Reaction with 2,4-pentanediol

The use of tartrate esters was an obvious place to start, especially since both enantiomers are readily available commercially and had already found widespread application in asymmetric synthesis (Figure 11) (e.g.. Sharpless asymmetric epoxidation).23.24 Reagents 36-38 are easily prepared and are reasonably enantioselective in reactions with achiral, unhindered aliphatic aldehydes (82-86% ee) typical results are given in Figure 12.3c,h Aromatic and a,p-unsaturated aldehydes, unfortunately, give lower levels of enantioselection (55-70% e.e.). It is also interesting to note that all other C2 symmetric diols that we have examined (2,3-butanediol, 2,4-pentanediol, 1,2-diisopropylethanediol, hydrobenzoin, and mannitol diacetonide, among others) are relatively ineffective in comparison to the tartrate esters (see Table ll).25... 

N-Heterocyclization.1 1,5-Pentanediol reacts with primary amines at 150-180° in the presence of a ruthenium catalyst to form N-substituted piperidines. For the reaction with aromatic amines RuC I QHs) is the catalyst of choice. On the other hand, the most effective catalyst for the reaction with aliphatic amines is RuC13 combined with either tributylphosphine or triethylphosphine. 

Reaction with chiral acetals. The chiral ketals derived from (2R,4R)-(-)-2,4-pentanediol (1) can be cleaved with high diastercoselectivity by aluminum hydride reagents, in particular DIBAH, CI2AIH, and Br,AlH. Oxidative removal of the chiral auxiliary affords optically active alcohols. This process provides a useful method for highly asymmetric reduction of dialkyl ketones. ... 

Pentanediol is often superior to other diols such as 2,3-butanediol for these reactions because of higher distereoselectivities in reactions with nucleophiles and the more facile cleavage of the resulting hydroxy ether by oxidation-p-elimination. Removal of the chiral auxiliary is usually carried out with Pyri-dinium Chlorochromate oxidation followed by p-elimination using KOH, K2CO3, piperidinium acetate, dibenzylammonium trifluoroacetate, " or DBU. In some cases, 1,3-butanediol is preferred because the final 3-elimination may be effected under milder conditions. ... 

The cyclization in Step B is an improvement of Butler s procedure for the synthesis of which employs less convenient reagents, KNH and l-bromo-3-chloroacetone acetal. Beside the acetals derived from neopentyl glycol, those derived from ethanol, 1,3-propanediol and 2,4-pentanediol have been synthesized by the present method. The second part of Step B involves the formation and the electrophilic trapping of cyclopropenyl anion 2, which is the key element of the present preparations. Step B provides a simple route to substituted cyclopropenones, but the reaction is limited to alkylation with alkyl halides. The use of lithiated and zincated cyclopropenone acetal, on the other hand, is more general and permits the reaction with a variety of electrophiles alkyl, aryl and vinyl halides, Me3SiCl, Bu3SnCl, aldehydes, ketones, and epoxides. Repetition of the lithiation/alkylation sequence provides disubstituted cyclopropenone acetals. 

Intramolecular pinacol coupling reactions are known, giving cyclic 1,2-diols. Dialdehydes have been cyclized by reaction with TiCls to give cyclic 1,2-diols in good yield. ° A radical-induced coupling of an a,03-dialdehyde led to cw-l,2-cyclo-pentanediol when treated with BuaSnH and AIBN. or induced photochemically. ... 

OXA-l,5-PENTANEDIOL (111-46-6) Combustible liquid (flash point 255 F/124°C). Vigorous reaction with strong oxidizers. Incompatible with aliphatic amines, amides, sulfuric acid, nitric acid, caustics, isocyanates. 

The polymerization for polyaddition of a monomer that possesses an additional functionality allows the production of dual-function particles. The acyl chloride of the azo-initiator 4,4 -azo-4-cyanopentanoic add was reacted with 2,4-diethyl-l,5-pentanediol to yield a diol-functionahzed monomer, in addition to the azo-bond functional groups [118]. The functionahzed diol was first polymerized in a polyaddition reaction with a diisocyanate subsequently, it was possible to cleave the azo-bonds and to polymerize styrene in the nanodroplets. Such an approach combines free-radical polymerization and polyaddition, to produce hybrid block-copolymer particles. 

Asymmetric Buchner reactions using chiral auxiliary have also been undertaken. The diazoketo substrate 126 for the chiral tethered Buchner reaction is prepared from optically pure (2/ ,4/f)-2,4-pentanediol in three steps the Mitsunobu reaction with 3,5-dimethylphenol, esterification with diketene, and diazo formation/deacetylation. Treatment of 126 with rhodium(II) acetate results in a quantitative yield of 127 with more than 99% ee. This compound is reduced with lithium aluminium hydride, and the resulting diol 128 undergoes epoxidation and concurrent acetal formation to give 129 as a single diastereomer. Hydrogenation of 129 with Raney nickel proceeds stereoselectively to yield saturated diol 130, which is converted to aldehyde 132 via acid hydrolysis followed by oxidation. Compound 132 is a versatile intermediate for natural product synthesis. 

