3-Cyclohexenols synthesis

Scheme 18.44 Sequential r4+21/r2.31 transformations in cyclohexenol synthesis itop— botton .

Scheme 18.44 Sequential [4+2]/[2,3] transformations in cyclohexenol synthesis (top" bottom ).

A novel procedure for the synthesis of an indole skeleton 81 was developed by Mori s group (Scheme 13).16e,16f Enantioselective allylic amination of 78 with A-sulfonated < r/ < -bromoaniline 79 followed by Heck cyclization of 80 provided chiral indoline 81. The treatment of a cyclohexenol derivative 78 with 79 in the presence of Pd2(dba)3-GHGl3 and ( )-BINAPO gave compound 80 with 84% ee in 75% yield. Total syntheses of (—)-tubifoline, (—)-dehydrotubifoline, and (—)-strychnine were achieved from compound 80. 

Ru complex and (CH3)3COK [(S, R)-34B] is also an excellent catalyst for hydrogenation of the cyclic enone [111]. The allylic alcohol product is a useful intermediate for the synthesis of carotenoid-derived odorants and other bioactive ter-penes. Hydrogenation of 2-cyclohexenone in the presence of the (S,S)-DIOP-Ir catalyst gives (R)-2-cyclohexenol in 25% ee (Fig. 32.43) [137]. 

Mixed cyanocuprates (RCuCN)LL The earlier synthesis of 2-cyclohexenols (9, 329 320) has been extended to provide a general route to highly substituted 2-cyclo-hcxenols as shown in equation (I). The crucial step involves a regiospecific 1,4-uddition of a cyonocupralc to an a-cxo-mcthylcne epoxide.2"... 

Hydrogenation of 2,4,4-trimethyl-2-cyclohexenone with rrans-RuCl2(tolbinap)(dpen) and (CH3)3COK under 8 atm of hydrogen gives 2,4,4-trimethyl-2-cyclohexenol quantitatively with 96% ee (Scheme 1.70) [256,275,276]. In this case, unlike in the reaction of aromatic ketones, the combination of the R diphosphine and S,S diamine most effectively discriminates the enantiofaces. The chiral allylic alcohol is a versatile intermediate in the synthesis of carotenoid-derived odorants and other bioactive terpens such as a-damascone and dihydroactinidiolide [277]. 

Montgomery and co-workers [36, 42] have shown that organozincs can also couple with alkynes and aldehydes via organonickel intermediates 26 with high degrees of chemo- and stereoselectivities to afford allylic alcohols 27 (Scheme 8.9). Recently, they reported a two-step, four-component synthesis of cyclohexenol de-... 

Overman et al. exercised the CBS reduction strategy during synthesis of the natural opium alkaloid (—)-morphine (50)21 (Scheme 4.3q). Enantioselective reduction of 2-allylcyclohex-2-en-l-one (51) with catecholborane in the presence of the (R)-oxazaborolidinc catalyst (l )-28a provided the corresponding (S)-cyclohexenol 52 in greater than 96% ee. Condensation of this intermediate with phenyl isocyanate, regioselective catalytic dihydroxylation of the terminal double bond, and protection of the resulting diol afforded 53 in 68% overall yield from 51. The ally lie silane 54 for the upcoming iminium ion-ally lsilane cycliza-tion step was obtained in 81% yield by a stereoselective Sn2 displacement of allylic carbamate. 

Mixed cyanocuprates, [RCuCN]Li. These cuprates (1) are prepared by addition of 1 equiv. of copper(I) cyanide to an alkyllithium in ether at -40°. [CH,CuCN]Li and [CeHsCuCNjLi add stereo- and regiospecifically to 1,3-cyclohexadiene monoepoxide (2) to give 3, which can be epoxidized by m-chloroperbenzoic acid to give 4 in high yield. The products (4) are valuable for stereocontrolled synthesis of trisubstituted cyclohexenols (scheme I). ... 

The osmylation of l-[Af-methylphenylsulfoximinomethyl]-l-hydroxy-2-cyclopentenols and -2-cyclohexenols, obtained in turn from the corresponding 2-cycloalkenones by the addition of lithiated, V,.S -dimethyl-5-phenylsulfoximine, occurs from the same side as the sulfoximino functionality with complete Ik topicity. Subsequent thermal elimination of the sulfoximine group allows the synthesis of optically pure 2,3-dihydroxycycloalkanones. This method can, therefore, be regarded as proceeding via an auxiliary-controlled osmylation92-93. 

With the chiral cyclohexenol 87 in hand, the synthesis of optically active morphine was carried out based on the similar reaction sequence as employed for their racemic synthesis (Scheme 18). Treatment of 87 with m-CPBA gave... 

Anionic oxy-Cope rearrangements of /ra/ts-divinylcyclohexenols also proceed with invariable E selectivity. For example, the oxy-Cope rearrangement of cyclohexenol 31 (prepared from monoterpene piperitone 30), the key step in the synthesis of medium-ring sesquiterpene ( + )-acoragermacrone, gives product 32 in a 75% overall yield935. 

Luche conditions have also been utilized in the synthesis of an electrophilic galactose equivalent, specifically for preparation of an O-linked glycopeptide isostere in the laboratory of Randall L. Halcomb.19 To accomplish this goal, per-acetylated cyclohexone 17 was reduced using NaBUi and CeCl3 to produce psuedoequatorial cyclohexenol 18. The reaction produced a 30 1 ratio of diastereomers favoring the product of axial hydride addition. 

Diels-Alder reactions. A synthesis of 2,6-disubstituted (also more highly substituted) 3-cyclohexenols is based on cycloaddition with preassemblage of alkadienols and alkenylboronates. Oxidation of the cycloadducts with Me,NO completes the process. 

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