Addition of Hydride Donors and
Organometallic Compounds to
Carbonyl Compounds
8
In Section 6.5 you learned that the acylations of hydride donors or of
organometallic compounds, which give aldehydes or ketones, often are followed
by an unavoidable second reaction: the addition of the hydride or organometallic
compound to the alde- hyde or the ketone. In this chapter, we will study the
intentional execution of such ad- dition reactions. They do not start from carbonyl
compounds produced in situ but from carbonyl compounds used as such.
8.1 Suitable Hydride Donors and
Organometallic Compounds and a Survey
of the Structure of Organometallic
Compounds
The addition of a hydride donor to an aldehyde or to a ketone gives an alcohol.
B
This addition is therefore also a redox reaction, namely, the reduction of a
carbonyl com- pound to an alcohol. Nevertheless, this type of reaction is
discussed here and not in the redox chapter (Chapter 14).
Hydride donors can be subdivided into three classes. They are
• ionic, soluble hydrido complexes of B or Al (“complex hydrides”),
• covalent compounds with at least one B¬H or one Al¬H bond, or
• organometallic compounds which contain no M¬H bond but do contain a
trans- ferable H atom at the C atom in the position b to the metal.
The first group of H nucleophiles includes NaBH4 (which can be used in
MeOH, EtOH, or HOAc), the considerably more reactive LiAlH4 (with which
one works in THF or ether), and alcoholysis products of these reagents such as
Red-Al [NaAlH2 (O¬CH2¬CH2¬OMe)2] or the sterically very hindered LiAlH(O-
tert-Bu)3. The last important hydride donor in this group is LiBH(sec-Bu) 3 (L-
Selectride), a sterically very hindered derivative of the rarely used LiBH4.
The hydride donor with a covalent M¬H bond which is most frequently used for
reducing carbonyl groups is iBu 2AlH (DIBAL stands for diisobutylaluminum hydride;
A
it can be used in ether, THF, toluene, saturated hydrocarbons, or CH 2Cl2).
, The most important organometallic compound which transfers an H atom along
with the electron pair from the b position to the carbonyl carbon is Alpine-Borane B
(cf. Fig- ure 8.19). It should be mentioned that certain Grignard reagents with
C¬H bonds in
,306 8 Addition of Hydride Donors and Organometallic Compounds
the b position (e.g., iBuMgBr) can act as H nucleophiles rather than C
nucleophiles (cf. Figure 8.22) with respect to the carbonyl carbon of sterically
hindered ketones. In this chapter, reagents which transfer a carbanion (in
contrast to an enolate ion) to the C atom of a C“O double bond are referred to as
C nucleophiles. The most im- portant nucleophiles of this kind are organolithium
compounds and Grignard reagents.
On the other hand, organocopper compounds transfer their carbanion moieties
to the carbonyl carbon far less easily and usually not at all.
In the majority of cases, organolithium compounds and Grignard reagents
contain polarized but covalent carbon—metal bonds. Lithioalkanes, -alkenes, and
-aromatics, on the one hand, and alkyl, alkenyl, and aryl magnesium halides, on
the other hand, are therefore formulated with a hyphen between the metal and
the neighboring C atom. Only lithiated alkynes and alkynyl Grignard
reagents are considered to be ionic—that is, species with carbon, metal bonds
similar to those in LiCN or Mg(CN)2. In covalent organolithium compounds and
covalent Grignard reagents neither the lithium nor the magnesium possesses a
valence electron octet. This is energetically dis- advantageous. In principle, the
same mechanism can be used to stabilize these metals, which monomeric boranes
BH3 n Rn use to attain a valence electron octet at the boron atom (Section 3.3.3):
the formation either of oligomers or, with suitable electron pair
donors, of Lewis acid/Lewis base complexes.
Alkyllithium compounds occur in hydrocarbon solutions as hexamers, tetramers,
or dimers depending on the alkyl substituent. For a given substituent, the degree
of as- sociation drops in diethyl ether or especially in THF solutions because the O
atoms of these solvents can occupy vacant coordination sites around the
electron-deficient lithium. The monomeric form of organolithium compounds
can sometimes be stabi- lized in hydrocarbons and always in ether or THF by
adding TMEDA (tetra- methylethylenediamine; Me2N ¬CH 2¬CH 2¬NMe 2). The N
atoms of this additive then occupy two of the three vacant coordination sites of the
lithium. The monomerization of oligomeric organolithium compounds takes
place most reliably in the presence of up to three equivalents of HMPA
(structural formula in Figure 2.16). The basic oxy- gen of this additive is an
excellent electron pair donor.
That the valence electron shell of magnesium can be filled up to some extent
through the interaction with the O atoms of suitable ethers is even a prerequisite
for obtain- ing Grignard reagents from halides and magnesium. In general, this
Grignard forma- tion can be done successfully only in diethyl ether, in THF, or
in the seldom used dimethoxyethane (DME) (mechanism: Figure 14.37). Ethyl
magnesium bromide is present in diethyl ether essentially as dimer A (Figure 8.1,
X Br, R Et). On the one hand, this species dissociates reversibly to yield a small
amount of the monomer. It also participates in the Schlenk equilibrium, i.e., in the
equilibration with Et2Mg and MgBr2 (Figure 8.1).
