T. Kawauchi and H. Taniguchi J. Chem. SOC.,Chem. Commun. 1982 132. 246 M. Bochmann R. A. Head and M. D. Johnson reaction but also furan and thiophene where carbonylation occurs at the @-position regioselectively to give @-furan (58%) and p-thiophene (35%) carboxylic acid anhydrides respectively.Dibromoethane is an important ingredient in the reaction although its exact function is uncertain. 00 ArH + co Pd(OAc),-BrCH,CH,Br ii II C0(15atm.) loooc b Ar-C-0-C-Ar (3246%) (11) Regular copolymers of ethylene or norbornadiene and CO are obtained under remarkably mild conditions (e.g. 350 p.s.i. CO 350 p.s.i. C2H4 25 "C) with [Pd(MeCN),][BF412.nPPh3(n = 1-3) as catalyst [equation The ethylene- CO polymer is highly crystalline (m.p. 260 "C) whereas the NBD-CO material has a molecular weight of 3380 (by osmometry). Reactions introducing one CO into an organic molecule are well known while in contrast double carbonylation is extremely rare. It is now found that tetraethyloxamide is obtained in 82% yield by carbonylation (1atm.) of (Et2NH)2NiBr2 at 20 0C.36 Carbonylation of trans-PdR(X) (PMe2Ph) (R = Me 00 0 II II II b R-C-C-NR'2 + R-C-NR'2 truns-PdR(X)(PMe2Ph)2+ R'2NH + CO l~~oo~tm.R'2NH =Et2NH,piperidine or morpholine (23) (13) X = I; R = Ph X = Br) also affords a-ketoamides (23) as the major product under similar conditions [reaction (13)].37 The latter reaction has been extended to the conversion of organic halides directly into a-ketoamides in >90% selec-ti~ity.~~ A range of metal complexes have been examined as catalysts but only with palladium is the double carbonylation observed [reaction (14)]. 00 II II RX + 2CO + 2R12NH CO(10 atm.) R-C-C-NR'z + R12NH2X (14) loo"c RX = PhBr PhI 3-bromopyridine or 2-bromothiophene 5 Miscellaneous Palladium Chemistry Aryl and vinyl phosphonates are obtained in good to excellent yield from the reaction of aryl or vinyl halides with 0,O-dialkylphosphonates in the presence of Pd(Ph,P) as catalyst [reaction (15)].39 1-Bromonaphthalene and 3-bromopyridine 35 A.Sen and T. Lai J. Am. Chem. SOC.,1982,104 3520; T. Kobayashi and M. Tanaka J. Organomet. Chem. 1982,231 C12. 36 H. Hoberg and H. J. Riegel J. Organomet. Chem. 1982,236 C53. 37 F. Ozawa and A. Yamamoto Chem. Lett. 1982,865. 38 F. Ozawa H. Soyama T. Yamamoto and A. Yamamoto Tetrahedron Lett. 1982,23,3383. 39 T. Hirao T. Masunaga T. Yamada Y. Ohshiro and T. Agawa Bull. Chem. SOC.Jpn. 1982 55 909. Organometallic Chemistry -Part (i) The Transition Elements also give the corresponding phosphonates in high yield.The reaction with vinyl bromides proceeds with retention of stereochemistry thus (E)-P-bromostyrene gives (E)-styrylphosphonate [reaction (16)]. 0 0 I1 II ArX + HP(0R)Z Pd(Ph,P),-Et,N 90 "C P ArP(OR) + Et3NHX (15) 0 (93%) Arylation of simple activated alkenes by benzoyl chloride occurs in the presence of a catalytic amount of Pd(OAc) and N-benzyldimethylamine as base [reaction ( 17)].40High stereochemical control is achieved with virtually exclusive formation PhCOCl + CH2=CHX Pd(OAc) PhCH=CHX + CO + HCI (17) base 130"c b (X = CO,Et CONMe, CN or Ph) of the (E)-isomer. Disubstituted alkenes react more slowly and a small amount of isomerization also takes place during the reaction. Functionalized vinylcyclopropanes exhibit both interesting antibiotic and insecti- cidal activities as well as having high potential as