Ketene cycloaddition

Last updated

Ketene cycloadditions are the reactions of the pi system of ketenes with unsaturated compounds to provide four-membered or larger rings. [2+2], [3+2], and [4+2] variants of the reaction are known. [1]

Contents

Introduction

Ketenes may react with unsaturated compounds to afford four-membered or larger rings. The first example of this phenomenon was observed in 1908, [2] and since then, cycloadditions of ketenes have expanded and gained synthetic utility. Examples exist of [2+2], [3+2], and [4+2] cycloaddition, and conjugated ketenes may act as 4π partners in [4+2] cycloadditions as well. [3] The unique transition state geometry of [2+2] ketene cycloadditions has important stereochemical consequences (see below).

(1)

KetGen.png

Mechanism and Stereochemistry

Prevailing Mechanism

Ketene cycloadditions proceed by a concerted, [2+2] cycloaddition mechanism. Ketenes, unlike most alkenes, can align antarafacially with respect to other alkenes. Thus, the suprafacial- antarafacial geometry required for concerted, thermal [2+2] cycloaddition can be achieved in reactions of ketenes. [4] This geometry has the interesting consequence that the bulkier substituent on the ketene will tend to end up on the more sterically hindered face of the cyclobutanone ring. In the transition state for cyclization, the small substituent points toward the alkene. This model also explains the greater reactivity of cis alkenes relative to trans alkenes in [2+2] ketene cycloadditions. [5]

(2)

KetMech.png

The configuration of the olefin is retained in the cycloaddition product. Electron-withdrawing substituents on the ketene and donating substituents on the alkene accelerate the reaction, [6] but disubstituted ketenes react slowly due to steric hindrance. [7] Orbital coefficients can be used to determine regioselectivity.

Enantioselective Variants

The use of chiral amine catalysts has allowed access to cycloaddition products in high enantiomeric excess. [8]

(3)

KetStereo.png

Scope and Limitations

Ketenes may participate in [2+2], [3+2], or [4+2] (as either the 2π or 4π component) cycloadditions. The periselectivity of a particular reaction depends on the structure of both the ketene and the substrate. Although the reaction is predominantly used to form four-membered rings, a limited number of substrates undergo [3+2] or [4+2] reactions with ketenes. Examples of all three modes of cycloaddition are discussed in this section.

Ketenes may dimerize, or two ketenes may react with one another to afford substituted cyclobutanones. There are typically two possible products depending on the precise double bonds that react. Disubstituted ketenes give only the 1,3-cyclobutanedione. [9]

(4)

KetScope1.png

Ketenes react with alkenes to provide cyclobutanones. If the product of a cycloaddition of ketene itself is desired, dichloroketene is typically used, followed by dehalogenation with zinc-copper couple. [10]

(5)

KetScope2.png

Cyclic and acyclic dienes generally give cyclobutanones, rather than Diels-Alder adducts. In reactions of cyclic dienes, the larger ketene substituent is placed in the endo position. [11] Fulvenes typically react in the ring, leaving the double bond intact. [12]

(6)

KetScope3.png

Ketenes undergo [2+2] cycloaddition with ketones and aldehydes to give β-lactones. Lewis acid catalysis is necessary for this process, unless the carbonyl compound possesses strongly electron- withdrawing substituents. [13]

(7)

KetScope4.png

[3+2] Cycloadditions may take place with 1,3-dipoles. This process appears to be concerted, but either double bond of ketenes can react. [14]

(8)

KetScope5.png

In contrast to simple dienes, which typically react in a [2+2] fashion or afford complex mixtures of [4+2] products, heterodienes often react in a [4+2] fashion. β-amino or -alkoxy unsaturated ketones, for instance, react with ketenes in a [4+2] sense to give synthetically useful yields of lactones. [15]

(9)

KetScope6.png

Examples in which a vinylketene serves as the 4π partner are rare, but ketene-containing heterodienes such as acyl ketenes react with many heterodienophiles to give heterocyclic products in good yield. [16]

(10)

KetScope7.png

Experimental Conditions and Procedure

Typical Conditions

Cycloadditions with reactants that are liquids at room temperature are best performed by simply mixing the two reactants without solvent. If one of the reactants is gaseous, it is more convenient to use a solvent. Although polar solvents and catalysts accelerate the cycloaddition, they are not of general utility since they also accelerate dimerization. The progress of the reaction can be estimated by disappearance of the characteristic yellow color of the ketene, by loss of the band at about 2100 cm−1 in the infrared spectrum, or by 1H NMR spectroscopy. Ketene, monoalkylketenes, and dimethylketene are usually allowed to react at or below room temperature, whereas the higher molecular weight ketenes can be heated to temperatures above 100°. The ketene is usually used in excess when dimerization is a major side reaction. The success of the reaction is often determined by the relative rates of cycloaddition and dimerization of the ketene.

