CH 3 TMG, DMF N H 3 CO 2 S. (PPh 3 ) 2 Pd 0

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1. (a) rovide a reasonable mechanism for the following transformation. I S 2 C 3 C 3 ( 3 ) 2 2, CuI C 3 TMG, DMF 3 C 2 S TMG = Me 2 Me 2 ICu ( 3 ) 2 0 I S 2 C 3 S 2 C 3 Cu I 3 3 3 C 2 S I 3 3 3 C 2 S 3 C 2 S I - CuI Cu Me 2 Me 2 CuI 3 C 2 S Tetrahedron Asymmetry 1996, 7, 1263

(b) Despite the seemingly similar transformation, the reaction conditions for the following coupling reaction are importantly different. rovide a mechanism consistent with these different conditions. I 2 (C 3 C) 2 a 2 C 3, DMF B L 2 0 I L tbu I - L I tbu tbu L I L L JC 2002, 67, 86 (c) Design one experiment that could distinguish between your mechanisms in (a) and (b) for the reaction in (b). Independently synthesize this substrate, for example, and subject it to the reaction conditions in (b). tbu

2. An attempt to carry out the following catalytic coupling reaction resulted mainly in the formation of triphenylamine (and associated byproducts) rather than the desired aryl ether. rovide a reasonable mechanism that explains the formation of triphenylamine and identify any other byproducts that would be formed. 2 (tbu 3 ) 2 (cat) 2 2 LiC 3, TF C 3 ot observed bserved (tbu 3 ) 2 2 (tbu 3 ) - (tbu 3 ) 2 2 2 (tbu) 3 (tbu) 3 2 LiC 3 (tbu) 3 C 2 Li

3. rovide a catalytic cycle for the reaction below including the mechanism of oxidative addition 5 mol% (Ac) 2 C3 15 mol% Bu 3 C 3 Solvent, Δ Answer C3 xidative Addition C 2 Ar (Bu 3 ) 2 (Bu 3 ) 2 xidative Addition β-hydride elimination Ar Ar (Bu 3 ) 2 C 3 (Bu 3 ) 2 C 3 1,2-hydride shift eductive Elimination C 3 (Bu 3 ) 2 The increased rate of oxidative addition with a polar protic solvent suggests an S 2 mechanism assisted by hydrogen bonding of the solvent to the oxygen lone pairs of the epoxide. The authors present the two mechanisms above and note that the stereogenic center alpha to the ketone is labile under the reaction conditions thus rendering determination of the operating mechanism impossible. Kulasegaram S.; Kulawiec,. J. Tetrahedron, 1998, 54, 1361.

4. The following metal carbonyl complexes were subjected to ligand substitution. rovide a rationale for each observation. a) The rate law for C exchnage in i(c) 4 is rate = k [i(c) 4 ]. rovide the formal oxidation state and electron count for i(c) 4. Then provide a mechanism for C exchange. 14 C i(c) 4 C 14 i(c) 3 C i(c) 4 : i(0), d 10, 18 e - i(c) 4 -C i(c) 3 14 C C 14 i(c) 3 Dissociative Mechanism b) The rate law for C exchnage inco(c) 3 is rate = k [Co(C) 3 ][C]. rovide the formal oxidation state and electron count for Co(C) 3. The provide a mechanism for C exchange. C C Co C (linear nitrosyl) Co(C) 3 : Co(-1), d 10, 18e - 14 C C 14 Co C C C Associative Mechanism C C Co C C C Co C 14 C 14 -C C C Co C C C C 14 C Co c) rovide an explanation for the differing rate laws for i(c) 4 and Co(C) 3. The cobalt complex can become electronically unsaturated by undergoing linear to bent isomrization. Thus, associative substitution can occur with the cobalt complex but cannot occur on the electronically saturated i(c) 4 complex. Basolo, JACS 1966, 88, 3929.

