Stereoselectivity in -cycloadditions

Fig. 18. Stereoselection in cycloaddition or fragmentation. Upper two modes of allowed orbital change. Lower decomposition of the diazene obtained from 3-pyrroline (Lemal and McGregor, 1966). The disrotatory path is allowed the conrotatory path would involve a change in orbital symmetry and is forbidden.

The spin state of the carbene is an essential feature for the stereoselectivity of carbene cycloaddition to double bonds and for the regioselectivity for insertion reactions, the singlet being stereoselective in cycloadditions. Typical carbene reactions are ... 

Typical acyclic olefins of symmetrically substituted types are the esters of maleic and fumaric acids. Though maleimides and maleates are both symmetrical cis-olefins, these two exhibit quite different stereoselectivity in cycloadditions to azomethine ylides. There are relatively limited examples known for the stereoselective cycloadditions of azomethine ylides to symmetrical acyclic olefins. These stereoselective cycloadditions are listed in Table IX, and nonstereoselective reactions in Table X. 

Znl2 was applied successfiilly as Lewis-acid in order to increase the diastereoselectivity of the reaction of a cyclic nitrone with a,P-unsaturated imide derivatives. - It is noteworthy that chiral auxiliaries efficient in numerous other transformations, exhibit only low stereoselection in cycloadditions of nitrones. " ... 

The heptafulvalene (266) gives with TCNE a [12 + 2] adduct (267) only, whereas with dimethyl butynedioate a [4 -i- 2] adduct (268) is formed. A -Ray studies on both adducts show considerable distortions. Peculiar stereoselectivities in cycloadditions to 7-substituted norbornadienes (269) are reported. On reaction with diazoethane (269) (R = Cl, Br, I, or OAc) gives a single 1 1 adduct with endo,anti geometry (270) which reacts further to give a 2 1 adduct (271). However, when R = OBu an exo-adduct is formed and when R = OH a mixture of three products, (270), (271), and the endo,syn-adduct, is produced. The orientation is explained by a n a interaction in (269 R = halogen) between the anti double bond and the... 

The experimental data indicate that the reaction between dipole 1 and dipolaro-philes 4 and 5 is not only regioselective but highly eWo-selective (endo.exo ratio higher than 95 5). Frequently, to account for the stereoselectivity in cycloaddition reactions, other interactions concerning parts of the frontier orbitals, which are not directly involved in forming new bonds, are invoked. These interactions are known as secondary effects and in this case, are clearly stabilizing the endo-transition state in preference to the exo-transtition state. 

The regio- and stereoselectivities of cycloadditions of trifluoroacetonitrile oxide, which is generated m situ by treatment of the tnfluoroacetohydroxamyl bromide etherate with tnethylamine in toluene (equation 31), have been determined in a senes of studies by Tanaka [55, 36, 37, 5 ]. The highly reactive nitnle oxide reacts regioselectively with a variety of activated terminal alkenes and alkynes (equations 32 and 33)... 

The origin of stereoselection in 1,3-dipolar cycloadditions to chiral alkenes 97G167. 

The complex obtained from commercially available chiral a-amino acids (AA) with Cu + ion induces asymmetry in the Diels-Alder reaction of 31 (R = H) with 32. By using 10% Cu(II)-AA (AA = L-abrine) the cycloaddition occurs e/iJo-stereoselectively in 48 h at 0°C with high yield and with acceptable enantioselectivity ee = 1A%). This is the first example of enantioselective Lewis-acid catalysis of an organic reaction in water [9b]. 

Enhanced stereoselectivity in aqueous intramolecular hetero-Diels-Alder cycloaddition of chiral acyinitroso compounds [17c, d, 99]... 

Aqueous cycloaddition using glyco-organic substrates. Facial stereoselectivity in Diels-Alder reactions of a chiral diene derived from D-glyceraldehyde [102]... 

Substituted 1,2,3,4-tetrahydroquinolines (e.g., 61) are formed with high regio- and stereoselectivity in high yield by intermolecular [A+2] cycloadditions of cationic 2-aza-butadienes and various dienophiles <95CC2137,96SL34>. 

The existence of ketenes was established over a hundred years ago, and, in recent years, asymmetric synthesis based on [2 + 2] cycloadditions of ketenes with carbonyl compounds to form chiral p-lactones has been achieved with high yields and high stereoselectivities. In 1994, Miyano et al. reported the use of Ca-symmetric bis(sulfonamides) as ligands of trialkylaluminum complexes to promote the asymmetric [2 + 2] cycloaddition of ketenes with aldehydes. The corresponding oxetanones were obtained in good yields and enantioselectivities... 

