Cyanohydrin acetates aldehydes

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. 

Know the meaning of nucleophilic addition, hemiacetal and acetal, aldehyde hydrate, cyanohydrin. 

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). 

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... 

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. 

RCH2.NO2 - RC=N. This conversion usually has been conducted via a Nef reaction to an aldehyde followed by formation and dehydration of an oxime. The transformation can be accomplished in one step by reaction of the primary nitro compound with PCI3 and pyridine (40-75% yield). This method can also be used to convert allylic nitro compounds into a,)3-unsaturated nitriles and to prepare aldehyde or ketone cyanohydrin acetates. 

The kinetic resolution of cyanohydrins via enantioselective acylation may be converted into a dynamic process by making use of the chemical instability of cyanohydrins (Scheme 3.15) [235], Thus, racemic cyanohydrins were generated from an aldehyde and acetone cyanohydrin (as a relatively safe source of hydrogen cyanide) under catalysis by an anion exchange resin. The latter also served as catalytic base for the in-situ racemization. Enantioselective acylation using PSL and tsopropenyl acetate led to the exclusive formation of the corresponding (S)-cyanohydrin acetates in 47-91% optical purity. 

Cyanohydrins eliminate HCN under basic conditions, giving the corresponding planar aldehyde or ketone. When combined with an asymmetric reaction, the equilibrium can be used for an efficient in situ racemization of cyanohydrins, leading to a DKR process. For example, chiral secondary cyanohydrins can be acylated by isopropenyl acetate in the presence of lipase and solid base such as anion-exchange resin (OH" form) [8a,b] or silica-supported ammonium hydroxide [8c] (Scheme 5.31). A range of aromatic cyanohydrin acetates can be obtained in high chemical and optical yields, although the efficiency is lower for aliphatic precursors [8a]. The success of DKR is ascribable not only to the stereochemical... 

P-Cyclodextrin is also an enantioselective catalyst for HCN-additions on some aromatic aldehydes, but not in the case of 3-phenoxy benzaldehyde [651]. Recently the enzymatic enantioselective cleavage of S-cyanohydrine acetate by lipases from bacteria or Candida cylindrica [652] has [653] been claimed in a patent. Similarly, the optically active S-3-phenoxy-4-fluorobenzaldehyde cyanohydrine 301 can also be prepared by these esteratic methods, preferentially at a pn between 3.5 and 6.0 [654, 655]. Optically active cyanohydrines must be stabilized e.g. by alkanephosphonic acids [646], to inhibit slow racemization, even in the absence of bases. 

Lipase-Catalyzed Hydrolysis of Cyanohydrin Acetates. Hydrolytic enzymes, especially lipases, are widely used for enantioselective transformations, and have been used to prepare optically active cyanohydrins. For example, the lipase-catalyzed kinetic resolution of racemic w-phenoxybenzaldehyde cyanohydrin acetate was an essential step in the synthesis of (li ,ci5,aiS)-cypermethrine 19). Another recent report described the lipase-catalyzed kinetic resolution of pentafluorobenzaldehyde cyanohydrin acetate 20). To examine this approach, 2- and 6-fluoro-3,4-dibenzyloxybenzaldehyde cyanohydrin acetates (12b,d) were prepared from the aldehydes 10b,d. Preliminary attempts to carry out lipase-catalyzed kinetic resolutions of Aese cyanohydrin acetates were unsuccessfiil (unpublished results). 

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of ctir-bonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into 0-TRIMETHYLSILYL-4-METH0XYMANDEL0-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotnmethylsilane A general synthesis of allemc esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADlENOATE. 

The other reactions of the aldehydes, which are extraordinarily reactive substances, need only he mentioned here. Such reactions are reduction to alcohols, formation of hydrazones, oximes, semicarbazones, bisulphite compounds, acetals and cyanohydrins (by addition of hydrogen cyanide). 

Olefination of the Aldehyde 178 using a stabilized Wittig reagent followed by protecting group chemistry at the lower branch and reduction of the a,p-unsaturated ester afforded the allylic alcohol 179 (Scheme 29). The allylic alcohol 179 was then converted into an allylic chloride and the hydroxyl function at the lower branch was deprotected and subsequently oxidized to provide the corresponding aldehyde 161 [42]. The aldehyde 161 was treated with trimethylsilyl cyanide to afford the cyanohydrin that was transformed into the cyano acetal 180. The decisive intramolecular alkylation was realized by treatment of the cyano acetal 180 with sodium bis(trimethylsi-lyl)amide. Subsequent treatment of the alkylated cyano acetal 182 with acid (to 183) and base afforded the bicyclo[9.3.0]tetradecane 184. 

Not surprisingly, active M11O2 is able to oxidize unsaturated cyanohydrins, resulting in the generation of acyl cyanides. Interestingly, both the formation of the cyanohydrins by reaction of aldehydes with cyanide, and the hydrolysis of acyl cyanides with MeOH, resulting in the formation of methyl esters, can be carried out in situ with the MnC>2 oxidation. Thus, Corey et al. proved68 that aldehydes can be directly transformed into methyl esters by treatment with NaCN and active MnC>2 in a mixture of acetic acid and methanol. This represents a useful protocol for the oxidation of unsaturated aldehydes to esters. 

With acid catalysis, alcohols add to the carbonyl group of aldehydes to give hemiacetals [RCH(OH)OR ]. Further reaction with excess alcohol gives acetals [RCH(OR )2]- Ketones react similarly. These reactions are reversible that is, acetals can be readily hydrolyzed by aqueous acid to their alcohol and carbonyl components. Water adds similarly to the carbonyl group of certain aldehydes (for example, formaldehyde and chloral) to give hydrates. Hydrogen cyanide adds to carbonyl compounds as a carbon nucleophile to give cyanohydrins [R2C(OH)CN],... 

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