Cyclic Alkyl Amino Carbenes
   HOME

TheInfoList



OR:

Cyclic(alkyl)(amino) carbenes (CAACs) are a class of stable singlet
carbene In organic chemistry, a carbene is a molecule containing a neutral carbon atom with a Valence (chemistry), valence of two and two unshared valence electrons. The general formula is or where the R represents substituents or hydrogen atoms. Th ...
ligands that feature one amino and one sp3
alkyl group In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl group is derived from a cy ...
adjacent to the carbene
carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...
atom. CAACs are a subset of N-heterocyclic carbenes (NHCs) in which the replacement of an
amino group In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
on the "classical" diaminocarbene with a saturated carbon atom results in a carbene ligand that is both a better σ-donor and π-acceptor than classical NHCs. The lone pair on the nitrogen atoms in classical NHCs allows for π-donation from both nitrogen atoms, while substitution of one nitrogen with a carbon atom results in weaker π-donation from only one nitrogen substituent, thus making CAACs stronger π-acceptors and more electrophilic than classical NHCs. Like NHCs, CAACs have tunable
steric Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is generally a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivi ...
and electronic properties that make them versatile
ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...
in both
transition metal In chemistry, a transition metal (or transition element) is a chemical element in the d-block of the periodic table (groups 3 to 12), though the elements of group 12 (and less often group 3) are sometimes excluded. The lanthanide and actinid ...
and
main group In chemistry and atomic physics, the main group is the group of elements (sometimes called the representative elements) whose lightest members are represented by helium, lithium, beryllium, boron, carbon, nitrogen, oxygen, and fluorine as arran ...
. CAACs have been heavily studied. CAACs form stable adducts with otherwise reactive or unstable molecules. In materials science, CAACs stabilize species that have promising photophysical properties for organic light emitting diodes (OLEDs) and have been shown to stabilize single molecule magnets (SMMs).


Classes and synthesis of CAACs


Traditional CAACs (CAAC-5)

Reported by
Bertrand Bertrand may refer to: Places * Bertrand, Missouri, US * Bertrand, Nebraska, US * Bertrand, New Brunswick, Canada * Bertrand Township, Michigan, US * Bertrand, Michigan * Bertrand, Virginia, US * Bertrand Creek, state of Washington * Saint-Bertr ...
in 2005, the first CAAC was synthesized by modification of the precursor
imine In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bon ...
formed from the reaction of 2,6-diisopropylaniline with 2-methylpropanal. This imine was deprotonated by lithium diisopropylamide (LDA) and 1,2-epoxy-2-methylpropane was then added to produce a lithium
alkoxide In chemistry, an alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They are written as , where R is the organyl substituent. Alkoxides are strong bases and, whe ...
. Addition of triflic anhydride (TfOTf) closes the cyclic system, producing an aldiminium salt that was deprotonated with LDA to yield the first CAAC "Ca". A common synthesis is the hydroiminiumation route developed by Bertrand in 2007. The precursor imine is first deprotonated by LDA, followed by addition of an
alkene In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or at the terminal position. Terminal alkenes are also known as Alpha-olefin, α-olefins. The Internationa ...
with a halogenated
substituent In organic chemistry, a substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. The suffix ''-yl'' is used when naming organic compounds that contain a single bond r ...
to form the alkenyl imine. Heating with HCl cyclizes the alkenyl imine to yield the aldiminium salt. Most aldiminium salts have been isolated in yields over 80%. Deprotonation with a strong base such as LDA or potassium bis(trimethylsilyl)amide (KHMDS) generates the CAAC.


Chiral CAACs

When the R1 and R2 are inequivalent, a chiral CAAC results.


Expanded ring CAACs (CAAC-6)

