Secondary alcohols ether synthesis from

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... 

In contrast, the results obtained in the methanolysis, acetolysis, and trifluoroacetolysis of the tosylate 91 were not the expected ones. Cram obtained the methyl ether 93, the acetate 94 and the trifluoro-acetate 95 with the same configuration and optical purity as in the direct synthesis from the alcohol 92. These solvolyses at the bridge carbon atom of [2.2]paracyclophane therefore proceed with complete retention of configuration. The rate of acetolysis of the tosylate 91 also deviates considerably from that of aliphatic secondary tosylates it is some 100 times faster than that of 2-butyl tosylate and about the same as that of a-phenylneopentyl tosylate, acetolysis of which is only slightly stereospecific. 

Synthesis of secondary alcohols from 1-aOcynes.2 Dihydroboration at room temperature of a terminal alkyne with either (1) or 9-BBN gives a 1,1-diborylalkane (3) this is treated at 0-5° with I eq. of methyllithium in ether. The product (4) rearranges to (5). An alkyl halide (100% excess) is then added, and the resultant secondary organo-borane (6) is oxidized with alkaline hydrogen peroxide. Secondary alcohols (7) are obtained in 70-85% yield. 

Acidic clays are widely applied in the dehydration of alcohols [38]. Although similar to zeolites in their capacity to induce the formation of both alkenes and ethers, selective alkene synthesis is possible. Various layered materials (clays, ion-exchanged montmorillonite, pillared layered clays) are very active and, in general, selective in transforming primary, secondary, and tertiary aliphatic alcohols to 1-alkenes [39-43]. Al -exchanged montmorillonite, however, induces ether formation from primary alcohols and 2-propanol [41]. Substituted 1-phenyl-1-ethanols yield the corresponding styrene derivatives at high temperature (653-673 K) [44]. 

Symmetrical Ether Synthesis from a Secondary Alcohol... 

Miscellaneous Reactions. Sodium bisulfite adds to acetaldehyde to form a white crystalline addition compound, insoluble in ethyl alcohol and ether. This bisulfite addition compound is frequendy used to isolate and purify acetaldehyde, which may be regenerated with dilute acid. Hydrocyanic acid adds to acetaldehyde in the presence of an alkaU catalyst to form cyanohydrin the cyanohydrin may also be prepared from sodium cyanide and the bisulfite addition compound. Acrylonittile [107-13-1] (qv) can be made from acetaldehyde and hydrocyanic acid by heating the cyanohydrin that is formed to 600—700°C (77). Alanine [302-72-7] can be prepared by the reaction of an ammonium salt and an alkaU metal cyanide with acetaldehyde this is a general method for the preparation of a-amino acids called the Strecker amino acids synthesis. Grignard reagents add readily to acetaldehyde, the final product being a secondary alcohol. Thioacetaldehyde [2765-04-0] is formed by reaction of acetaldehyde with hydrogen sulfide thioacetaldehyde polymerizes readily to the trimer. 

Picolyl ethers are prepared from their chlorides by a Williamson ether synthesis (68-83% yield). Some selectivity for primary versus secondary alcohols can be achieved (ratios = 4.3-4.6 1). They are cleaved electrolytically ( — 1.4 V, 0.5 M HBF4, MeOH, 70% yield). Since picolyl chlorides are unstable as the free base, they must be generated from the hydrochloride prior to use. These derivatives are relatively stable to acid (CF3CO2H, HF/anisole). Cleavage can also be effected by hydrogenolysis in acetic acid. ... 

Picolyl ethers are prepared from their chlorides by a Williamson ether synthesis (68-83% yield). Some selectivity for primary vs. secondary alcohols can be achieved (ratios = 4.3-4.6 1). Picolyl ethers are cleaved electrolytically ( —1.4 V,... 

A variant of the Williamson ether synthesis uses thallium alkoxides. The higher reactivity of these can be of advantage in the synthesis of ethers from diols, triols and hydroxy carboxylic acids, as well as from secondary and tertiary alcohols on the other hand however thallium compounds are highly toxic. 

