Alcohols precursors

OleFns and Fatty Alcohols. Alkylbenzyldimethylammonium (ABDM) quatematies are usually prepared from a-olefin or fatty alcohol precursors. Manufacturers that start from the fatty alcohol usually prefer to prepare the intermediate alkyldimethylamine direcdy by using dimethylamine and a catalyst rather than from fatty alkyl chloride. Small volumes of dialkyldimethyl and alkyltrimethyl quatematies in the Cg—range are also manufactured from these precursors (Fig. 4). 

Both reactants in the Williamson ether synthesis usually originate in alcohol precursors. Sodium and potassium alkoxides ar e prepar ed by reaction of an alcohol with the appropriate metal, and alkyl halides are most commonly made from alcohols by reaction with a hydrogen halide (Section 4.7), thionyl chloride (Section 4.13), or phosphonrs tri-bromide (Section 4.13). Altenratively, alkyl p-toluenesulfonates may be used in place of alkyl halides alkyl p-toluenesulfonates are also prepared from alcohols as their immediate precursors (Section 8.14). 

The dimerization reactions of 2-vinylindoles and their alcohol precursors have also been explored, giving rise to the formation of several dimeric structures, such as the 6,12-dihydroindolo[3,2-h]carbazole derivative 160, which was obtained on dimerization of 2-(a-hydroxyethyl)indole under acidic conditions (71JOC1759). 

In a related study, 161 was reported from a dimerization of a 3-vinylindole precursor (61JOC4254). Previously, a compound with the structure 162 had been suggested as a product originating from a dimerization of an alcohol precursor under acidic conditions (63G238). It has recently been demonstrated that the alcohol 163, when treated with aluminum trichloride in the presence of acetic anhydride, produced the indolocarbazole 160, which could be isolated in 41% yield as an 83 17 mixture of cis and trans isomers (98JOC2909). 

These materials, when exposed to continuous high humidity, especially in the presence of an electrical field, hydrolyze into the acid and alcohol precursors from which they are made. The acid plus water present make a conductive material that will cause the material to short the electrical circuit. The process by which the decomposition of the TS polyester takes place is very gradual at first and then accelerates so that extended testing of the material is necessary to be sure that the particular polyester composition used is resistant to hydrolytic degradation. 

In a similar fashion, 2-cumyladamantane (12, R = Ph) is formed in nearly quantitative yield upon treatment of the easily synthesized 2-cumyl-2-adaman-tanol (11, R = Ph)154 with triethylsilane and methanesulfonic acid in dichloromethane at —78°.155 The high yield of a single very strained hydrocarbon product in each reaction is quite surprising in view of the very complex interconversions of carbocations known to take place from the alcohol precursors.140,151 152 156... 

The isomeric propargylic stannylated aldehyde intermediate, on the other hand, could be prepared from the alcohol precursor without competing cyclization to an seven-membered enol ether product (Eq. 9.105). Treatment of this stannane with SnCl4 afforded the cis-disubstituted tetrahydrofuran stereoselectively. Presumably, this reaction proceeds through an allenyl trichlorostannane intermediate. 

The limited extent of intramolecular rearrangements undergone by the chiral oxonium ions 35 and 36 at 720 torr and at 40 °C (Table 22) allows their use for probing the regio- and stereochemistry of the displacement reactions of Scheme 19. In this case, the allylic alcohol, precursor of the chiral oxonium ions 35 and 36, acts as the nucleophile NuH. The relevant results are condensed in Scheme 21. 

How Does Arabidopsis Assemble Homoterpene Volatiles 11.4.1 Formation of Alcohol Precursors... 

A Ci3 branched alcohol ethoxylate containing an average of 7 EO units per mole of alcohol (C13BAE-7). The alcohol precursor was made by catalytic addition of CO and H2 to highly branched propylene tetramer. 

The advent of sulfamate ester oxidative cyclization makes available a myriad of oxathia-zinane derivatives from simple alcohol precursors. These unusual heterocycles have enjoyed only sparing use despite their potential as electrophiHc azetidine equivalents. By contrast, five-membered ring sutfamidates and cycHc sulfates are broadly recog-... 

Steiically congested cw-aziridines such as 137 were prepared from the deiivatized amino allyl alcohol precursor 136 through a palladium-catalyzed cyclization reaction <99TL1331>. This methodology has also been extended to the cyclization of amino allenes <99JOC2992>. 

