Allyl alcohols 32 -monosubstituted

For the addition of ethylene, EtOAc as solvent was particularly advantageous and gave 418 in 60% yield (Scheme 6.86). The monosubstituted ethylenes 1-hexene, vinylcyclohexane, allyltrimethylsilane, allyl alcohol, ethyl vinyl ether, vinyl acetate and N-vinyl-2-pyrrolidone furnished [2 + 2]-cycloadducts of the type 419 in yields of 54—100%. Mixtures of [2 + 2]-cycloadducts of the types 419 and 420 were formed with vinylcyclopropane, styrene and derivatives substituted at the phenyl group, acrylonitrile, methyl acrylate and phenyl vinyl thioether (yields of 56-76%), in which the diastereomers 419 predominated up to a ratio of 2.5 1 except in the case of the styrenes, where this ratio was 1 1. The Hammett p value for the addition of the styrenes to 417 turned out to be -0.54, suggesting that there is little charge separation in the transition state [155]. In the case of 6, the p value was determined as +0.79 (see Section 6.3.1) and indicates a slight polarization in the opposite direction. This astounding variety of substrates for 417 is contrasted by only a few monosubstituted ethylenes whose addition products with 417 could not be observed or were formed in only small amounts phenyl vinyl ether, vinyl bromide, (perfluorobutyl)-ethylene, phenyl vinyl sulfoxide and sulfone, methyl vinyl ketone and the vinylpyri-dines. 

Epoxidation of (Z)-2-methyl-2-hepten-l-ol gave epoxy alcohol 61 (80% yield, 89% ee) [2], of (Z)-2-methyl-4-phenyl-2-buten-l-ol gave 62 (90%, 91% ee) 177], and of (2T)-1 -hydroxy squalene gave 63 (93%, 78% ee) [85]. The epoxy alcohol 64 had >95% ee after recrystallization [91], In the epoxidation of (Z)-2-r-butyl-2-buten-l-ol, the allylic alcohol with a C-2 r-butyl group, the epoxy alcohol was obtained in 43% yield and with 60% ee [38], These results lead one to expect that other 2,3Z-disubstituted allylic alcohols will be epoxidized in good yield and with enantioselectivity similar to that observed for the 3Z-monosubstituted allylic alcohols (i.e., 80-95% ee). 

Three different principles of selectivity are required to achieve this result. First, the difference in rate of epoxidation by the catalyst of a disubstituted versus a monosubstituted olefin must be such that the propenyl group is epoxidized in complete preference to the vinyl group. The effect of this selectivity is to reduce the choice of olefinic faces to four of the two propenyl groups. Second, the inherent enantiofacial selectivity of the catalyst as represented in Figure 6A.1 will narrow the choice of propenyl faces from four to two. Finally, the steric factor responsible for kinetic resolution of 1-substituted allylic alcohols (Fig. 6A.2) will determine the final choice between the propenyl groups in the enantiomers of 80. The net result is the formation of epoxy alcohol 81 and enrichment of the unreacted allylic alcohol in the (35)-enantiomer. 

The rationale that explains the kinetic resolution of the 1-monosubstituted allylic alcohols predicts that a 1,1-disubstituted allylic alcohol will be difficult to epoxidize with the Ti-tartrate catalyst. In practice, the epoxidation of 1,1-dimethylallyl alcohol (88) with a stoichiometric quantity of the Ti-tartrate complex is very slow, and no epoxy alcohol is isolated... 

Figure 3 Epoxy alcohols from asymmetric epoxidation of (3 )-monosubstituted allylic alcohols...

A more complex picture was painted in a further study by Rapoport, which indicated that both the mechanism and reactivity sequence are dependent upon the alkene structure and reaction conditions 1,2-disubstituted alkenes (1) reacting via an oxaselenocyclobutane intermediate with a reactivity sequence CH > CH2 > CH3 geminally disubsdtuted alkenes (2) with a reactivity sequence CH > CH2 > CH3 and trisubstituted alkenes (3) with a reactivity sequence CH2 > CH3 > CH, ( )-allylic alcohols being the preferred products as established by Blichi types (2) and (3) reacting via carbenium ion intermediates (4) without four-membered ring closure or by unspecified cyclic transition states. Rapoport s evidence also showed the final step to occur by 5n1 or 5n1 processes and not by 5n2. Monosubstituted alkenes, particularly arylpropenes, commonly react with rearrangement. ... 

Monosubstitution or different substituents at C-l of the allylic moiety open up the possibility for formation of (E)- or (Z)-allylic alcohols in acyclic systems. The transition state with one substituent R at C-l in an equatorial position ( transoid transition state) seems to be about 1.5 keal/mol more stable than the cisoid transition state7. The sigmatropic rearrangement via the energetically preferred transition state yields (T)-alkenes, usually with a selectivity of greater than 95 %86,87. 

The influence of a stereogenic center at C-l seems to override that of the stereogenic heteroatom. In selenoxides monosubstituted at C-1, the R1 substituent will occupy the equatorial position. One of the diastereoniers will rearrange via the exo, the other via the endo, transition state to give the same allylic alcohol, e.g., for the (C)-alkene as shown overleaf. 

