Chapter 9 Clayden Organics 大学有机化学

H2O, ROH (oxygen nucleophile)
Nu = organometallic reagents
Why are organometallics nucleophilic?
metals (such as Li, Mg, Na, K, Ca, and Al) all have lower electronegativity than carbon. Hence in organolithium compounds and Grignard reagents the key bond is polarized towards carbon - making carbon a nucleophilic centre.
The filled C–Li s orbital that arises is closer in energy to the carbon’s sp3 orbital than to the lithium’s 2s orbital, so we can say that the carbon’s sp3 orbital makes a greater contribution to the C–Li s bond. Reactions involving the filled s orbital will therefore take place at C rather than Li.
Organolithiums can also remove halogen atoms from aryl (Ar-X), allyl (C=C-X) and alkyl (R) halides (X = Br or I usually).
more basic; less stable
less basic; more stable
stage 3: acid quench
Making 1o alcohols from organometallics and HCHO
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Making secondary and tertiary alcohols
Summary organometallic additions to carbonyl compounds
Organometallics as bases - Deprotonation of alkynes
Applications
The metal derivatives of alkynes can be added to carbonyl electrophiles
farnesol
Halogen-metal exchange
the halides cannot contain any functional groups that would react with the Grignard reagent
How to make organolithium reagents
- made from lithium metal and alkyl halides - each inserting reaction requires two atoms of lithium - generates one equivalent of lithium halide salt
R–Zn–R
Application of transmetallation
X
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Using Organometallic Reagents to Make C-C Bonds (part 2)
Based on Clayden’s Organic Chemistry, Chapter 9
Nucleophilic addition to C=O
Transmetallation: exchange of metal ions
Organolithiums can be converted to other types of organometallic reagents by transmetallation by treating with the salt of a less electropositive metal.
Choice of two possible routes
(Pent-3-en-2-ol)
Recall (Chapter 6, slide 15):
Organometallic reagent: preparation of 3o alcohols
More choices than preparation of 2o alcohols but similar considerations are used in selecting which synthetic route to take:
Organometallic reagent: preparation of 2o alcohols
WHICH ONE TO CHOOSE THEN?
Depends largely on which one is more available or synthetically accessible
Using Organometallic Reagents to Make C-C Bonds
Based on Clayden’s Organic Chemistry, Chapter 9
The aim of this chapter is …..
Structure – Chapters 2, 4 and 7 Reactivity – Chapters 5, 6 and 8 Making organic molecules means making C–C bonds. In this chapter we are going to look at one of the most important ways of making C–C bonds: using carbonyl compounds and organometallics, such as : organolithiums reagents and Grignard reagents.
Since the carbon’s sp3 orbital makes a greater contribution to the C–Li s bond, the s bond resembles a filled C sp3 orbital - in other words it resembles a lone pair on carbon.
Organometallic reagents act as nucleophiles towards the electrophilic carbonyl group.
In Chapter 6:
Nu = -CN, H- (NaBH4, LiAlH4), RMgX (carbon nucleophile),
Application of halogen-exchange reaction
Note the very low temperature employed to prevent n-BuLi attacking other functional groupne (a fungicide)
Oxidation of alcohols
oxidation
oxidation
oxidation
Good oxidizing agents: Cr(VI) compounds
Tertiary alcohols can be made from ketones, and secondary ones from aldehydes.
Overall: a nucleophilic addition reaction
H+ Nu: Nu Nu
Nu: could be organometallic reagents
stage 1: formation of the organometallic stage 2: reaction with electrophile
Deprotonation of alkynes Transmetallation
Halogen-metal exchange
Organometallic reagent: preparation of carboxylic acid from CO2
Carbon dioxide is a carbonyl compound, and it is an electrophile
Organometallics as bases
Organometallics react very rapidly and highly exothermically with water to produce alkanes
Large pKa values = weak acid BUT strong conjugate base
more electropositive lithium goes into solution as ionic salts
Reactivity as a nucleophile: RLi > RMgX > RCeX2 > R2Zn
ZnBr2
• the high reactivity of RLi is sometimes undesirable because it is also a strong base and may react in other ways (sidereactions) in addition to being a nucleophile • on the other hand, RCeX2 (relatively less reactive) may give better yield in addition reaction to CH2-C=O than RLi or RMgX