Alcohols homoallylic

Under oxidation with PCC, migration of alkenes into conjugation with aldehydes or ketones can be avoided by the addition of calcium carbonate (see page 47). 

Kiibel, and W. Steglich, Angew. Chem. Internat. Edn., 1977,16, 394. 

Reactions.—The absolute configuration and enantiomeric purity of chiral secondary carbinols/ and also of primary alcohols chiral at can be determined 

ROH+Cl2PO(NMe2) Reagents i, base ii, Mc2NH iii, Li-Et2NH 

R R CHOH R R CH0P(NMe2)3C104 R R CHN3 + OP(NMe2)3 

A report has appeared on the protection of phenols as their methylthiomethyl (MTM) ethers, which can be formed from sodium phenoxides and chloromethyl 

Hydroborating agent AUene R Hydroboration Yield % Isomeric 

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Regioselective Hydrogenation- allylic and homoallylic alcohols are hydrogenated faster than isolated double bonds... 

Allyllic ether 53 is oxidized regioselectively to the /3-alkoxy ketone 54, which is converted into the a,/i-unsaturated ketone 55 and used for annulation[99]. The ester of homoallylic alcohol 56 is oxidized mainlv to the 7-acetoxy ketone 57[99]. 

The 4-hydroxy-1-alkene (homoallylic alcohol) 81 is oxidized to the hetni-acetal 82 of the aldehyde by the participation of the OH group when there is a substituent at C3. In the absence of the substituent, a ketone is obtained. The hemiacetal is converted into butyrolactone 83[117], When Pd nitro complex is used as a catalyst in /-BuOH under oxygen, acetals are obtained from homoallylic alcohols even in the absence of a substituent at C-3[l 18], /-Allylamine is oxidized to the acetal 84 of the aldehyde selectively by participation of the amino group[l 19],... 

The reaction of alkenyl mercurials with alkenes forms 7r-allylpalladium intermediates by the rearrangement of Pd via the elimination of H—Pd—Cl and its reverse readdition. Further transformations such as trapping with nucleophiles or elimination form conjugated dienes[379]. The 7r-allylpalladium intermediate 418 formed from 3-butenoic acid reacts intramolecularly with carboxylic acid to yield the 7-vinyl-7-laCtone 4I9[380], The /i,7-titisaturated amide 421 is obtained by the reaction of 4-vinyl-2-azetidinone (420) with an organomercur-ial. Similarly homoallylic alcohols are obtained from vinylic oxetanes[381]. 

The alkenyloxirane 126 in excess reacts with aryl and alkenyl halides or triflates in the presence of sodium formate to afford the allylic alcohol 127[104], Similarly, the reaction of the alkenyloxetane 128 gives the homo-allylic alcohol 130[105]. These reactions can be explained by insertion of the double bond in the Ar—Pd bond, followed by ring opening (or /3-eliraination) to form the allylic or homoallylic alkoxypalladium 129, which is converted into the allylic 127 or homoallylic alcohol 130 by the reaction of formate. The 3-alkenamide 132 was obtained by the reaction of the 4-alkenyl-2-azetizinone 131 with aryl iodide and sodium formate [106]. 

The four-membered vinyloxetane 280 is cleaved with Pd(0j and used for allylation a homoallylic alcohol unit can be introduced into the keto ester 281 as a nucleophile with this reagent to form 282[168],... 

Organoboranes are reactive compounds for cross-coupling[277]. The synthesis of humulene (83) by the intramolecular cross-coupling of allylic bromide with alkenylborane is an example[278]. The reaction of vinyiborane with vinyl-oxirane (425) affords the homoallylic alcohol 426 by 1,2-addition as main products and the allylic alcohol 427 by 1,4-addition as a minor product[279]. Two phenyl groups in sodium tetraphenylborate (428) are used for the coupling with allylic acetate[280] or allyl chloride[33,28l]. 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

HOFFMAN - YAMAMOTO Stereoselective adylations Synthesis of syn or anti homoallylic alcohols from Z or E crotylboronate and aldehydes (Hoffman) or of syn homoallylic alcohols from crotylstannanes, BF3 and aldehydes (Yamamoto)... 

Homoallyl alcohol (3) Metalation of (E) butene (1 05 equiv) with n BuLI (t equiv) and KOtBu (1 equiv) in THF at SO C for 15 mm followed by treatment of (E)-crotyl potassum salt with B(OiPr)3 at 79°C gave after quenching with 1 N HCI and extraction with EtjO containing 1 equiv of diisopropyl tartarate. the crotyl boronate 2 A solution of decanall (156 mg 1 mmol) was added to a toluene solution of 2 (1 1 15 equiv) (0 2 M) at 78 C containing 4A molecular sieves (15-20 mg/L) After 3 h at -78°1 N NaOH was added, followed by extraction and chromatography to afford 208 mg of 3 (90%), anti syn 99 1... 

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. 

Careful studies of the reaction of the fluoroamine with the homoallylic alcohols 3 -fluoro-19-hydroxycholest-5-ene and 3a- and 3j5-hydroxy-17j5-acetoxyestr-5(10)-ene which bear on the proposed mechanism have been reported recently. 

Treatment of (70a) with methanesulfonyl chloride in pyridine gives rise to vinylcylopropane (73) which can be converted back to the homoallylic alcohol (70a) under conditions similar to those used for converting cyclopropyl carbinol (69a) to the B-homo-7)5-ol (70a). 

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. °... 

Tnfluoromethyl homoallyl alcohols also dehydrate easily with phosphorus oxychloride-pyridine complex, but it is very difficult to remove water from their saturated analogues by the same method [82] (equation 52)... 