intermediates in organic synthesis.Vinyl cyclopropane carboxylates are readily prepared in a high yield synthesis by simple Pd(diphos),-catalysed cyclization of 6-acetoxy-4-heptenoates (24) as shown in equation (18).41Other Pd phosphine complexes are ineffective for the reaction which gives the (E)-isomer preferentially [(E):(2)= 7 13. Me i. NaH-DME ii Pd(diphos), 40°C ' MeC0 + (18) (24) PdCl,(MeCN) catalyses the 1,3-alkyl migration of 1-alkenyl ethyl acetals (25) to give a-alkylated (E)-a,@-unsaturated carbonyl compounds (26) in excellent yield [reaction (19)].42 After short reaction times (0.5-1 h) quantitative formation of the a-alkyl-P- ethoxy carbonyl compound is achieved which eliminates ethanol on further reaction to give (26).40 A. Spencer J. Organomet. Chem. 1982,240,209; H. U. Blaser and A. Spencer I. Organomet. Chem. 1982 233,267. J.-P. Genet M. Balabane and F. Charbonnier Tetrahedron Lett. 1982,23 5027. 42 M. Takahashi N. Ishii H. Suzuki Y. Moro-oka and T. Ikawa Chem. Lett. 1981 1361. M. Bochmann R. A. Head and M. D. Johnson 0 EtOzOKr3 0.5-1 h+ EtO k'\RJ] -R1+R2 (19) R' (26) R' *= Me Et Pr" (25) R2 = H Me Et Pr" R3 = Me Et 6 Reduction The chemoselective reduction of C=C double bonds in a,& unsaturated carbonyl compounds can be achieved under very mild conditions using Bun3SnH with Pd(Ph,P) as catalyst and water as proton Most functional groups are tolerated; however the reaction is very sensitive to electronic influences [reaction (20)].Nearly quantitative yields are obtained if R = H C1 or NO2 but no reaction occurs if R = NMe2. The value of the method has been further demonstrated by the reduction of citral p-ionone and withanolide D. In all cases only reaction of the double bond conjugated to an aldehyde or keto function was observed. The evidence suggests that radicals do not play a part in these reactions. Zinc chloride or acetic acid are strong promoters presumably by activating the carbonyl function towards nucleophilic attack.44 Bis(q5-cyclopentadieny1)titaniumdichloride (3 molo/o) catalyses the reduction by Grignard reagents of alkyl and aryl carboxylic acids to the corresponding aldehydes.The reaction proceeds at room temperature in fair to good yields whereas no aldehydes were obtained from a,@-unsaturated carboxylic acids. Scheme 9 outlines the suggested mechanism.45 Cp2TiC12 + 2Pr'-CH2MgBr 1 R-C-H II0 OMgBrI IH + Hzo RCOMgBr Cp2Ti-CH2Pr' H2C=CMe2 RCOOMgBr PriCH2MgBr H Scheme 9 43 E. Keinan and P. A. Gleize Tetrahedron Lett. 1982 23.411. 44 P. Four and F.Guibk Tetrahedron Lett. 1982,23 1825. F. Sato T. Jinbo and M. Sato Synthesis 1981 871. Organornetallic Chemistry -Part (i) The Transition Elements Low-valent titanium reagents prepared from TiC1 and magnesium powder in CH2C12-Et20 (4 l) provide a generally applicable method for the high yield synthesis of disubstituted hydrazines from nitrosamines [reaction (2 l)].The success R2N.NO -+ R2NNH2 (21) of the reaction depends critically on the oxidation state of the Ti best results being obtained if the reagent is formally Ti".46 Reductions with TiC14-LiA1H4 lead to N-N bond cleavage to give amines.For the reductive formation of C-C bonds however different combinations of metal halides and reducing agents are required. In the deoxygenative dimerization of benzaldehyde to stilbene for example NbC1,-NaA1H4 (2 :1)is far superior to NbC1,-LiAlH4 and NbCl,-Mg is unrea~tive.