Vinyllithium reageants, generated using Schlosser s reagent, attack monosubstituted oxiranes to produce homo-allylic alcohols (Equation 27) <1996T1433>. The addition reaction of lithiated alkynes to epoxides was observed to... 

Limitations of the reaction due to the substitution pattern of the allylic alcohols were overcome by the use of tetrapropylammonium perruthenate (TRAP) as a catalyst and monosubstituted, disubstituted and trisubstituted allyl alcohols were converted into the corresponding saturated aldehydes and ketones [5]. Intermediacy of the ruthenium alkoxide in this reaction was evidenced from the complete lack of reactivity of the trimethylsilyl ether derived from the allylic alcohol. 

Nickel catalysts also catalyze Grignard substitution to allylic compounds including allyl alcohol [230-233] ethers [230,231,234,235 Eq. (106) 231] amines, albeit in a low product yield [231] sulfides [231,236,237], including thioacetals [238] thiols [231] selenides [239] carboxylates [240] phosphates [94,121] and halides [Eq. (107) 230], most likely via intermediate / -allyl-Ni species. Monosubstitution of bis-allyl ether was possible [Eq. (108) 235]. Most of the literatures cited in the foregoing disclosed regiochemical outcome associated with these allylic substitutions. 

In 2001, Deng and coworkers found that nucleophilic catalysts such as (DHQD)2AQN (11) can also affect the parallel kinetic resolution of racemic anhydrides by alcoholysis, that is, the two substrate enantiomers are converted into regioisomeric esters. A variety of monosubstituted racemic succinic anhydrides were converted in the presence of (DHQD)2AQN (11, 15-20 mol%) and allyl alcohol as a nucleophile to both regioisomeric hemiesters 49 and 50 with synthetically reliable ee values (up to 98% ee) and yields (Scheme 11.26) [41]. The obtained regioisomeric 2-or 3- aryl succinates could be converted to the P- and a-aryl-y-butylolactones, which constitute valuable synthons for various pharmaceuticals. 

We return to two compounds we made earlier by the AE reaction propranolol 7 and diltiazem 67. In both cases the synthesis is easier as we do not have to start with an allylic alcohol. The synthesis of propranolol41 uses the allyl ether 188 that gives the diol 189 with good ee in the AD reaction for a monosubstituted alkene. Transformation to the epoxide 190 shows no loss of ee. Reaction with /-Pi NIE was already known to give propranolol 7. This is a very short synthesis from easily made starting materials. 

Isomerization of allylic alcohols to saturated carbonyl compounds. In the presence of this ruthenium complex, allylic alcohols rearrange to saturated aldehydes or ketones. The rate depends on the number of substituents on the double bond, with highest rates in the case of monosubstituted alkenes. 1,1-Disubstilutcd alkencs rearrange faster than 1,2-disubstitutcd alkencs. 

Mansuy, D., J. Leclaire, M. Fontecave, and M. Momenteau (1984). Oxidation of monosubstituted olefins by cytochromes P450 and heme models Evidence for the formation of aldehydes in addition to epoxides and allylic alcohols. Biochem. Biophys. Res. Commun. 119, 319—325. 

Isomerization of allylic aicohois. This cationic complex (1) is a very active catalyst for hydrogenation of alkenes, even of tri- and tetrasubstituted alkenes. Since it can sometimes effect isomerization of the substrate as well, it was examined as a catalyst for isomerization of allylic alcohols to carbonyl compounds, a reaction that ordinarily requires fairly drastic conditions. After activation with hydrogen, 1 can effect this isomerization in THF at 20°. Primary and secondary allylic alcohols with monosubstituted double bonds are isomcrized in quantitative yield at 20°, Alcohols with more substituted double bonds require more catalyst and/or higher temperatures (60°). Dismutation is not observed in this system. Examples ... 

Specifically, the allylic alcohols 832 are selectively oxidized by IBX to ketones 833 in high yield (Scheme 3.330) [1134]. The oxidation of alcohols 834 with IBX selectively affords 5-monosubstituted 3-acyl-4-0-methyl tetronates 835, which are structurally similar to the tetrodecamycin antibiotics [1135]. 

This reaction was first reported by Kriewitz in 1899. It is the condensation between formaldehyde and olefins to form unsaturated primary alcohols under conditions of high temperature (e.g., 170°C). In this reaction, water or acetic acid is usually applied as the solvent, and an acid is added as a catalyst, such as sulfuric acid. Under these conditions, formaldehyde and some ketones function as an enophile. The double bond in the new unsaturated alcohol is adjacent to its original position in the starting olefin," with the exception of camphene, which gives an allylic alcohol. For the acylic olefins in this condensation, the isobutylene-type olefins are much more reactive than the monosubstituted olefins or 1,2-disubstituted olefins. The further extension of this reaction involving an intramolecular condensation of an a-alkoxycarbenium ion with a double bond to form a hydropyran derivative is known as the Prins-Kriewitz cyclization. ... 

---