Oppolzer and Robbiani have reported highly stereoselective total syntheses of alkaloids such as chelidonine by an intramolecular o-quinodimethene/nitrostyrene-cycloaddition (Scheme S.7).34 (Benzocyclobutane is used as a source of quinodimethene). The high regio- and stereoselectivity in the intramolecular cycloaddition is remarkable a strong preference for transition state, exo-N02, over transition state, emfo-N02, is responsible for the stereoselectivity. 

Pyrazolopyrazolopyrazines can be prepared from a stereoselective dipolar cycloaddition between the alkene group of 284 and diazomethane (Equation 45). Ten equivalents of diazomethane are used in this reaction when only 1 equiv is used, the corresponding methyl ester of the starting material was formed <20020L773>. 

In this paper we review the techniques and applications of microwave irradiation in cycloaddition reactions. This mode ofheating requires not only appropriate micro-wave equipment and glassware, but also a new experimental outlook. A special section will focus on modifications of chemo-, regio- and stereoselectivity which result from use of microwaves, and possible explanations of this behavior will be given. 

Highly stereoselective intramolecular cycloadditions of unsaturated N-substituted azomethine ylides have been conducted under microwave irradiation. Oritani reported that a mixture of the aldehyde 137 and N-methyl- or N-benzylglycine ethyl ester (138) on the surface of silica gel, irradiated under microwaves for 15 min, generated azomethine ylides 139 that subsequently underwent in situ intramolecular cycloadditions to afford the corresponding tricyclic compounds 140 in 79 and 81% yield, respectively (Scheme 9.42) [93],... 

Methylmagnesium bromide (191) exerts a great influence on the stereoselectivity of the reactions between mesitonitrile oxide 10 and the Baylis-Hillman adducts 192. In the absence of a Grignard reagent, a mixture of isomers is formed in which compounds 194 are the main products. The presence of a Grignard reagent reverses the stereoselectivity (Scheme 9.59). When Fisera [107] performed these reactions under microwave irradiation, the reaction times decreased from days to less than 5 min without any loss of stereoselectivity for noncatalyzed cycloadditions, but with a small change in the stereoselectivity in the chelated reactions. 

Intermolecular Cycloaddition at the C=C Double Bond Addition at the C=C double bond is the main type of 1,3-cycloaddition reactions of nitrile oxides. The topic was treated in detail in Reference 157. Several reviews appeared, which are devoted to problems of regio- and stereoselectivity of cycloaddition reactions of nitrile oxides with alkenes. Two of them deal with both inter- and intramolecular reactions (158, 159). Important information on regio-and stereochemistry of intermolecular 1,3-dipolar cycloaddition of nitrile oxides to alkenes was summarized in Reference 160. 

A characteristic feature of contemporary investigations in the held under consideration, is the interest in cycloaddition reactions of nitrile oxides with acetylenes in which properties of the C=C bond are modified by complex formation or by an adjacent metal or metalloid atom. The use of such compounds offers promising synthetic results. In particular, unlike the frequently unselec-tive reactions of 1,3-enynes with 1,3-dipoles, nitrile oxides add chemo-, regio-and stereoselectively to the free double bond of (l,3-enyne)Co2(CO)6 complexes to provide 5-alkynyl-2-oxazoline derivatives in moderate to excellent yield. For example, enyne 215 reacts with in situ generated PhCNO to give 80% yield of isoxazoline 216 (372). 

L-glycero D7d proceed with high stereoselectivity in the cases of D7a, D7c and D7 d. They yield the corresponding adducts (616), (617) and (618) (Scheme 2.270). In the case of the racemate D7c/D7d, the cycloaddition proceeds with a significant kinetic resolution (783). 

At the same time, cycloaddition does not occur when the tether length is increased by one more atom (110). The stereoselectivity of cycloaddition depends on both the tether length (n = 1 or 2) and the configuration of the reacting C,C double bond, which was established in several reactions (110). 

Lewis acids can be efficiently used to increase the reactivity of reactants in cycloaddition reactions. At the same time improved regio- and stereoselectivities can be achieved. 

In cycloaddition reactions involving the acridizinium and isoquino-linium ions, the presence of a positive charge leads with great stereoselectivity to products which could not be predicted by the rule of Alder and Stein. A charge-transfer complex arising from the attraction... 

Bicyclopropylidene (1) does not undergo an intermolecular Diels-Alder reaction with furan and 2-methoxyfuran even under high pressure. Intramolecular cycloadditions of compounds 160 with a furan tethered to bicyclopropylidene, however, were easily brought about under high pressure (10 kbar) and gave cycloadducts 161 stereoselectively in yields ranging from 32 to 95% (Scheme 35) [58]. 

Intramolecular oxime-alkene cycloaddition has been proved to proceed with complete stereoselectivity in carbohydrate derived hydroxylamine 171 (equation 112). 

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