Cyanohydrin acetate

Cholestane-3/3,5a-diol 3-acetate, 397 Cholestane-4a,5a-diol 4-tosylate, 398 Cholestane-5a,6a-diol 6-tosylate,394 5a-Cholestan-2-one, 57, 88, 427 10(5 4 H)ijAeo-Cholestan-5-one, 398 10(5 6)ij ieo-Cholestan-5-one, 392, 394 5a-Cholestan-3-one cyanohydrin, 359 5a-Cholestan-3-one cyanohydrin acetate, 360 5a-Cholestan-2a,3a-oxide, 42 5a-Cholestan-2/3,3/3-thiirane, 43 Cholest-5-ene-3, 19-diol, 268 Cholest-5-ene-3, 25-diol, 71 5(10->l/3H)flfc eo-cholest- 10(19)-ene-3/8,5a-diol 3-acetate, 397, 398 Cholest-4-ene-3,6-dione, 105 Cholest-4-en-3-one, 318 Chromium trioxide, 147, 150 5a-Conanine-3/3-ol-ll-one 3-acetate, 259 Cupric bromide, 210, 211 Cuprous chloride-catalyzed conjugate addition, 76, 80... 

The product obtained from this distillation usually contains small amounts of acetone cyanohydrin acetate, as evidenced by an ester carbonyl band at 1740 cm.-1 in its infrared spectrum. This material does not interfere with the nitration reactions of the reagent. It may be removed by fractionation through a more efficient column. 

Several reports on DKR of cyanohydrins have been developed using this methodology The unstable nature of cyanohydrins allows continuous racemization through reversible elimination/addition of HCN under basic conditions. The lipase-catalyzed KR in the presence of an acyl donor yields cyanohydrin acetates, which are not racemized under the reaction conditions. 

In 1992, Oda et al. reported a one-pot synthesis of optically active cyanohydrin acetates from aldehydes, which were converted to the corresponding racemic cyanohydrins through transhydrocyanation with acetone cyanohydrin, catalyzed by a a strongly basic anion-exchange resin [46]. The racemic cyanohydrins were acetylated by a lipase from P. cepacia (Amano) with isopropenyl acetate as the acyl donor. The reversible nature of the base-catalyzed transhydrocyanation enabled continuous racemization of the unreacted cyanohydrins, thereby effecting a total conversion (Figure 4.21). 

Inagaki, M. Hiratake, J. Nishioka, T Oda, J. One-pot synthesis of optically active cyanohydrin acetates from aldehydes via lipase-catalyzed kinetic resolution coupled with in situ formation and racemization of cyanohydrins. J. Org. Chem. 1992, 57, 5643-5649. 

The combination of ortho metallation and meta nucleophilic acylation was used to prepare a key intermediate in a synthesis of deoxyfrenolicin (42), as outlined in Scheme 11. The complex of anisole is orf/io-metallated with n-butyllithium and quenched with chlorotrimethylsilane the resulting [(o-(tri-methylsilyl)anisole)Cr(CO)3] (43) is then metallated again, converted to the arylcuprate, and coupled with ( )-2-hexenyl bromide to give the complex of l-trimethylsilyl-2-methoxy-3-(2-hexenyl)benzene (44). Addition of the carbanion from the cyanohydrin acetal of 4-pentenal, followed by the standard iodine oxidation and subsequent hydrolysis of the cyanohydrin acetal to regenerate the carbonyl group... 

This process has been coupled with meta addition of a carbonyl anion equivalent and the controlled exo addition of the incoming nucleophile to generate acorenone and acorenone B stereospecifically from [(o-methylanisole)Cr(CO)3] (63 Scheme 14).123 The first step is addition of a cyanohydrin acetal anion (64) to the less-hindered meta position in [(o-methylanisole)Cr(CO)3]. Addition of allylMgBr to the resulting ketone, anti-Markovnikov addition of HBr to the alkene, substitution for Br by CN, and coordina-... 

While the addition-oxidation and the addition-protonation procedures are successful with ester enol-ates as well as more reactive carbon nucleophiles, the addition-acylation procedure requires more reactive anions and the addition of a polar aptotic solvent (HMPA has been used) to disfavor reversal of anion addition. Under these conditions, cyano-stabilized anions and ester enolates fail (simple alkylation of the carbanion) but cyanohydrin acetal anions are successful. The addition of the cyanohydrin acetal anion (71) to [(l,4-dimethoxynaphthalene)Cr(CO)3] occurs by kinetic control at C-P in THF-HMPA and leads to the a,p-diacetyl derivative (72) after methyl iodide addition, and hydrolysis of the cyanohydrin acetal (equation 50).84,124-126... 

Addition of a cyanohydrin acetal anion to [(benzene)Cr(CO)3] followed by reaction with allyl bromide produces the cyclohexadiene derivative (73) in 94% yield, which undergoes a Diels-Alder reaction rapidly to give a tricyclic framework (74). After quenching with methyl iodide and disassembling of the cyanohydrin group, the diketone (75) is obtained in 50% yield overall (equation 51).125 These products are obviously interesting as potential intermediates for synthesis. 

