Having a variety of species including radicals, cations, anions, and transition metal species as part of the repertoire, carbonylation chemistry is becoming more and more rich in synthetic methodology. Recent innovations with regard to the reaction devices available for carbonylation have been significant, including autoclaves that have the ability to permit light irradiation under CO pressure, compact CO boosters to create very high CO pressure conditions, flow reactor systems equipped with a mass flow controllers to ensure excellent gas-liquid mixing, and twin-tube reactors available for carbonylation with ex-situ generated CO. In this account, we survey the recent evolution of modern carbonylation techniques beginning with novel carbonylation reactions developed in our laboratory, like borohydride-mediated carbonylation, light induced carbonylation, and carbonylation based on radical/ion hybrid reactions. We believe that with innovations in synthetic methods and equipment, each carbonylation reaction will be easily run in a device specifically suitable for optimal performance in that reaction.
The phase-vanishing (PV) method is based on spontaneous reaction controlled by diffusion of reagents into fluorous media, such as perfluorohexanes (FC-72) and polyperfluoroethers. Thus, the original PV reaction utilizes a triphasic test tube method composed of a bottom reagent phase, a middle fluorous phase, and a top substrate phase. In such a triphasic system, the fluorous phase acts as a liquid membrane to transport the bottom reagents to the top organic phase containing substrates. In the end, the bottom layer disappears and two phases remain. Since the first demonstration of the PV method by bromination of alkenes with molecular bromine, a number of applications have been developed thus far. These include halogenation of alcohols with SOBr2 and PBr3, demethylation of methoxyarenes with BBr3, cyclopropanation of alkenes by CH2I2-AlEt3, and Friedel–Crafts acylation of aromatic compounds with SnCl4. A fluorous triphasic U-tube method is effective for chlorination of alcohols based on lighter (less dense) reagents such as SOCl2 and PCl3. A system using a solution containing reagents as a bottom phase is useful for oxidation with m-CPBA, which may be defined as a new category for the “extractive PV” method. Recent advances include a “quadraphasic” PV method, in which an aqueous “scavenger” phase is added to the original triphasic PV method to remove acidic by-products. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 351–363; 2008: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20161
This account presents an overview of our recent endeavors to achieve practical organic syntheses using a variety of microreaction devices. Herein are our achievements in ionic liquid-based catalytic reactions, photochemical transformation, and heterogenous hydrogenation reactions, where flow regime precisely controls residence time and product selectivity.
Free-radical chemistry has come a long way in a relatively short period of time. The synthetic practitioner takes for granted the wealth of mechanistic and rate constant data now available and can apply free-radical techniques to the synthesis of many different classes of target molecule with confidence. Despite this, there are still mechanistic anomalies that need to be addressed. This Account highlights recent work involving nucleophilic radicals with low-lying unoccupied orbitals, such as acyl, oxyacyl, silyl, stannyl, and germyl radicals. Through interesting singly occupied molecular orbital (SOMO)–π* and highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) interactions during these reactions, the radicals involved are able to mask as electrophiles, providing high levels of regiocontrol and efficient methods for the synthesis of important heterocycles.
The carbonylation of vinyl radicals gives α,β-unsaturated acyl radicals. This transformation was successfully applied to tandem radical reactions, resulting in assembling three and four components. In these reactions, both halogen abstraction from vinyl halides and hetero atom radical additions to alkynes are used to generate the parent vinyl radicals. Ab initio calculations and density functional methods predict that α,β-unsaturated acyl radicals and the isomeric α-ketenyl radicals are not canonical forms, but are isomeric species that undergo interconversion. Calculations also indicate that α,β-unsaturated acyl radicals are more stable than α-ketenyl radicals, whereas α-ketenyl radicals containing a heteroatom, such as Si, Ge, and Sn, at α-position are more stable than the corresponding α,β-unsaturated acyl radicals. This represents a promising resource for developing new synthetic applications that involve the use of the α-ketenyl radicals. Indeed, following the prediction by calculation, we succeeded in trapping of a tin-attached α-ketenyl radical by imines and amines in an intramolecular fashion. We were also able to achieve the intermolecular trapping of α-ketenyl radicals, providing a new method for alkyne carbonylation by hybrid radical/ionic reactions.
