Olefins, reaction with nitrones

Nitrones, reaction with olefins, 46, 130 Nitronium tetrafluoroborate, from nitric add, boron trifluoride, and hydrogen fluoride, 47, 56 in nitration of aromatic rings, 47, 60... 

Although nitrile oxide cycloadditions have been extensively investigated, cycloadditions of silyl nitronates, synthetic equivalent of nitrile oxides in their reactions with olefins, have not received similar attention. Since we found that the initial cycloadducts, hl-silyloxyisoxazolidines, are formed with high degree of stereoselectivity and can be easily transformed into isoxazolines upon treatment with acid or TBAF, intramolecular silylnitronate-olefin cycloadditions (ISOC) have emerged as a superior alternative to their corresponding INOC reactions [43]. Furthermore, adaptability of ISOC reactions to one-pot tandem sequences involving 1,4-addition and ISOC as the key steps has recently been demonstrated [44]. 

Target nitronates (24) are 1,3-dipoles and, consequently, can also be involved in [3+ 2]-cycloaddition reactions with olefins. However, it can a priori be expected that the rate of the second cycloaddition will be substantially lower. 

Other Types of Nitronates in [3 + 2]-Cycloaddition Reactions with Olefins As mentioned above, of all known types of nitronates, only alkyl and silyl nitronates can be involved in [3 + 2]-cycloaddition reactions with olefins. However, furoxans (161), which can also be considered as cyclic nitronates, can react with active dipolarophiles under extreme conditions to give nitrosoacetals (162) (Scheme 3.131, Eq. 1). 

While numerous nitrones react with olefins to form isoxazolidines (l-oxa-2-azacyclo-pentanes) by a formally simple [3 + 2] cycloaddition reaction, there have been few calorimetric investigations of this process. Among these is the reaction of some -substituted... 

The reaction of a-methyl-A-phenyl nitrone (I0g)45 and a-(n-propyl)-V-phenylnitrone (10h)7,4 with styrene gives isoxazolidines of type I. The reaction of nitrone lOh with olefins 7, such as /V-phenylmaleimide4M7 and acenaphthylene,48 gives fused isoxazolidines V. An unstable nitrone (lOi) can be trapped by V-phenylmaleimide to give a cycloadduct V.49... 

The reaction of nitrone 101 with such olefins 5 as propylene, n-hexene, allyl alcohol, styrene, acrylic acid, methyl acrylate, acrylonitrile, and butadiene are all regiospecific to give S-substituted isoxazolidines of type l.77 The reaction with olefins 6 seems to be regio- and stereo-specific thus, nitrone 101 and methyl methacrylate give cycloadduct lilt as the sole product.77 Similarly, 101 and 1 -methyl-1-phenylethylene gives adduct Hit.77 In the reactions with olefins 7 or 8, the stereospecificity is more evident.77,78 The isoxazolidine obtained is always one of the two possible epimers. The reaction of nitrone 101 with trisubstituted olefins is highly stereoselective.64 Some results are summarized in Table III. 

A cycloaddition reaction of the halogen-substituted nitrone (289) with olefins in the presence of AgBp4 provides reactive iminium salts in a regio- and stereo-specific manner. These react with various nucleophiles to give 1,2-oxazine derivatives as shown. In a study of the reactions of P-enamino-esters with carbonyl compounds, WamholF et have isolated a series of acyclic and... 

Olefins, reaction with nitrones, 46,130 cjs-Olefins f lom disubstituted acetylenes by selective reduction v ith modi fied palladium (Lindlar) catalyst, 46,92... 

Nitro compounds have been converted into various cyclic compounds via cycloaddition reactions. In particular, nitroalkenes have proved to be useful in Diels-Alder reactions. Under thermal conditions, they behave as electron-deficient alkenes and react with dienes to yield 3-nitrocy-clohexenes. Nitroalkenes can also act as heterodienes and react with olefins in the presence of Lewis acids to yield cyclic alkyl nitronates, which undergo [3+2] cycloaddition. Nitro compounds are precursors for nitrile oxides, alkyl nitronates, and trialkylsilyl nitronates, which undergo [3+2]cycloaddition reactions. Thus, nitro compounds play important roles in the chemistry of cycloaddition reactions. In this chapter, recent developments of cycloaddition chemistry of nitro compounds and their derivatives are summarized. 

In addition to this, asymmetric 1,3-dipolar cyclization reactions of nitrones with olefins,40 41 catalytic enantioselective cyanation of aldehydes,42 catalytic enantioselective animation,43 and aza-Michael reactions44 have been reported, and high enantioselectivities are observed. 

Scheme 60). 1,3-Dipolar cycloaddition reactions of nitrones with olefins are catalyzed by a chiral Ni11 or Pd11 catalyst.283,284... 

Both C-alkylation products and the corresponding O-alkyl nitronates were detected in the reaction mixture prepared by the reactions of above mentioned salt with primary alkyl halides (Scheme 3.9, Eq. 1). However, isoxazolidines (1) are the main identified products of the reactions with secondary or tertiary alkyl halides. The possible pathway of their formation is shown in Scheme 3.9. Here, the key event is generation of the corresponding olefins from alkyl halides. These olefins can be trapped with O-nitronates that are simultaneously formed in [3 + 2]-cycloaddition reactions. Presumably, these olefins are generated through deprotonation of stabilized cationic intermediates (see Scheme 3.9). 