Polymer-bound diene 25 was subjected to a Diels-Alder reaction with tiglic aldehyde 26 in the presence of tetrame-thylsilane (TMS)-triflate for the construction of the bicyclic core structure (Scheme 16.4). Cycloadduct 27 was obtained as a mixture of four isomers that were formed in a ratio of 67 16 16 1 endolendo lexolexo ) with the desired endo isomer predominating. To improve the stereoselectivity, tiglic aldehyde was converted into the quasi-Ca-symmetric chiral acetal 28 derived with (R,R)-2,4-pentanediol. This chiral dienophile underwent an asymmetric Diels-Alder reaction at -78°C. Removal of the chiral auxiliary from the acetal 29 resulted in the cycloadduct 27 as a mixmre of the four isomers in a ratio of 87 4 9 0.1 endolendo lexolexo ), demonstrating that the stereoselectivity of the main isomer increased from 67% to 87%. ... 

Reaction with Di- and Polyols. Although intermolecular dehydration between two molecules of alcohols to afford acyclic ethers usually does not occur with the DEAD-TPP system, intramolecular cyclization of diols to produce three to seven-membered ethers is a common and high yielding reaction. Contrary to an early report, 1,3-propanediol does not form oxetane. Oxetanes can be formed, however, using the trimethyl phosphite modification of the Mitsunobu reaction. The reaction of (5)-1,2-propanediol and ( )-l,4-pentanediol with DEAD and TPP affords the corresponding cyclic ethers with 80-87% retention of stereochemistry at the chiral carbon, while (5)-phenyl-1,2-ethanediol affords racemic styrene oxide. In contrast to the reaction of the same 1,2-diols with benzoic acid (eq 4), oxyphos-phonium salts (25a) and (25b) have been postulated as key intermediates in the present reaction (eq 20). ... 

Vinyl ethers and a,P unsaturated carbonyl compounds cyclize in a hetero-Diels-Alder reaction when heated together in an autoclave with small amounts of hydroquinone added to inhibit polymerisation. Acrolein gives 3,4-dihydro-2-methoxy-2JT-pyran (234,235), which can easily be hydrolysed to glutaraldehyde (236) or hydrogenated to 1,5-pentanediol (237). With 2-meth5lene-l,3-dicarbonyl compounds the reaction is nearly quantitative (238). 

Esters. The monoisobutyrate ester of 2,2,4-trimethyl-1,3-pentanediol is prepared from isobutyraldehyde ia a Tishchenko reaction (58,59). Diesters, such as trimethylpentane dipelargonate (2,2,4-trimethylpentane 1,3-dinonanoate), are prepared by the reaction of 2 mol of the monocarboxyhc acid with 1 mol of the glycol at 150—200°C (60,61). The lower aUphatic carboxyHc acid diesters of trimethylpentanediol undergo pyrolysis to the corresponding ester of 2,2,4-trimethyl-3-penten-l-ol (62). These unsaturated esters reportedly can be epoxidized by peroxyacetic acid (63). 

The reaction products of TYZOR TPT with 2—4 moles of 1,3-diols having two to three alkyl substituents, such as 2,2,4-trimethyl-l,3-pentanediol, gives complexes that could be used as cross-linking agents for hydroxy group containing powdered lacquer resins (76). 

On the other hand, Davies5 , studying the reaction of adipic add with 1,5-pentanediol in diphenyl oxide or diethylaniline found an order increasing slowly from two with conversion. From this result he concluded that Flory s1,252-254> and Hinshelwood s240,241 interpretations are erroneous. Two remarks must be made about the works of Davies5 experimental errors relative to titrations are rather high and kinetic laws are established for conversions below 50%. Under such conditions the accuracy of experimental determinations of orders is rather poor. 

Chiral acetals/ketals derived from either (R,R)- or (5,5 )-pentanediol have been shown to offer considerable advantages in the synthesis of secondary alcohols with high enantiomeric purity. The reaction of these acetals with a wide variety of carbon nucleophiles in the presence of a Lewis acid results in a highly diastereoselective cleavage of the acetal C-0 bond to give a /1-hydroxy ether, and the desired alcohols can then be obtained by subsequent degradation through simple oxidation elimination. Scheme 2-39 is an example in which H is used as a nucleophile.97... 

From a practical point of view, the catalytic asymmetric hydrogenation of the corresponding diones will be the preferred method if high yields and high enantioselectivity can be ensured. Recently, over 98% yield with more than 99% ee has been achieved by optimizing the reaction conditions.64 For example, asymmetric hydrogenation of 2,4-pentanedione catalyzed by Ru-BINAP complex in the presence of hydrochloric acid gave 2,4-pentanediol in more than 95% yield and over 99% ee (Scheme 6-29).64... 

As depicted in Fig. 6, syntheses of enantiomerically pure 116 and 117 have been carried out [236]. Lipase AK-catalysed asymmetric acetylation of meso-2,4-dimethyl-1,5-pentanediol A yielded (2R,4S)-5-acetoxy-2,4-dimethylpen-tanol B. Protection of the free hydroxy group as the terf-butyldimethylsilyl (TBS) ether, saponification of the acetate, and oxidation furnished the aldehyde C. Reaction of C with ethylmagnesium bromide gave a diastereomeric mixture of the corresponding secondary alcohols which could be resolved by asym-... 

The same group also demonstrated an efficient, two-step asymmetric synthesis of (S)-2-phenylpiperidine as an extension of the N-heterocycUzation of primary amines with diols the results are illustrated in Scheme 5.25. First, the reaction of enantiomerically pure (R)-l-phenylethylamine and 1-phenyl-1,5-pentanediol was conducted to produce a diastereomeric mixture of the corresponding N-(l-phenyl-ethyl)-2-phenylpiperidines 32 and 33 with 92% diastereomeric excess (de). Hydrogenation of this diastereomeric mixture of 32 and 33 with Pd/C catalyst then gave (S)-2-phenylpiperidine in 96% yield (78% ee). 

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