Cyclo-addition reactions stereochemistry

Numerous Amaryllidaceae alkaloids include phenanthridine skeletons, one of whose constructive methods constitutes an IEDA strategy. In some cases, the functionality on the dienophile influences the stereochemistry of cyclo addition reactions under high-pressure conditions. For example, the reactions of ( )-buta-l,3-dienyl acetate (6) and the quinolin-2(lH)-ones 7 gave rise to different configurations in the products 8 and 9, depending on the functional groups at the 4-position of 7 (Scheme 3). These results reflect... 

An approach very closely related to that of Woodward and Hoffmann is the so-called Hiickel-Mobius approach 35> based on the rule An +2 electron systems prefer Hiickel geometries and An electron systems prefer Mobius geometries 36>. When no symmetry exists and there is no cyclic orbital array the allowedness or forbiddenness of a reaction can be determined by following the form of the MO s during the reaction 37>. A detailed quantum mechanical study of the stereochemistry of thermal and photo cyclo-addition reactions has been reported38), and a quantum mechanical discussion of the applicability of the Woodward-Hoffmann rules can be found in a paper by George and Ross 39>. 

The stereochemistry of dienes has been found to have a pronounced effect in the concerted cyclo-additions with benzyne 64>65h A concerted disrotatory cyclo-addition of tetrafluorobenzyne, leading for example with trans- (3-methylstyrene to (63, R = Me), is likely and in accord with the conservation of orbital symmetry 68>. However while the electro-cyclic rearrangement of (63, R = H) to (65, R = H) is not allowed, base catalysed prototropic rearrangement is possible. A carbanion (64, R = H) cannot have more than a transient existence in the reaction of tetrafluorobenzyne with styrene because no deuterium incorporation in (65) was detected when either the reaction mixture was quenched with deuterium oxide or when the reaction was conducted in the presence of a ten molar excess of deuteriopentafluorobenzene. 

From an historical point of view, the earliest indication of spin-selective reactivity of carbenes was exhibited by the stereochemistry of the cyclo-propanation reaction. The Skell Hypothesis (Skell and Woodworth, 1956) suggests that a spin-prohibition requires the addition of a triplet carbene to an olefin to occur in at least two steps. In turn, the obligatory formation of an... 

The experimental ratio of ds- to trans-cyclopropane 43 46, i.e. the stereo-specifity of the reaction cannot be considered as a simple indication of singlet or triplet percentage of RaC , since the stereochemistry of the cyclo-addition depends on many factors. Photolysis produces the exdted 5i-state of the diazoalkane 41. This compound can lose nitrogen and form the singlet carbene 42 (So-state). 42 can add directly in a stereospecific manner if ki is large. If, however, intersystem crossing 42 45 (Aisc is large) competes favorably with... 

Treatment of the alcohol ( ) with trifluoromethylsulfonic anhydride (triflic anhydride) at -78 C afforded the ester (1 ) which could be isolated and characterized. We knew from previous experience (2J that sulfonyl esters vicinal to an isopropylidene acetal are relatively stable. The triflate T,) reacted cleanly with potassium azide and 18-crown-6 in dichloromethane at room temperature. The crystalline product [68% overall from (1 )] was not the azide ( ) but the isomeric A -triazoline ( )- Clearly the initially formed azide (18) had undergone intramolecular 1,3-cyclo-addition to the double bond of the unsaturated ester (21- ). The stereochemistry of the triazoline (1 ), determined by proton nmr spectroscopy, showed that the reaction was stereospecific. There are several known examples of this reaction ( ), including one in the carbohydrate series ( ). When the triazoline was treated with sodium ethoxide ( ) the diazoester ( ) was rapidly formed by ring-opening and was isolated in 85% yield, Hydrogenolysis of the diazo group of (M) gave the required pyrrolidine ester ( ) (90%). 

In 1989, the irradiation of (E,E)-2,4-hexadiene S3 sensitized by meso-porphyrin IX dimethyl ester led to the formation of cis-3,6-dimethyl-l,2-dioxene (62), which was the major product detected at — 78 °C in Freon 11 [69]. Endoperoxide 62 was purified under vacuum at 0.75 mmHg, and collected in a trap (98% isolated yield). Dienes that can adopt a cisoid conformation, such as 53 or ( , )-l,4-di phenyl butadiene, were photooxidized by the corresponding endoperoxides in high or quantitative yield in a suprafacial Diels-Alder reaction [60, 70], Dienes that cannot readily adopt cisoid conformations, such as (fc, Z)-2,4-hexadienes and (Z, Z)-2,4-hexadienes, lose their stereochemistry in the singlet oxygen [2 + 4]-cyclo-addition [60], (E,Z)- and (Z,Z)-dienes give a complex mixture of hydroperoxides and aldehydes, which suggests the intervention of intermediate zwitterions or 1,4-diradicals [71]. 

A good example of a cyclo-addition is the Diels-Alder reaction, a [4 + 2] process. The formation of (1) from dimethyl troni, frti s-2,5-hexadienoate and maleic anhydride illustrates very well the high stereospecificity of these processes. The relative stereochemistry of the two methoxycarbonyl groups in... 

The stereochemistry of cheletropic reactions has been discussed in Section 3.3.4. The linear cheletropic reactions usually offer the best scope for orbital overlap and would normally be expected to be the preferred reaction pathways. Generally the extniaon reactions (i.e. the loss of the species Xyz) are more numerous than cheletropic cyclo-additions because the Xyz species is often a molecule of high thermodynamic stability, and in such cases the reactions are essentially uni-directional. ... 

Cycloadditions. In fact, cycloadditions like the Diels-Alder reaction are syn additions wherein the maximum overlap of the interacting n bonds eventually further governs the stereochemistry. In Diels-Alder reaction the 1, 4-addition of the double bond of a dienophile I i.e., 2, 4-cyclo hexene-1, 4-dione) to a conjugated diene II to generate a 6-membered ring, such that up to four new stereocenteres (i.e., chiral centres) may be created simultaneously at one go, as depicted below ... 

Disubstituted-a-bromocyclopropylcarboxamides eliminate HBr when treated with t-BuOK and 18-crown-6 ether in DMSO (dimethyl sulfoxide) at 40 °C, forming a cyclo-propene intermediate that adds an alcohol (nucleophile) at C(3) on the least hindered face of the cyclopropene ring. This is followed by an epimerization at C(l) forming (g) the most stable product, that is, a tra 5 -l,2,2,3-tetrasubstituted cyclopropane. The position of the nucleophile on C(3) is determined by the size of the groups on C(2) and the stereochemistry of the final addition product trans-) is determined by the epimerization at C(l). Two procedures are used for these reactions, with the best yields from the two methods ranging from 63 to 92% with diasteromeric ratios between 9 1 and 46 1 dr. 

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