Allylation 10-camphorsulfonic acid

The synthesis of the right-wing sector, compound 4, commences with the prochiral diol 26 (see Scheme 4). The latter substance is known and can be conveniently prepared in two steps from diethyl malonate via C-allylation, followed by reduction of the two ethoxy-carbonyl functions. Exposure of 26 to benzaldehyde and a catalytic amount of camphorsulfonic acid (CSA) under dehydrating conditions accomplishes the simultaneous protection of both hydroxyl groups in the form of a benzylidene acetal (see intermediate 32, Scheme 4). Interestingly, when benzylidene acetal 32 is treated with lithium aluminum hydride and aluminum trichloride (1 4) in ether at 25 °C, a Lewis acid induced reduction takes place to give... 

One of the first optically active allenes reported was synthesized by enantioselective dehydration of a racemic allylic alcohol in the presence of (+)-10-camphorsulfonic acid as the chiral catalyst125,126. The initial optical rotation of the tetraarylallene is low, but can be increased to [a],2/1 +351 (cyclohexane) after several recrystallizations. 

On treatment with camphorsulfonic acid/pyridine, methyl ( )-1-[(.S )-4-mcthylphcnylsuirinyl]-2-alkenoates undergo, enantioselectively, a sequential prototropic shift and allylic sulfoxide/ sulfenate rearrangement to produce methyl (R,/f)-4-hydroxy-2-alkcnoates in 64- 72% optical purity63a. 

A practical method for the enantioselective addition of an allylic nucleophile to an aldehyde has been acid-mediated allyl transfer, as exemplified by the conversion of 1 and 2 to 3. While this method worked well for crotyl, allyl transfer itself suffered from eroded ee s. Teck-Peng Loh of the National University of Singapore has found (Tetrahedron Lett. 2004,45,5819) that camphorsulfonic acid (CSA) mediates this conversion without racemization. The alcohol 1 is prepared by addition of allyl Grignard to camphor, so both enantiomers are readily available. 

Dioxene can be used to prepare trisubstituted annulated furans in a three-step sequence. By lithiation of 1,4-dioxene, followed by carbonyl addition, an allylic alcohol 13 is obtained, which can be reacted with silyl enol ethers in the presence of a Lewis acid to furnish disubstituted dioxanes of type 14. These compounds rearrange to furans under mild conditions upon treatment with camphorsulfonic acid (Scheme 16) <1999TL2521>. 

Allylation of Aldehydes. Synthesis of enantiomerically pure allyl alcohols can be accomplished by catalytic asymmetric addition of divinylzinc to aldehydes using a camphorsulfonic acid-derived catalyst (eq 22). ... 

Abbreviations Ac, acetyl AIBN, 2,2 -azobisisobutyronitrile All, allyl Alloc, allyloxycarbonyl Bn, benzyl BOM, benzyloxymethyl BPC, p-phenylbenzoyl Bu, butyl t-Bu, tert-butyl Bz, benzoyl CAN, ammonium hexanitratocerate (IV) Cbz, bezyloxycarbonyl CDl, carbonyldiimizazole ClAc, chloroacetyl Cp, cyclopentadienyl CSA, DL-lO-camphorsulfonic acid DABCO, l,4-diazabicyclo[2.2.2]octane DAST, diethylaminosulfur trifluoride dba, dibenzylideneacetone DBU, l,8-diazabicyclo[5.4.0]undec-7-ene DCC, iV,iV-dicyclohexylcarbodiimide DDQ, 2,3-dichloro-5,6-dicyano-l,4-benzoqui-none DEAD, diethyl azodicarboxylate DEIPS, diethylisopropylsilyl DIBAL, diisobutylaluminum hydride DMAP,... 

Dehydration of allylic alcohols with strong acid leads to allenes if an isomerization to an alkyne is not possible. This method has been used for the synthesis of tetraarylallenes and tetra-r-butylallene. This method was also used for the first synthesis of an optically active allene by an enantioselective dehydration using (-l )-camphorsulfonic acid. ... 

BCnight and co-workers approached the synthesis of the unnatural ( + )-enantiomer of lupinine (ent-344) by first resolving racemic 2-(piperidin-2-yl)-ethanol with (+ )-camphorsulfonic acid (357,358). The (i -( + )-enantiomer 362 was then converted into the substituted acetic ester 363, the enolate of which was stereoselectively allylated to give 364 and 365 in isolated yields of 71% and 12%, respectively (Scheme 45). The major isomer 364 was readily hydroborated and cyclized to the bicyclic ester 366, reduction of which completed the first reported synthesis of (+ )-lupinine (ent-344). The optical rotation was measured as +19.5° (c 1, EtOH), which compared favorably with the rotation of natural (- )-lupinine (-21°) recorded under similar conditions (359). It was also hoped that epimeriza-tion of 366 would give the thermodynamically more stable compound 377 in which the ester group is equatorial, after which reduction would provide access to (- )-epilupinine (ent-331). However, the product obtained after these transformations was optically inactive, which indicated that epimerization was accompanied by racemization, probably through base-induced retro-Michael reaction followed by Michael recyclization. 

