Carbonyl cycloaddition with heteroatomic

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]. 

In addition to olefins, carbon heteroatom multiple bonds can also participate in the cycloaddition with various carbonyl ylides (Scheme 4.28). 

Cycloadditions of carbonyl ylides, generated from the reaction of carbenes with heteroatom lone pairs have been reviewed (91ACR22,91CRV263). 

The catalytic hetero-Diels—Alder reaction is also of particular interest, since it allows a convenient access to prepare six-membered heterocycles. The hetero-Diels—Alder reaction is classified into two groups, as shown in Scheme 136 (a) [4 + 2]-cycloaddition of 1,3-dienes with a carbon-heteroatom or heteroatom-heteroatom double bond198 and (b) [4 + 2]-cycloaddition of a,/Tunsaturated carbonyl compounds with olefins.199... 

At the present, our studies with alkynylcarbene complexes of Cr and W suggest that their cycloadditions with electron-rich olefins follow, mainly, a concerted [2+2] pathway by activation of the triple bond[6], whereas, the intramolecular Co-induced carbonylative cycloaddition of the corresponding allylamino complexes seems to be facilitated by the alternative influence of the metal on the heteroatom side. A strict control of the stereochemistry in these reactions has been observed making these complexes valuable auxiliaries in organic synthesis. Efforts to broaden the scope of application are under way. 

The chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

Carbon-heteroatom multiple bonds can also participate in cycloaddition reactions with carbonyl ylides leading to the synthesis of interesting heterocycles (Scheme 4.18). 

This and other similar cycloadditions, however, when unactivated hydrocarbons without heteroatom substituents participate in Diels-Alder reaction, are rarely efficient, requiring forcing conditions (high temperature, high pressure, prolonged reaction time) and giving the addition product in low yield. Diels-Alder reactions work well if electron-poor dienophiles (a, p-un saturated carbonyl compounds, esters, nitriles, nitro compounds, etc.) react with electron-rich dienes. For example, compared to the reaction in Eq. (6.86), 1,3-butadiene reacts with acrolein at 100°C to give formy 1-3-cyclohexene in 100% yield. 

Largely because of the widespread interest in cycloadditions, a number of syntheses of dihydropyrans have been developed involving the interaction of four and two atom fragments. Both variations on the [4 + 2] cycloaddition are successful either the diene or the dienophile may be the source of the heteroatom (Scheme 43). A review of heterodiene syntheses with unsaturated carbonyl compounds contains comprehensive lists of dihydropyrans (75CRV651). 

The Regioselectivity ofHetero Diels-Alder Reactions. In a few cases, carbonyl, nitrosyl, cyano, and other double bonds with one or more electronegative heteroatoms have acted as dienophiles in Diels-Alder reactions. The carbonyl group has a HOMO and a LUMO as shown in Fig. 1.51. The energies of both orbitals are relatively low, and most of their Diels-Alder reactions will therefore be guided by the interaction between the HOMO of the diene and the LUMO of the carbonyl compound. This explains the regioselectivity in the cycloaddition of dimethylbutadiene 6.176 and formaldehyde, and between 1-substitituted butadienes 6.177 and nitrosobenzenes. 

Although the early examples of the 4ir participation of heterodienes in [4 + 2] cycloaddition reactions describe their reactions widi electron-deficient aJkenes, e.g. the thermal dimerization of a,3 unsaturated carbonyl compounds, the introduction of one or more heteroatoms into the 1,3-butadiene framewoiic does convey electrophilic character to the heterodiene. Consequently, such systems may be expected to participate preferentially in LUMOdiene-controlled Diels-Alder reactions with electron-rich, strained, or simple alkene and alkyne dienophiles. The complementary substitution of the heterodiene with one or more electron-withdrawing substituents further lowers the heterodiene Elumo, accelerates the rate of heterodiene participation in the LUMOdioie-conn-olled Diels-Alder reaction, and enhances the observed regioselectivity of the [4 + 2] cycloaddition reaction. ... 

Dipoles always contain a heteroatom as the central atom of the trio, either sp or sp hybridised. Amongst other examples, cycloadditions have been demonstrated with azides (N=N -N-R), nitrile oxides (R-C N -0 ) and nitrile ylides (R-C N -C Ra), where the central atom is sp-hybridised lutrogen, and with nitrones (R2C=N" (R)-0 ), carbonyl ylides (R2C=0 -C R2) and azomethine ylides (R2C=N (R)-C R2), where the central atom is sp hybridised. 

The hetero-cycloaddition of C—C unsaturated bonds with C=0 and C=N bonds constructs heterocycles through concerted formation of both a carbon—carbon and a carbon—heteroatom bond.177 The hetero-Pau-son—Khand reaction using CO, alkyne, carbonyl group is a typical hetero-[2 + 2 + 1]-cycloaddition, giving five-membered heterocycles. Hetero-Diels— Alder reaction, that is, hetero-[4 + 2]-addition, produces six-membered heterocycles. 

Alkylidenephosphoranes (a.La. phosphorus yUdes) of the general formula Ph3P=CR R (1) have been frequently used in key steps of heterocycle synthesis. Numerous papers and review articles [1-4] testify their versatility in the construction of rings with sizes ranging from three to well beyond 20 and with virtually any number, kind and distribution of heteroatoms. The Wittig alkenation of carbonyl groups is doubtless the most common, though not the only, reaction of P-ylides that has been employed in the cyclization of bifunctional precursors. The cycloaddition between acyl ylides (1 = H,... 

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