CHEM 153 PRACTICE TEST #1 ANSWER KEY

Transcription

1 CEM 153 PACTICE TEST #1 ASWE KEY

2 Provide a mechanism for the following transformation, indicating the electron count and oxidation state of each organometallic intermediate: u 3 (C) 12 (5 mol%) TF, 135 C (sealed tube) (ote: for simplicity, the trimeric precatalyst may be assumed to dissociate to catalytically active u(c) 4 monomers) u(c) 4 u(0), 16e - -C, Ligand substitution Associative? (C) 3 u u(0), 16e - xidative addition (proximity-driven) u C C C Ligand substitution Associative? u(ii), 18e - -C, Ligand substitution Dissociative? (C) 2 u u(0), 14e - eductive elim. ' u C C u(ii), 16e - Migratory insertion u C C u(ii), 18e - Pyridine coordination to the metal is key to the success of this reaction: otherwise, oxidative addition to the formyl C- bond does not occur to an appreciable extent.

3 Q. The hydroacylation of olefins provides direct access to ketones via the coupling of an aldehyde and an olefin: (P 3 ) 3 h (5 mol%) + 'C o-xylene 150 C ' i) Provide a mechanism for this reaction, indicating the electron count, oxidation state, and likely geometry for each organometallic intermediate. 'C ' 3 P h 3 P h 3 P P 3 xidative addition 3 P P 3 h(i), 16e - Square planar h(iii), 18e - ctahedral ' 3 P h -P 3 Ligand P 3 substitution Dissociative h(iii), 18e - ctahedral Migratory insertion 3P ' h ' +P 3 Ligand substitution Associative 3 P h 3 P ' eductive elimination ' P 3 h(iii), 16e - Trigonal bipyramidal? h(i), 16e - Square planar ii) The most common side-product of this reaction (which usually consumes most of the aldehyde used) is shown below: + 'C (P 3 ) 3 h (5 mol%) o-xylene 150 C Provide a mechanism for the formation of this side-product. ' 3 P h 3 P P 3 h(i), 16e - Square planar 'C xidative addition ' P 3 ' 3 P h 3 P h 3 P Ligand dissociation P P 3 3 h(iii), 18e - h(iii), 16e - Trigonal bipyramidal? ctahedral C deinsertion 3 P h C P 3 h(i), 16e - Square planar eductive elimination ' ' 3 P h C P 3 h(iii), 18e - ctahedral

4 iii) Jun has developed a catalyst system which overcomes this problem by adding 2-amino-3-picoline as a cocatalyst: (P 3 ) 3 h (5 mol%) + 'C C 3 (20 mol%) ' 2 Toluene 150 C Provide a mechanism which demonstrates why this additive eliminates the formation of the side-product observed in ii). C 3 'C C 3 (P 3 ) 3 h C 3 2 Imine formation ' Ligand subst'n Associative 3 P P 3 ' ' h 3 P P 3 This key intermediate cannot undergo C deinsertion, because the formyl group is masked as an imine. lefin coordination, migratory insertion, reductive elimination as before ' 2 Imine hydroylsis C 3 ' 'C C '

5 The following coupling was observed: Br B() 2 Pd(P 3 ) 4 (5 mol%) 3 C C 3 a 2 C 3 TF / i) Draw mechanisms for the formation of 2 and 3 from 1, indicating the electron count and oxidation state of each organometallic intermediate. Br Pd(P 3 ) 2 (Pd(0), 14e - ) xidative addition Br P 3 Pd P 3 lefin insertion (Pd(II), 16e - ) (Pd(II), 16e - ) Br Pd P 3 P 3 β-ydride elim. B() 2 Transmetallation ( 3 P) 2 Pd()Br (Pd(II), 16e - ) Pd P 3 P 3 a 2 C 3 Pd(P 3 ) 2 eductive elimination Pd(P 3 ) 2 (Pd(II), 16e - ) a 2 C 3 TF / 2 3 C C 3 Aromatization ii) When = S 2 Ar, 2:3 = 100:0. When = Bn, 2:3 = 33:66. Provide an explanation for the divergent reactivity of these two substrates. It is postulated that the sulfonamide oxygen atoms coordinate to Pd (sulfoxides and related structures are good ligands for Pd(II) compounds), thus blocking the free coordination site necessary for β-hydride elimination. When the sulfonamide group is not present, β-hydride elimation is a competitive pathway, suggesting that the benzylamino group does not effectively ligate Pd in the same manner (due to steric and/or electronic factors - certainly a strong case could be made for sterics). P 3 S Pd Br P 3

6 iii) The coupling of a variety of arylboronic acids with 1 was investigated. The ratio of 2:3 increased in the order p-b() 2 < B() 2 < p-fb() 2. Provide a mechanistic explanation for this observation. The dependence of the product distribution upon the arylboronic acid used suggests that transmetallation is the product-determining step in this reaction system. In general, electron-poor arylboronic acids undergo transmetallation most readily, likely due to a more polarized Ar-B bond. When electron-rich arylboronic acids are used, and the transmetallation step becomes more difficult, the β-hydride elimination pathway becomes dominant. iv) Based upon your explanation in iii), suggest improvements to the reported experimental conditions (ie. changes in metal, ligand, solvent, base, etc.) which would minimize formation of 3. Any change to the system which accelerates transmetallation will minimize formation of 3, based upon the discussion above. Thus, using the Kishi modification (TlEt or Tl as base), or Fu conditions (KF as base) could provide an improvement by generating a more reactive boronate species for transmetallation. An alternate (and somewhat less elegant) solution would be to employ a huge excess of the arylboronic acid, thereby driving the transmetallation reaction to completion.

