Alcohols homoallylic tertiary

P-Cleavage of homoallylic alcohols.1 Homoallylic tertiary potassium alkox-ides undergo cleavage in HMPT (or DMF) of the allylic C—C bond to give the enolate of a ketone (equation I). A rigid bicyclic system is not essential for the cleavage. 

This reaction can also be used to prepare homoallylic alcohols. Reaction of 3-butene-2-ol (1) with ClSi(CH3)3 and Nal in acetonitrile followed by a reaction with a ketone and zinc provides a homoallylic tertiary alcohol (2) in 52% yield. 

Ketones are less electrophilic than aldehydes and the ene adducts are tertiary alcohols that are much less acid stable than the secondary alcohols produced from aldehydes. Ene adducts can be isolated from the EtAlCh-catalyzed reactions of cycloalkanones and reactive ene components, i.e. 1,1-disubstituted alkenes with one end of the double tend sterically accessible and the other end capable of stabilizing a positive charge in an intermediate. The yields are moderate at best (6-55%), but the reaction does provide an extremely simple route to homoallylic tertiary alcohols. 

A series of homoallylic tertiary alcohols [3] with structure 1-aryl-l-(A -cyclohexenyl)ethanol are synthesized by treating p-haloacetophenone with B-2-cyclohexen-l-yl-9-BBN (Eq. 6.9). Apparently, it is not feasible to convert 1-chloro- or l-bromo-2-cyclohexene into the corresponding Grignard reagent. 

Two approaches for the synthesis of allyl(alkyl)- and allyl(aryl)tin halides are thermolysis of halo(alkyl)tin ethers derived from tertiary homoallylic alcohols, and transmetalation of other allylstannanes. For example, dibutyl(-2-propenyl)tin chloride has been prepared by healing dibutyl(di-2-propenyl)stannane with dibutyltin dichloride42, and by thermolysis of mixtures of 2,3-dimethyl-5-hexen-3-ol or 2-methyl-4-penten-2-ol and tetrabutyl-l,3-dichlorodistannox-ane39. Alternatively dibutyltin dichloride and (dibutyl)(dimethoxy)tin were mixed to provide (dibutyl)(methoxy)tin chloride which was heated with 2,2,3-trimethyl-5-hexen-3-ol40. 

Ketones were also reacted under these conditions, leading to tertiary ethers. Thus, by mixing equimolar quantities of a carbonyl (aldehyde or ketone), allyl-silane and a silylated alcohol, followed by the addition of a catalytic amount of TMSOTf, homoallylic ethers can be obtain in good yields via a three-component coupling reaction (Scheme 13.22). 

Scheme3.4. Generation of allyl anions from bulky tertiary homoallyl alcoholates [14].

The accelerated rate for alcoholysis with le, which was observed for the 10 % Pd/C catalytic system, was also seen with the Mn(CO)sBr catalyst. Reactions of le with primary, secondary or tertiary alcohols resulted in moderate yields of the corresponding silyl ketals after 2 h (Table 8 and 9). When mono-alkoxy silane from 3-hydroxy butyrate (lg) was treated with homoallyl alcohol in the presence of Mn(CO)sBr as the catalyst under the standard conditions, 76 % of the silyl ketal was obtained. These silyl ethers possess neighboring carbonyl groups that can participate in the reaction by forming a more reactive pentacoordinated silicon center upon addition of the silane to the metal center.. 

In contrast with unreactive, unfunctionalised terminal alkenes, allylic and homoallylic ethers (22, 24) and alcohols (20) from which the product organolithiums (21, 23, 25) can be chelated in a (preferably) five-membered, oxygen-containing ring, carbolithiate rapidly and cleanly.23 Coordination overrides any preference for the lithium to be bonded to the primary carbon, but cannot overcome the unfavourability of forming a tertiary organolithium - 26 gives 27, but 28 cannot be carbolithiated. Coordination to sulfur in similar thioethers 29 works too. 

