9 Carbenes, Carbenoides and Nitrenes

Introduction Carbenes are molecules containing divalent carbon atoms, but carbenes are neutral molecules. It is possible to have several divalent carbons in a single molecules (hexacarbene)

Introduction Carbenoids are molecules in which all the carbons are tetravalent, but which have properties resembling those of carbenes. Typically, carbenoides have carbon atoms that are simultaneously bonded both to metal atoms and to halogen atoms. Nitrenes are compounds such as ::N-C6H5, that contain monovalent nitrogen atoms. Nitrenoid containes a nitrogen atom linked to both an electropositive atom and a electronegative atom.

Formation of Carbenes and Nitrenes The thermal decomposition are obtained either from organo- diazo compounds or by a-elimination reactions of organo- halides. The decomposition of organodiazo compounds are frequently catalyzed by salts of heavy metals such as copper, palladium and rhodium – intermediates is carbenoides

Formation of Carbenes and Nitrenes Preparation of diazo compounds (1) Lithium or sodium salt of p-toluenesulfonylhydrazone (2) Base-catalyzed decomposition of N-nitrosoamides

Formation of Carbenes and Nitrenes Preparation of diazo compounds (3) Oxidation of hydrazones of carbonyl compounds (4) Thermal rearrangements of diazirines

Formation of Carbenes and Nitrenes Preparation of halocarbenes Reactions of strong bases with organic polyhalides that lack hydrogens on b-carbons. Instead, the bases abstract protons from the polyhalogenated carbons.

Formation of Carbenes and Nitrenes Preparation of halocarbenes Reactions of strong bases with organic polyhalides that lack hydrogens on b-carbons. Instead, the bases abstract protons from the polyhalogenated carbons. The a-halolithium compounds act as carbenoids rather than dissociating to form free carbenes

Formation of Carbenes and Nitrenes Carbenoids formed from reactions of dihalides with heavy metals are relatively stable at room temperature, and are more selective in their reactions than most carbenes. Simmons-Smith reagent Nitrenes are most frequently formed by thermolysis or pyrolysis of organic azides a-Elimination reactions

Singlet and Triplet Carbenes Singlet state – two unshared electrons have paired spins and are located in a single orbital, leaving a second orbital vacant. (carbocation and carbanion type) Triplet state – two electrons have unpaired spins, and one electron is located in each nonbonded orbital. (diradical type) According to Hund’s rule, triplet forms of carbenes should be more stable than singlet forms. In the case of CH2:, about 9 kcal/mol is different between two states. However, substituents with hetero atom (B, N, X) stabilze singlet structures more strongly than triplet structures. CH2: more stable in triplet state CCl2: more stable in singlet state

Singlet and Triplet Carbenes Several heterocyclic carbenes are indefinitely stable at room temperature and can be melted at high temperature and resolidified without decomposition. Theoretical calculation indicate that these molecules do possess a good deal of aromatic stabilization.

Singlet and Triplet Carbenes In carbenes with relatively small singlet-triplet gaps, intersystem crossing between the singlet and triplet forms is faster than other reactions of the triplets, in which reactions may proceed via the singlet forms even though only small amounts of those forms are in equilibrium with the triplet forms. The ratio of reactions attributable to singlet vs triplet forms may be increased in more polar solvents. Singlet and triplet forms of carbenes differ in their geometries.

Singlet and Triplet Carbenes Carbenes having relatively linear structures are more likely to have triplet structures, while relatively nonlinear carbenes are more likely to be singlets. n = 9 or 10 : singlet n = 11 or 12 : triplet

Addition to Double Bonds Cyclopropane Formation Addition to double bonds and triple bonds can yield cyclopropanes and cyclopropenes.

Addition to Double Bonds Cyclopropane Formation Intramolecular addition to double bonds has proved to be useful procedure for the formation of polycyclic molecules.

Addition to Double Bonds Cyclopropane Formation The reactions of carbethoxycarbene with benzene provided bicyclic intermediates which rapidly undergo electrocyclic reactions to form cycloheptatriene derivatives. However, reactions of carbenes with polycyclic aromatic molecules yield stable cyclopropane structures.

Addition to Double Bonds Cyclopropane Formation The reactions of carbethoxycarbene with benzene provided bicyclic intermediates which rapidly undergo electrocyclic reactions to form cycloheptatriene derivatives. However, reactions of carbenes with polycyclic aromatic molecules yield stable cyclopropane structures.

Addition to Double Bonds 1,4- and 1,6-Addition Reactions Carbenes add to double bonds of conjugated dienes to form cyclopropanes in 1,2-cycloaddition processes. 1,4-Additions to form five-membered rings proceed in the s-cis conformers.

Addition to Double Bonds 1,4- and 1,6-Addition Reactions Only intramolecular 1,4-addition is observed in the reactions of carbene 4. Retro 1,4-addition reactions of carbenes with dienes can proceed quite easily.