6-membered CAACs have been synthesized by slight modification to the CAAC-5 procedure; the main change is manifested in increasing the chain length of the alkene used in step 2. Modification of the backbone from CAAC-5 to CAAC-6 increases both the σ-donating and π-accepting strength of the ligand. CAAC-6 was shown to be more effective in the α-arylation of
ketone In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
s with
aryl chlorides In organic chemistry, an aryl halide (also known as a haloarene) is an aromatic compound in which one or more hydrogen atoms directly bonded to an aromatic ring are replaced by a halide ion (such as fluorine F''−'', chlorine Cl−1,−3,−5, bro ...
than the analogous CAAC-5. Compared to Ru-CAAC-5, Six-membered Ru-CAAC-6 complexes also showed higher initiation rates for
olefin metathesis In organic chemistry, Olefin Metathesis or Alkene Metathesis is an organic reaction that entails the redistribution of fragments of alkenes (olefins) by the Bond cleavage, scission and regeneration of carbon-carbon double bonds. Because of the ...
, but increased steric bulk limited their catalytic activity. Classic diamino NHCs have been synthetically modified to produce more ambiphilic carbenes by expanding the size of the backbone. 6-, 7-, and 8-membered rings (NHC-6, NHC-7, and NHC-8, respectively) have been reported for diamino NHCs. As the size of the backbone ring increases, so does the nucleophilicity at the carbon center. The traditional 5-membered CAACs show similar nucleophilicity to the eight-membered NHC with calculated highest occupied molecular orbitals (HOMO) of 5.290 eV (CAAC-5) vs. 5.110 eV (NHC-8), decreasing the motivation to synthesize expanded ring CAACs. As a result, ring-expanded CAACs have not been widely explored.


Bicyclic CAACs (BICAACs)

Bicyclic(alkyl)(amino) carbenes (BICAACs) are CAACs containing a
bicyclic A bicyclic molecule () is a molecule that features two joined rings. Bicyclic structures occur widely, for example in many biologically important molecules like α-thujene and camphor. A bicyclic compound can be carbocyclic (all of the ring ...
backbone. The bicyclic system forces the substituents on the carbon to adopt a "fan-like" geometry closer to that of a diamino NHC. As a result, BICAACs show stronger σ-donating and π-accepting properties compared to monocyclic CAACs. To synthesize BICAACs, the starting imine contains a cyclic alkene. The synthesis then follows the hydroiminiumation route in which the cyclization by HCl results in a bicyclic aldiminium salt that is then deprotonated to form the free carbene.


Bidentate CAACs

In 2016, the versatility of CAACs was further expanded to include bidentate CAACs containing a secondary pendant donor atom. By starting from a linear rather than a branched imine starting material, a donor group R can be added at the sp3 carbon by first deprotonating the carbon to be substituted using
tert-butyllithium ''tert''-Butyllithium is a chemical compound with the Chemical formula, formula (CH3)3CLi. As an organolithium compound, it has applications in organic synthesis since it is a strong base (chemistry), base, capable of deprotonation, deprotonating ...
, then adding the alkene by an SN2-type reaction (Scheme 5). Bidentate CAACs featuring alkene,
ether In organic chemistry, ethers are a class of compounds that contain an ether group, a single oxygen atom bonded to two separate carbon atoms, each part of an organyl group (e.g., alkyl or aryl). They have the general formula , where R and R†...
, amine, imine, and
phosphine Phosphine (IUPAC name: phosphane) is a colorless, flammable, highly toxic compound with the chemical formula , classed as a pnictogen hydride. Pure phosphine is odorless, but technical grade samples have a highly unpleasant odor like rotting ...
donors have been reported. Bidentate CAAC-Au(I) complexes have been used for C-C oxidative addition of
biphenylene Biphenylene is an organic compound with the formula (C6H4)2. It is a pale, yellowish solid with a hay-like odor. Despite its unusual structure, it behaves like a traditional polycyclic aromatic hydrocarbon. Bonding Biphenylene is a polycyclic h ...
. Bidentate CAAC-Cu(I) compelxes have shown promise as catalysts for hydroarylation and anti-Markovnikov hydrohydrazination reactions.


Properties of CAACs


Electronic properties

The C-O stretching frequencies of ''cis''- hCl(CO)2(L)and ''cis''- rCl(CO)2(L) where L = NHC or CAAC allows for the determination of overall donating ability of L analogous to the Tolman electronic parameter (TEP). CAACs show lower C-O stretching frequencies (2013–2036 cm−1) than their NHC counterparts (2039–2049 cm−1), indicating that they are stronger donors. The Ï€-accepting abilities of NHCs and CAACs can be compared using 31P
NMR Nuclear magnetic resonance (NMR) is a physical phenomenon in which atomic nucleus, nuclei in a strong constant magnetic field are disturbed by a weak oscillating magnetic field (in the near and far field, near field) and respond by producing ...
shifts of the L-PPh adduct. CAACs show an downfield-shifted 31P NMR signals (56.2-68.9 ppm) compared to classical NHCs (-61.2 to -10.2 ppm) for 5-membered heterocyclic carbenes. These signals indicate higher C-P bond character, and therefore better π-backbonding from the phosphinidene to the CAAC ligands. By correlation to the TEPs for these complexes, the stronger σ-donating abilities for CAACs can be extracted. The experimental superiority of σ-donor/π-acceptor CAACs compared to diaminocarbene NHCs is supported by DFT calculations of the frontier molecular orbitals of CAACs and NHCs. The more nucleophilic (higher HOMO) and
electrophilic In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carr ...
(lower LUMO) character of CAACs manifests in contraction of the singlet-triplet gap Δ''E''ST from 285.1 kJ/mol for the saturated H-substituted NHC to 193.5 kJ/mol for the analogous saturated H-substituted CAAC. The electronic properties of CAACs are affected by ring size. 6-membered CAACs increases the N-C-C angle, decreasing hybridization and thereby increasing p character of the carbene center. This increased p character raises the HOMO, decreasing the Δ''E''ST further.


