Epoxides Chemoselective synthesis

The current research areas with ruthenium chemistry include the effective asymmetric hydrogenation of other substrates such as imines and epoxides, the synthesis of more chemoselective and enantioselective catalysts, COz hydrogenation and utilization, new methods for recovering and recycling homogeneous catalysts, new solvent systems, catalysis in two or three phases, and the replace-... 

During the synthesis of such compounds, the epoxide is often installed at an early stage for example, dihydroquinoline 31 (Scheme 18) is readily epoxidized with MCPBA, and subsequent formation of the bis-alkynyl iodides followed by bis-intramolecular Stille coupling occurs with complete chemoselectivity <2006ARK261>. 

Transesterification can be used to cleave the acyl group from an ester to release the alcohol. The mildness of the reaction conditions enables chemoselective transformation. A siloxy group /S to a ketone group was not eliminated (Eq. 225) [524], and formation of an epoxide from the unprotected bromohydrin did not occur (Eq. 226) [525]. Similarly, in the synthesis of an avermectin derivative, delactonization was carried out by the titanium-based method as shown in Eq. (227) [526]. 

Alane (AIH3) and its derivatives have also been utilized in the reduction of carboxylic acids to primary alcohols. It rapidly reduces aldehydes, ketones, acid chlorides, lactones, esters, carboxylic acids and salts, tertiary amides, nitriles and epoxides. In contrast, nitro compounds and alkenes are slow to react. AIH3 is particularly useful for the chemoselective reduction of carboxylic acids containing halogen or nitro substituents, to produce the corresponding primary alcohols. DIBAL-H reduces aliphatic or aromatic carboxylic acids to produce either aldehydes (-75 °C) or primary alcohols (25 C) Aminoalu-minum hydrides are less reactive reagents and are superior for aldehyde synthesis. ... 

During the total synthesis of (+)-phyllanthocin, A.B. Smith and co-workers installed the epoxide functionality chemo-and stereoselectively at the C7 carbonyl group of the intermediate diketone by using dimethylsulfoxonium-methylide in a 1 1 solvent mixture of DMSO-THF at 0 °C. The success of this chemoselective methylenation was attributed to the two a-alkoxy substituents, which render the C7 carbonyl group much more electrophilic than Cl 0. 

Lithium tri-fert-Butoxyaluminohydride is a bulky chemo- and stereoselective hydride reducing agent. Aldehydes are reduced chemoselectively in the presence of ketones and esters at low temperature. Ethers acetals, epoxides, chlorides, bromides, and nitro compounds are unaffected by this reagent. Reviews (a) Seyden-Penne, J. Reductions by the Alumino- and Borohydrides in Organic Synthesis Wiley-VCH NewYork, 1997, 2" edition, (b) Malek, J. Org. React. 1985, 34, 1-317. 

The synthesis was planned around the reaction of a specific enolate of ester 136 with the epoxide 137. This reaction was expected to give mainly trans 138 and is chemoselective both because of the usual enolate problem and because 137 contains a terminal alkyne. The lithium enolate was too basic and the aluminium enolate was used instead. The reaction gave an 85 15 mixture of trans and cis 138 and also an 85 15 mixture of trans and cis 139 after cyclisation. Dihydroxylation by osmylation gave a mixture of diols 140 this was deliberate so that they could determine the stereochemistry at C-2 . To the surprise of the chemists, natural rubrynolide was identical to one of the minor (i.e. cis) diols in the 15% part of the mixture. Careful NMR analysis showed that it was 135a. 

The alkene that is attacked is an enol ether and is much more nucleophilic than the other simple alkene. Similarly nucleophilic reagents attack only alkenes that are conjugated with an electron-withdrawing group. Chemoselective epoxidation is usually straightforward. The peracid epoxidation is stereospeciiic the alkene 22 is E and so the epoxide 23 is trans (or anti). The other epoxidation is stereoselective as it is a two stage process and gives the more stable trans (or anti) epoxide 21 by choice. There is an example later in the synthesis of vemolepin. 

There are two problems of chemoselectivity in this synthesis. How do we cleave one double bond in (22) without cleaving the other, and how do we control the cyclisation of (20) Epoxidation of (22) selectively attacks the more substituted double bond to give (23) which can be opened to (20) in two steps.The cyclisation of (20) can be controlled by conditions strong base gives (19) by thermodynamic control and weak base enolises only the aldehyde (kinetic control) to give (21). 

The Rubottom oxidation has found widespread application in organic synthesis. A few recent examples of the use of this methodology for the construction of complex molecules are described below. As noted above, the stereoselectivity in these reactions is usually controlled by steric effects, which dictate the face-selectivity of the epoxidation step. The chemoselectivity is generally controlled by electronic effects, as the electrophilic oxidants react more rapidly with the electron-rich enol ether than with other double bonds in the substrate. 

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