~~ The coupling reaction is applicable to aromatic aldehydes and ketones (to give stilbene derivatives) and to benzyl and ally1 alcohols (Scheme 10). The latter may give rise to various dimerization isomers.47 NbCI,-NaA1H4 eoH 80"C,2h ' Scheme 10 A mixture of TiC13 and LiAlH (2 1)reacts with 2-ene-1,4-diols and 2-yne-1,4- diols to yield 1,3-dienes.The ene-diols may carry aromatic and linear or cyclic aliphatic substituents. Methyl ethers may be used in diols (Scheme 1l).48 RZC-CH=CH-CR2 RzC=CH-CH=CR;? I I OH OH 1 Me Me P~~C-CGC-CP~~ 1Ph2C=C=C=CPhz I I OH OH Scheme 11 46 I. D. Entwistle R. A. W. Johnstone and A. H. Wilby Tehahedron 1982,38,419. 47 M. Sat0 and K. Oshima Chem. Lett. 1981 157. 48 H. M. Walborsky and H. H. Wust J. Am. Chem. SOC.,1982,104,5807. 250 M. Bochmann R. A. Head and M. D. Johnson 7 Grignard Analogues There has been increasing interest in recent years in the use of transition-metal alkyl complexes for alkylation reactions since they exhibit greater selectivity than their lithium magnesium or zinc analogues.For example addition of tetramethyl-titanium monoalkyltitanium alkoxides or their Zr analogues to 2-phenylpropanol gives an erythro :threo ratio of 93 :7; Li or Mg alkyls only 2 :1.Alkylation of benzil with MeTi(OBu') or TiMe gives (27) and (28) with an erythro :threo ratio of 2 :98. Zirconium lithium and magnesium alkyls however show the reverse asymmetric induction (erythro:threo -80:20). Titanium alkyls react with (29) to give (31) exclusively presumably via the chelate (30) (Scheme 12). The reactivity of the Ti reagents decreases in the order ally1 > methyl > n-butyl. Sterically highly hin- dered compounds that no longer react with LiMe can still be alkylated with ZrMe4.49 thrm erythro 7:93 ph Me OH Ph Me OH 'C-c! + 'C-C./ ' I"Me HO/ I "Ph Ph Ph Ho Ph Me (27) (28) TiMe, MeTi(OPr')3 98 :2 MeZr(OPr")319:81 1 .. Ph (29) Scheme 12 Titanated hydrazones of aldehydes and ketones react with aliphatic and aromatic aldehydes with high erythro-selectivity and in high yields." Alkenyltitanium 49 M. T. Reetz R. Steinbach J. Westermann R. Urz B. Wenderoth and R. Peter Angew. Chem. 1982 94 133. M. T. Reetz R. Steinbach and K. Kesseler Angew. Chem. 1982 94 872. Organometallic Chemistry -Part (i)The Transition Elements 25 1 triphenoxide induces a high degree (up to 97%) of diastereoselectivity in the alkylation of aldehydes and unsymmetrical ketones. Only products with terminal double bonds were isolated not the thermodynamically more stable isomers with disubstituted C=C bonds.The diastereoselectivityand the preferred configuration depends on the steric requirements of the substituents of the carbonyl compound (Scheme 13).51 R' OH R~-C-R~ + Me-Ti(OPh) - R'>(/\\ II Me 0 diastereoselectivity R' = But > H = Me > Et > Pr' R2 = Ph Scheme 13 Similar reactions with 2-methylpropanal and benzaldehyde demonstrate that during alkyl addition lk (like)topicity is preferred.52Aliphatic aldehydesgive >go% of diastereoisomerB (Scheme 14). With substituted benzaldehydes,electron-donor groups increase the diastereoselectivity up to 98% ; electron acceptors have the opposite effect.The reactions are most selective at low temperature (-50 to -100 "C). RCH + MeCH=CH-CH2-Ti(OPh)3 II 0 &/ \ 0 0 Me*HCH2Ti RYH H Me 1ul-addition 1[&-addition R L Me Me A B Scheme 14 The related alkylation