7 Propose a detailed mechanism for the following transformation, including electron count and oxidation state for all organometallic intermediates. Account for the fact that the reaction proceeds efficiently without the addition of a base. C 4 9 C B C2 C 3 3 mol% Pd(P 3 ) 4 TF, 65 C C C % C 2 Pd(P 3 ) 2 (Pd(0), 14e -- ) xidative addition C 6 13 C 4 9 Pd 3 P C 2 C 3 P 3 σ-propargyl / σ-allenyl equilibration C 6 13 C 4 9 Pd C 2 C 3 3 P P3 (Pd(II), 18e - ) (Pd(II), 16e - ) C 2 deinsertion C 2 B: Decarboxylation off the palladium carbonate species liberates carbon dioxide and generates a palladium methoxide, which accelerates the transmetallation reaction as shown below (and discussed in class). This means of access to the palladium methoxide species obviates the need for external base. C 6 13 C P Pd P3 C 3 (Pd(II), 16e - ) C 6 13 C P Pd C 3 3 P B() 2 B() 2 Transmetallation C 6 13 C 4 9 Pd 3 P P3 eductive elim. C 6 13 C 4 9 (Pd(II), 16e - ) Pd(P 3 ) 2

8 Propose a mechanism for the following transformation, including the oxidation state and electron count for all organometallic intermediates. (ote that dimeric square-planar Ir I species may be broken up by the addition of a fourth ligand to form monomeric square-planar Ir I.) [Ir(CD)] 2 (1 mol%) a 2 C 3 3 C Toluene, 100 C 94% yield a 3 C (CD)Ir Ir(CD) (CD)Ir Ir(CD) Ligand Ligand substitution substitution Ir(I), d 8, 16e - Associative Associative Ir(I), d 8, 16e - (CD)Ir CC 3 Ir(I), d 8, 16e - Ligand substitution Associative Migratory insertion (note regioselectivity) a C 3 (CD)Ir Ir(I), d 8, 16e - (CD)Ir β-acetate elimination Ir(I), d 8, 16e - The regioselectivity observed in this reaction merits comment. A number of explanations for the observed outcome are possible. The reaction parallels, to some extent, the regioselectivity for heteroatom-substituted olefins in the eck reaction. owever, whether the acetoxy group can be considered to be an electron-donating group is debatable. A stronger case may be made for the steric argument, which favors formation of the least hindered alkyliridium species. ote also that Wacker-type reactivity of the bound olefin with sodium benzyloxide (ie. without transmetallation to Ir) is another possibility. The observed regioselectivity then follows the standard trend for Wacker reactivity (ie. generation of the least hindered primary alkylmetal species). (CD)Ir CC 3 abn (CD)Ir Bn Ir(I), 16e - CC 3 - a + β-acetate elim. aac, [Ir(CD)] 2

9 In attempting the following Stille coupling, the cine substitution product 1 was observed predominantly instead of the ipso product 2: I Sn 3 Pd 2 (dba) 3 As C 1 2 To investigate the mechanism for formation of the cine product, the authors conducted the following crossover experiment: Sn 3 I n-bu Pd 2 (dba) 3 As C n-bu D only products observed Sn 3 D Based on these results, the authors invoked intermediate A in the mechanism: L n Pd 0 Ar A Provide a mechanism for the formation of the cine substitution product, invoking A as a key intermediate.

10 I Pd( 3 As) 2 3 As As 3 Pd I Ligand substitution xidative add'n PdSn I As 3 3 Pd(II), 16e - Pd(II), 16e - Migratory insertion (T transmetallation) ( 3 As) 2 Pd Ar ( 3 As) n Pd Ar - 3 SnI α-elimination Ar As 3 Pd Sn 3 I Pd(0), 14e- 3 As As 3 Pd If n = 2, Pd(0), 14e - Pd(II), 14e - B: The transition state for this α-elimination reaction shares several features with the 4-center array invoked for transmetallation reactions. The formation of a new Sn-I bond provides the driving force for conversion of a Sn-C bond to Pd-C, resulting in this case in a Pd carbenoid. Pd(0), 14e - Pd( 3 As) 2 Carbopalladation chemistry, rather than standard transmetallation chemistry, provides a mechanism for functionalizing the vinylstannane at the cine position.