A tandem reaction is a reaction in which several bonds are formed in sequence without isolating intermediates. The tandem reaction below goes through three key reactions: a) a Suzuki-type coupling to generate 3, then b) deprotection of R₁ and installation of a triflate leaving group to generate 4, and finally c) a Heck-type coupling reaction to make 5. Using your knowledge of metal-catalyzed coupling reactions, please answer the following questions. OMe Pd(PPh3)4 (or PdL4) LOR NaOEt, THF (solvent), 50 °C R₁ = TBS 1) TBAF (TBS deprotection) 2) TfO₂, Et₂N PdL₂ cat. R₁ Tf Et,N, THF 60 °C Br OMe 1 R₁-TBS (alcohol protecting group) OH HO-B

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loudon 6th edition organic chemistry

A tandem reaction is a reaction in which several bonds are formed in sequence without
isolating intermediates. The tandem reaction below goes through three key reactions: a) a
Suzuki-type coupling to generate 3, then b) deprotection of R₁ and installation of a triflate
leaving group to generate 4, and finally c) a Heck-type coupling reaction to make 5. Using
your knowledge of metal-catalyzed coupling reactions, please answer the following
questions.
OMe
Pd(PPh3)4 (or PdL4)
LOR₁
3
NaOEt, THF (solvent), 50 °C R₁ = TBS
1) TBAF (TBS deprotection)
2) TfO2, Et₂N
PdL₂ cat.
R₁ = Tf Et₂N, THF 60 °C
Br
OH
Оме
1 R₁ = TBS
(alcohol protecting
group)
HO-B
The third and final step of this tandem reaction is a Heck-type coupling that follows the
catalytic cycle below. Each step of the catalytic cycle has been named, please fill in the
boxes with the structure of each key intermediate and populate the table with the number
of L- and X-type ligands, oxidation state, dn notation, and total electron count for each
metal complex (i-v).
5 (Product)
HOTf
L-Pd°-L
i.
Oxidative
addition of 4
Reductive
elimination
H
L-Pd-OTf
L
+L
1
Catalyst
regeneration
5
B-hydride
elimination
Ligand
substitution
-L
ii.
1,2-
Insertion
iii.
iv.
Complex
#X type
ligands
#L type Pd Oxidation dn Notation
Total electron
ligands
State
count
i.
ii.
iii.
iv.
Transcribed Image Text:A tandem reaction is a reaction in which several bonds are formed in sequence without isolating intermediates. The tandem reaction below goes through three key reactions: a) a Suzuki-type coupling to generate 3, then b) deprotection of R₁ and installation of a triflate leaving group to generate 4, and finally c) a Heck-type coupling reaction to make 5. Using your knowledge of metal-catalyzed coupling reactions, please answer the following questions. OMe Pd(PPh3)4 (or PdL4) LOR₁ 3 NaOEt, THF (solvent), 50 °C R₁ = TBS 1) TBAF (TBS deprotection) 2) TfO2, Et₂N PdL₂ cat. R₁ = Tf Et₂N, THF 60 °C Br OH Оме 1 R₁ = TBS (alcohol protecting group) HO-B The third and final step of this tandem reaction is a Heck-type coupling that follows the catalytic cycle below. Each step of the catalytic cycle has been named, please fill in the boxes with the structure of each key intermediate and populate the table with the number of L- and X-type ligands, oxidation state, dn notation, and total electron count for each metal complex (i-v). 5 (Product) HOTf L-Pd°-L i. Oxidative addition of 4 Reductive elimination H L-Pd-OTf L +L 1 Catalyst regeneration 5 B-hydride elimination Ligand substitution -L ii. 1,2- Insertion iii. iv. Complex #X type ligands #L type Pd Oxidation dn Notation Total electron ligands State count i. ii. iii. iv.
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