New approaches in radical carbonylation chemistry are described. We have successfully integrated tin mediated radical carbonylation chemistry into modern fluorous applications and separation techniques. We revealed that radical carbonylation reactions can be performed using fluorous tin mediators, such as fluorous tin hydride and fluorous allyltin reagents. Fine tuning of the reaction conditions resulted in a good efficiency equivalent to conventional tin mediators. The tedious procedure of removing organotin byproducts can be circumvented through the use of fluorous/organic liquid-liquid extraction or fluorous liquid-solid phase extraction with fluorous reverse phase silica (FRPS). Also described are newly developed tandem carbonylation reactions that are based on species hybridization approaches. Using a radical/anionic hybrid system based on zinc-induced one-electron reduction, we achieved a three-component coupling reaction consisting of 4-alkenyl iodides, carbon monoxide, and electron-deficient alkenes. We observed two types of annulations processes, namely [4 + 1](radical)/[3 + 2](anionic) and [5 + 1](radical)/[3 + 2](anionic), which lead to the production of bicyclo[3.3.0]octanols and bicyclo[3.2.1]octanols, respectively. We found a radical/palladium hybrid system to be useful in the construction of new cyclic systems that incorporate two or three molecules of carbon monoxide. © 2002 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 2: 249–258, 2002: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10026
This review covers two radical carboxylation methods using carbon monoxide, both of which were developed by our group. The first method, atom transfer carbonylation, converts alkyl iodides into carboxylic acid esters or amides and the second method, remote carboxylation, converts saturated alcohols into δ-lactones. Both methods rely upon radical carbonylation chemistry to introduce carbon monoxide, but the key steps are conceptually different. The first method utilizes an atom transfer reaction from an alkyl iodide to an acyl radical leading to an acyl iodide and the latter employs a one-electron oxidation reaction to convert an acyl radical into an acyl cation. The iodine atom transfer carbonylation process is reversible and therefore highly inefficient unless it is performed in concert with an ionic system to shift the equilibrium in the direction of an acyl iodide. In the latter process, a 1,5-translocation scheme to shift the radical from oxygen to the δ-carbon is successfully coupled with the carbonylation–oxidation sequence. Carboxylations of alkyl halides by transition metal catalyzed methods are often problematic because of the inherent weakness of alkyl–metal bonds. Existing methods for carbonylative δ-lactone synthesis using transition metal catalysts are limited to unsaturated alcohols. Thus, these two radical carboxylation methods nicely complement existing transition metal catalyzed carboxylations.
Although known since the 1950s, free-radical carbonylation has not received much attention until only recently. In the last few years the application of modern free-radical techniques has revealed the high synthetic potential of this reaction as a tool for introducing CO into organic molecules. Clearly now is the time for a renaissance of this chemistry. Under standard conditions (tributyltin hydride/CO) primary, secondary, as well as tertiary alkyl bromides and iodides can be efficiently converted into the corresponding aldehydes. Aromatic and α,β-unsaturated aldehydes can also be prepared from the parent aromatic and vinylic iodides. If the reaction is carried out in the presence of alkenes containing an electron-withdrawing substituent, the initially formed acyl radical subsequently adds to the alkene, leading to a general method for the synthesis of unsymmetrical ketones. This three-component coupling reaction can be extended successfully to allyltin-mediated reactions. Thus, β,γ-enones can be prepared from organic halides, CO, and allyltributylstannanes. In a remarkable one-pot procedure alkyl halides can be treated with a mixture of alkene, allyltributylstannane, and carbon monoxide in a four-component coupling reaction that provides β-functionalized δ,ϵ-unsaturated ketones by the formation of three new C―C bonds. The reaction of 4-pentenyl radicals with CO leads to acyl radical cyclization, which provides a useful method for the synthesis of cyclopentanones. Certain useful one-electron oxidations can be combined efficiently with free-radical carbonylations. These findings and others discussed in this article clearly demonstrate that free-radical carbonylation can now be considered a practical alternative to transition metal mediated carbonylation.