Example Procedure [17]

(11)

KetScope8.png

In a flame-dried, 100-mL three-necked flask equipped with argon atmosphere, stirrer, reflux condenser, and constant pressure addition funnel was placed 0.40 g (18 mmol) of activated zinc, 0.576 g (6 mmol) of 1-heptyne, and 50 mL of anhydrous ether. To this stirred mixture was added dropwise over 1 hour a solution of 1.79 g (12 mmol) of phosphorus oxychloride (freshly distilled from potassium carbonate), trichloroacetyl chloride (12 mmol), and 10 mL of anhydrous ether. The mixture was then stirred at reflux for 4 hours and the residual zinc removed by filtration on a pad of Celite. The ether solution was washed with water, 5% sodium bicarbonate solution, and brine, and dried over potassium carbonate. After removal of ether under reduced pressure, the product was purified by bulb-to-bulb distillation at 100° bath temperature (0.1 mm), to give 1.08 g (90%) of the title compound as a clear oil. IR νmax (neat) 1800, 1585 cm−1; 1H NMR (CDCl3) δ 6.12 (m, 1H, J = 2 Hz), 2.7 (t, 2H, J = 6 Hz), 2.0–0.7 (m, 9H). Anal. Calcd. for C9H13Cl2O: C, 52.19; H, 5.85. Found: C, 52.10; H, 5.79.

Related Research Articles

<span class="mw-page-title-main">Diels–Alder reaction</span> Chemical reaction

In organic chemistry, the Diels–Alder reaction is a chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene derivative. It is the prototypical example of a pericyclic reaction with a concerted mechanism. More specifically, it is classified as a thermally-allowed [4+2] cycloaddition with Woodward–Hoffmann symbol [π4s + π2s]. It was first described by Otto Diels and Kurt Alder in 1928. For the discovery of this reaction, they were awarded the Nobel Prize in Chemistry in 1950. Through the simultaneous construction of two new carbon–carbon bonds, the Diels–Alder reaction provides a reliable way to form six-membered rings with good control over the regio- and stereochemical outcomes. Consequently, it has served as a powerful and widely applied tool for the introduction of chemical complexity in the synthesis of natural products and new materials. The underlying concept has also been applied to π-systems involving heteroatoms, such as carbonyls and imines, which furnish the corresponding heterocycles; this variant is known as the hetero-Diels–Alder reaction. The reaction has also been generalized to other ring sizes, although none of these generalizations have matched the formation of six-membered rings in terms of scope or versatility. Because of the negative values of ΔH° and ΔS° for a typical Diels–Alder reaction, the microscopic reverse of a Diels–Alder reaction becomes favorable at high temperatures, although this is of synthetic importance for only a limited range of Diels-Alder adducts, generally with some special structural features; this reverse reaction is known as the retro-Diels–Alder reaction.

<span class="mw-page-title-main">Pericyclic reaction</span> Note bout pericyclic reaction

In organic chemistry, a pericyclic reaction is the type of organic reaction wherein the transition state of the molecule has a cyclic geometry, the reaction progresses in a concerted fashion, and the bond orbitals involved in the reaction overlap in a continuous cycle at the transition state. Pericyclic reactions stand in contrast to linear reactions, encompassing most organic transformations and proceeding through an acyclic transition state, on the one hand and coarctate reactions, which proceed through a doubly cyclic, concerted transition state on the other hand. Pericyclic reactions are usually rearrangement or addition reactions. The major classes of pericyclic reactions are given in the table below. Ene reactions and cheletropic reactions are often classed as group transfer reactions and cycloadditions/cycloeliminations, respectively, while dyotropic reactions and group transfer reactions are rarely encountered.

In organic chemistry, a cycloaddition is a chemical reaction in which "two or more unsaturated molecules combine with the formation of a cyclic adduct in which there is a net reduction of the bond multiplicity". The resulting reaction is a cyclization reaction. Many but not all cycloadditions are concerted and thus pericyclic. Nonconcerted cycloadditions are not pericyclic. As a class of addition reaction, cycloadditions permit carbon–carbon bond formation without the use of a nucleophile or electrophile.

The 1,3-dipolar cycloaddition is a chemical reaction between a 1,3-dipole and a dipolarophile to form a five-membered ring. The earliest 1,3-dipolar cycloadditions were described in the late 19th century to the early 20th century, following the discovery of 1,3-dipoles. Mechanistic investigation and synthetic application were established in the 1960s, primarily through the work of Rolf Huisgen. Hence, the reaction is sometimes referred to as the Huisgen cycloaddition. 1,3-dipolar cycloaddition is an important route to the regio- and stereoselective synthesis of five-membered heterocycles and their ring-opened acyclic derivatives. The dipolarophile is typically an alkene or alkyne, but can be other pi systems. When the dipolarophile is an alkyne, aromatic rings are generally produced.