with the crotyl carbamate derivative (32) gives nearly exclusively the (threo-)S-hydroxenol carbamate (33). The regioselectivity of the carbonyl addition is maintained even with 1-alkylated titanium reagents such as (34) (Scheme 15). All reactions proceed at -78 "C,1h in excellent yieldsnS3 " D. Seebach and L. Widler Helv. Chim. Acta 1982,65 1972. J2 L. Widler and D. Seebach Helv. Chim. Ada 1982 65 1085. '' R. Hanko and D. Hoppe Angew Chem. 1982,94,378. M. Bochmann R. A. Head and M. D.Johnson OH (32) M = Ti(NEt,) 2.-(33) Y = O2CNPrI2 threo OH Scheme 15 Whereas lithiated alkynyl esters (35) react with ketones to give a-addition products titanium reagents undergo exclusive y-addition.'* Only one diastereoisomer of the allene (36) is formed as well 2s very little (37) (Scheme 16; (36) :(37) = ca.95 :5). However this reaction appears to be very sensitive to Scheme 16 substituent effects. A similar titanium alkyl (35 R3 = Me& Ph Et; X = Me OTHP) is highly selective for the acetylenic a-addition products [(38a) :(38b)l ratio up to 95 :5].55A recent review describes these stereospecific reactions and proposes an unequivocal nomenclature for product configuration and diastereoselective additions.56 s4 D. Hoppe and C. Riemenschneider Angew.Chem. 1982,94,64. " M. Ishiguro N. Ikeda and H. Yamamoto J. Org. Chem. 1982,47 2225. 56 D. Seebach and V. Prelog Angew. Chem. 1982,94,696. Organometallic Chemistry -Part (i) The Transition Elements 253 Group v and VI alkyl complexes such as RM& R2MX3 (M = Nb Ta; X = C1 OEt)” and RCrC12(THF)58 react selectively with aldehydes and not with ketones. Good results were obtained even if R carried &hydrogen atoms (Pr” Bu”). The chloride-free phenylating agent PhCr(a~ac)~ has also been made.59 With C-H acidic ketones such as acetone it gives benzene 2-phenylpropan-2-01 and mesityl oxide as aldol condensation product. By analogy with Grignard reagents a nickel norbornene complex reacts with CO to give exclusively the exo-carboxylic acid on hydrolysis.60 The reaction provides a convenient high-yield route for the direct conversion of olefins into acids without an alkyl halide intermediate.cis-exo-Adducts are also the product of reacting norbornene with long-chain (q3-allyl)palladium complexes.61 Substitution of Pd in the intermediate (39) by l-lithio-3-(2-tetrahydropyranyloxy)-l-octyne affords (40) a prostaglandin endoperoxide analogue. Saponification of the ester group gives a compound which shows inhibition of blood platelet aggregation approximately half that of PGEI even without being stereochemically pure or optically active (Scheme 17). &J+y PdHfacac -*E PdHfacac E (39) 90% OTHP 1 I Li-C=C-CHC,H 1 A OH (40)E = C02Me Scheme 17 8 Catalytic C-C coupling Reactions Palladium complexes have often been used to catalyse Grignard cross-coupling reactions.Asymmetric induction by 0.5 mol% PdC12[(R)- (S)-PPFA] (41) in the reaction of (E)-vinyl bromides with a-(trimethylsily1)benzyl magnesium bromide gives allylsilanes in exceptionally high optical yields (85-95% e.e.).The R-isomers are formed preferentially in all cases.62 The (R)-(E)-allylsilanes react with elec- trophiles stereospecifically to give (S)-(E)-products via attack anti to the SiMe3 leaving group. (2)-Allylsilanes give (R)-isomers (Scheme 18). ’’ T. Kauffmann E. Antfang B. Ennen and N. Klas Tetrahedron Lett. 1982,23 2301. ” T. Kauffmann A. Hamsen and C. Beirich Angew. Chem. 1982 94 145. 