Homoallyl alcohols, isomerization

These are usually obtained from the isomeric conjugated ketone, and are sometimes useful as intermediates, offering an alternative to enol derivatives. They may also be formed as a result of double bond introduction or by oxidation of homoallylic alcohols if so the conditions must be mild because they generally represent a less stable isomer. 

In contrast to the behavior of homoallylic alcohol (70a) when treated with methanesulfonyl chloride is pyridine, heating A -19-methanesulfonate (68b) in pyridine gives the 5)5,19-cyclo-6-ene (72). Vinylcyclopropane (72) is inert to the conditions used for converting vinylcyclopropane (73) to the A ° -B-homo-7)5-ol (70a). The latter results are only consistent with the existence of two discrete isomeric carbonium ion intermediates which give rise to isomeric elimination products. °... 

Transmetalation to give l-methyl-2-propenylaluminum followed by isomerization to 2-butenyl isomers may be involved in reactions between aldehydes and 2-butenyl(tributyl)-stannane induced by aluminum(III) chloride in the presence of one mole equivalent of 2-propanol. Benzaldehyde and reactive, unhindered, aliphatic aldehydes give rise to the formation of linear homoallyl alcohols, whereas branched products are obtained with less reactive, more hindered, aldehydes66,79. 

Starting from 2,4,6-octatriene and pivaldehyde, the conjugated homoallylic alcohol 8 is obtained as the sole product. Cycloheptatriene-derived complexes react with aldehydes and C02 to afford mixtures of the isomeric 1,3- and 1,4-cycloheptadienyl carbinols or acids, respectively. Interestingly, analogous reactions with methyl chloroformate or dimethyl carbamoyl chloride produce the conjugated dienyl ester 9 or amide 10 as unique products [19,20]. 

Intramolecular hydrosilylation.1 Hydrosilylation of internal double bonds requires drastic conditions and results in concomitant isomerization to the terminal position. However, an intramolecular hydrosilylation is possible with allylic or homoallylic alcohols under mild conditions by reaction with 1 at 25° to give a hydrosilyl ether (a), which then forms a cyclic ether (2) in the presence of H2PtCl6-6H20 at 60°. Oxidative cleavage of the C—Si bond results in a 1,3-diol (3). 

A recent study has indicated that the skeletal rearrangement step in the B12-catalysed isomerization of methylmalonyl-CoA to succinyl-CoA occurs not by a radical pathway but by an anionic or organocobalt pathway. A computational study of the isomerization of allyl alcohol into homoallyl alcohol by lithium amide has pointed to a process proceeding via a transition state in which the proton is half transferred between carbon and nitrogen in a hetero-dimer. l,l-Dilithio-2,2-diphenylethene... 

However, a more detailed study of the reaction of the mono(allyl)titanium complexes -19 carrying different alkyl groups at the double bond with different aldehydes revealed in some cases the highly diastereoselective (>98%) formation of significant amounts of the isomeric homoallyl alcohols 4 besides 6 (Table 1.3.1). 

When either an alcohol or an amine function is present in the alkene, the possibility for lactone or lactam formation exists. Cobalt or rhodium catalysts convert 2,2-dimethyl-3-buten-l-ol to 2,3,3-trimethyl- y-butyrolactone, with minor amounts of the 8-lactone being formed (equation 51).2 In this case, isomerization of the double bond is not possible. The reaction of allyl alcohols catalyzed by cobalt or rhodium is carried out under reaction conditions that are severe, so isomerization to propanal occurs rapidly. Running the reaction in acetonitrile provides a 60% yield of lactone, while a rhodium carbonyl catalyst in the presence of an amine gives butane-1,4-diol in 60-70% (equation 52).8 A mild method of converting allyl and homoallyl alcohols to lactones utilizes the palladium chloride/copper chloride catalyst system (Table 6).79,82 83... 

Homoallylic alcohols are oxidized, in the presence of pyridinium trifluoroacetate, with no migration of the alkene into conjugation with the carbonyl, even in cases in which such migration can occur under very mild acidic catalyses. On the other hand, the stronger acid H3PO4 is able to produce such isomerizations.14b... 

The Swern oxidation of homoallylic alcohols leads to a (3,y-unsaturated carbonyl compound, which sometimes suffers an in situ base-induced isomerization of the alkene into conjugation with the carbonyl group.239... 