Significantly, silylcuprates react with carbamates with syn stereoselectivity59, similar to their reactions with organocuprates62, whereas other nucleofugal groups, such as acetate or methanesulfonate, are displaced in an anti fashion23,27,57. Thus, both enantiomeric (or epimeric) allenes can be obtained from the same propynyl alcohol precursor. 

The propargylic alcohol group may be exploited as an allylic alcohol precursor (Eq. 6A.2) and may be generated by nucleophilic addition to an electrophile [25] or by addition of a formaldehyde equivalent to a preexisting terminal acetylene group [26], Once in place, reduction of the propargylic alcohol with lithium aluminum hydride or, preferably, with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) [27] will produce the trans allylic alcohol. Alternately, catalytic reduction over Lindlar catalyst can be used to obtain the cis allylic alcohol [28]. The addition of other lithium acetylides to ketones produces chiral secondary alcohols, which also can be reduced by the preceding methods to the cis or trans allylic alcohols. Additional synthetic approaches to allylic alcohols may be found in the various references cited in this chapter. 

The epoxy alcohol 47 is a squalene oxide analog that has been used to examine substrate specificity in enzymatic cyclizations by baker s yeast [85], The epoxy alcohol 48 provided an optically active intermediate used in the synthesis of 3,6-epoxyauraptene and marmine [86], and epoxy alcohol 49 served as an intermediate in the synthesis of the antibiotic virantmycin [87], In the synthesis of the three stilbene oxides 50, 51, and 52, the presence of an o-chloro group in the 2-phenyl ring resulted in a lower enantiomeric purity (70% ee) when compared with the analogs without this chlorine substituent [88a]. The very efficient (80% yield, 96% ee) formation of 52a by asymmetric epoxidation of the allylic alcohol precursor offers a synthetic entry to optically active 11 -deoxyanthracyclinones [88b], whereas epoxy alcohol 52b is one of several examples of asymmetric epoxidation used in the synthesis of brevitoxin precursors [88c]. Diastereomeric epoxy alcohols 54 and 55 are obtained in combined 90% yield (>95% ee each) from epoxidation of the racemic alcohol 53 [89], Diastereomeric epoxy alcohols, 57 and 58, also are obtained with high enantiomeric purity in the epoxidation of 56 [44]. The epoxy alcohol obtained from substrate 59 undergoes further intramolecular cyclization with stereospecific formation of the cyclic ether 60 [90]. 

In a new syntiiesis of diltiazem (98b R = Ac, X = CH2CH2NMe2), a calcium antagonist used in the treatment of hypertension, die key step is die diastereoselective reduction of a-ketolactam (97) to die alcohol precursor (98a R = X = H).158 The reduction of the 1,5-benzothiazepine (97) was achieved using an NaBH4-(5)-amino acid combination (,S)-f-leucine was most efficient, and was readily recovered unracemized. 

Whittaker and co-workers805,806 have also prepared a number of terpenoid bicyclic ethers, such as isomeric 1,6-dihydrocarveols 199 (HSO3F—S02,78°C) from unsaturated alcohols or diols.805 806pura-Menth-l-en-9-ol and a related diol afforded the seven-membered ring systems 200. The oxolane moiety in compound 201 was generated from the corresponding unsaturated alcohol precursor in 2 equivalents of triflic acid.807... 

Advantageous use of homochiral cyclohexadiene-cis-l,2-diol, available by means of biocatalytic oxidation of chlorobenzene with toluene dioxygenase, has enabled the synthesis of all four enantiomerically pure C18-sphingosines (Nugent, 1998), which are known inhibitors of protein kinase C and important in cellular response mediation for tumor promoters and growth factors. The four requisite diastere-omers of azido alcohol precursors were accessed by regioselective opening of epoxides with either azide or halide ions. 

A simple example involves the reaction of the silyl ether 213, made from the corresponding 4-hydroxy-alkene by treatment with (bromomethyl)chloro-dimethylsilane, with tributyltin hydride and a radical initiator. Bromine abstraction and intramolecular cyclization with the double bond leads to the bicyclic 214, which upon oxidation with hydrogen peroxide gives the branched-chain 215 in an overall yield of 73% from the alcohol precursor of 213 (Scheme 21). When the sequence is conducted with the C-4 epimeric starting alcohol, the final product again has the hydroxymethyl group cis-related to the hydroxy group.217... 

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