Employing protocol V with the methanesulfonamide catalyst 122, a 93 7 er can be obtained in the cyclopropanation of cinnamyl alcohol. This high selectivity translates well into a number of allylic alcohols (Table 3.12) [82]. Di- and tri-substi-tuted alkenes perform well under the conditions of protocol V. However, introduction of substituents on the 2 position leads to a considerable decrease in rate and selectivity (Table 3.12, entry 5). The major failing of this method is its inability to perform selective cyclopropanations of other hydroxyl-containing molecules, most notably homoallylic alcohols. 

An elegant application of the Vilsmeier reaction is the synthesis of substituted biphenyls as reported by Rao and RaoJ Starting with homoallylic alcohol 8, the biphenyl derivative 9 was obtained from a one-pot reaction in 80% yield ... 

Pineschi and Feringa reported that chiral copper phosphoramidite catalysts mediate a regiodivergent kinetic resolution (RKR) of cyclic unsaturated epoxides with dialkylzinc reagents, in which epoxide enantiomers are selectively transformed into different regioisomers (allylic and homoallylic alcohols) [90]. The method was also applied to both s-cis and s-trans cyclic allylic epoxides (Schemes 7.45 and 7.46,... 

An unprecedented nickel-catalyzed reductive coupling between an epoxide and an alkyne to give synthetically useful homoallylic alcohols has been developed by Jamison [55a], and was recently used in a short enantioselective synthesis of am-... 

Pd(0)-catalyzed hydrogenolysis of vinylepoxides offers an attractive regio- and dia-stereoselective route to homoallylic alcohols (Scheme 9.36) [104, 155, 156]. Thus, hydrogenolysis of ( ) olefin 88 affords syn isomer 89 with inversion of configuration at the allylic carbon, while subjection of (Z) isomer 90 to identical reaction conditions results in the anti isomer 91. The outcomes of these reactions are ex-... 

Hydroxy-l-alkenyl diisopropylcarbamates 2 (X = OCb), in this respect, occupy a medium position since they are stable in strongly acidic and basic protic solvents. For deblocking vinyl carbamates, the presence of catalytic amounts of mercuric or palladium(II) salts is required. Due to this stability, several reactions of homoallylic alcohols, proceeding with high diastereo-selectivity, e g., epoxidation, are applicable in order to introduce further hetero-substituents. 

Table 2. Homoallylic Alcohols by Addition of Alkenylmagnesium Halides to Carbonyl Compounds... 

Allylboron compounds have proven to be an exceedingly useful class of allylmetal reagents for the stereoselective synthesis of homoallylic alcohols via reactions with carbonyl compounds, especially aldehydes1. The reactions of allylboron compounds and aldehydes proceed by way of cyclic transition states with predictable transmission of olefinic stereochemistry to anti (from L-alkene precursors) or syn (from Z-alkene precursors) relationships about the newly formed carbon-carbon bond. This stereochemical feature, classified as simple diastereoselection, is general for Type I allylorganometallicslb. 

Z)-2-Butenylpotassium is generated from 4.5 mL (50 mmol) of (Z)-2-butene, 2.8 g (25 mmol) or /-BuOK. and 10.8 mL (25 mmol) oT 2.3 M butyllithium in THF for 15 min at —45 JC. This solution is cooled to — 78 C and 30 mmol of a 1 M solution of methoxy(diisopinocampheyl)borane in diethyl elher is added dropwise. The mixture is stirred for 30 min at — 78 °C, then is treated with 4mL (33 mmol) of boron trifluoride-diethyl ctherate complex this removes methoxide from the intermediate ate complex. This solution is immediatelv treated with 35 mmol of an afdchyde. Isolated yields of homoallylic alcohols are 63-79%. 

The surprising selectivity in the formation of 4 and 5 is apparently due to thermodynamic control (rapid equilibration via the 1,3-boratropic shift). Structures 4 and 5 are also the most reactive of those that are present at equilibrium, and consequently reactions with aldehydes are very selective. The homoallylic alcohol products are useful intermediates in stereoselective syntheses of trisubstituted butadienes via acid- or base-catalyzed Peterson eliminations. 

Isopinocampheyl(l-isopinocampheyl-2-octenyl)borinic acid (1), available with a diastereomer-ic purity of approximately 80 85% de, reacts smoothly with aldehydes at —15 °C in tetrahy-drofuran to provide a homoallylic alcohol with 79-85% ee after oxidative workup (30% hydrogen peroxide, 40 °C)6. 

Improved methods for the preparation of reagents such as isopinocampheyl(l-isopinocam-pheyl-2-alkenyl)borinic acids will certainly lead to a more enantioselective synthesis of anti-homoallylic alcohols, since the enantiomeric purity of the reagent is the only significant limitation to the synthetic utility of this reagent system. 

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. 

A )-1-Methyl-2-butenylstannanes similarly give ann-homoallylic alcohols on healing with aldehydes, only traces of the sjn-isomers being detected. Moreover, these reactions are highly stereoselective for formation of (Z) double bonds in the products. It would appear that small amounts (ca. 10%) of the (Z)-isomers in the (A)-l-methyl-2-butenylstannanes (see Section 1.3.3.3.6.1.1.2.) do not interfere because they are significantly less reactive17. 

One limitation of these noncatalyzed allyl(trialkyl)- and allyl(triaryl)stannane-aldehyde reactions is the high temperature required unless the aldehyde is activated towards nucleophilic attack. Allyltin halides are much more reactive because of their enhanced Lewis acid character however 2-butenyltin halides show reduced syn I anti selectivity45, and give other products including linear homoallylic alcohols and tetrahydropyrans47. 

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. 

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