Addition to Double Bonds 1,4- and 1,6-Addition Reactions Several 1,6-addition reactions have been reported, but their mechanism are unclear. The reaction proceed via triplet state implying that the addition is not concerted.

Addition to Double Bonds Stereochemistry of Additions to Double Bonds Triplet carbenes initially add to double bond to form triplet diradicals in whch rotation around single bonds are usually faster than intersystem crossing to singlet to result in the nonstereospecific reactions.

Addition to Double Bonds Stereochemistry of Additions to Double Bonds Singlet carbenes usually add stereospecificcally to alkenes, forming cyclopropanes that retain the geometries of the alkenes.

Addition to Double Bonds Stereochemistry of Additions to Double Bonds Simmons-Smith reactions of alkenes also provided cyclo- propnaes stereospecifically with retention of the alkene geometry. Nitrenes react in a manner similar to carbenes

Addition to Double Bonds Reactivities in Addition Reactions Most singlet carbenes add to alkenes substituted with EDG in preference to those substituted with EWG. Carbenes substituted with halogens or other EWG show the greatest preference for reaction with electron-rich double bond. The preference pi-bond of an alkene initially interacts with the empty p orbital of a carbene (electrophilic stage) and unshared electron pair on the original carbenic carbon can participate in forming the cyclopropane ring (nuclephilic stage), in which two-stages reactions appear to be single-step reactions.

Addition to Double Bonds Reactivities in Addition Reactions Carbenes substituted with strongly EDG such as methoxy or dialkylamino groups, have been found to be nucleophilic reagents which will add rapidly to electron-poor double bonds.

Addition to Double Bonds Reactivities in Addition Reactions p-Tolylchlorocarbene add to both electron-rich and electron- poor double bonds in preference to typical alkene double bonds. (ambiphilic carbenes) Stereochemistry of cyclopropane formation from nucleophilic carbenes showed inversion which involves the formation of a zwitterionic intermediate.

Addition to Double Bonds Reactivities in Addition Reactions Triplet forms of carbenes are less affected by electron- donating or electron-withdrawing substitutents on double bonds than are single forms. However, triplet carbenes react very rapidly with conjugated double bonds in which reactions can proceed via resonance stabilized diradical intermediates.

Insertion Reactions Singlet Carbenes Singlet methylene can react with alkanes and cycloalkanes by insertion into carbon-hydrogen bonds with non-selectivity primary C-H tertiary C-H vinylic C-H allylic C-H

Insertion Reactions Singlet Carbenes Other singlet carbenes are more selective than methylene. Dichlorocarbene can insert into allylic or benzylic C-H bonds but does not react with nonallylic primary or secondary bonds. It will insert into some tertiary C-H bonds.

Insertion Reactions Singlet Carbenes Insertion of singlet carbenes into C-H bonds proceed with retention of configuration.

Insertion Reactions Singlet Carbenes Carbenes do not insert into unstrained C-C bonds, but insertions into very strained C-C bonds take place. Remarkably, even addition to two single bonds has been observed.

Insertion Reactions Triplet Carbenes Triplet carbenes can also insert into C-H bonds, but insertions appear to proceed by multistep processes. Initially, triplet carbenes abstract hydrogen atoms from C-H bonds to form radical pairs, which combine to form the insertion products.

Rearrangements Hydrogen and Alkyl Group Migrations 1,2-Migration of hydrogens occur extremely easily in singlet carbenes. Hydrogen migrations in three-membered ring carbenes would yield highly strained double bonds

Rearrangements Hydrogen and Alkyl Group Migrations Alkyl groups in carbenes tend to migrate much more slowly than hydrogens, and their migrations are usually barely detectable. Alkyl migration are common if they result in the expansion of strained rings.

Rearrangements Hydrogen and Alkyl Group Migrations Alkyl migration also predominates when a hydroxy group can stabilizes formation of an empty orbital at the migration origins. Alkyl group migrations in nitrenes are more competitive with hydrogen migrations than in carbenes, but hydrogen Migrations still predominate

Rearrangements The Nature of the Rearrangement Process 1,2-Migrations of hydrogens and alkyl groups in carbenes are often described as insertions of the divalent carbons into neighboring C-H and C-C bonds. However, it seems more useful to regard these reactions as analogous to carbocation rearrangements.

Rearrangements Rearrangements of Carbenoides Formed from Vinyl Halides Formation of Alkynes Rearrangement of carbenoids, in which the bonds between the vinyl carbons and halogen ions are at least partially broken before rearrangement take place. The carbenoide intermediate can be intercepted by the addition of alkenes, Yielding cyclopropane derivatives.

Rearrangements Rearrangements of Carbenoides Formed from Vinyl Halides Formation of Alkynes Carbenoide intermediates can be demonstrated by the use of isotopically labeled starting materials. Rearrangements are stereospecific, and that it is invariably the groups trans to the halogens that migrate.