<span class="mw-page-title-main">Claisen rearrangement</span> Chemical reaction

The Claisen rearrangement is a powerful carbon–carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen. The heating of an allyl vinyl ether will initiate a [3,3]-sigmatropic rearrangement to give a γ,δ-unsaturated carbonyl, driven by exergonically favored carbonyl CO bond formation.

<span class="mw-page-title-main">Cheletropic reaction</span> Chemical reaction in which a ring is formed/broken by adding/removing a single atom

In organic chemistry, cheletropic reactions, also known as chelotropic reactions, are a type of pericyclic reaction. Specifically, cheletropic reactions are a subclass of cycloadditions. The key distinguishing feature of cheletropic reactions is that on one of the reagents, both new bonds are being made to the same atom.

<span class="mw-page-title-main">Woodward–Hoffmann rules</span>

The Woodward–Hoffmann rules, devised by Robert Burns Woodward and Roald Hoffmann, are a set of rules used to rationalize or predict certain aspects of the stereochemistry and activation energy of pericyclic reactions, an important class of reactions in organic chemistry. The rules are best understood in terms of the concept of the conservation of orbital symmetry using orbital correlation diagrams. The Woodward–Hoffmann rules are a consequence of the changes in electronic structure that occur during a pericyclic reaction and are predicated on the phasing of the interacting molecular orbitals. They are applicable to all classes of pericyclic reactions, including (1) electrocyclizations, (2) cycloadditions, (3) sigmatropic reactions, (4) group transfer reactions, (5) ene reactions, (6) cheletropic reactions, and (7) dyotropic reactions. Due to their elegance, simplicity, and generality, the Woodward–Hoffmann rules are credited with first exemplifying the power of molecular orbital theory to experimental chemists.

The Perkow reaction is an organic reaction in which a trialkyl phosphite ester reacts with a haloketone to form a dialkyl vinyl phosphate and an alkyl halide.

<span class="mw-page-title-main">Wolff rearrangement</span>

The Wolff rearrangement is a reaction in organic chemistry in which an α-diazocarbonyl compound is converted into a ketene by loss of dinitrogen with accompanying 1,2-rearrangement. The Wolff rearrangement yields a ketene as an intermediate product, which can undergo nucleophilic attack with weakly acidic nucleophiles such as water, alcohols, and amines, to generate carboxylic acid derivatives or undergo [2+2] cycloaddition reactions to form four-membered rings. The mechanism of the Wolff rearrangement has been the subject of debate since its first use. No single mechanism sufficiently describes the reaction, and there are often competing concerted and carbene-mediated pathways; for simplicity, only the textbook, concerted mechanism is shown below. The reaction was discovered by Ludwig Wolff in 1902. The Wolff rearrangement has great synthetic utility due to the accessibility of α-diazocarbonyl compounds, variety of reactions from the ketene intermediate, and stereochemical retention of the migrating group. However, the Wolff rearrangement has limitations due to the highly reactive nature of α-diazocarbonyl compounds, which can undergo a variety of competing reactions.

<span class="mw-page-title-main">Staudinger synthesis</span> Form of chemical synthesis

The Staudinger synthesis, also called the Staudinger ketene-imine cycloaddition, is a chemical synthesis in which an imine 1 reacts with a ketene 2 through a non-photochemical 2+2 cycloaddition to produce a β-lactam3. The reaction carries particular importance in the synthesis of β-lactam antibiotics. The Staudinger synthesis should not be confused with the Staudinger reaction, a phosphine or phosphite reaction used to reduce azides to amines.

The divinylcyclopropane-cycloheptadiene rearrangement is an organic chemical transformation that involves the isomerization of a 1,2-divinylcyclopropane into a cycloheptadiene or -triene. It is conceptually related to the Cope rearrangement, but has the advantage of a strong thermodynamic driving force due to the release of ring strain. This thermodynamic power is recently being considered as an alternative energy source.

Trimethylenemethane cycloaddition is the formal [3+2] annulation of trimethylenemethane (TMM) derivatives to two-atom pi systems. Although TMM itself is too reactive and unstable to be stored, reagents which can generate TMM or TMM synthons in situ can be used to effect cycloaddition reactions with appropriate electron acceptors. Generally, electron-deficient pi bonds undergo cyclization with TMMs more easily than electron-rich pi bonds.

