Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CHEM333 (RBL) > 9. Sonogashira And Heck > Flashcards

9. Sonogashira And Heck Flashcards

1
Q

What is the Sonogashira reaction primarily used for?

A

Making sp*-sp bonds

Traditionally using a copper (I) salt as co-catalyst.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are alkynes useful for in the context of the Sonogashira reaction?

A

They can be turned into other things.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is a significant byproduct concern when using copper in the Sonogashira reaction?

A

Copper-mediated oxidative dimerization (homocoupling) of the alkyne, called Glaser coupling.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

When was Glaser coupling first reported?

A

1869

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the typical reaction conditions for the Sonogashira reaction?

A

Mild, usually room temperature with an excess of an organic amine as base.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What must be avoided to prevent Pd(0) from reoxidizing to Pd(II)?

A

Air exposure.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What step in the Sonogashira mechanism is thought to be slow?

A

Either oxidative addition or transmetallation, depending on conditions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Why are vinyl halides more reactive in the Sonogashira reaction?

A

They work well compared to other halides.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the pKa of alkynes, indicating their acidity?

A

Approximately 25.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

In the proposed mechanism, how is an alkyne made more acidic?

A

By forming a π complex with the copper co-catalyst.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What can be assumed about the reaction if a copper salt is not used?

A

The alkyne coordinates to Pd before being deprotonated by the base.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is an example of a large-scale synthesis using the Sonogashira reaction?

A

Synthesis involving couplings to either end of acetylene.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What drives the deprotection with tetrabutylammonium fluoride in the large-scale synthesis?

A

The strength of the Si-F bond.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What was the yield percentage for the first large-scale synthesis example?

A

71% for 2 steps.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which drug was synthesized using the Sonogashira reaction with a copper-free approach?

A

Grazoprevir (for hepatitis).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the role of Pd(OAc)2 in the second large-scale synthesis example?

A

It acts as a catalyst with P(t-Bu)3.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What was the yield percentage for the Grazoprevir intermediate synthesis?

A

83% for 2 steps.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the reaction type demonstrated with vinyl chlorides in the final example?

A

Antifungal synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What stereochemical feature is retained at the sp’ center during the reaction?

A

Stereochemistry

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What catalyst is used to generate allyliodide in the reaction?

A

Ki

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What solvent is used in the reaction involving Ki?

A

MeCN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the yield percentage of the reaction catalyzed by Ki?

A

81%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the coupling reaction that is an environmentally friendly version of Sonogashira?

A

Sonogashira couplings

24
Q

What type of solvents are being switched to in Sonogashira couplings for environmental friendliness?

A

Aqueous solvents

25
Q

What is the name of the reaction also known as Mizoroki-Heck reaction?

A

Heck reaction

26
Q

What is the reactivity order of aryl/vinyl halides in the Heck reaction?

A

I > Br > OTF&raquo_space; Cl

27
Q

What type of alkenes is the Heck reaction mostly used for?

A

Terminal (monosubstituted) alkenes

28
Q

What is the first step in the mechanism of the Heck reaction?

A

Oxidative addition

29
Q

What does the alkene do after oxidative addition in the Heck reaction mechanism?

A

Coordinates to Pd

30
Q

Fill in the blank: The mechanism of the Heck reaction involves _______ elimination.

A

Reductive

31
Q

What type of addition occurs during the alkene coordination in the Heck reaction?

A

Syn addition

32
Q

What is thought to be the nature of the process during syn addition in the Heck reaction?

A

Concerted process

33
Q

What is formed from the reductive elimination step in the Heck reaction?

A

HX and regenerates Pd (0)

34
Q

What is the role of Pd(OAc)2 in the Heck reaction?

A

Catalyst in the coupling of terminal alkenes with aryl halides

Pd(OAc)2 is a palladium compound commonly used as a catalyst in various cross-coupling reactions.

35
Q

What type of alkenes does the Heck reaction not work well with?

A

Unpolarised alkenes in the middle branch

Unpolarised alkenes can lead to a mixture of stereoisomers and are less reactive in the Heck reaction.

