Diazo compounds cycloaddition reaction

Ketenes rarely produce [3+ 2]-cycloaddition products with diazo compounds. The reaction possibilities are complex, and nitrogen-free products are often obtained (5). Formation of a cyclopropanone represents one possibihty. Along these lines, the synthesis of (Z)-2,3-bis(trialkylsilyl)cyclopropanones and (Z)-2-trialkylsilyl-3-(triethylgermyl)cyclopropanones from diazo(trialkylsilyl)methanes and appropriate silyl- or germylketenes has been reported (256,257). It was found that subsequent reaction of the cyclopropanone with the diazoalkane was not a problem, in contrast to the reaction of diazomethane with the same ketenes. The high cycloaddition reactivity of diazomethylenephosphoranes also extends to heterocumulenes. The compound R2P(C1)=C=N2 (R = N(/-Pr)2) reacts with CS2, PhNCO and PhNCS to give the corresponding 1,2,3-triazole derivative (60). 

Lewis Acid-Catalyzed Site-Selective Cycloadditions of 2,6-Diazasemibullva-lenes with Isocyanides, Azides and Diazo Compounds Novel Reaction Patterns Leading to Diaza- and Triaza-Brexadiene Derivatives. 

Herein, the author reports Lewis acid-catalyzed diverse cycloaddition reactions of NSBVs 6-1 with a wide variety of isocyanides, azides, and diazo compounds. These reactions afforded 5,8-diaza- and 2,5,9-triaza-brexadiene derivatives as highly fused A -containing polycyclic frameworks, which are structurally and chemically interesting cage-shaped compounds, but not readily accessible by other means. Unique and unprecedented rearrangement-cycloaddition patterns are revealed. These reaction patterns are not only different from our previously reported reaction with DMAD or RNCO, but most notably, very different from the reactions... 

Zhang S, Zhang WX, Xi Z (2013) Lewis acid-catalyzed site-selective cycloadditions of 2,6-diazasemibullvalenes with isocyanides, azides and diazo compounds novel reaction patterns leading to diaza- and triaza-brexadiene derivatives. Angew Chem Int Ed 52 3485-3489... 

From Diazo Compounds via 1,3-Dipolar Cycloaddition. This method has been utilized widely in heterocychc chemistry. Pyrazohne (57) has been synthesized by reaction of ethyl diazoacetate (58) with a,P-unsaturated ester in the presence of pyridine (eq. 12) (42). 

A large number of pyridazines are synthetically available from [44-2] cycloaddition reactions. In one general method, azo or diazo compounds are used as dienophiles, and a second approach is based on the reaction between 1,2,4,5-tetrazines and various unsaturated compounds. The most useful azo dienophile is a dialkyl azodicarboxylate which reacts with appropriate dienes to give reduced pyridazines and cinnolines (Scheme 89). With highly substituted dienes the normal cycloaddition reaction is prevented, and, if the ethylenic group in styrenes is substituted with aryl groups, indoles are formed preferentially. The cycloadduct with 2,3-pentadienal acetal is a tetrahydropyridazine derivative which has been used for the preparation of 2,5-diamino-2,5-dideoxyribose (80LA1307). 

Although the most general cycloaddition reaction of diazo compounds is that they react as 1,3-dipoles, recently some reactions have been reported in which they react as 1,2-dipoles,... 

It was not their reactivity but their chemical inertness that was the true surprise when diazirines were discovered in 1960. Thus they are in marked contrast to the known linear diazo compounds which are characterized by the multiplicity of their reactions. For example, cycloadditions were never observed with the diazirines. Especially surprising is the inertness of diazirines towards electrophiles. Strong oxidants used in their synthesis like dichromate, bromine, chlorine or hypochlorite are without action on diazirines. Diazirine formation may even proceed by oxidative dealkylation of a diaziridine nitrogen in (186) without destruction of the diazirine ring (75ZOR2221). The diazirine ring is inert towards ozone simple diazirines are decomposed only by more than 80% sulfuric acid (B-67MI50800). 

Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

The best known of metal carbene reactions, cydopropanation reactions, have been used since the earliest days of diazo chemistry for addition reactions to the carbon-carbon double bond. Electron-donating groups (EDG) on the carbon-carbon double bond facilitate this catalytic reaction [37], whereas electron-withdrawing groups (EWG) inhibit addition while facilitating noncatalytic dipolar cycloaddition of the diazo compound [39] (Scheme 5). There are several reviews that describe the earlier synthetic approaches [1, 2,4, 5,40-43], and these will not be duplicated here. Focus will be given in this review to control of stereoselectivity. 

Normally, the dominant reaction between acyl diazo compounds and simple ,(l-unsalurated carbonyl compounds is a cycloaddition. 

If an aliphatic amino group is next to an electron-withdrawing group such as CO2R, CN, CHO, COR and has a hydrogen, reaction with aqueous nitrous acid gives a diazo compound (Eq. 11.4). Such compounds are used widely in 1,3-dipolar cycloaddition reactions, which will be covered in Chapter 12. 

