Anti-Alcohols

Facial selectivities of spiro[cyclopentane-l,9 -fluorene]-2-ones 30a-30e were studied by Ohwada [96, 97]. The carbonyl tz orbital can interact with the aromatic % orbital of the fluorene in a similar manner to spiro conjugation [98-102]. The ketones 30 were reduced to alcohols by the action of sodium borohydride in methanol at -43 °C. The anti-alcohol, i.e., the syn addition product of the reducing reagent with respect to the substituent, is favored in all cases, irrespective of the substituent at C-2 or C-4 of the fluorene ring (2-nitro 30b syn anti = 68 32), 4-nitro... 

Elliot Ness, well-known to viewers of television s The Untouchables, spearheaded street-level anti-alcohol enforcement during the Prohibition era of the 1920s. After graduating from the University of Chicago, Ness was hired in 1929 as a special agent of the U.S. Department of Justice. The... 

Stereoselective reduction of -keto amides.1 a-Methyl-p-keto amides are reduced by this silane in combination with tris(diethylamino)sulfonium difluorotri-methylsilicate (10, 452-453) in DMPU to the anti-alcohol, but are reduced by this silane in TFA to the syn-alcohol. 

Anti syn diastereomeric ratio. Value of the anti alcohol.0 Containing <1% of water. 

Syn anti diastereomeric ratio. h Value of the syn alcohol. 3,4-Methylenedioxyphenyl. d Containing 0.5% of water. e Ethyl ester, /Value of the anti alcohol. 4 atm of H2. 

Sukul NC, De A, Dutta (Nag) R, Sukul A, Sinhababu SP. 2001. Nux vomica 30 prepared with and without succussion shows anti-alcoholic effect on toads and distinctive molecular association. Hr Horn J90 79-85. 

The anti alcohol is observed to be formed in greater amounts (85 15) on reduction of the ketone with LiAlH4. Steric factors governing attack of the hydride reagent again explain the major product observed. 

Step 2 Chelation-controlled reduction of the ketone produces the anti-alcohol diastereoselectively. 

There have been two reports of elaboration of the oxazole moiety. Meyers et al. (67) resolved the racemic alcohols 111 via the cyclic acetal of the syn secondary hydroxy groups of 146, formed by reaction with the dimethyl acetal of mesityl aldehyde. The free anti alcohol 111 could be recovered from this process. 

However, CeCb is a poor chelating Lewis acid. The stereochemistry of the reaction is reversed in this case, which can be explained on the basis of an open-chain Felkin-Ahn model. The anti-alcohol 6.68 is produced by the attack of hydride from the less hindered side to the most stable conformation, C of CeCb complex. The D conformation is less stable than C (Scheme 6.26). 

In the oxidation of a diastereomeric mixture of carveol (syrr.anti = 42 58), the syn alcohol is stereoselectively oxidized and the anti alcohol is recovered in 98 % diastereomeric purity. This shows that the catalytic activity of (C6p5)2BOH is very sensitive to steric hindrance in the alcohols (Eq. 108). In oxidations of equimolar mixtures of geraniol and j8-citronellol, geranial is obtained in 96 % yield and most of the /8-citro-nellol is recovered imchanged (Eq. 109). The selective conversion of allylic alcohols in the presence of saturated alcohols is particularly noteworthy. 

The addition of methylzinc (and cadmium) organometallics to chiral aldehydes proceeds with low stereoselectivity and leads to a mixture of syn- and anti-alcohols (see Scheme 22). A better dia-stereoselectivity can be achieved by using the mixed copper-zinc reagents RCu(CN)ZnI. ° In contrast, the more reactive diallylzinc reacts with several a-alkoxy aldehydes of type (43) to give anti addition... 

The reaction of ( )- and (Z)-71 with aldehydes has been demonstrated to proceed smoothly with high regio- and diastereoselectivity [50]. Reaction of the ( )-71 provides almost exclusively the syn homoallylic alcohols, while (Z)-71 provides the corresponding anti alcohols. The stereochemical course of the reaction has been attributed to the intermediacy of a chairlike, six-membered transition structure assembly which incorporates all three elements and places the C(3) substituent in pseudoequa-torial or pseudoaxial orientations according to olefin geometry (Scheme 10-29). 

