Oxygen, singlet, Diels-Alder reaction

In addition, particularly micro-channel processing is demanded here as the reaction is dangerous owing to the explosive nature of the endoperoxide formed as intermediate. This handling of explosive or toxic compounds for Diels-Alder reactions is also described in [21]. Owing to the use of only small volumes, the hazardous potential can be substantially minimized. This was exemplarily shown for the addition of singlet oxygen. 

Chiral oxazolidine compounds have also been used as chiral auxiliaries for asymmetric Diels-Alder reactions. Adam et al.8 demonstrated the cycloaddition of optically active 2,3-dimethyl oxazolidine derivatives with singlet oxygen. As shown in Scheme 5-9, the reaction of chiral substrate 39 with singlet oxygen provides product 40 in high diastereomeric ratio. 

Scheme 6.85 Formation of l,2-dioxa-3,4-cyclohexadienes (415) by addition of singlet oxygen to conjugated enynes and retrograde dehydro Diels-Alder reaction of415.

Wasserman and Keehn ") have also carried out the photosensitized auto-oxidation of anti-[2.2](l,4)naphthalenophane (34A). Irradiation of anti-34 in methanol and simultaneous reaction with singlet oxygen affords the oxidation product 127 in 20% yield. The primary step in the reaction is assumed to be formation of a peroxide (128) whose geometry permits an intra-annular Diels—Alder reaction as second step methanol-ysis then leads to 127 which was isolated. 

Danishefsky dienes [98] cycloadd to Cjq in refluxing toluene or benzene [5, 38, 99-101]. The diene 103 adds in 60% yield to Cjq to give the desilylated ketone 104 [5,101]. Acid-catalyzed methanol elimination then furnishes the enone 105 in 82% yield (Scheme 4.17). As already described, this enone can be reduced by DIBAL-H to the corresponding alcohol for further functionalization. The same a,(3-un-saturated alcohol can also be obtained in better yield by Diels-Alder reaction of Cg0 with butadiene, followed by oxidation with singlet oxygen to the allylic hydroperoxide and PPhj reduction to the desired alcohol [101]. This sequence yields the allylic alcohol in 53%, starting from Cjq without the need of isolating intermediates. 

Due to the formal analogy to the classical Diels-Alder reaction, the mechanism of cyclic peroxide formation through cycloadditions of 1,3-dienes with O2 was considered for a long time to involve a concerted suprafacial [4 4- 2]-cycloaddition of a super-dienophile, namely a singlet oxygen to 1,3-dienic system In such a case, the concerted or almost concerted cycloaddition must be c -stereospecific and the stereochemical properties of the diene must be reflected in the three-dimensional structure of cyclic peroxide according to well-defined rules. Indeed, it was found in early stereochemical... 

As in 4-9, it is not the ground-state oxygen (the triplet), that reacts, but the excited singlet state,782 so the reaction is actually a Diels-Alder reaction (see 5-47) with singlet oxygen as dienophile 783... 

Tetradehydrodianthracene undergoes 4 + 2-cycloaddition with electron-deficient dienes such as 1,2,4,5-tetrazines.263 The Diels-Alder reactions of [3.3 ortho-anthracenophanes witli A-(p-nitro, chloro, or methoxy-substituted phenyl)malehnides yield approximately equal quantities of inside and outside adducts.264 The photooxidation of bulky water-soluble 1,4-disubstituted naphthalenes with singlet oxygen yields both the expected 1,4- and the unexpected 5,8-endoperoxides.265... 

Review. The varied uses of singlet oxygen in organic syntheses have been reviewed (70 references). The best known are the ene reaction of alkenes, which results in an allylic hydroperoxide, and the Diels-Alder reaction with 1,3-dienes to form 1,4-endoperoxides. 

The total synthesis proceeds in >10 steps on solid phase and includes various transformations, including an asymmetric Diels-Alder reaction, oxidation with singlet oxygen, and olefin metathesis. This synthesis sequence is among the most advanced and demanding solid-phase syntheses developed so far for chemical genomics experiments. It demonstrates that the total synthesis of complex natural products in multi-step sequences on solid phase is feasible. 

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]. 

Owing to the inherent lack of stereochemical features in the singlet oxygen molecule, stereoselectivity is directed by the substrate. In view of the formal analogy to the classical Diels-Alder reaction, a stereochemical requirement imposed by the concerted mechanism is that the configuration of the diene system is retained in the cycloadduct, as occurs for diene... 

It was suggested27-288 that all these compounds would be generated from the unstable endoperoxide (20) (originated from a Diels-Alder reaction of singlet oxygen with the dienio pyrrole system) through various paths, as indicated in Scheme I. 

The tellurophenopyridazine (M) decomposed under the influence of light and oxygen to 4,5-dibenz-oylpyridazine (66) via the peroxide (65) derived from Diels-Alder reaction of singlet oxygen widi (64 Scheme 24). Tellurapyrylium dyes such as (67) react with singlet oxygen within a few seconds to give dihydroxides (68 Scheme 25). ... 

DIELS-ALDER REACTIONS Bis(triphen-ylphosphine)dicyanonickel(O). 2-Chloro-acrylonitrilc. 2-Chloroacrylyl chloride. Cyclopropcnc. Dichloromaleic anhydride. Dicyanoacctylenc. Indanocyclone. Oxygen, singlet. 4-Phcnyl-l, 2,4-triazoline-3,5-dione. 

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