5. When the following Suzuki coupling between α-bromophenylacetate 1 and 3,5-dimethyl phenyl boronic acid 2 was attempted, the expected cross coupling product was not obtained. Instead, the only product observed was homocoupling product 3. rovide a mechanism for this transformation. BIA 2 2 1 Me B() 2 2 2.5mol% 2 (dba) 3 *C 3 2.5mol% BIA Cs 2 C 3, dioxane Me T BSEVED 3 2 (dba) 3 *C 3 dba C 3 Me Me B() 2 B() 2 Me () 2 B Me B() 2 = 2 2 Zhang, TL 2002, 43, 2525.

6. nly 0.14mol% Bu 3 Sn and a stoichiometric amount of KC were used to affect palladium-catalyzed cyanation of aryl halides. 0.5 mol% 2 (dba) 3 1.5 eq KC 0.27 mol% Bu 3 Sn 2.5 mol% (t-bu) 3 C 90% isolated yield acetonitrile, 80 o C, 17h a) rovide a mechanism for the following transformation. 2 (dba) 3 (t-bu) 3 dba C (t-bu) 3 (t-bu) 3 (t-bu) 3 (t-bu) 3 C (t-bu) 3 (t-bu) 3 Bu 3 Sn Bu 3 SnC b) Why is it critical for this specific reaction that the reaction by catalytic in tin? K Bu 3 SnC K Bu 3 SnC K Bu 3 Sn KC transmetalation (and/or ate- complex formation) critical for reaction Bu 3 SnC (and other cyanide sources) is known to deactivate (0) thus preventing oxidative addition into an aryl halide (though it does not interfere with transmetalation or reductive elimination). The electron-deficient cyanide ligand binds strongly to (0) since it is isoelectronic with C and a better π acceptor. KC is insoluble in acetonitrile but the tributyltincyanide and its ate complex are. Therefore, it is necessary to have only a very small amount of Bu 3 SnC present at any one time so that oxidative addition can compete with catalyst deactivation. K Yang L 2004, 6, 2837.

7. rovide a mechanism for the following i-catalyzed arylation reaction. S Mg (2 eq) 3 mol% i 2 ( 3 ) 2 TF, reflux i 2 ( 3 ) 2 2 Mg 2 Mg 3 3 i 3 i 3 S 3 3 i 3 3 i S S Mg Mg Takei TL 1979, 1, 43

2. ickel-catalyzed cross-coupling reactions are notorious for deteriorating the enantiomeric excess of chiral alkyl halides. rovide a catlytic cycle for the iyama-tamao cross-coupling reaction below that gives a rationale for the observed changes in cis / trans ratios. It is important to note that the reaction works best with secondary alkyl bromides. 7.5 mol% 1.0 equiv exo / endo = 6 / 94 F 3 Si 1.5 equiv 6.5 mol% i 2 diglyme 3.8 equiv CsF, DMS, 60 C exo / endo = 95 / 5 7.5 mol% 1.0 equiv cis / trans = 95 / 5 F 3 Si 1.5 equiv 6.5 mol% i 2 diglyme 3.8 equiv CsF, DMS, 60 C cis / trans = 55 / 45 Answer i 2 F 4 Si Cs 2 SiF 4 2 Cs Transmetallation i cis / trans = 55 / 45 eductive xidative Addition Elimination i i eductive Elimination Transmetallation SiF 4 Cs F 4 Si Cs i i Stereogenic center is destroyed by radical formation

9. (0) can be oxidized to (II) with Cu 2 or benzoquinone. ecently, a great deal of research has focussed on the use of molecular oxygen for the oxidation of (0) to (II). rovide a mechanism for the 2 mediated oxidation of (0) to (II) shown below. 2 C 3 toluene 3 C C 3 2 2 Answer 2 xidative Addition Ac C 3 C 3 Ac Ac 2 2 Ac Ac Ac For an excellent review of palladium oxidase catalysis see: Stahl, S. S. Angew. Chem. Int. Ed. 2004, 43, 3400-3420