Steric properties

CAACs also show distinctve steric profiles. It is easy to produce symmetric NHCs, in which the N substituents are the same on either side of the carbene center. This is not the case for CAACs, which are synthesized by adding the N and C substituents in two different steps, allowing for more facile tuning of each substituent. The substituents on the carbene center are asymmetric and have differing hybridization between the sp2 nitrogen and sp3 carbon atom. This
quaternary carbon A quaternary carbon is a carbon atom bound to four other carbon atoms. For this reason, quaternary carbon atoms are found only in hydrocarbons having at least five carbon atoms. Quaternary carbon atoms can occur in branched alkanes, but not in ...
atom in the α-position allows for variable steric effects by changing the substituents at both N and C. The presence of the steric bulk at the α-position to the carbene rather than beta (attached to N) results in more steric encumberment at the carbene center. This effect is evident in the higher percent buried volume (%VBur) of CAACs compared to diamino NHCs at a distance of 0 Å from the carbene. For carbenes bearing a diiopropylphenyl group at the N substituent(s), the %VBur for CAACs (79.0-83.1) is markedly higher than the classical NHC (70.3). This effect can be used to stabilize highly reactive main group and transition metal compounds. Because excessive steric hindrance can be an issue for some reactivity, NHCs and CAACs bearing substituents with multiple spatial conformations (e.g.
cyclohexyl Cyclohexane is a cycloalkane with the molecular formula . Cyclohexane is non-polar. Cyclohexane is a colourless, flammable liquid with a distinctive detergent-like odor, reminiscent of cleaning products (in which it is sometimes used). Cyclo ...
) offer "flexible steric bulk" for catalysis. The asymmetry of CAACs amplifies this flexible steric bulk by allowing for flexibility on only one side of the ligand. This asymmetric ligand scaffold has been exploited in developing novel catalysts for asymmetric transformations and
small molecule In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; ...
activation.


CAAC Stabilization of Reactive Compounds

A major benefit of CAACs compared to other carbene or phosphine ligands is in their ability to stabilize highly reactive complexes that could not otherwise be isolated. The strong σ-donor and π-acceptor properties, as well as the steric bulk offered by CAAC ligands has allowed for the stabilization of numerous low-valent complexes across the periodic table.


s-block elements

Adducts of CAACs with Group 1 and 2 elements have been reported and shown to enhance their catalytic and redox properties compared to the elements alone. Group 1 (alkali metal) and Group 2 (alkaline earth metal) elements are very electropositive and are often seen in the +1 or +2 oxidation state. The strong π-accepting character of CAACS allowed for the isolation of the first example of a neutral Be(0) complex, which could not be isolated by attempts with diamino NHCs. A stable low valent Mg(I) radical has been reported, supported by a CAAC ligand which localizes the unfavorable spin density.


d-block elements

Reflecting their steric bulk, CAAC's stabilize low-coordinate complexes. The 14e, Rh(I) species hCl(CO)(CAAC)is one example. Other examples are d(allyl)(CAAC)sup>+ and u(CAAC)(η2-toluene)sup>+. CAAC's form tricoordinate Co(0), Fe(0), and Mn(0) complexes. EPR evidence supports these
paramagnetic Paramagnetism is a form of magnetism whereby some materials are weakly attracted by an externally applied magnetic field, and form internal, induced magnetic fields in the direction of the applied magnetic field. In contrast with this behavior, ...
complexes are stabilized by offloading spin density onto the carbene ligand.


