Alcohol bicyclic secondary

In addition to this, there are several reports of asymmetric esterification of racemic alcohols with anhydrides as acyl donors. Examples include various primary and secondary alcohols, bicyclic secondary alcohols of the norbomane type, amino alcohols, and ferrocenes. This is exemplified in eq 9 for 1 -phenylethanol. ... 

There are also several reports on the enantioselective hydrolysis of bicyclic secondary alcohols possessing the bicy-clo[2.2.1]heptane and bicyclo[2.2.2] octane framework. Again, with this type of substrate the lipases appear to exhibit strong preference for the endo isomers with the (/ )-configured esters preferentially hydrolyzed. 

Bunton et al. (1963) have reported a preliminary study on the exchange of two bicyclic secondary alcohols. Isoborneol (11) undergoes exchange and racemization at about equal rates in a 0-48n perchloric acid in 40 60 (v/v) aqueous dioxan. 

Bicyclic secondary alcohols open to cycloalkenyl cations. For example, fenchol (VIII) produces l-isopropyl-3-methylcyclohexenyl cation (IX) in over 90% yield, and the same cation forms from borneol and camphene, but in lower yield (Deno and Houser, 1963). 

Bicyclic tertiary alcohols, like bicyclic secondary alcohols, generally ring-open to cycloalkenyl cations. 

Secondary bicyclic alcohols are quantitatively oxidized by Jones reagent however rearranged products are obtamed [5f ] (equation 47)... 

The optically active //-amino alcohol (1 / . 3 R. 5 / )-3-(di phenyl hydroxymethyl )-2-azabicyclo[3.3.0]octane [(li ,3i ,5i )-121], can be derived from a bicyclic proline analog. It catalyzes the enantioselective addition of diethylzinc to various aldehydes. Under mild conditions, the resulting chiral secondary alcohols are obtained in optical yields up to 100%. The bicyclic catalyst gives much better results than the corresponding (S )-proline derivative (S )-122 (Scheme 2-47).114... 

Various aldehydes 184 and alcohols have been shown to be competent in the redox esterification of unsaturated aldehydes in the presence of the achiral mesityl triazo-lium pre-catalyst 186. Both aromatic and aliphatic enals participate in yields up to 99% (Table 13). Tri-substituted enals work well (entry 3), as do enals with additional olefins present in the substrate (entries 4 and 7). The nucleophile scope includes primary and secondary alcohols as well as phenols and allylic alcohols. Intramolecular esterification may also occur with the formation of a bicyclic lactone (entry 8). 

Reaction of the bicyclic 1,3,4-oxadithiolane (113) with triphenylphosphine in refluxing toluene led to an equilibrium mixture of the 1,3-oxathietane (114) and the thiocarbonyl derivative (115) (Scheme 29) <93BCJ1714>. Raney nickel can be used to desulfurize both 1,2,4-trithiolanes (to methylene compounds) and 5,5-disubstituted 1,2,4-oxadithiolane 2-oxides (116) which give rise to secondary alcohols (Equation (20)) <90BSB265>. 

Protection of the secondary alcohol as the corresponding methoxy methyl (MOM) ether, followed by removal of the Boc group with ZnBr2 in dichloromethane and acylation of the incipient secondary amine with bromoacetyl bromide in the presence of K2CO3 afforded the bromoacetamide 114 in 86% yield from 113. Treatment of 114 with methanolic ammonia afforded the corresponding glycinamide which was directly subjected to cyclization in the presence of NaH in toluene/HMPA to afford the bicyclic compound 115 in 79% overall yield from 114. Next, a one-pot double carbomethoxylation reaction was performed by the sequencial addition of n-BuLi in THF followed by addition of methylchloroformate, that carbomethoxylated the amide nitrogen atom. Subsequent addition of four equiv of methyl chloroformate followed by the addition of 5 equiv of LiN(TMS)2 afforded 116 as a mixture of diastereomers in 93% yield that were taken on directly without separation. 