36
Q

What is a potential outcome when using electron-rich alkenes in the Heck reaction?

A

A mixture of products or opposite regiochemistry

The reactivity of electron-rich alkenes can lead to different product distributions.

37
Q

Fill in the blank: The Heck reaction can be catalyzed by finely divided _______ metal.

A

palladium

Palladium black can catalyze reactions but is often less efficient than other forms of palladium.

38
Q

What is the typical temperature range for a Heck reaction using Pd/C and Na2CO3?

A

180-190 °C

This temperature range is used to achieve higher yields in palladium-catalyzed reactions.

39
Q

True or False: The Heck reaction can be performed without any ligands.

A

True

Some Heck reactions can proceed without added phosphine or other ligands, relying instead on the palladium metal itself.

40
Q

What is the significance of using greener solvents in the Heck reaction?

A

To make the reaction more sustainable

Efforts to improve the environmental impact of the Heck reaction include the use of sustainable solvents and recycling of catalysts.

41
Q

What is the coupling product of the Heck reaction when using aryl bromides?

A

Alkenyl aryl compounds

The Heck reaction typically forms alkenyl aryl compounds through the coupling of alkenes and aryl halides.

42
Q

What is the yield percentage range when employing DMSO as a solvent in the Heck reaction?

A

72-95%

High yields are often achievable with appropriate conditions and solvent choices in the Heck reaction.

43
Q

What is the purpose of converting NaBr into Br2 in the context of the Heck reaction?

A

To produce more aryl bromide

Recycling byproducts can enhance the efficiency of the overall synthetic process.

44
Q

Fill in the blank: In large-scale applications, the initial product of the Heck reaction is often _______ in situ.

A

hydrogenated

This strategy helps in finalizing the desired product while minimizing the number of reaction steps.

45
Q

What type of coupling reaction is characterized by R’-Ar-NH2 + HO2C-R’?

A

Amide coupling

Amide coupling reactions often utilize coupling reagents like carbodiimides (e.g., DCC) for the formation of amide bonds.

46
Q

What is the main limitation of SNAr coupling reactions?

A

Limited to (hetero)aromatics which can stabilize a negative charge

SNAr reactions involve nucleophilic aromatic substitution and require specific electronic conditions.

47
Q

What is the outcome of the Buchwald-Hartwig reaction?

A

Ar-oR’ → Ar-Br + H2N-R’

This reaction is a common method for forming C-N bonds using palladium catalysis.

48
Q

Which coupling reaction is known for being the most popular method for sp?-sp? coupling?

A

Suzuki Miyaura

The Suzuki reaction is known for its mild conditions and tolerance of functional groups.

49
Q

What is required for the ligand exchange step in Suzuki coupling?

A

A strongish base

The ligand exchange step involves the replacement of ligands on the palladium catalyst to facilitate the reaction.

50
Q

What type of coupling reaction involves the conversion ArE R’ → Ar-Br + = R’?

A

Sonogashira

The Sonogashira reaction is used for coupling aryl halides with terminal alkynes.

51
Q

What is a characteristic of the Heck reaction?

A

General method for sp?-sp coupling

The Heck reaction involves the coupling of aryl halides with alkenes, often leading to more complex structures.

52
Q

Which method uses transmetallation with cuprate when copper is used?

A

Heck reaction

This method can utilize copper salts to enhance the coupling efficiency.

53
Q

What are the general conditions for catalytic coupling reactions?

A

Conditions may need optimizing; Pd and some phosphine ligands are expensive

Catalytic reactions often require specific conditions to achieve optimal yields.

54
Q

What is the main advantage of the Suzuki Miyaura reaction?

A

Mild conditions, tolerates functional groups

This makes it a versatile choice for complex molecular synthesis.

55
Q

Fill in the blank: The Buchwald-Hartwig reaction involves the transformation of Ar-oR’ to _______.

A

Ar-Br + H2N-R’

This highlights the formation of aryl halides through palladium-catalyzed reactions.

CHEM333 (RBL) (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions