Epoxide intramolecular opening

The asymmetric lithiation/substitution of Af-Boc-Af-(3-chloropropyl)-2-alkenylamines 395 by w-BuLi/(—)-sparteine (11) provides (5 )-Af-Boc-2-(alken-l-yl)pyrrolidines 397 via the allyllithium-sparteine complexes 396 (equation 106) . Similarly, the piperidine corresponding to 397 was obtained from the Af-(4-chlorobutyl)amine. Intramolecular epoxide openings gave rise to enantioenriched pyrrolidinols. Beak and coworkers conclude from further experiments that an asymmetric deprotonation takes place, but it is followed by a rapid epimerization a kinetic resolution in favour of the observed stereoisomer concludes the cyclization step. 

Silylation followed by selenium dioxide oxidation converted 13 into 14. Epoxidation of the derived TES ether proceeded by addition of oxygen to the more open face of the alkene, leading to 15. Ozonolysis followed by diastereoselective one-carbon homologation provided 17. This set the stage for intramolecular epoxide opening by the carboxylate, to give 2, in which all of the stereogenic centers of tetrodotoxin have been established. 

Cyclization of hydroxy epoxides to tetrahydrofurans or tetrahydropy-rans.1 CSA is the most efficient and convenient catalyst for this intramolecular epoxide opening. The cyclization of trans-epoxides is particularly useful because it can lead to either 5- or 6-membered cyclic ethers as shown in equation (I) and (II). 

Addition of the reagent derived from lithiation of optically active iodide 66 to the previously prepared, racemic ketone a-44 gave the expected 1 1 mixture of diastereomeric adducts 67 and 68. In contrast to our earlier model studies, intramolecular epoxide opening proceeded to completion without the addition of a Lewis acid (Figure 20). While diastereomers 67 and 68 were readily separable by chromatography, an unequivocal determination of relative stereochemistry by spectroscopic methods was not possible. Each isomer was therefore carried... 

The catalytic asymmetric synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine was developed by J. Lee et al. using an intramolecular epoxide opening 5-exo-tet) followed by ring expansion. The acyclic c/s-epoxide substrate was prepared in good yield and in greater than 94% ee by the Jacobsen epoxidation from the corresponding (Z)-alkene. ... 

Cyclic phosphonate analogues of PMEA (36) have been obtained after stereoselective cyclisation of an acyclic phosphonyl intermediate to the phos-phonyltetrahydrofuran nucleoside derivative. A series of cyclopropylphos-phonate analogues (37) has been synthesised stereoselectively via intramolecular epoxide opening reaction of y,5-epoxyalkanephosphonates with subsequent Mitsunobu coupling reaction to purine bases. Acyclic phosphonate derivatives of thymine (38-43) have been prepared and evaluated as multisubstrate analogue inhibitors of Escherichia coli thymidine phosphor-... 

While obviously natural enediynes 2-4 behave in the same way, in dynemicin the cascade of events is different. However, this molecule also displays a delivery unit (the anthraquinone), a safety catch (the epoxide) and a trigger (the quinone). Bioreduction of the quinone unleashes two lone pairs (one on the nitrogen and one on the upper hydroquinone oxygen) which bring about intramolecular epoxide opening. ... 

This synthetic approach to quinine and its diastereomers is based on a simultaneous formation of a quinuclidine ring and a hydroxyl group by intramolecular epoxide opening with the piperidine nitrogen. This process results in an inversion at C-8. 

Epoxide opening reactions have also been employed in the synthesis of southern half fragments. For example, the synthesis of optically active model system 82 by Barret and Capps [125] includes addition of a lithio-dithiane to ketone 81 and a subsequent intramolecular epoxide opening as key steps. Chirality was introduced in this case by a known yeast mediated reduction of ethyl 2-oxocyclohexane-carboxylate to afford optically active 80. 

The fused tricyclic system of hirsutellones A-C, embodied by 125, was generated by a concise and stereoselective intramolecular epoxide opening/Diels-Alder cascade reaction of epoxide... 

Seven- and Eight-membered Rings.- A new total synthesis of zoa-patanol has been published which uses as the key step an acid-catalysed intramolecular epoxide opening reaction (see Scheme... 

Caryophyllane-2,6-a- and -P-oxides have been prepared from (— )-isocaryophyll-ene. Intramolecular epoxide opening has been studied for seven diols prepared by oxidation of the exocyclic double-bond of caryophyllene and isocaryophyllene epoxides. ... 

A diastereoselective synthesis of a-tocopherol 87 features a Shi epoxidation with ent-2 and a carefully controlled intramolecular epoxide opening cyclization for the formation of the chromanol ring. Good conversion and high enantioselectivity have been achieved in the epoxidation step. ... 

Table 5.2 Intramolecular epoxIde-openIng reactions of epoxy aryl halides using phosphine-based active copper.

Scheme 5.1 Intramolecular epoxide opening to afford a bicyclic product.

Typical Procedure for Intramolecular Epoxide-Opening Reaction... 

In the preparation of 4 thiopentofuranoside (22) (Scheme 3) from 3-hydroxyptopanal, the carbon-chain was first extended and functionalized by Wittig and Sharpless methodology. The reaction of the resulting 3,4-anhydro-2-deoxypentose diethyl acetal (19) with CSj was accompanied by intramolecular epoxide opening to give the cyclic xanthate (20) which, after... 

Closing this section on intramolecular epoxide opening, we are also including one case of radical-induced ring fission that may serve very well for the construction of highly substituted cyclopentanes [44]. 

Scheme 27 Stereochemical consequences of intramolecular epoxide opening...

Additional investigations of chiral salen metal complexes revealed that the corresponding Co-salen complex 142 promotes intramolecular epoxide openings with alcohols in an enantioselective fashion [126]. This approach was elegantly utilized by Danishefsky in an asymmetric total synthesis of the neurotrophic growth factor merrilactone A (144 Scheme 9.17) [127]. 

Figure 8 Ether formation by intramolecular epoxide opening depends on the chain length.

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