Rearrangements Rearrangements of Carbenoides Formed from Vinyl Halides Formation of 1-Halocyclopentenes Base-induced rearrangements of halomethylenecyclobutanes principally yield 1-halocyclopentenes along with only small amounts of cyclopentenyl ethers forming from the reactions of halomethylenecyclobutanes with alkoxide. Double migration is increased when the halides Ion is a good leaving group (I->Br->Cl->>F-)

Rearrangements Rearrangements of Carbenoides Formed from Vinyl Halides Formation of 1-Halocyclopentenes Proposed mechanism for the double migration Double migration appear to be closely related to rearrangements leading to acetylenes, except that the departing halide ions attack the sites from which the ring carbons are migrating.

Rearrangements Rearrangements of Acylcarbenes Wolff rearrangements When a-diazoketones are photoirradiated, or heated at high temperature, they lose nitrogen and rearrange to form ketenes. Ketenes react rapidly with water, alcohols, and amines to give carboxylic acid derivatives.

Rearrangements Rearrangements of Acylcarbenes Wolff rearrangements a-Diazoketones can also undergo Wolff rearrangements, resulting in migrations of alkoxy groups. Reaction proceeds simultaneously with loss of nitrogen and without formation of free carbenes, but photochemical process involved the free carbene intermediates

Rearrangements Rearrangements of Acylcarbenes Wolff rearrangements a-Diazoketones can be prepared by reactions of acid chlorides with diazomethane Rearrangements proceed stereospecifically with retention of configurations of the migrating groups

Rearrangements Rearrangements of Acylcarbenes Oxirene formation Photolysis of a-diazobutanone labeled with isotopic carbon (13C) in the carbonyl group yielded dimethylketene, in which the isotopic label was equally distributed in dimethylketene. Proposed Mechanism Oxirene formation appears to occur only when a-diazoketones maintain conformations in which the carbonyl oxygens are anti to the departing nitrogen molecules.

Rearrangements Retro Carbene Rearrangements Rearrangements of Strained Rings Several compounds containing very highly strained double bonds undergo rapid hydrogen or groups migration to form carbenes.

Rearrangements Retro Carbene Rearrangements Rearrangements of Strained Rings

Rearrangements Retro Carbene Rearrangements Rearrangements of Strained Rings The most common reactions in which strained alkenes are converted to carbenes are in the photochemical or thermal ring openings of cyclopropenes, resulting in the formation of allylic carbenes.

Rearrangements Retro Carbene Rearrangements Rearrangements of Strained Rings When ring opening of a cyclopropene results in cleavage of the bond to a vinyl position bearing a hydrogen atom, the ring opening may be accompanied by a hydrogen migration to form a vintl carbene. Second migration can result in formation of an acetylene.

Rearrangements Retro Carbene Rearrangements Rearrangements of Alkynes Thermolysis of o-tolylacetylene at 700 oC yields indene as the only significant product. Thermolysis of biphenylacetylene yields 1,2-benzoazulene.

Rearrangements Retro Carbene Rearrangements Rearrangements of Alkynes Thermolysis of isotopically labeled phenylacetylene results in distribution of the isotopic carbon between the two triply bonded carbons. (hydrogen and aromatic migration) Migrations of alkyl groups are much slower than migration of hydrogens or aryl groups.

Rearrangements Retro Carbene Rearrangements Rearrangements of Arylcarbenes and Arylnitrenes Arylcarbenes can undergo remarkably complicated rearrangements. Thermolysis of phenyldiazomethane in the gas phase yields heptafulvalene.

Rearrangements Retro Carbene Rearrangements Rearrangements of Arylcarbenes and Arylnitrenes o-Tolyldiazomethane, m-tolyldiazomethane and p-tolyldiazo- methane yielded a mixture of benzocyclobutene and styrene on thermolysis at 420 oC. O-Tolyldiazomethane give a higher yield of benzocy- clobutene than other isomers

Rearrangements Retro Carbene Rearrangements Rearrangements of Arylcarbenes and Arylnitrenes A mixture of benzocyclobutene and styrene was also formed from thermolysis of 7, illustrating the ready interconversion of arylcarbenes and molecules with seven-membered rings.

Rearrangements Retro Carbene Rearrangements Rearrangements of Arylcarbenes and Arylnitrenes Proposed mechanism for the rearrangements of arylcarbene

Rearrangements Retro Carbene Rearrangements Rearrangements of Arylcarbenes and Arylnitrenes In a somewhat more complex mechanism, each arylcarbene initially forms a bicyclic cyclopropene which could then open to form the 7-membered ring allen (or carbene)

Rearrangements Retro Carbene Rearrangements Rearrangements of Arylcarbenes and Arylnitrenes Similar bicyclic cyclopropenes can be preprared by quite different methods and undergo rearrangements similar to those of arylcarbenes.

Rearrangements Retro Carbene Rearrangements Rearrangements of Arylcarbenes and Arylnitrenes In a third possible mechanism, the allenes are in equilibrium with bicyclic cyclopropylidene. Arylnitrenes undergo rearrangements similar to those of arylcarbenes, forming 7-membered heterocyclic cumulenes