Allylic alcohols, trisubstituted

Combined with the efficient and regiospecific alkylation of allylic sulphones shown in the Scheme (contrast the corresponding alkylation of allylic sulphox-ides), this method can give allylic alcohols trisubstituted on the carbon-carbon double bond. The sequence can also be adapted to open up two new routes to exocyclic a-methylene-carbinols (32) (Scheme 15)/" either by overall [1,3] transposition of oxygen from (33), or from ketones via the vinyl sulphones (34), which are isomerized to the thermodynamically favoured allylic isomers (35). 

The AE reactions on 2,5,5-trisubstituted allyl alcohols have received little attention, due in part the limited utility of the product epoxides. Selective ring opening of tetrasubstituted epoxides are difficult to achieve. Epoxide 39 was prepared using stoichiometric AE conditions and were subsequently elaborated to Darvon alcohol. Epoxides 40 and 41 were both prepared in good selectivity and subsequently utilized in the preparation of (-)-cuparene and the polyfunctoinal carotenoid peridinin, respectively. Scheme 1.6.12... 

The synthesis of the trisubstituted cyclohexane sector 160 commences with the preparation of optically active (/ )-2-cyclohexen-l-ol (199) (see Scheme 49). To accomplish this objective, the decision was made to utilize the powerful catalytic asymmetric reduction process developed by Corey and his colleagues at Harvard.83 Treatment of 2-bromocyclohexenone (196) with BH3 SMe2 in the presence of 5 mol % of oxazaborolidine 197 provides enantiomeri-cally enriched allylic alcohol 198 (99% yield, 96% ee). Reductive cleavage of the C-Br bond in 198 with lithium metal in terf-butyl alcohol and THF then provides optically active (/ )-2-cyclo-hexen-l-ol (199). When the latter substance is treated with wCPBA, a hydroxyl-directed Henbest epoxidation84 takes place to give an epoxy alcohol which can subsequently be protected in the form of a benzyl ether (see 175) under standard conditions. 

A mild, Fe(CO)5-catalyzed isomerization of this type was reported by Gree and coworkers [173]. Allylic alcohols having mono-, di-, trisubstituted alkene are readily converted into their corresponding ketones, whereas polyunsaturated derivatives do not rearrange (Scheme 54). 

Although the introduction of a substituent at both C-a and C-P may be expected to destabilize the transoid state of rearrangement due to additional 1,2-allylic interactions, the tendency to form an -double bond exclusively is retained in the synthesis of trisubstituted olefins as well. The first such report, shortly following the initial Evans report , was made by Grieco who achieved a completely stereospecific general synthesis of ( )-y-substituted methallyl alcohols, including the synthesis of racemic ( )-nuciferol (45, equation 24) . Subsequently, other examples of nearly or completely stereospecific syntheses of ( )-) , y-substituted allylic alcohols have also been pub-lished - " . On the other hand, in the synthesis of y,y-disubstituted allylic alcohols a diminished stereoselectivity has been observed. In this case, the /Z ratio depends on the... 

Organozinc reagents have been used in conjunction with a-bromovinylboranes in a tandem route to Z-trisubstituted allylic alcohols. After preparation of the vinylborane, reaction with diethylzinc effects migration of a boron substituent with inversion of configuration and exchange of zinc for boron.176 Addition of an aldehyde then gives the allylic alcohol. The reaction is applicable to formaldehyde alkyl and aryl aldehydes and to methyl, primary, and secondary boranes. 

Selenium dioxide reveals a useful stereoselectivity when applied to trisubstituted gem-dimethyl alkenes. The products are predominantly the Zs-allylic alcohol or... 

The use of silylketals derived from allylic alcohols and 1-substituted nitroethanols for the stereocontrolled synthesis of 3,4,5-trisubstituted 2-isoxazolines via intramolecular 1,3-dipolar cycloaddition has been demonstrated. Here again, the use of silyl nitronates (ISOC) increases the level of selectivity compared to INOC (Eq. 8.92).145... 

We will describe representative procedures for the epoxidation of a disub-stituted aromatic allylic alcohol (A), a trisubstituted aromatic allylic alcohol (B) and a disubstituted aliphatic allylic alcohol (C). 

Epoxides can also be converted to allylic alcohols using electrophilic reagents. The treatment of epoxides with trisubstituted silyl iodides and an organic base such as DBN gives the silyl ether of the corresponding allylic alcohols.119... 

Type III (no homodimerization) Acrylonitrile," protected 3° allylamines" Vinyl trialkoxysilanes, vinyl siloxanes 1,1-Disubstituted olefins, " non-bulky trisubstituted olefms, vinyl phosphonates, " vinyl phosphine oxides,phenyl vinyl sulfone, acrylonitrile, 4° allylic carbons (all alkyl substituents), protected 3° allylic alcohols, 7,Aolefm of 2-subst. 1.3- butadienes, 7,Aolefin of electronically deactivated 1.3- butadienes ... 

Type IV (spectators to CM) 1,1-Disubstituted olefms " 1,1-Disubstituted olefms, disub. o ,/ -unsaturated carbonyls, 4° allylic carbon-containing olefins, perfluorinated alkane olefins, 3° allylamines (protected)" Vinyl nitro olefins, protected trisubstituted allyl alcohols, a,/ -olefin of 2-subst. 1.3- butadienes, a,/ -olefm of electronically deactivated 1.3- butadienes ... 

Z)-Trisubstituted aRylic alcohols. The conditions used by Bestmann et al. (7, 329) for preparation of (Z)-disubstitutcd alkcncs via the Wittig reaction also can provide a stereoselective route to (Z)-trisubstiluted allylic alcohols. An example is the reaction of ethylidenetriphenylphosphorane with the THP ether of hydroxy-acetone (equation 1). The stereoselectivity is decreased with other protecting... 

Trisubstituted epoxides react to give allylic alcohols in which the hydroxyl group is linked to the less substituted carbon. 

Later, the chiral bicyclic phosphine catalyst 5a was also used for kinetic resolution of allylic alcohols with isobutyric anhydride [8, 9]. The best results were obtained for trisubstituted allylic alcohols - selectivity factors ranged from 32 to 82 at -40 °C. 

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