The most familiar of the sulfonic adds derived from camphor is 10-camphorsulfonic add (44, Reychler s acid45). Both enantiomers are commercially available and convenient procedures exist for their preparation by sulfonation of camphor (ref 46 exemplifies the racemate, but the procedure works equally well for optically active camphor). The free acid is often applied to the resolution of basic compounds such as amines. A detailed review on the use of derivatives of this acid as auxiliaries has been given3. Esters of this add are normally obtained by the reaction of the alcohols with the sulfonyl chloride which is also commerdally available (or readily obtained by the reaction of the free acid with phosphorus pentachloride or thionyl chloride46,48). Such esters with unsaturated alcohols have been used for diastereoselective [1,2] sigma tropic rearrangements (Section D.1.6.3.3.). Allyl esters have been used for enantioselective alkylation reactions, in which camphorsulfonic acid reacts as the chiral leaving group (Section D.1.1.2.2.). 

Scheme 4.307]. If water is an objectionable component or low solubility a problem THP removal can be accomplished by an acetal exchange process using methanol or ethanol as solvent. Scheme 4.308 illustrates the deprotection of an acid-sensitive allylic alcohol using camphorsulfonic acid in methanol. Pyridi-nium p-toluenesulfonate in methanol or ethanol (pH 3.0) can also be used but higher temperatures (45-55 °C) are required [Scheme 4.309], Ion exchange resins in methanol cleave THP ethers at room temperature. Other THP deprotection conditions to beware or exploit are CAN in the presence of pH 8 buffer, DDQ in aqueous acetonitrile, and Montmorilonite clay in methanol. ... 

Acid-catalysed addition of primary, secondary, and tertiary alcohols to 3,4-dihy-dro-2//-pyran in dichloromethane at room temperature is the only general method currently in use for preparing THP ethers and the variations cited below concern the choice of acid. The reaction proceeds by protonation of the enol ether carbon to generate a highly electrophilic oxonium ion which is then attacked by the alcohol. Yields are generally good. Favoured acid catalysts include p-toluenesulfonic acid or camphorsulfonic acid. To protect tertiary allylic alcohols and sensitive functional groups such as epoxides, the milder acid pyridinium p-toluenesulfonate has been employed (Scheme 4.316]. A variety of other acid catalysts have been used such as phosphorus oxychloride, iodotrimethylsilane- and bis(trimethylsilyl)sulfate. but one cannot help but suspect that in all of these cases, the real catalyst is a proton derived from reaction of the putative catalysts with adventitious water. Scheme 4.317 illustrates the use of bis(trimethylsilyl)sulfate in circumstances where other traditional methods failed. - For the protection of tertiary benzylic alcohols, a transition metal catalyst, [Ru(MeCN)2(triphos)](OTf)2 (0.05 mol%) in dichloromethane at room temperature is effective. ... 

Tang et al. described the enantioselective bromoesterification of allylic sulfonamides with NBS as bromine source and benzoic acid as nucleophile, catalysed by (DHQD)2PHAL in combination with (-l-)-camphorsulfonic acid additive. Unfunctionalised olefins were also used as substrates with... 

The Overman pyrrolidine synthesis is a tandem reaction, or cascade, used to generate acylpyrrolidine derivatives. This process begins with condensation of an allylic alcohol/ether-containing secondary homoallylic amine with an aldehyde, followed by an aza-Cope rearrangement and subsequent Mannich reaction. Commonly, this reaction is run in refluxing benzene with an acidic additive, such as c/-10-camphorsulfonic acid (CSA). 

Fig. 14 Microwave-assisted synthesis of pyrazoles and isoxazoles on cellulose. Reagents and conditions a Camphorsulfonic acid, DMF, MW 80 °C, 15 min, open vessel b NH2XH, MW 82 °C, 15 min, open vessel. X = N,0 Y = NH, NEt, O R = Me, i-Pr, BUCH2, PhCH2, Et(Ph)CH, R = alkyl, allyl, and ar)4 groups...

The novel nitrenium ion-mediated alkene bis-functionalization used by Bowen and Wardrop in their synthesis of swainsonine (cf Scheme 76 Section 3.5.2) also featured in their total synthesis of (-f)-castanospermine (654) (Scheme 90). The derivatized xylopyranoside (+)-681, prepared in four steps fixrm D-xylose, was converted in stepwise fashion into lactone (—)-682 by rearrangement of the allyl ether to the corresponding enol ether, hydrolysis to a mixture of lactol anomers, and oxidation. Carefijl methano-lysis in the presence of camphorsulfonic acid and adjustment of the pH to 7... 

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