p-block elements

CAAC ligands have also unlocked previously unachievable main group complexes of Groups 13-15.
Group 13 The Group 13 network (, ) was a Jewish collaborationist organization in the Warsaw Ghetto during the German occupation of Poland in World War II. The rise and fall of the Group was likely a proxy for power struggles between various facti ...
consists of electron deficient elements that tend to behave as
Lewis acids A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any sp ...
. A variety of CAAC adducts of group 13 elements have been explored. More notably, however, is the isolation of neutral group 13
radicals Radical (from Latin: ', root) may refer to: Politics and ideology Politics *Classical radicalism, the Radical Movement that began in late 18th century Britain and spread to continental Europe and Latin America in the 19th century *Radical politics ...
of B, Al, and Ga by reduction of a CAAC-MCl2 complex. CAACS have also been shown to stabilize nucleophilic
borylene A borylene is the boron analogue of a carbene. The general structure is R-B: with R an organic moiety (chemistry), moiety and B a boron atom with two unshared electrons. Borylenes are of academic interest in organoboron chemistry. A diradical, sin ...
s and their corresponding radical cations.
Group 14 The carbon group is a periodic table group consisting of carbon (C), silicon (Si), germanium (Ge), tin (Sn), lead (Pb), and flerovium (Fl). It lies within the p-block. In modern IUPAC notation, it is called group 14. In the field of semi ...
is dominated by organic chemistry, but CAACs have brought light to the reactivity of the heavier congeners. CAACs have been shown to stabilize more reactive carbon radicals by
electron delocalization In chemistry, delocalized electrons are electrons in a molecule, ion or solid metal that are not associated with a single atom or a covalent bond.IUPAC Gold Boo''delocalization''/ref> The term delocalization is general and can have slightly diff ...
across the CAAC ligand. For instance, CAAC-stabilized carboxyl radicals can be isolated and stored at room temperature under
inert atmosphere An inert gas is a gas that does not readily undergo chemical reactions with other chemical substances and therefore does not readily form chemical compounds. Though inert gases have a variety of applications, they are generally used to prevent u ...
. CAACs can also stabilize bonding between the heavier group 14 and group 15 elements; numerous examples of
homonuclear In chemistry, homonuclear molecules, or elemental molecules, or homonuclear species, are molecules composed of only one element. Homonuclear molecules may consist of various numbers of atoms. The size of the molecule an element can form depends ...
Si-Si, Si=Si, P-P, P=P, As-As, and Sb-Sb. Two coordinate CAAC-stabilized Sb(I) and Bi(I) carbone analogues have also been isolated; this reactivity is distinctive given the propensity for Sb and Bi complexes to
dimerize In chemistry, dimerization is the process of joining two identical or similar Molecular entity, molecular entities by Chemical bond, bonds. The resulting bonds can be either strong or weak. Many symmetrical chemical species are described as dim ...
.


CAACs in Catalysis


Transition metal catalysis

CAAC-supported ruthenium
ethenolysis In organic chemistry, ethenolysis is a chemical process in which internal olefins are degraded using ethylene () as the reagent. The reaction is an example of olefin metathesis, cross metathesis. The utility of the reaction is driven by the low ...
catalysts to produce linear alpha olefins (LAOs) from
biomass Biomass is a term used in several contexts: in the context of ecology it means living organisms, and in the context of bioenergy it means matter from recently living (but now dead) organisms. In the latter context, there are variations in how ...
-derived compounds. This was the first reported instance of olefin metathesis using
ethylene Ethylene (IUPAC name: ethene) is a hydrocarbon which has the formula or . It is a colourless, flammable gas with a faint "sweet and musky" odour when pure. It is the simplest alkene (a hydrocarbon with carbon–carbon bond, carbon–carbon doub ...
gas. These catalysts were extremely active, producing turnover numbers (TON) greater than 100,000 at 1-3 ppm catalyst loading.
Coinage metal The coinage metals comprise those metallic chemical elements and alloys which have been used to mint coins. Historically, most coinage metals are from the three nonradioactive members of group 11 of the periodic table: copper, silver and gold. ...
CAAC complexes have been well studied. CAAC-Au(I) complexes have been shown to catalyze the production of allynes via cross coupling,
hydroamination In organic chemistry, hydroamination is the formal Addition reaction, addition of an bond of an amine across an Carbon–carbon bond, carbon-carbon multiple bond of an alkene, alkyne, diene, or allene. In the ideal case, hydroamination is Atom eco ...
, hydroamoniumation, and methylamination reactions. CAAC-Cu(I) complexes have been employed in cross-coupling reactions, hydroarylation, and small molecule activation. CAAC-Cu(I)BH4 is an efficient catalyst for the reduction of
carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...
to
formate Formate (IUPAC name: methanoate) is the conjugate base of formic acid. Formate is an anion () or its derivatives such as ester of formic acid. The salts and esters are generally colorless. Fundamentals When dissolved in water, formic acid co ...
with a turnover number of 1800, which is a great improvement from other first row transition metal catalysts with TONs typically below 500. CAAC-Cu(I) catalysts have also been used for biologically-relevant asymmetric catalysis such as asymmetric conjugate
borylation Metal-catalyzed C–H borylation reactions are transition metal catalyzed organic reactions that produce an organoboron compound through functionalization of aliphatic and aromatic C–H bonds and are therefore useful reactions for carbon–hydroge ...
(ACB). Inclusion of a
chiral Chirality () is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek language, Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is dist ...
center on the CAAC ligand allows for the production of β-substituted α,β-unsaturated
ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...
s with moderate enantioselectivities (up to 55%).