Isoprenylation of Isopropenyl groups.1 Cyclic terpenes substituted by an isopropenyl group can be converted into sesquiterpenes with the bisabolane skeleton by addition of HOC1 under biphasic conditions to give an allylic chloride (10, 208-209) followed by a zinc-induced reaction with isovaleraldehyde to form an isomeric mixture of homoallylic alcohols. 

A homoallyl alcohol has been used to generate an allylrhodium species via retro-allylation.173 Subsequent reaction with an aldehyde (RCHO) yields the corresponding secondary alcohol, R-CH(OH)CH2-C(Me)=CH2, in situ. This can be isomerized in the same pot to yield saturated ketone, R-C(=0)CH2-CHMe2. 

The C—Si bond formed by the hydrosilation of alkene is a stable bond. Although it is difficult to convert the C—Si bond to other functional groups, it can be converted to alcohols by oxidation with MCPBA or H2O2. This reaction enhances the usefulness of hydrosilylation of alkenes [219], Combination of intramolecular hydrosilylation of allylic or homoallylic alcohols and the oxidation offers regio- and stereoselective preparation of diols [220], Internal alkenes are difficult to hydrosilylate without isomerization to terminal alkenes. However, intramolecular hydrosilation of internal alkenes can be carried out without isomerization. Intramolecular hydrosilylation of the silyl ether 572 of the homoallylic alcohol 571 afforded 573 regio- and stereoselectively, and the Prelog-Djerassi lactone 574 was prepared by applying this method. 

Isomerization of Homoallyl Alcohols Through Activation of the sp3 C-H Bond... 

Asymmetric allylboration has also been applied to y-methoxyallyl derivatives. Isomerically pure (Z)-y-methoxyallyldiisopinocampheylborane (rf31), prepared from Ipc2lSOMe and the lithium anion of allyl methyl ether, reacts with various aldehydes to afford the yyn - j-m e (boxy homoallylic alcohol (32a) in a highly regio- and stereoselective manner17 (Scheme 3.In). This one-pot synthesis of enantiomerically pure 1,2-diol derivatives went as smoothly as the asymmetric Brown crotylation, affording products with uniformly high diastereoselectivity. 

This catalytic system is also applicable to isomerization of allylic alcohols. Under reaction conditions which are the same as, or milder than, those for the rearrangement of homoallylic alcohols, the allylic alcohols isomerized rapidly [12bj. 

It has been shown recently that homoallylic alcohols (309) undergo regiocontrolled carbonylation-lactonization to form (310) or (311) in good yield (equation 109). In the reaction of cis-3-hexenol, (315) is formed as a side product to (313), presumably via the isomerization of intermediate (312) to (314) (Scheme 11). 

Unequalled in elegance is the double Still-Wittig rearrangement of (48), which gave the bis-(ZZ)-homoallylic alcohol (49) in 95% isomeric purity (equation 16). (Z)-Selectivity has also been noted for the Wittig rearrangement of an acid dianion (equation 17). ... 

Taking the product-oriented view, homoallylic alcohols (82 equation 18) with syn configuration can be prepared from ( )- or (Z)-alkenes in 95% isomeric purity (Table 6). Less numerous and less selective — but again including the choice of ( )- or (Z)-ethers as starting materials — are the syntheses of the anti epimers (84 equation 19) (Table 7). 

Allyl-allyl cross-coupling of allyl bromides (Structure 1) and allyl sulfides (2) carrying homoallylic alcohol or ester functions takes place under irradiation with hexamethylditin (see eq. (1)). The reaction cleanly leads to 2,6-dienes (3) and no isomerization of allylic bromides is oberserved [56]. 

The Moffatt oxidation was utilized in the endgame of the total synthesis of (+)-paspalicine by A.B. Smith et al. The advanced intermediate hexacyclic homoallylic alcohol was subjected to the Moffatt oxidation conditions using pyridinium trifluoroacetate as the acid catalyst. Under these conditions, the desired p,y-unsaturated ketone and the rearranged a,p-unsaturated ketone (paspalicine) were formed in a 5 1 ratio. The final step was the Rh-catalyzed isomerization of the p,y-unsaturated ketone to the natural product. 

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