59 T. Ito T. Ono K. Maruyama and A.Yamamoto Bull. Chem. SOC.Jpn. 1982 55 2212. 6o H. Hoberg and D. Schaefer J. Organomet.Chem. 1982,236 C28. 61 R. C. Larock J. P. Burkhart and K. Oertle Tetrahedron Lett. 1982,23 1071. 62 T. Hayashi M. Konishi H. Ito and M. Kumada J. Am. Chem. SOC.,1982 104,4692. M. Bochrnann,R. A. Head and M. D. Johnson Ph SiMe EbPh + BrMg-C-SiMe r3; ,Ph-Ph -, PheBr I H I HH H (R) 95% e.e. 6) E = But,MeCO CH2OH Scheme 18 The synthesis of macrocycles usually requires working in high dilution in order to avoid intermolecular condensations. A new approach to forming medium and large rings utilizes Pd-catalysed allylic substitution reactions and permits substrate concentrations of 0.1 to 0.5 M.By attaching the catalyst to an insoluble support a dilution effect arises from the substrate having to diffuse to relatively few active sites Neutral cyclization precursors such as vinyl epoxides (42) give high yields of cyclic products.Use of a soluble Pd catalyst leads only to oligomers. Temperature control is critical clean cyclizations occur at 65 "C,lower temperatures give other products (Scheme 19).63 71% S (42) S = -SO;?Ph n =\ Scheme 19 '' B. M. Trost and R. W. Warner J. Am. Chem. SOC.,1982,104,6112. Organometallic Chemistry -Part (i) The Transition Elements Catalysis of nucleophilic substitutions of allylic substrates is usually dominated by palladium. However recent findings suggest that molybdenum complexes may play a similarly useful role and allow considerable flexibility in stereocontrol by ligand variation.64 For example whereas stoichiometric nucleophilic attack by (43) on complex (44)gives only one product (43,attack on complex (46)gives a 1 1 mixture of (45)and (47)(Scheme 20).In catalytic reactions with 5-20mol% R4% oc I Mo(bipy) + (43)-* oc’ I CI (46) (47) E = C02Me Scheme 20 Mo(CO)~or M~(CO)~(bipy) chelating ligands (2,2’-bipyridyl or dimethoxyethane) favour products of the type (47).Chelating ligands such as bipy or 0,N-bis(trimethylsi1yl)acetamide(TSA) which is used as a base to generate the nucleophile in lieu of sodium hydride also control the stereochemistry of the alkylation of (48)with diethyl malonate (Scheme 21). (48) E = C02Me base E catalyst E NaH Mo(C0)4(bipy) 85 :15 NaH MO(C0)6 50 50 TSA MO(C0)6 >95 :(5 Scheme 21 Transition-metal-promoted reactions continue to prove useful in natural product synthesis.The cycloaddition of chromium carbene complexes with disubstituted 64 B. M. Trost and M. Lautens J. Am. Chem. SOC. 1982,104,5543. M. Bochmann R. A. Head and M. D. Johnson alkynes and the Pd-catalysed carbalkoxylation are interesting features in the syn- thesis of nanomycin A and deoxyfrenolicin (49).65The latter is outlined in Scheme 22. NR,' -+ L = co Scheme 22 The cobalt-mediated [2 + 2 + 2lcycloaddition reaction has been employed in a novel synthesis of the steroid framework by simultaneously constructing the B C and D-rings from a suitable A-ring precursor.66 The cycloaddition proceeds in good yield to give (50).Oxidative removal of Co with FeC13-MeCN gives a novel diene which can be converted into (*)-estrone (Scheme 23). n Scheme 23 M. F. Semmelhack J. J. Bozell T. Sato W. Wulff E. Spiess and A. Zask J. Am. Chem. SOC.,1982 104,5850. E. D. Sternberg and K.P. C. Vollhardt J. Org. Chem. 1982,47 3447.