Synthesis of Six-membered Cyclic Nitronates by the [4 + 2]-cycloaddi-tion Reaction The [4 + 2]-cycloaddition reaction of conjugated nitroalkenes (42) with olefins (43) is the most powerful and widely used method for the synthesis of six-membered cyclic nitronates (35) (Scheme 3.38). 

It should be emphasized that in no case were derivatives of AN containing the C-Si bond detected, although the formation of these compounds in certain silylation reactions as kinetic products cannot be ruled out. In particular, this can be expected for nitronates (51 h,i) (Scheme 3.57) generated in the reactions of silylated dimethylformamides with conjugated nitro olefins (202), because this reaction with other Michael substrates affords products with the C-Si bond. 

For the overwhelming majority of nitronates, the reactions with monosubstituted olefins are characterized by the head-to-head approach of the olefin, that is, the substituent R is present at the C-5 atom. A general conclusion about stereoselectivity of this reaction (endo or exo approach of olefin to the dipole (Scheme 3.127)) cannot be drawn. However, the exo approach prevails for nitronates. (Possible factors responsible for discrimination of the facial approach will be discussed below in Section 3.4.3.5). 

It is of no benefit to analyze, stereoselectivity, the reaction under consideration in the general case. However, it should be noted that the exo approach of olefin is preferable in more cases. As can be seen from Chart 3.11, if olefin molecules contain two different double bonds or a double bond and a triple bond, only one double bond can be selectively involved in the reaction with acyclic nitronates. 

The mechanism of this reaction has not been studied in detail. However, it can be represented as a sequence of reactions. The first reaction is, in fact, [3+ 2]-cycloaddition of olefin to furoxan (161). Under severe conditions, the resulting intermediate A undergoes fragmentation to give five-membered cyclic nitronate B. The latter is involved in the usual addition reaction with an excess of olefin to form isolable bicyclic product (162) (301, 378, 379). 

Main Aspects of Chemistry and Stereochemistry of Cyclic Nitroso Acetals Chemistry of cyclic nitroso acetals or nitrosals (the term was introduced by Prof. Seebach) has attracted interest only after the discovery of the 1,3-dipolar cycloaddition reaction of nitronates with olefins in 1962 by the research group of Prof. Tartakovsky. (Principal data on nitroso acetals up to 1990 were summarized in the review by Rudchenko (395).)... 

Points b to d should be explained in more detail for intermolecular cycloaddition reactions of acyclic nitronates A with monosubstituted olefins. Regioselectivity of the process is determined by the character of the approach of olefin to the dipole (head-to-head or head-to-tail, (Chart 3.16, part (1)). In the former case, the substituent R is bound to the C-5 atom in the latter case, to the C-4 atom. 

Earlier, [3+ 2]-cycloaddition reactions of nitronates have been described in terms of the FMO theory. For example, French researchers studied reactions of olefins containing EWG groups with nitronates by the FMO—INDO method (248, 338b, 419). Recently, more modem methods have been used for calculations of FMO and the potential energy surfaces for several analogous reactions (87, 399,... 

Another attempt to perform a general mechanistic consideration of [3 + 21-cycloaddition reactions of nitronates with olefins has been made relatively recently by Prof. Denmark and coworkers (162) using modern quantum-chemical methods, which allow one to correctly calculate the potential energy surfaces for model substrates. Since these data have been summarized in the recent review (335), it is not necessary to consider them as comprehensively as the study in (337). 

This approach has been comprehensively described in Reference 99 and two monographs 427 and 428. Hence, we will not consider this approach in detail, the more so that selected aspects of [4+ 2]-cycloaddition reactions of conjugated nitroalkenes with olefins were discussed in Section 3.2.1.2.2.2. Many concerned with the synthesis of six-membered cyclic nitronates, many problems of [3+ 2]-cycloaddition of six-membered cyclic nitronates were also considered above (see Sections 3.4.3.1.4 and 3.4.3.3). 

Recently, it has been demonstrated (495) that the [3+ 2]-cycloaddition reactions of 3-bromo-substituted six-membered cyclic nitronates (400), which are constructed from olefins (401) and l-bromo-l-nitro-2,4/-methoxyphenylethylene, with olefins (402) produce 3-vinylisoxazolines (403) or five-membered cyclic nitronates (404) in good yields (Scheme 3.221). 

The nitrone group of the isatogen ring functions as a 1,3-dipolar system and takes part in a number of cycloaddition reactions with substituted olefins and acetylenes. The resulting adducts, in most cases, are not easily isolated and undergo further reactions, particularly nucleophilic addition and/or ring expansion, to give a variety of products. 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

An intramolecular cycloaddition reaction is also a vital feature of Oppolzer s synthesis (Scheme 5).336 Here the cycloaddition reaction occurs on an unsaturated nitrone ester (39) (not isolated). Again, the aldehyde derived from oxidation of the diol (40) gave entirely the ( )-olefin on reaction with crystalline a-methoxy-carbonylethylidenetriphenylphosphorane, which allowed the synthesis of (+)-chanoclavine I (34) to be completed in an overall yield of 14% from indole-4-aldehyde. In contrast, the Horner-Emmons reaction on the aldehyde from... 

CyelaaddiEoitt. Ordinarily, unactivated olefinic double bonds do not undergo Diels-Alder or 1,3-cycloaddition reactions. The outstanding property of a-chloro-nitrones is that, in the presence of silver ions, they undergo cycloaddition reactions with... 

---