High enantiomeric excess in organocatalytic desymmetrization of meso-diols using chiral phosphines as nucleophilic catalysts was achieved for the first time by Vedejs et al. (Scheme 13.21) [36a], In this approach selectivity factors up to 5.5 were achieved when the C2-symmetric phospholane 42a was employed (application of chiral phosphines in the kinetic resolution of racemic secondary alcohols is discussed in Section 12.1). A later study compared the performance of the phos-pholanes 42b-d with that of the phosphabicyclooctanes 43a-c in the desymmetrization of meso-hydrobenzoin (Scheme 13.21) [36b], Improved enantioselectivity was observed for phospholanes 42b-d (86% for 42c) but reactions were usually slow. Currently the bicyclic compound 43a seems to be the best compromise between catalyst accessibility, reactivity, and enantioselectivity - the monobenzoate of hydrobenzoin has been obtained with a yield of 97% and up to 94% ee [36b]. 

A novel one-pot Dess-Martin oxidation was developed for the construction of the y-hydroxy lactone moiety of the CP-molecules in the laboratory of K.C. Nicolaou. Bicyclic 1,4-diol was treated with 10 equivalents of DMP in dichloromethane for 16h to promote a tandem reaction first, the bridgehead secondary alcohol was selectively oxidized to the ketone, followed by a ring closure to afford the isolable hemiketal, which was further oxidized by DMP to give a keto aldehyde. Trace amounts of water terminated the cascade to give a stable diol, which was not further oxidized with DMP. Subsequent TEMPO oxidation furnished the desired y-hydroxy lactone. 

The tricyclic ring system containing the fully functionalized CD ring of taxol was prepared from (S)-(+)-carvone by T.K.M. Shing et al. The bicyclic a-hydroxy ketone (4-hydroxy-5-one) was isomerized by an Intramolecular redox reaction in the presence of catalytic amounts of aluminum isopropoxide. This example was a special case where both reactants were in the same molecule the ketone was the oxidant for the Oppenauer oxidation, whereas the secondary alcohol was the hydride donor for the MVP reduction. The conversion to the thermodynamically more stable 5-hydroxy-4-one proceeded in good yield. 

The stereocontrolled synthesis of 5 -substituted kainic acids was achieved by A. Rubio et a. The C3 and C4 substituents were introduced by the Wharton fragmentation of a bicyclic monotosylated 1,3-diol. When this secondary alcohol was exposed to KOf-Bu, the corresponding fragmentation product was obtained in moderate yield. Jones oxidation of the aldehyde to the carboxylic acid followed by hydrolysis of the ester and removal of the Boc group resulted in the desired substituted kainic acid. 

The HF-SbFs system works well in the Gattermann-Koch formylatlon of arenes and the Koch carbonylation of alkanes [54]. For instance, biphenyl is diformylated in HF-SbFs-CO to afford 4,4 -diformylbiphenyl as a major isomer (Scheme 14.20). The carbonylation of alkanes with C5-C9 carbon atoms in the HF-SbFs-CO system affords mixtures of C3-C8 carboxylic acids after hydrolysis of the generated secondary carbenium ions [55]. Successive treatment of methylcyclopentane with CO in HF-SbF and with water produces cyclohexanecarboxylic acid as a major product (Scheme 14.21) [56]. It seems that a tertiary methylcyclopentyl cation readily isomerizes to the more stable cyclohexyl cation before being trapped by CO. Bicyclic a, -unsaturated ketones are functionahzed by HF-SbF or FSOsH-SbFs under a CO atmosphere to give saturated keto esters after methanolysis (Scheme 14.22) [57]. Alcohols with short carbon chains also react with CO in HF-SbFs to give the corresponding methyl esters [58]. y-Butyrolactones are carboxy-lated under the same conditions to afford 1,5-dicarboxyhc acids [59]. 

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