The Davies group has described several examples of a rhodium-catalyzed decomposition of a diazo-compound followed by a [2+1] cycloaddition to give divinyl cyclopropanes, which then can undergo a Cope rearrangement. Reaction of the pyrrol derivative 6/2-51 and the diazo compound 6/2-52 led to the tropane nucleus 6/2-54 via the cyclopropane derivative 6/2-53 (Scheme 6/2.11) [201]. Using (S)-lactate and (R)-pari lolaclorie as chiral auxiliaries at the diazo compound, a diastereoselectivity of around 90 10 could be achieved in both cases. 

Reactivity of diazo compounds towards 1,3-dipolar cycloaddition reactions with 1 -[1,2,3]-, 2H-[1,2,3]-, [1,3,2]-, and [l,2,4]diazaphospholes has been rationalized by FMO approach using DFT calculations [107], In most of the cases, HOMODipole-LUMOn. . .. interaction has been found to control the reactivity and among... 

The synthesis of 1,2,3-selenadiazole derivatives has been reported. The reaction of aroyl chlorides such as 102 with potassium isoselenocyanate and ethyl diazoacetate yielded 5-(aroylimino)-2,5-dihydro-l, 2,3-selenadiazole-4-carboxylate esters such as 104. A reaction mechanism via the initial formation of the corresponding aroyl isoselenocyanate 103 followed by a 1,3-dipolar cycloaddition of the diazo compound with the C=Se bond is proposed <00HCA539>. 

C6 and C9 are at opposite ends of a four-carbon unit, but since one of these atoms (C7) is saturated and quaternary, a Diels-Alder reaction is unlikely (can t make diene). The combination of a diazo compound with Rh(II) generates a carbenoid at C9. The nucleophile 06 can add to the empty orbital at C9, generating the 06-C9 bond and a carbonyl ylide at C6-06-C9. Carbonyl ylides are 1,3-dipoles (negative charge on C9, formal positive charge on 06, electron deficiency at C6), so a 1,3-dipolar cycloaddition can now occur to join C2 to C6 and Cl to C9, giving the product. Note how a relatively simple tricyclic starting material is transformed into a complex hexacyclic product in just one step ... 

The reaction of (trialkylsilyl)vinylketenes with nucleophilic carbenoid reagents, such as sulfur ylides and diazo compounds, has been used for synthesis of substituted cyclopentenones by stereoselective 4 + 1-annulation (Scheme 12). The strategy relies on the remarkable ability of silyl substituents to stabilize ketenes and suppress their tendency to undergo dimerization and 2 - - 2-cycloaddition. 

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

The ability to produce 1,3-dipoles, through the rhodium-catalyzed decomposition of diazo carbonyl compounds, provides unique opportunities for the accomplishment of a variety of cycloaddition reactions, in both an intra- and intermolecular sense. These transformations are often highly regio- and diastereoselective, making them extremely powerful tools for synthetic chemistry. This is exemplified in the number of applications of this chemistry to the construction of heterocyclic and natural-product ring systems. Future developments are likely to focus on the enantioselective and combinatorial variants of these reactions. 

In search of a convenient procedure for preparing diazo substrates for the cycloaddition to Cgg, Wudl introduced the base-induced decomposition of tosyl-hydrazones [116]. This procedure allows the in situ generation of the diazo compoimd without the requirement of its purification prior to addition to Cgg. Since they are rapidly trapped by the fullerene, even unstable diazo compounds can be successfully used in the 1,3-dipolar cycloaddition. In a one-pot reaction the tosyUiydrazone is converted into its anion with bases such as sodium methoxide or butylHfhium, which after decomposition readily adds to Cgg (at about 70 °C). This method was first proven to be successful with substrate 142. Some more reactions that indicate the versatility of this procedure are shown in Table 4.4. Reaction of 142 with CgQ under the previously described conditions and subsequent deprotection of the tert-butyl ester leads to [6,6]-phenyl-C5j-butyric acid (PCBA) that can easily be functionalized by esterification or amide-formation [116]. PCBA was used to obtain the already described binaphthyl-dimer (obtained from 149 by twofold addition) in a DCC-coupling reaction [122]. 

Diazo-substituted 1,2,3-triazoles undergo regiospecific dipolar cycloaddition reactions with electron-rich unsaturated compounds. Thus, 4-diazo-5-phenyl-4//-1,2,3-triazole (272, R = Ph) reacts with 1 -morpholinyl-2-nitroethene (273) in CH2CI2 at 20 °C by a net 1,7-cycloaddition and elimination of morpholine to give the product (274) (Scheme 53). 4-Diazo-5-cyano-4/f-1,2,3-triazole (272, R = CN) similarly adds to phenylacetylene to form compound (275) <87JOC5538>. 

Scheme 12 shows synthesis of 1,2,3-thiadiazoles by the Wolff, Hurd-Mori and Pechmann-Nold methods. Pechmann s and Wolffs are the oldest of the methods. The Pechmann-Nold synthesis involves the [3 + 2] cycloaddition of diazo-compounds to isothiocyanates or thiocarbonyl compounds (modified Pechmann synthesis). The use of thiocarbonyl compounds in the [3 + 2] cycloaddition step has broadened the scope of this reaction and made the starting materials more readily accessible. Wolffs method requires the synthesis of diazoketones that are treated with a thionating reagent to produce 1,2,3-thiadiazoles. With the development of new methods of diazotransfer reactions, the diazoketone precursors have become easily attainable and with further attention to the thionating reagents, this reaction is also useful for the synthesis of 1,2,3-thiadiazoles. 

---