Enal epoxidation

Fig. 15 Amines used in conjunction with TRIP for the epoxidation of enones and enals...

Z)-awh-4-Hydroxy-l-aIkenyl carbamates 363, when subjected to substrate-directed, vanadyl-catalysed epoxidation , lead to diastereomerically pure epoxides of type 364 (equation 99)247,252,269 qqjggg epoxides are highly reactive in the presence of Lewis or Brpnsted acids to form -hydroxylactol ethers 366 in some cases the intermediate lactol carbamates 365 could be isolated . However, most epoxides 364 survive purification by silica gel chromatography . The asymmetric homoaldol reaction, coupled with directed epoxidation, and solvolysis rapidly leads to high stereochemical complexity. Some examples are collected in equation 99. The furanosides 368 and 370, readily available from (/f)-0-benzyl lactaldehyde via the corresponding enol carbamates 367 and 369, respectively, have been employed in a short synthesis of the key intermediates of the Kinoshita rifamycin S synthesis . 1,5-Dienyl carbamates such as 371, obtained from 2-substituted enals, provide a facile access to branched carbohydrate analogues . 

PCC reacts with tertiary allylic alcohols, forming an intermediate chromate ester that evolves giving a conjugated enone or enal. Sometimes, the isomeric chromate ester produces the epoxidation of the alkene, giving an epoxy alcohol that can be further oxidized to an epoxy ketone. 

To avoid the C4a-C5 epoxide issue, a new route to the keto enal "73-a" was pursued [Scheme 15]. Triol 71 could be attained via LAH reduction of epoxy diol 49, and acylation of 71 would lead to the acetate 72 whose stereochemistry was assigned by X-ray analysis. The subsequent TPAP oxidation of 72 followed by deacylation and PCC oxidation led to the keto-enal "73-a" in 73% overall yield. 

Enals vinyl silyl ketones.1 The anion of I reacts smoothly with va rious electrophiles (alkyl halides, epoxides, carbonyl compounds). The products are converted to (E)-enals by oxidation with 30% H202. 

Chiral asymmetric epoxidations have been intensively investigated due to the fundamental importance of epoxides in organic chemistry [69, 70], Nevertheless, catalytic asymmetric Lewis acid epoxidation of a,/i-unsaturated aldehydes remains a challenge to chemists. Recently, Jorgensen and co-workers developed the first asymmetric approach to epoxides of enals, in which chiral pyrrolidine 11 was used as catalyst and H2O2 as oxidant, thus following the concept of iminium catalysis (Scheme 3.9) [71-73]. Importantly, reaction conditions are tolerant to a variety of functionalities and this chemical transformation proceeds in different solvents, with no loss of enantioselectivity. (For experimental details see Chapter 14.13.1). 

General Procedure for Chiral Amine-Catalyzed Epoxidations of Enals with H202 [50] (p. 104)... 

Deoxygenation. This substance reduces epoxides to alkenes in 85-95% yield, generally with retention of configuration, particularly in reduction of trans-tpox-ides. This reduction proceeds more readily than that of carbonyl or ester groups, but a,(3-enals are coupled reductively by 1 at 25° to diallylic ethers. 

Epoxidation of enones, enals, a,unsaturated esters.1 Epoxidation of these substrates is generally effected with alkaline hydrogen peroxide, but can also be effected with this new reagent with high stereoselectivity. 

In a short known reaction sequence, enal 250 was obtained from commercially available material 184). With methylamine and magnesium sulfate imine 251 was formed and combined with acyl chloride 252 185) (>4 steps). The use of low temperatures for this acylation led exclusively to the less substituted dienamide 253. The desired basic skeleton of dendrobine 254 was obtained by cyclizing 253 at 180°C in an acceptable 50% yield, Adduct 254 was accompanied by small amounts of the exo-adduct. Epoxidation led exclusively to exo-epoxide 255, which by means of trimethylsilyltriflate was converted into the allylic silyl ether. Acid treatment liberated the hydroxy group and subsequent oxidation of alcohol 256 led to enone 163, an intermediate of Inubushi s dendrobine synthesis and thus concluded this formal synthesis. The intermediate 163 was obtained from commercially not available materials in seven steps in 22.5% overall yield. To reach ( )-dendrobine according to Inubushi et al. would afford six additional steps, reducing the overall yield to 0.4% without including the preparation of the starting materials from commercially available compounds. 

An oxidative rearrangement took place during the MCPBA epoxidation of the secondary allylic alcohol auraptenol, leading to the enal shown in equation (20). This reaction has been used in an approach to casegravol and in a synthesis of amottinin. The reason why the intermediate epoxy alcohol undergoes rearrangement in this case is not known beyond the possibility that the m-chlorobenzoic acid by-product could act as an acidic catalyst. 

Treatment of 1,1-disubstituted epoxides of the gibberellin family with sulfuiyl chloride results in the formation of the corresponding a,3-enal in good yield, as shown in equation (31). Four examples were reported in which alcohols, esters, lactones and sdkenes survive. The postulated mechanism involves an electrophilic opening of the epoxide with elimination, followed by oxidation of the primary chlorosulfate ester. A steroidal 3-spirooxirane also undergoes this reaction, but the yield is poor and several products are obtained, suggesting that the overall scope of this reaction may be limited. 

A polymeric binaphthyl zinc complex has been used for related epoxidation reactions <1999JOC8149>.A bimetallic samarium-based Lewis acid complex catalyzes the nucleophilic epoxidation of unsaturated carbonyl compounds very efficiently <2002JA14544>. The use of amino acids has organocatalysts for asymmetric epoxidations of enones and enals has been investigated <2005OL2579, 2005JA6964>. 

The chiral titanated bislactim ether 104 undergoes 1,2-addition to a,(3-unsaturated aldehydes. With enal 105, it gives adduct 106, the epoxidation and subsequent hydrolysis of which forms the branched-chain amino-acid derivative 107 [84] (Scheme 13.42). 

After reduction of the enal with diisobutylaluminium hydride, the Wittig olefination of D-glycer-aldehyde acetonide (7 )-24 with Ph3P=CHCHO gives the ( )-allylic alcohol 129. The Katsuki-Sharpless enantioselective epoxidation [89] applied to 129 allows the preparation of D-arabinitol (= D-lyxitol) and ribitol, a meso alditol (Scheme 13.47). Similarly, Wittig olefination of R)-2A with Ph3P=CHCH(OEt)2, followed by acidic hydrolysis of the diethyl acetal and subsequent reduction of the enal with diisobutylaluminium hydride, provides the (Z)-allylic alcohol 130. Diastereoselective epoxidation and hydrolysis leads to D-arabinitol or xylitol, another meso alditol [90a]. 

Xylitol has been derived from the product of photo-oxidation of cyclopentadiene [204], (Z)-(4RS)-4,5-epoxypent-2-enal (Scheme 13.105). Chemoselective reduction of the formyl group gives cis-hydroxyepoxypentene 448, which is directly acetylated into 449. Treatment of 449 with tetrabutylammonium acetate in AC2O opens the epoxide with formation of 450. De-O-acetylation gives 451, the epoxidation of which with p-nitroperbenzoic acid generates a 3 7 mixture of epoxides 452 and 453, isolated as peracetates. The major epoxide 453 is hydrolyzed into xylitol via the orthoester 454. 

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