Homoallyl alcohols, tertiary

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. 

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. 

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

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. 

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.. 

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... 

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. 

Studies on the nonracemic methylenecyclododecyl ethers (164 equation 37) led to similar conclusions. With HMPA as a cosolvent the secondary allylic ether (164a) afforded mainly (86 14) the ( )-homoallylic alcohol (165a) of 95% ee. The tertiary ether (164b) yielded a 98 2 ( ) (Z) mixture, but the major product (165b) was 40% racemic. A dissociative rearrangement process could account for this result. Without HMPA both ethers rearranged in poor yield (5-30%) to nearly 1 1 mixtures of ( )- and (Z)-cycloalkenes. 

Deallylation. Tertiary homoallylic alcohols lose the allyl group on heating with (PhjPjjRuClj under CO. Cleavage of cyclic alcohols is shown below. 

In addition, recent studies towards the synthesis of bryostatin 1 have described high diastereoselectivity for the chelation-controlled condensation of the substituted stannane 68 with ent-33 leading to the desired i yn-product 69 via 70 (Scheme 5.2.17).While ketones have rarely been explored as reactive electrophiles for stereoselective allylations, proximate coordination of a Lewis acid through a-chelation can produce favorable results, as illustrated in the exclusive formation of the tertiary homoallylic alcohol 72 from 71 (Scheme 5.2.17).28... 

The carbonyl-ene reaction is a source of homoallylic alcohols, although the scope is somewhat limited. Synthesis of chiral tertiary a-hydroxycarboxylic esters from glyoxyUc esters has been studied, and many metal catalysts of varying degree of effectiveness have been identified. The Ag-catalyzed reaction between enol silyl ethers and a glyoxylic ester is stericaUy controlled by the Pd-SEGPHOS complex. ... 

Not surprisingly, Martin s sulfurane mediates the production of acyclic dienes from allylic and homoallylic alcohols. In Heathcock s synthesis of altohyrtin C, secondary homoallylic alcohol 55 reacted with sulfurane 1 to yield the desired ( T)-alkene 56 in greater than 84% yield.26 Interestingly, Tse generated diene 58 from tertiary allylic alcohol 57 in 95% yield with only 5% of the undesired trisubstituted diene isomer.27... 

Since many other functional groups are tolerated in this reaction, a great variety of useful synthetic intermediates have been assembled 4-styryl-2-azetidinones, 4,5-diphenyl-3-styryloxazolin-2-ones, jS-alkoxystyrenes, allylic and homoallylic alcohols. " The coupling between vinylic iodides and tertiary allylic alcohols to construct isoprenoid segments has also been demonstrated."... 

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