Neither the mechanism for all addition reactions of hydride donors to the
, carbonyl carbon nor the mechanism for all addition reactions of organometallic
compounds to the carbonyl carbon is known in detail. It is even doubtful
whether only ionic inter- mediates occur. For instance, for some LiAlH4
additions an electron transfer mecha-
Fig. 8.1. Schlenk
Et X Et
equilibrium of ethyl A Mg Mg Et2Mg + MgX2
magnesium halides. R2O X OR2
Organometallic Compounds to
Carbonyl Compounds
8
In Section 6.5 you learned that the acylations of hydride donors or of
organometallic compounds, which give aldehydes or ketones, often are followed
by an unavoidable second reaction: the addition of the hydride or organometallic
compound to the alde- hyde or the ketone. In this chapter, we will study the
intentional execution of such ad- dition reactions. They do not start from carbonyl
compounds produced in situ but from carbonyl compounds used as such.
8.1 Suitable Hydride Donors and
Organometallic Compounds and a Survey
of the Structure of Organometallic
Compounds
The addition of a hydride donor to an aldehyde or to a ketone gives an alcohol.
B
This addition is therefore also a redox reaction, namely, the reduction of a
carbonyl com- pound to an alcohol. Nevertheless, this type of reaction is
discussed here and not in the redox chapter (Chapter 14).
Hydride donors can be subdivided into three classes. They are
• ionic, soluble hydrido complexes of B or Al (“complex hydrides”),
• covalent compounds with at least one B¬H or one Al¬H bond, or
• organometallic compounds which contain no M¬H bond but do contain a
trans- ferable H atom at the C atom in the position b to the metal.
The first group of H nucleophiles includes NaBH4 (which can be used in
MeOH, EtOH, or HOAc), the considerably more reactive LiAlH4 (with which
one works in THF or ether), and alcoholysis products of these reagents such as
Red-Al [NaAlH2 (O¬CH2¬CH2¬OMe)2] or the sterically very hindered LiAlH(O-
tert-Bu)3. The last important hydride donor in this group is LiBH(sec-Bu) 3 (L-
Selectride), a sterically very hindered derivative of the rarely used LiBH4.
The hydride donor with a covalent M¬H bond which is most frequently used for
reducing carbonyl groups is iBu 2AlH (DIBAL stands for diisobutylaluminum hydride;
A
it can be used in ether, THF, toluene, saturated hydrocarbons, or CH 2Cl2).
, The most important organometallic compound which transfers an H atom along
with the electron pair from the b position to the carbonyl carbon is Alpine-Borane B
(cf. Fig- ure 8.19). It should be mentioned that certain Grignard reagents with
C¬H bonds in
,306 8 Addition of Hydride Donors and Organometallic Compounds
the b position (e.g., iBuMgBr) can act as H nucleophiles rather than C
nucleophiles (cf. Figure 8.22) with respect to the carbonyl carbon of sterically
hindered ketones. In this chapter, reagents which transfer a carbanion (in
contrast to an enolate ion) to the C atom of a C“O double bond are referred to as
C nucleophiles. The most im- portant nucleophiles of this kind are organolithium
compounds and Grignard reagents.
On the other hand, organocopper compounds transfer their carbanion moieties
to the carbonyl carbon far less easily and usually not at all.
In the majority of cases, organolithium compounds and Grignard reagents
contain polarized but covalent carbon—metal bonds. Lithioalkanes, -alkenes, and
-aromatics, on the one hand, and alkyl, alkenyl, and aryl magnesium halides, on
the other hand, are therefore formulated with a hyphen between the metal and
the neighboring C atom. Only lithiated alkynes and alkynyl Grignard
reagents are considered to be ionic—that is, species with carbon, metal bonds
similar to those in LiCN or Mg(CN)2. In covalent organolithium compounds and
covalent Grignard reagents neither the lithium nor the magnesium possesses a
valence electron octet. This is energetically dis- advantageous. In principle, the
same mechanism can be used to stabilize these metals, which monomeric boranes
BH3 n Rn use to attain a valence electron octet at the boron atom (Section 3.3.3):
the formation either of oligomers or, with suitable electron pair
donors, of Lewis acid/Lewis base complexes.
Alkyllithium compounds occur in hydrocarbon solutions as hexamers, tetramers,
or dimers depending on the alkyl substituent. For a given substituent, the degree
of as- sociation drops in diethyl ether or especially in THF solutions because the O
atoms of these solvents can occupy vacant coordination sites around the
electron-deficient lithium. The monomeric form of organolithium compounds
can sometimes be stabi- lized in hydrocarbons and always in ether or THF by
adding TMEDA (tetra- methylethylenediamine; Me2N ¬CH 2¬CH 2¬NMe 2). The N
atoms of this additive then occupy two of the three vacant coordination sites of the
lithium. The monomerization of oligomeric organolithium compounds takes
place most reliably in the presence of up to three equivalents of HMPA
(structural formula in Figure 2.16). The basic oxy- gen of this additive is an
excellent electron pair donor.
That the valence electron shell of magnesium can be filled up to some extent
through the interaction with the O atoms of suitable ethers is even a prerequisite
for obtain- ing Grignard reagents from halides and magnesium. In general, this
Grignard forma- tion can be done successfully only in diethyl ether, in THF, or
in the seldom used dimethoxyethane (DME) (mechanism: Figure 14.37). Ethyl
magnesium bromide is present in diethyl ether essentially as dimer A (Figure 8.1,
X Br, R Et). On the one hand, this species dissociates reversibly to yield a small
amount of the monomer. It also participates in the Schlenk equilibrium, i.e., in the
equilibration with Et2Mg and MgBr2 (Figure 8.1).
Neither the mechanism for all addition reactions of hydride donors to the
, carbonyl carbon nor the mechanism for all addition reactions of organometallic
compounds to the carbonyl carbon is known in detail. It is even doubtful
whether only ionic inter- mediates occur. For instance, for some LiAlH4
additions an electron transfer mecha-
Fig. 8.1. Schlenk
Et X Et
equilibrium of ethyl A Mg Mg Et2Mg + MgX2
magnesium halides. R2O X OR2
