Allylic ketals

STEREOCONTROLLED PREPARATION OF 3-ACYLTETRAHYDROFURANS FROM ACID-PROMOTEO REARRANGEMENTS OF ALLYLIC KETALS (2S,3S)-3-ACETYL-8-CARBOETHOXY-2,3-DIMETHYL-1-OXA-8-AZASPIRO[4.5] DECANE... 

An interesting use of the nickel-catalyzed allylic alkylation has prochiral allylic ketals as substrate (Scheme 8E.47) [206]. In contrast to the previous kinetic-resolution process, the enantioselectivity achieved in the ionization step is directly reflected in the stereochemical outcome of the reaction. Thus, the commonly observed variation of the enantioselectivity with respect to the structure of the nucleophile is avoided in this type of reaction. Depending on the method of isolation, the regio- and enantioselective substitution gives an asymmetric Michael adduct or an enol ether in quite good enantioselectivity to provide further synthetic flexibility. 

Scheme 8E.47. Nickel catalyzed alkylation of cyclic allylic ketal.

This procedure, when combined with the preparation of allyl ketals (p. 34), provides a general method for obtaining allyl substitution alpha to a carbonyl group. A discussion of some of these applications, as well as the vinyl allyl ether rearrangement which is involved, has been given by Hurd and Pollack. Also, the procedure can be repeated to allow the introduction of more than one allyl group. 

Promoted Rearrangements of Allylic Ketals (2S,3S)-3-Acetyl-8-carboethoxy-2,3-dimethyl-1-oxa-8-azaspiro-[4.5]decane. 

This order was chosen so that DDQ (dichlorodicyanobenzoquinone) treatment would not oxidize a dep otected allylic alcohol at C.73, and so that the C.47 hemiketal would still be protected (as the ketal) during basic hydrolysis (step 3). 

The cleavage proceeds by initial reduction of the nitro groups followed by acid-catalyzed cleavage. The DNB group can be cleaved in the presence of allyl, benzyl, tetrahydropyranyl, methoxy ethoxy methyl, methoxymethyl, silyl, trityl, and ketal protective groups. 

A variety of conjugated dienones are reduced by lithium-ammonia, presumably via dienyl carbanions analogous to the allyl carbanions encountered in enone reductions. Cross-conjugated l,4-dien-3-ones afford 4-en-3-ones as the major reduction products, indicating that the cyclohexadienyl carbanion (55) protonates largely at C-1. Some protonation at C-5 does occur as shown by examination of the NMR spectrum of the crude reduction product derived from the 17-ethylene ketal of androsta-l,4-diene-3,17-dione. The 17-ethylene ketal of androst-4-ene-3,17-dione is formed in 75%... 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Most of the alkylations were carried out by adding a solution of 3,3-ethylenedioxypregna-5,16-dien-20-one in tetrahydrofuran to a solution of lithium in liquid ammonia to the point of color discharge. Treatment with the alkyl halide then furnishes the corresponding 17a-alkyl derivative (10). After hydrolysis of the 3-ketal group, 17a-methyl-, ethyl-, propyl-, butyl-, hexyl-, octyl-, allyl-, and benzylprogesterones are obtained. 

Esters and acetylated hydroxyl groups are completely stable under the experimental conditions, but with ketals 10 29,110,112 yields are generally observed in the thermal reaction. Double bonds do not seem to interfere seriously with the course of the reaction provided that the geometric relationship of the free hydroxyl group to the angular methyl group is not changed drastically. In some cases allylic acetoxylation occurs, e.g., at C-7 of A -steroids. ° Ketones are usually stable (especially under photo-lytic conditions) but occasionally a-acetoxylation has been observed. 

MeOH, reagent prepared by heating Bu2SnO and Bu3SnP04, heat 2 h, 90% yield." This method is effective for primary, secondary, tertiary, benzylic, and allylic THP derivatives. The MEM group and ketals are inert to this reagent, but TMS and TBDMS ethers are cleaved. 

In-mediated propargylation of acetals and ketals with various allyl or propargyl bromides in aqueous media successfully provided the corresponding homoallylic or homopropargyhc (and allenyhc) alcohols (Eq. 8.81)207... 

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