Small molecule activation

The ambiphilic nature of CAACs gives them properties previously attributed to transition metals, such as the ability to undergo
oxidative addition Oxidative addition and reductive elimination are two important and related classes of reactions in organometallic chemistry. Oxidative addition is a process that increases both the oxidation state and coordination number of a metal centre. Oxidat ...
and
reductive elimination Reductive elimination is an elementary step in organometallic chemistry in which the oxidation state of the metal center decreases while forming a new covalent bond between two ligands. It is the microscopic reverse of oxidative addition, and is ...
. The small singlet-triplet gap inherent in CAACs allows for these ligands to activate small molecules and enthalpically strong bonds, including CO, H2, B-H in HBpin, Si-H, P-H, P4, C-H, and N-H in NH3. As a result, CAACs can be implemented as economical metal-free catalysts for a variety of transformations that traditionally needed the aid of transition metal catalysts. Given that many transition metals are scarce and expensive, activation of small molecules using CAACs has important implications for the development of sustainable processes.


Photochemistry

Copper and gold CAAC complexes exhibit
photoluminescence Photoluminescence (abbreviated as PL) is light emission from any form of matter after the absorption of photons (electromagnetic radiation). It is one of many forms of luminescence (light emission) and is initiated by photoexcitation (i.e. phot ...
, relevant to organic light emitting diodes (OLEDs). Two coordinate (linear) Cu-CAAC complexes have weaker
intermolecular interactions An intermolecular force (IMF; also secondary force) is the force that mediates interaction between molecules, including the electromagnetic forces of attraction or repulsion which act between atoms and other types of neighbouring particles (e.g. ...
than other OLED candidates, allowing them to reach quantum efficiencies over 99%. Modification of the steric bulk around the carbene center allows for optimization of the excited state lifetimes, where shorter lifetimes are preferred for highest OLED efficiency. CAAC-Cu(I) complexes are also thermally stable up to 270 Â°C and emit at ambient temperatures, making them good candidates for OLED devices.


Single molecule magnets

Single-molecule magnet A single-molecule magnet (SMM) is a metal-organic compound that has superparamagnetic behavior below a certain blocking temperature at the molecular scale. In this temperature range, an SMM exhibits magnetic hysteresis of purely molecular origin.< ...
(SMMs) are an emerging field with implications for
data storage Data storage is the recording (storing) of information (data) in a storage medium. Handwriting, phonographic recording, magnetic tape, and optical discs are all examples of storage media. Biological molecules such as RNA and DNA are con ...
and
quantum computing A quantum computer is a computer that exploits quantum mechanical phenomena. On small scales, physical matter exhibits properties of wave-particle duality, both particles and waves, and quantum computing takes advantage of this behavior using s ...
. The strong accepting character of CAACs allows for the stabilization of the high spin states characteristic to SMMs. Iron and chromium SMMs stabilized by CAACs have been reported.{{Cite journal , last=Roy , first=Sudipta , last2=Mondal , first2=Kartik Chandra , last3=Roesky , first3=Herbert W. , date=2016-03-15 , title=Cyclic Alkyl(amino) Carbene Stabilized Complexes with Low Coordinate Metals of Enduring Nature , url=https://pubs.acs.org/doi/10.1021/acs.accounts.5b00381 , journal=Accounts of Chemical Research , volume=49 , issue=3 , pages=357–369 , doi=10.1021/acs.accounts.5b00381 , issn=0001-4842, url-access=subscription These complexes undergo slow magnetic relaxation, making them promising SMMs.


References

Heterocyclic compounds with 1 ring Nitrogen heterocycles Carbenes