Addition of diethyl aluminum chloride at — 78 °C to a,/ -unsaturated oxazolidinone (154) affords an aluminum enolate that, on hydroxylation with (63a), gives the / -ethyl-a-hydroxy amide (155) with high anti selectivity (Equation (38)) <91AG(E)694>. Formation of the enolate of oxazoline thiol ester (156) under chelation (NaHMDS) and stereoelectronic (NaHMDS/HMPA) control gives the syn and anti alcohols (157), respectively, on hydroxylation with (63a) in good to excellent yield and better than 95% diastereoselectivity (Scheme 28) <93JOC6180>. A counterion dependent reversal in stereochemistry has also been reported for the hydroxylation of chiral amide enolates where the auxiliary was 2-pyrrolidinemethanol <85TL3539>. 

The initial transmetalation of 249 leads to 250 via anti-SE substitution and additional isomerizations provide 251 and 252. The closed, six-membered transition state 253 from 250 is used to rationalize formation of the E-anti-alcohol 254 as the major product, whereas the minor -xyn-adduct 256 is generated from 252 via the closed arrangement 255. The stereochemical consequences for InCh trans-metalations are complimentary to the syn outcome of reactions for y-(alkoxy)allylstannanes. As a result, the technique has been utilized in organic synthesis, with the illustration of several applications in Scheme 5.2.56. ... 

Other additives can induce the formation of chelates. a-Phosphinyloxyketones 3.98 undergo a stereoselective reduction to anti alcohols with NaBH4-CeCl3 in... 

The known bicyclo[3.1. Ojhexene 167 was hydroborated and oxidized to afford anti alcohol 168 in up to 80% yield. Chromic acid oxidation of 168 was followed by p elimination of malonate anion with EtaN to produce enone 169 (86%). Initial deprotonation of 169 followed by the addition of cuprate 166 afforded an 82% yield of 170. As expected, Michael addition to the enone occurred anti to the malonate unit. Reduction of ketone 170 with LiBH4 gave a 4 1 mixture of Cy alcohols, the major product being the desired a-hydroxy isomer. Chromatographic separation of the alcohols, followed by protection and ester cleavage, then gave the diacid 171. 

Cyclic compounds have fewer degrees of freedom than their acyclic counterparts and this means that not only can we expect a higher level of control, but the resulting stereochemistry is easier to visualise. So reduction of the achiral ketone 80 could lead to the syn alcohol 81 or the anti alcohol 82. The question is which do we get and why ... 

Now it is worth making enantiomerically enriched 90. One method already in the literature14 involved reduction of racemic 90 with horse liver alcohol dehydrogenase. This is an enzymatic kinetic resolution (chapters 28 and 29) and at 50% reduction the products are 31% unreacted ketone 90 in good ee, 33% of one enantiomer of the anti-alcohol 93 in perfect (100%) ee, and a trace of the vvn-alcohol 93. 

Carbamide, nitrolime. White to grey-black powder. Skin-caustic. Releases cyanide. Used as fertilizer, defoliant, herbicide, pesticide and veterinary anthelmintic. Citrated form used as an anti-alcohol treatment as per disulfiram. 

The Li—F chelation is also useful for stereoselective reactions. In particular, chelation between lithium of enolates and a fluorine of a trifluoromethyl group results in conformational fixation of substrates, leading to markedly enhanced stereoselection. This concept has often been employed to achieve stereocontrol in fluorinated enolate chemistry. Morisawa reported Li—F chelation-controlled stereoselective a-hydroxylation of enolate of 40 [22]. The oxidant approaches from the less hindered side of the Li—F chelated enolate intermediate (41), affording anti-alcohol (42) exclusively (Scheme 3.11). The syn-alcohol (45) was prepared by NaBlrh reduction of ketoester (43) via a reaction course predicted by Felkin-Anh s model (44). 

The experimental observation is that hydride reduction (Felkin-Anh control) of the ketone 7.153 gives the anti-alcohol anti-7.154 as the major product, but electron-transfer reduction gives its syn diastereoisomer syn-7.154.1067 This is in contrast to the reduction on p. 423, which differs in having a silyl group on the oxygen atom in a neutral radical. 

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