Addition of Carbenes to Alkenes

Addition of Carbenes to Alkenes

What reactive intermediates have you seen before in organic chemistry?

Carbenes

only two bonds

How many valence electrons does the C have?

How will this affect its stability and reactivity?

Based on this structure, would you expect a carbene to be an electrophile or nucleophile?

What other reactions have you seen that form 3 membered rings? Which reaction does this most resemble?

Diazo compound

How would you write the other resonance structure?

Is this reaction entropically favorable? Would it be reversible?

syn addition

Other reactions of Singlet Carbenes

C-H insertion

Insertion into O-H and N-H bonds

ylide formation

High reactivity of carbenes makes them useful for mapping enzyme active sites.

Photoaffinity Labeling and Carbenes

Photoaffinity Labeling (PAL): technique used to map the active site of enzymes

Naturally Occurring Amino Acid

With the exception of the amino acid glycine, where R = H, all amino acids are chiral.

Jones: Table 25.1 p. 1272 lists the 20 amino acids commonly found in proteins.

When single structure contains both a cation and anion within it, it is called a zwitterion.

In proteins, the amino group of 1 amino acid is attached to the carboxylic acid group of another amino acid.

The reaction produces an amide functional group.

peptide: dipeptide

peptide bond

Proteins are often referred to as polypeptides.

R= any of the structures found for the naturally occurring amino acids.

Enzymes are proteins that catalyze organic reactions within organisms. The region where catalysis occurs is known as the active site. Since enzymes are polypeptides, they consist of sequence of amino acids. The topology or shape of the active site along with the amino acids residues present determines catalytic activity.

Methods for Determining Structure at the Active Site

X-ray crystallography
Nuclear Magnetic Resonance (NMR) Spectroscopy
Site Directed Mutagenesis
PAL

Reversible Binding

Synthesize

where

: A functional group that readily is converted to a highly reactive intermediate (e.g. carbene)

: radioactive isotope

The modified substrate is designed to bind more or less equally well with the enzyme.

The modified substrate is allowed to bind to the enzyme-substrate complex. This complex is irradiated (shine light on). A highly reactive intermediate forms and reacts to give a permanent covalent bond to the enzyme.

Carbenes: highly reactive

C-H insertion
O-H or N-H insertion
addition to C=C
form ylides

1,3-Dipole Additions

heterocycles: ring compounds containing at least 1 heteroatom

heteroatom: any atom other than C

What heterocyclic compounds have you seen already?

e.g. 1,3-dipole resonance forms

Concerted reaction: Do you expect it to be syn or anti?

e.g.

Reaction of O₃ with Alkenes: Ozonolysis

Oxidative Work up:

H₂O₂, H₂O
H₂O₂, CH₃COOH

Reductive Work up: Zn, H₂O

Zn, CH₃COOH
H₂, Pd/C
CH₃SCH₃ (dimethyl sulfide)

Oxidation of Alkenes to Diols

KMnO₄: potassium permanganate

OsO₄: osmium tetroxide

How could the trans diol be synthesized from cyclohexene?

Addition to Alkynes

Addition of H-X

(X=Cl, Br)

How many p bonds are in an alkyne?

vicinal dihalide geminal dihalide

Mechanism

a vinyl cation

Vinyl carbocations are less stable than 1° carbocations. They may not be the reactive intermediate in the reaction. Instead, a cyclic ion may be involved.

sp hybridized, C is more electronegative, sp² hybridized

destabilizes the (+) charge