Reduction of an epoxide

Regtosdective reduction of an epoxide. A key step in a short synthesis of (+)-muscarine (6) from the dibenzoate of 2,5-anhydro-D-glucitol (1) involves reduction of the epoxide 2. Use of SMEAH gives a 12 1 mixture of 3 and 4 use or LiAlH4 gives the same diols in the ratio 3 1. ... 

The paper reports a selective reduction of an epoxide in the presence of a ketone group (equation I). 

In the field of natural product it is occasionally observed that reduction of an epoxide derivative leads to the sterically lees-favored product—e g. to a secondary instead of the expected tertiary alcohol. It is of oourse impossible to find every example of this occurrence in the literature, but the cases shown below >7M-UBS suffice to illustrate this important phenomenon (Eqs. 898 and 308). In all probability these abnormal cleavages can be accounted for by assuming hydroxyl... 

Alkyl phenyl telluriums, obtained from alkyl halides and arenetellurolates, are reduced by triphenyl tin hydride to alkanes under mild conditions1. The alkanes were obtained in yields ranging from 71 to 95%. 5oe-Cholestan-3a-yl phenyl tellurium was similarly reduced to 5 a-cholestane in 89% yield. The reaction appears to be highly chemoselective as indicated by the reduction of an epoxide to an alcohol in the presence of a carbonyl group1. 

Reduction of an Epoxide to an Alcohol (Section 11.9B) Regioselective hydride ion transfer from lithium aluminum hydride to the less hindered carbon of the epoxide gives... 

Lynch JE, Choi WB, ChurchiU HRO, Volante RP, Reamer RA, Ball RG. Asymmetric synthesis of CDP840 by Jacobsen epoxidation. An unusual syn selective reduction of an epoxide. J. Org. Chem. 1997 62(26) 9223-9228. 

The poor stability on exposure to air and water, particularly at elevated temperatures, which results in a reduction in conductivity, also poses problems. In the case of polypyrrole it has been found that conductivity can, however, be maintained either by the drastic measure of storing under the protective layer of the inert gas argon or embedding polypyrrole film in a matrix of an epoxide resin-glass-fibre composite. 

Diols can be prepared either by direct hydroxylation of an alkene with 0s04 followed by reduction with NaHSOj or by acid-catalyzed hydrolysis of an epoxide (Section 7.8). The 0s04 reaction occurs with syn stereochemistry to give a cis diol, and epoxide opening occurs with anti stereochemistry to give a trans diol. 

The principal side reaction to epoxide coupling is hydrolysis. Particularly at acid pH values, the epoxide ring can hydrolyze to form adjacent hydroxyls. This diol can be oxidized with periodate to create a terminal aldehyde residue with loss of one molecule of formaldehyde (Chapter 1, Section 4.4). The aldehyde then can be used in reductive amination reactions. The reaction of an epoxide group with an ammonium ion generates a terminal primary amine group that also can be used for further derivatization. 

The combination of (EtO)3SiH/CsF (or KF) provides a convenient reagent for the reduction of esters to alcohols.76,80,83 The yields are in the 70% range. Potassium tetraethoxyhydridosilicate also reduces esters in moderate yields.288 The combination of PM HS/CpiTiCE/n-BuLi reduces esters in high yields even in the presence of an epoxide and a trisubstituted olefin (Eq. 140).289 The reagent combination can reduce a methyl ester in the presence of a tert-butyl ester (Eq. 141).290... 

I he procedure described is patterned after the method suggested by Vogel, Schubart, and Boll, and it illustrates a general method of preparing oxepins. Furthermore, the first step represents an example of the Birch reduction of an aromatic hydroearl )on. The second step is illustrative of the selective epoxidation of a diene system. ... 

An example of a whole-cell process is the two-step synthesis of an enantiopure epoxide by asymmetric reduction of an a-chloro ketone (Scheme 6.4), catalyzed by recombinant whole cells of an Escherichia coli sp. overexpressing an (R)-KRED from Lactobacillus kefir and GDH from Thermoplasma acidophilum, to the corresponding chlorohydrin, followed by non-enzymatic base-catalyzed ring closure to the epoxide [17]. 

Aldol products do not have to come from an aldol condensation. In another example of catalysis by a small organic molecule, Jeffrey Bode of UC Santa Barbara reports (J- Am. Chem. Soc. 2004,126, 8126) that the thioazolium salt 7 effects the rearrangement of an epoxy aldehyde such as 6 to the aldol product 8. This is a net oxidation of the aldehyde, and reduction of the epoxide. As epoxy aldehydes such as 6 are readily available by Sharpless asymmetric epoxidation, this should be a general route to enantiomerically-aldol products. The rearrangement also works with an aziridine aldehyde such as 9, to give the ff-amino ester 10. 

Catalytic reduction of steroid epoxides received considerable attention before the development of complex metal hydride reducing agents. Hydrogenation of 3 ,4a-epoxy steroids over platinum in acetic acid (Eq. 360), for example, gives rise to a mixture of 3 -hydroxy and 3 -acetoxy steroids.Reductive cleavage thus occur in the same direction as with lithium aluminium hydride in this particular instance —t.r. it gives an axis alcohol. 

The second of the three types of qualitative teste mentioned above involves acid-catalyzcd cleavage of an epoxide with periodic acid.38 The IOf ion then oxidizes the resulting 1,2-diol in the usual manner, while itself undergoing reduction to iodato. In the presence of AgH ion, the gradual formation of iodate will be marked by precipitation of silver iodate (Eq. 983). An obvious drawback to this procedure is that any other functional groups capable of reducing IOf iou will interfere with epoxide detection. 

Epoxide opening gives the needed trans isomer. Reduction of an alkylated cyclohexanone gives mostly the cis. 

An elegant stereospecific synthesis of (+)-muscarine (2 R = NMe3) has been achieved by reduction of the epoxide (1) (easily produced from D-mannitol) with sodium bis-(2-methoxyethoxy)aluminium hydride to give predominantly (2 R = OH) on monotosylation, this forms (2 R = OTs). Chromatographic resolution and treatment with trimethylamine yielded (-l-)-muscarine (2 R = NMea).1... 

Hydride Reduction of a Carbonyl Group 454 Reaction of a Tertiary Alcohol with HBr(S[ 1) 480 Reaction of a Primary Alcohol with HBr (SN2) 480 Reaction of Alcohols with PBr3 485 (Review) Acid-Catalyzed Dehydration of an Alcohol 487 The Pinacol Rearrangement 495 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 649 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 650... 

The trans allylic alcohol needed to make this compound was made using one of the methods we introduced in Chapter 3i reduction of an alkynyl alcohol with LiAlEL]. Here is the full synthesis alkylation of an ester enolate with prenyl bromide gives a new ester, which itself is turned into an alkylating agent by reduction and tosylation. The alkyne is introduced as its lithium derivative with the alcohol protected as a THP acetal. Hydrolysis of the acetal with aqueous acid gives the hydroxy-alkyne needed for reduction to the E double bond, which is then epoxidized. 

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