Structures on the cover

Increased Nucleophilicity of Heavier Nucleophiles (Section 1.6.1.1, p. 28).

I stated that heavier atoms are more nucleophilic because they are more polarizable. This argument is very common, but there is evidence that it is not valid. I^- is indeed much more nucleophilic than Cl^- in MeOH (the traditional solvent for measuring nucleophilicity), but in aprotic solvents and in the gas phase, Cl^- is slightly more nucleophilic than I^-. If nucleophilicity were determined by polarizability, then it would not be solvent-dependent.

Example of the Benzylic Acid Rearrangement (Section 2.5.1, p. 83).

The second line of the example is incorrect. The C-Cl σ bond in the first two structures in the second line of the example should be replaced with a C=O π bond. The correct mechanism is:

Mechanism of the Mitsunobu Reaction (Section 2.6.2, p. 89).

In the second step of the given mechanism, the carboxylate deprotonates the alcohol, which then attacks the phosphoniohydrazine to displace N from P. The book notes that the deprotonation step violates the pK_a rule (pK_a alcohol = 17, pK_b of carboxylate = 5). A better alternative has the carboxylate displace N from P in S_N2 fashion, giving an acyloxyphosphonium ion and an nitrogen anion. The latter then deprotonates the alcohol, generating an alkoxide, which displaces P from O to give the requisite alkoxyphosphonium ion and to regenerate the carboxylate.

Aromatic Substitution of Anilines via Diazonium Salts (Section 3.4.2, pp. 121-122).

Examples of Cycloadditions (Section 4.1.1, p. 141).

The product of the [4 + 2] cycloaddition at the top of the page is incorrect. The correct product is the 1,4-disubstituted compound.

Good Diels-Alder Dienes (Section 4.3.1.1, pp. 163-164).

Pentavalent N in nitrile oxide mechanism (p. 168)

Stereospecificity of the Wittig reaction (Section 4.3.3, p. 179).

The Wittig reaction is said to be allowed by the Woodward-Hoffmann rules because of the participation of a d orbital on the P atom, which makes the Wittig reagent's HOMO antisymmetric. This explanation has appeared in the literature for many, many years, but calculations have shown that the d orbital of a P atom is much too high in energy to participate in a π bond with a C(p) orbital. Instead, the π bond is made up of a C(p) orbital and a C-P σ* orbital (hyperconjugation).

Why, then, does the Wittig reaction proceed, even though it violates the Woodward-Hoffmann rules? The Woodward-Hoffmann rules say that the symmetries of the HOMO and LUMO of the reagents in a pericyclic reaction have a strong effect on the TS energy. In the TS of a pericyclic reaction involving compounds with "normal" π bonds, there are strong interactions among orbitals both between the reactants and within each reactant. In P=C π bonds, however, the overlap between the constituent orbitals is much poorer, and so the influence of symmetry on the reaction is much weaker. In this case the strength of the bonds being made and broken is much more important than symmetry, and the reaction proceeds. The same is true of the retrocycloaddition.

Another way of thinking of this problem: Every π bond can also be written as a 1,2-diradical. This resonance structure is very important for P=C π bonds. Symmetry influences TS energy only through the π bond resonance structure. Because there is such a strong 1,2-diradical component in P=C π bonds, there is only a small increase in energy due to mismatched symmetry upon cycloaddition of the P=C π bond and a C=O π bond, and it is far outweighed by the energy gained by forming new P-O and C-C σ bonds. The same is true of the retrocycloaddition.

Origin of the Endo Rule (Section 4.3.4, p. 182).

The preference for endo adducts in Diels-Alder reactions and other cycloadditions is said to be due to secondary orbital interactions in the TS for the cycloaddition. Recent investigations have shown that the endo selectivity in many reactions can be explained by hydrophobic, steric, and electrostatic effects. Secondary orbital interactions do not have to be invoked.

• The endo/exo ratios in the Diels-Alder reactions of CH₂=CHCN with cyclopentadiene and CH₂=CH-CH=CHMe depend on the solvent. In nonpolar solvents, the exo adducts are favored; in polar solvents, the endo adducts are favored. The endo preference of this reaction in polar solvents can be attributed to the greater polarity of the endo TS.

• The preferences for endo TSs in Diels-Alder reactions of butadiene and isoprene with simple dienophiles such as acrolein and methyl acrylate can be explained by an electrostatic repulsion between the in H atoms of the diene and the carbonyl group of the dienophile in the exo TSs. The two groups are further apart and hence the repulsion is weaker in the endo TSs. Lewis acids increase the preference for the endo TS by increasing the cationic character of the carbonyl C.

• When cyclopentadiene undergoes Diels-Alder reactions with CH₂=CHCOX (X = OH, Me, OMe), endo products are observed, but when it reacts with CH₂=CMeCOX, exo products are observed. The simplest explanation is that the exo substituent on the dienophile experiences a steric interaction with the CH₂ group of cyclopentadiene. In both CH₂=CHCOX and CH₂=CMeCOX, the smaller substituent is placed in the exo position.

• The preference for the endo product is often much smaller than commonly assumed. For example, the endo preference in the kinetically controlled Diels-Alder reaction of furan and maleic anhydride, one of the more frequently cited examples of strong endo preference, is in fact very small (0.2 kcal/mol). Apparently experimental errors have contributed to the confusion.

Mechanism of Orthoester Claisen Rearrangement (Section 4.4.1, p. 188).

A line of graphics is missing from the mechanism, which is correctly drawn as follows:

Mechanism of Dehalogenation (Section 5.2, p. 228).

There is an error in the second step of the propagation. It should read as follows:

Oxidation state and d Electron Count (Section 6.1.1.2, p. 261).

Problem 6.1 (Section 6.2.1.6, p. 275).

The number of CO ligands is given incorrectly. The problem should read as follows:

Problem 6.1. NMO oxidizes one CO ligand of the alkyne-Co₂(CO)₆ complex to CO₂ and gives an alkyne-Co₂(CO)₅ complex. Write a mechanism for this transformation.

Introduction to Metal-Catalyzed Reactions (Section 6.3, p. 279).

The last sentence of the second paragraph should read,

Often the number and nature of the ligands on the metal are unknown, and so the metal center and its associated ligands are indicated merely as L_nM.

Late-Metal-Catalyzed Hydrogenations and Hydrometallation (Section 6.3.1.1, p. 280).

The third sentence of the fourth paragraph should read,

β-Hydride elimination then gives H—Pd(II)—H and CO₂.

Thanks to Francisco Velazquez for alerting me to this error.