The addition-protonation procedure maintains the arene-chromium bond and allows further application of the activating effect of the metal. In an approach to the synthesis of anthraquinone antibiotics, the dihydronaphthalene complex (79) was allowed to react with a cyanohydrin acetal anion and then quenched with acid.129 The resulting tetralin complex (80) could be metallated effectively and carried on to a key intermediate (81) in anthraquinone construction (equation 54)... 

A central element in the synthetic strategy presented here for the preparation of the chiral polyol chain is the use of chiral cyanohydrin acetals, which are reacted diastercoseleclively under substrate control with C2-symmetric electrophiles... 

In contrast to the case of HMPC, most lipases hydrolyze the racemic acetate of CPBA 9 to give a mixture of the insecticidally active (S)-CPBA 2 and the (R)-acetate 1J). Thus, the desired (S)-CPBA J2 could be separated from the (R)-acetate 10 by means of a continuous counter-current extraction using n-heptane solvent at 80°C. However, it is important to utilize the recovered (R)-acetate W for an efficient process. Fortunately, since the proton of the asymmetric carbon of the cyanohydrin acetate is labile, the antipodal (R)-acetate is easily racemized by treatment with weak organic base such as triethylamine without any side reactions. The racemized acetate J9 thus obtained was recycled as shown in Figure 6. Therefore, all of the racemic acetate 9 was converted to the desired (S)-CPBA 2 in this recycling process. The (S)-CPBA 2 obtained was esterified with (S)-2-(4-chlorophenyl)-3-methylbutyryl chloride to produce the most insecticidally active stereoisomer V2 of fenvalerate, namely esfenvalerate. The relative biocidal activities between... 

This methodology was employed to prepare many heterocyclic cyanohydrin acetates in high yields and with excellent enantioselectivities, Candida antarctica lipase A (CAL-A) being the lipase of choice (Scheme 5.7) [23]. A recent detailed study of the reaction conditions revealed that the carrier on which the lipase is immobilised is important generally Celite should be used for aromatic substrates. With Celite R-633 as support for Candida antarctica lipase B (CAL-B)... 

Inagaki M, Hiratake J, Nishioka T, Oda J (1991) Lipase-catalyzed kinetic resolution with in situ racemization one-pot synthesis of optically active cyanohydrin acetates from aldehydes. J Am Chem Soc 113 9360-9361... 

The same CALB preparation was appUed in many dynamic kinetic resolutions combining two types of catalysts with each other. In the presence of homogeneous transition metal catalysts that catalyze the racemization and heterogeneous acids or bases or immobilized transition metals Novozym 435 was not deactivated [1, 26-28]. This is all the more remarkable since the reactions catalyzed by these catalysts include redox reactions at elevated temperatures (>60°C). When Novozym 435 was applied for the enantioselective synthesis of cyanohydrin acetates (10) from aliphatic aldehydes (7), good results were achieved (Scheme 2.2) for this dynamic kinetic resolution (DKR) [29]. Here NaCN is used as the base for the dynamic racemic formation and degradation of the cyanohydrins (6 and 8). 

When Upases are immobiUzed on Celite they can readily be used in dry organic solvents. Pseudomonas cepacia (also named B. cepacia) Upase was immobiUzed in the presence of sucrose on Hyflo super-cel CeUte [36, 40, 41] and used in the first enantioselective synthesis of cyanohydrin acetates via a DKR. Similarly, other successful syntheses of cyanohydrin acetates via DKR were catalyzed by Upases immobiUzed on CeUte [42]. This is in contrast to Novozym 435, which had successfully been used for the DKR of aUphatic cyanohydrin acetates (see Section 2.2.1 and Scheme 2.2) [29]. When Novozym 435 was used for the enantioselective synthesis of mandelonitrile acetate (la) via DKR, the reaction did not proceed [43]. It was... 

The carbon nucleophiles which will add to 1,3-diene-Fe(CO)3 complexes include LiCH2-X (where X = C02Me, CN, SPh) as well as the cyanohydrin acetal carbanions and... 

With the 1,4-dimethoxynaphthalene ligand, cyano-stabilized anions (including cyanohydrin acetal anions) and ester enolates equilibrate even at low temperature and strongly favor addition at the a-position (C-5). The kinetic site of addition is also generally C-a. However, the 2-lithio-l,3-dithiane anion and phenyllithium do not equilibrate over the temperature range -78 to 0°C. The sulfur-stabilized anions favor addition at C-/3 (equation 119) 134,190 phenyllithium... 

The immobilized lipase from Pseudomonas cepacia (Amano) afforded good en-antioselectivities for the formation of a range of cyanohydrin acetates derived from aromatic aldehydes (Fig. 9-5). Polymer-supported quinidine could also be employed... 

Figure 9-5. Examples of cyanohydrin acetates formed by dynamic resolution.

Table 11.1-20). A very good illustration for the potential of enantiomer-differentiating acylation catalyzed by lipases is provided by the high-yield synthesis of a series of aromatic cyanohydrin acetates (la-g) from aldehydes, acetone cyanohydrin and vinyl acetate in the presence of Pseudomonas cepacia lipase and a basic anion-exchange resin in diisopropyl ether which proceeds under kinetic resolution coupled with in situ formation and racemization of the cyanohydrin representing a dynamic kinetic resolution. For further examples see Table 11.1-24. 

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