Chiral Bronsted acids can also promote the asymmetric addition of allylic tin reagents to carbonyl compounds. Baba and coworkers have found that a stoichiometric amount of (fl)-BINOL (37) acts a chiral promoter for the allylation of unactivated ketones with tetraallyltin and in the presence of MeOH, the corresponding nonracemic tertiary homoallylic alcohols are obtained with up to 60% ee [50]. Later, Woodward et al. improved this process and achieved a catalytic enantioselective allylation of aryl ketones by employing (fl)-monothio-binaphthol 36 as a chiral Bronsted catalyst [49]. For instance, in the presence of 20 mol% of the chiral acid 36 and 40 mol% of H20 in toluene, acetophenone (42) was allylated by a 0.7 0.3 mixture of tetraallyltin (41) and butyltriallylltin (55) to give the (jR)-enriched allylated product 56 almost quantitatively with 89-86% ee (Scheme 8). 

In 1989, Sakurai et al. reported that allyltrifluorosilanes react with a variety of a-hydroxy ketones in the presence of stoichiometric amount of triethylamine to yield the corresponding tertiary homoallylic alcohols in an extremely high regio-and diastereoselective manner10 (Scheme 3.2h). Upon reacting with a-hydroxy acetone, the (L )-crotylsilane 4E gave 6-syn as a major product in 83% yield with... 

C). Also, the presence of a lithium alkoxide group allows the cyclization of primary as well as tertiary alkyllithiums at temperatures as low as — 78 °C. Thus, cyclopentanol derivatives 160 are easily obtained from alcohols 159 in very high yields and as single diastereoisomers (Scheme 45). As shown with thioether 161, when the alkoxide group is placed in a homoallylic position, the reaction is even more effective and cyclized product... 

Reaction with cyclopropyl alcohols and ketones. The primary and secondary cyclopropyl alcohols 1 and 2 are converted by reaction with P2I4 or PI, mainly into the corresponding iodides. In contrast, the tertiary a-cyclopropyl alcohol 3 is converted into the homoallylic iodide 4 under very mild conditions. a-Cyclopropyl aldehydes and ketones are also cleaved by P2I4 to -y-iodo carbonyl compounds in high yield, particularly when the solvent is acetone. 

The epoxidation of the homoallylic alcohol (100) is regio- and stereo-selective (equation 36). Epoxi-dation of (100) from the -face involves a transition state which can be approximate by the conformer (102) complexed with MCPBA in this conformation there is steric interference between the tertiary allylic hyctogen and ethyl group. Inspection of conformation (103) reveals that in the transition state leading to the a-epoxide there is steric interaction between the ethyl and allyl groups the steric interaction in (103) is much larger than the interaction in (102). 

A different usage of such oxazin-l,4-diones in synthesis is exemplified by the preparation of the enantiomerically pure acyloin (417). The S-proline derivative (413) was treated with an allylsilane in the presence of a Lewis acid to give a mixture of optically active tertiary homoallyl alcohols... 

Since epoxidation at the vinyl double bond is unproductive, it is desirable to direct reaction on the al-lene moiety. This can be accomplished by taking advantage of the hydroxy-directed epoxidation of allylic alcohols using the t-butyl hydroperoxide/vanadium(V) system.The directing effects of both allylic and homoallylic type hydroxy groups have been examined at both positions of the vinylallene unit. " At the 1-position (64), primary, secondary and tertiary allylic tdcohols are effective, while only primary homoallylic alcohols have bran examined (equation 35). Presumably the directing effect of the hydroxy groups favors formation of the intermediate allene oxide (65). A sample of the compounds prepared by this route is shown in Scheme 32. ... 

Reduction of (I) with DIBAH in THF leads mainly to the homoallylic alcohol (4) formed by direct, MarkownikoIT addition of the hydride to the epoxide. Reduction of (1) with lithium aluminum hydride gives exclusively the tertiary allylic alcohol (S). 

Tietze et al. emphasized the usefulness of chiral trimethylsilyl ethers of readily accessible amino alcohol derivatives in allylation of aldehydes and ketones [43]. As a consequence, careful design of the norpseudoephedrine derivatives and proper choice of silicon Lewis acids have led to the convergent preparation of enantiomerically enriched secondary and tertiary homoallylic alcohols in high yields (Sch. 12) [43a], It should be noted that the configuration of the newly formed stereogenic center of the secondary homoallylic alcohols is the opposite of that in the allylation of ketones [43c], They also described in detail mechanistic studies of the above allylation reaction by use of and NMR. 

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