Dienol ethers, synthesis

Another Japanese group developed the Baccatin III synthesis shown in Scheme 13.58. The eight-membered B-ring was closed early in the synthesis using a Lewis acid-induced Mukaiyama reaction (Step B-l), in which a trimethylsilyl dienol ether served as the nucleophile. 

TITANIUM-MEDIATED ADDITION OF SILYL DIENOL ETHERS TO ELECTROPHILIC GLYCINE A SHORT SYNTHESIS OF 4-KETOPIPECOLIC ACID HYDROCHLORIDE (Pipecolic acid, 4-oxo-, hydrochloride)... 

Another work of Duhamel and Ancel [59] related this synthesis of retinal via (3-ionylideneacetaldehyde. Condensation of methallyl-magnesium chloride with diethyl phenyl orthoformate (EtC CHOPh) led after bromination of the ene-acetal, deshydrohalogenation (NaOH 50%), ethanol elimination with hexamethyldisilazane (HMDS) and ISiMes, to the bromo-dienol ether. This latter was submitted to bromine lithium exchange and the lithio enol ether was then condensed with p ionylideneacetaldehyde to give retinal, Fig. (28). 

Pyrans lack aromatic properties and behave as dienolic ethers showing the instability predicted by MO calculations. Hence, the parent compound proved elusive and was not synthesized until 1962. Although several routes are available for the synthesis of this ring system, such is the variation in stability of 4//-pyrans no one method can be described as of widespread application. Routes to the 4//-pyran ring system have been reviewed <80H(14)337>. 

Fig. 9.32. Mechanism of the acid-catalyzed El elimination of methanol from 0,0-acetals. Synthesis of an enol ether and a dienol ether, respectively.

A Fischer carbene complex containing an w-silyl group like 115 underwent a facile 1,2-silyl migration to the corresponding vinylsilane 116 (equation 79)186. Herndon and Patel applied the reaction to the synthesis of a dienol ether 117 (equation 80)187. 

The technique has been applied to the total synthesis of ( )-oxylubimin (134) through hydroxylation of dienol ether (135).The stereoselectivity is good, particularly when compared to the equivalent select -vities obtained using MCPB A, MoOPH or manganese triacetate. 

In studies directed towaids the synthesis of the fungal isonitrile antibiotic isonitrin B (103), a cy-clopentanoid metabolite related to trichoviridine (104), various trialkylsilyl enol ethers were irradiated with propionaldehyde to produce equimolar amounts of stereoisomeric bicyclic oxetanes (105). The corresponding silyl dienol ethers, however, gave little oxetane product owing to preferential diene photopolymerization. The use of vinyl epoxide derivatives such as (106), however, offers a possible access to the epoxycyclopentanoid system with simultaneous control of the face selectivity of the photoaddition by the epoxide moiety. 

Lewis acid catalyzed alkylations of cross-conjugated silyl dienol ethers provide routes to a -alkylated ketones. A short synthesis of the sesquiterpene ( )-ar-turmerone has been accomplished using the cross-conjugated TMS dienol ether of mesityl oxide (equation 9). ... 

The use of chiral diamine 60 with Sn(OTf)2/Bu2Sn(OAc)2 promotes Mukaiya-ma aldol reactions, and such an example was used in a recent synthesis of Tax-ol , in which adduct 61 was obtained with 99% ds and 96% ee (Scheme 9-20) [42J. Other notable contributions to this field have been made using dienolate chemistry. For example, the titanium complex 62 promotes aldol reactions of silyl dienol ethers (Scheme 9-21). Products 63 and ent-63 were then used in the synthesis of macrolactin A (64) [43],... 

A number of ring-A-reduced 6-hydroxylated corticoids were synthesized from hydrocortisone or cortisone, and an improved synthesis of 6/3-hydroxy-5/3-pregnane-3,20-dione involved autoxidation of the dienol ether (307) to the 6/8-hydroxypregn-4-en-3-one (308) and subsequent hydrogenation.The... 

The total synthesis of ( )-trichostatin A has been carried out by two routes [67] one uses the y-alkylation of a silyl dienol ether with an acetal which gives the ether in a Mukaiyama reaction. A Wittig olefination followed by DDQ oxidation gives a ketoester which reacts with hydroxylamine to give trichostatin A in 22% overall yield (Scheme 20). 

The first synthesis of limaspermine (156) takes advantage of the fact that iron carbonyl complexes of type (157) can be regarded as stable equivalents of cyclohexenone y ations. Reaction of (157) with the malonate anion, followed by removal of the metal, gave a dienol ether (158), from which limaspermine (156) was... 

The chiral alcohols are mainly employed as esters or enol ethers. Esters with carboxylic acids can be obtained by any convenient esterification technique. Dienol ethers were obtained by transetherification with the ethyl enol ether of a 1,3-diketone, followed by Wittig reaction8 silyldienol ethers were obtained by the method of Danishefsky11-12 and simple enol ethers by mercury-catalyzed transetherification13. Esters and enol ethers have been used as chiral dienophiles or dienes in diastereoselective Diels-Alder reactions (Section D. 1.6.1.1.1.1.). (R)-l-Phenylethanol [(R)-4] has been used for enantioselective protonation (Section C.) and the (S)-enantiomer as chiral leaving group in phenol ethers for the synthesis of binaphthols (Section B.2.) the phenol ethers are prepared as described for menthol in the preceding section. (S)-2-Octanol [(S)-2] has found applications in the synthesis of chiral allenes (Section B.I.). 

Mono-enolisation of a 1,5-diketone, then the formation of a cyclic hemiacetal, and its dehydration, produces dienol ethers (4//-4-pyrans) which require only hydride abstraction to arrive at the pyrylium oxidation level. The diketones are often prepared in situ by the reaction of an aldehyde with two mols of a ketone (compare Hantzsch synthesis, section 5.15.1.2) or of a ketone with a previously prepared conjugated ketone - a chalcone in the case of aromatic ketones/aldehydes. It is the excess chalcone which serves as the hydride acceptor in this approach. 

One of the first eye-catching synthetic applications of arene-chromium chemistry was the synthesis of the sp/ro-sesquiterpenes ( )-acorenone and ( )-acorenone B (rac-7) disclosed by Semmelhack and Yamashita in 1980 [14]. These authors twice exploited the meta-selective nucleophile addition to anisole-Cr(CO)3 derivatives (Scheme 1). Starting from complex rac-1, such a reaction is first used for the regioselective introduction of an acyl sidechain to give 2 after oxidative workup. A few steps later, the nitrile rac-4 (obtained from rac-3 by complexation and separation of the diastereomeric products by preparative HPLC) is deprotonated to form the spiro addition product rac-5, from which the enone rac-6 is obtained after protonation and hydrolysis of the initially formed dienol ether. The final conversion of rac-6 into acorenone B (rac-7) efficiently proceeds over five steps and involves a diastereoselective hydrogenation of an exo-methylene group. 

Since research on the total synthesis of carotenoids began, the enol ether and the aldol condensations have been frequently used for the formation of carbon-carbon double bonds. In general, the enol ether reaction has been employed successfully for the condensation of a wide range of acetals and sometimes of ketals with enol ethers and dienol ethers. 

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