In comparison to the N- and S-counterparts, alkoxides possess lower nucleophilicity. Therefore, the reductive elimination process to form the C—O bond is much slower than those to form C— N and C—S bonds [103]. Palucki, Wolfe and Buchwald developed the first intramolecular Pd-catalyzed synthesis of cyclic aryl ethers from o-haloaryl-substituted alcohols [104]. For example, 3-(2-bromophenyl)-2-methyl-2-butanol (91) was converted to 2,2-dimethylchroman (92) under the agency of catalytic Pd(OAc)2 in the presence (S)-(-)-2,2 -bis(di-p-tolylphosphino)-l,r-binaphthyl (Tol-BINAP) as the ligand and K2CO3 as the base. The method worked well for the tertiary alcohols, moderately weE for cychc secondary alcohols, but not for acyclic secondary alcohols. 

It has been reported that (TMS)3SiCl can be used for the protection of primary and secondary alcohols [55]. Tris(trimethylsilyl)silyl ethers are stable to the usual conditions employed in organic synthesis for the deprotection of other silyl groups and can be deprotected using photolysis at 254 nm, in yields ranging from 62 to 95%. Combining this fact with the hydrosilylation of ketones and aldehydes, a radical pathway can be drawn, which is formally equivalent to the ionic reduction of carbonyl moieties to the corresponding alcohols. 

Thus, a wide variety of vinyl ethers could be synthesized using this method (Scheme 10.5). This catalyhc vinylation system was found to be applicable to the synthesis of vinyl ethers from secondary and tertiary alcohols. No deuterium was introduced into the resulhng phenyl vinyl ether when phenol-d was allowed to... 

Tojo and co-workers reported a one-pot synthesis of alkyl nitrates from alcohols via the alkyl iodide the alcohol is treated with a mixture of iodine, triphenylphosphine and imidazole in diethyl ether-acetonitrile, and the resulting alkyl iodide is reacted in situ with silver nitrate (Equation 3.8). Reported yields for primary alcohols are good to excellent but yields are lower for secondary alcohols. 

A similar strategy has been employed in the synthesis of a dihydropyran required to achieve the synthesis of (—)-lanlimalide (Scheme 23). Thns, ally-lation of the secondary alcohol resnlting from a methallylation of 3-tri-n-butylstannylacrolein provided unsymmetrical ether 182, which is closed to a pyran with a ring-closing metathesis using Schrock s molybdennm catalyst. 

The generation of hydroxy ketones by the brominolysis of stannylenes has been used several times in total synthesis. Experiment G [see Eq. (15)] describes a key step in the total synthesis of the antibiotic (+)-spectinomycin [12,13]. It is remarkable that the two oxygen atoms bound to the tin atom originate from hydroxyl groups, which are port of different functions, a hemiketal and a secondary alcohol. The oxidation is selective for one alcoholic function ont of three. The same product was obtained by W-bromosuccinimide oxidation of the tributylstarmyl ether. 

Alcohols react with a large excess of dimethoxymethane, (bp 41-42 °C) via an acetal exchange process at room temperature in the presence of acidic catalysts such as phosphorus pentoxide.459 474-475 The reaction was adapted to the construction of a 1,3-dioxane ring system in a synthesis of Mycalamide B [Scheme 4<257].47A After installing a MOM ether at a hindered secondary alcohol 257,1, the ketone was converted to its TBS enol ether 257J. Oxidation with wi-chloroperoxybenzoic acid returned a stable oxirane 257.4 that reacted with dimethoxymethane and phosphorus pentoxide to afford the desired L3-dioxane ring in 257 6 in 77% overall yield from 257J. Presumably, O-alkyla-... 

The Williamson reaction, discovered in 1850, is still the best general method for the preparation of unsymmetrical or symmetrical ethers.The reaction can also be carried out with aromatic R, although C-alkylation is sometimes a side reaction (see p. 515). The normal method involves treatment of the halide with alkoxide or aroxide ion prepared from an alcohol or phenol, although methylation using dimethyl carbonate has been reported. It is also possible to mix the halide and alcohol or phenol directly with CS2CO3 in acetonitrile, or with solid KOH in Me2SO. The reaction can also be carried out in a dry medium,on zeolite-or neat or in solvents using microwave irradiation. Williamson ether synthesis in ionic liquids has also been reported. The reaction is not successful for tertiary R (because of elimination), and low yields are often obtained with secondary R. Mono-ethers can be formed from diols and alkyl halides. Many other... 

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