A (4+3) cycloaddition is a cycloaddition between a four-atom π-system and a three-atom π-system to form a seven-membered ring. Allyl or oxyallyl cations (propenylium-2-olate) are commonly used three-atom π-systems, while a diene plays the role of the four-atom π-system. It represents one of the relatively few synthetic methods available to form seven-membered rings stereoselectively in high yield.

[6+4] Cycloaddition is a type of cycloaddition between a six-atom pi system and a four-atom pi system, leading to a ten-membered ring. Because this is a higher-order cycloaddition, issues of periselectivity arise in addition to the usual concerns about regio- and stereoselectivity. Six-atom pi systems that have been employed in the reaction include tropone and tropone derivatives, fulvenes, and cycloheptatriene cobalt complexes.

In organic chemistry, enone–alkene cycloadditions are a version of the [2+2] cycloaddition This reaction involves an enone and alkene as substrates. Although the concerted photochemical [2+2] cycloaddition is allowed, the reaction between enones and alkenes is stepwise and involves discrete diradical intermediates.

The imine Diels–Alder reaction involves the transformation of all-carbon dienes and imine dienophiles into tetrahydropyridines.

Metal-catalyzed intermolecular carbenoid cyclopropanations are organic reactions that result in the formation of a cyclopropane ring from a metal carbenoid species and an alkene. In the Simmons–Smith reaction the metal involved is zinc.

The inverse electron demand Diels–Alder reaction, or DAINV or IEDDA is an organic chemical reaction, in which two new chemical bonds and a six-membered ring are formed. It is related to the Diels–Alder reaction, but unlike the Diels–Alder reaction, the DAINV is a cycloaddition between an electron-rich dienophile and an electron-poor diene. During a DAINV reaction, three pi-bonds are broken, and two sigma bonds and one new pi-bond are formed. A prototypical DAINV reaction is shown on the right.

A metal-centered cycloaddition is a subtype of the more general class of cycloaddition reactions. In such reactions "two or more unsaturated molecules unite directly to form a ring", incorporating a metal bonded to one or more of the molecules. Cycloadditions involving metal centers are a staple of organic and organometallic chemistry, and are involved in many industrially-valuable synthetic processes.

The Danheiser benzannulation is a chemical reaction used in organic chemistry to generate highly substituted phenols in a single step. It is named after Rick L. Danheiser who developed the reaction.

References

  1. ↑ Hyatt, J. A.; Reynolds, P. W. Org. React. 1994, 45, 159. doi : 10.1002/0471264180.or045.02
  2. ↑ Frances Chick and Norman Thomas Mortimer Wilsmore (1908) "Acetylketen: a polymeride of keten," Journal of the Chemical Society, Transactions, 93 : 946-950.
  3. ↑ Staudinger, H. Die Ketene, Verlag von Ferdinand Enke, Stuttgart, 1912.
  4. ↑ Moore, H. W.; Wilbur, D. S. J. Org. Chem.1980, 45, 4483.
  5. ↑ Rey, M.; Roberts, S.; Dieffenbacher, A.; Dreiding, A. S. Helv. Chim. Acta1970, 53, 417.
  6. ↑ Isaacs, N. S.; Stanbury, P. F. J. Chem. Soc., Chem. Commun.1970, 1061.
  7. ↑ Huisgen, R.; Mayr, H. Tetrahedron Lett.1975, 2965.
  8. ↑ Wynberg, H.; Staring, E. J. J. Am. Chem. Soc.1982, 104, 166.
  9. ↑ Tenud, L.; Weilenmann, M.; Dallwigk, E. Helv. Chim. Acta1977, 60, 975.
  10. ↑ McMurry, J. E.; Miller, D. D. Tetrahedron Lett.1983, 24, 1885.
  11. ↑ England, D. C.; Krespan, C. G. J. Org. Chem.1970, 35, 3300.
  12. ↑ Stadler, H.; Rey, M.; Dreiding, A. S. Helv. Chim. Acta1984, 67, 1854.
  13. ↑ Metzger, C.; Borrmann, D.; Wegler, R. Chem. Ber.1967, 100, 1817.
  14. ↑ Texier, F.; Carrié, R.; Jaz, J. J. Chem. Soc., Chem. Commun.1972, 199.
  15. ↑ Mosti, L.; Menozzi, G.; Bignardi, G.; Schenone, P. Il Farmaco (Ed. Sci.)1977, 32, 794 [C.A. 1978, 88, 62262n].
  16. ↑ Jäger, G.; Wenzelburger, J. Justus Liebigs Ann. Chem.1976, 1689.
  17. ↑ Hassner, A.; Dilon, J. L. J. Org. Chem. 1983, 48, 3382.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.