Cyanohydrin tosylates

Diels-Alder reaction of 2-bromoacrolein and 5-[(ben2yloxy)meth5i]cyclopentadiene in the presence of 5 mol % of the catalyst (35) afforded the adduct (36) in 83—85% yield, 95 5 exo/endo ratio, and greater than 96 4 enantioselectivity. Treatment of the aldehyde (36) with aqueous hydroxylamine, led to oxime formation and bromide solvolysis. Tosylation and elimination to the cyanohydrin followed by basic hydrolysis gave (24). 

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... 

A thiazole derivative that incorporates a fragment of the amphetamine molecule shows some CNS stimulant activity more specifically, the compound antagonizes the depression caused by overdoses of barbiturates and narcotics. Reaction of benzalde-hyde with sodium cyanide and benzenesulfonyl chloride gives the toluenesulfony1 ester of the cyanohydrin (141). Reaction of this with thiourea leads directly to aminophenazole (143) It is probable the reaction proceeds by displacement of the tosylate by the thiourea sulfur to give 142 addition of the amino group to the nitrile followed by tautomerization affords the observed product. ... 

The different steric hindrance of hydroxyl groups in (3R)- and (3S)-cyanohydrins was revealed by activation of a-hydroxynitriles through O-tosylation to afford the (R)-tosylate in 85% yield and the (S)-tosylate in... 

On the other hand, optically active 43 and 44 were synthesized as follows.401 Treatment of 2,3,4-tri-0-benzyl-l,5-di-0-tosyl-D-arabinitol (277) with three equimolar proportions of methylenetriphenylphos-phorane gave the cyclic phosphorane (278), which was stereoselectively converted into the cyanohydrin (279) by way of the corresponding C-methylene and inosose derivatives. Compound 279 was converted into 43 and 44 by way of the corresponding carboxylic acid (280), and unsaturated nitrile (281), respectively. Compound 39 was derived from the inosose (282), obtained from quebrachitol, through a 21-step conversion.402 Introduction of a hydroxymethyl group into 282 was accom-... 

Mode of synthesis A. cyanohydrin, by way of 2-nmino-2-deoxy-aldonic acid B. scission of sugar derivative epoxide with ammonia C. interconversion of hexosamine series D. hemihydrogenation of a-amino nitrile466 E. rearrangement of ketosyl-amine F. Removal of last carbon atom of hexosamine G. Hydrazinolysis (with inversion) of 2-0-tosyl-pentose. 6 Physical constants taken from this reference. c Derivatives (only) isolated. 

This type of reaction has some precedence i.e., cyanohydrin formation (KCN, DMSO), followed by intramolecular displacement of a tosylate by the incipient alkoxide leads to the formation of a 2-cyano oxetane system. Furthermore, KCN in MeOH results in the addition of methanol across a nitrile group. Nerdel, F. Weyerstahl, P. Lucas, K. Tetrahedron Lett. 1965, 5751. 

Although nitriles lack an acyl group, they are considered acid derivatives because they hydrolyze to carboxylic acids. Nitriles are frequently made from carboxylic acids (with the same number of carbons) by conversion to primary amides followed by dehydration. They are also made from primary alkyl halides and tosylates (adding one carbon) by nucleophilic substitution with cyanide ion. Aryl cyanides can be made by the Sandmeyer reaction of an aryldiazonium salt with cuprous cyanide. a-Hydroxynitriles (cyanohydrins) are made by the reaction of ketones and aldehydes with HCN. 

In the benzoin condensation, one molecule of aldehyde serves as an electrophile. If a carbanion is generated from protected cyanohydrins, a-aminonitriles or dithioacetals, it can react with electrophiles such as alkyl halides, strongly activated aryl halides or alkyl tosylates to form ketones. Amongst other electrophiles which are attacked by the above carbanions are heterocyclic A -oxides, carbonyl compounds, a,p-unsaturated carbonyl compounds, a,3-unsaturated nitriles, acyl halides, Mannich bases, epoxides and chlorotiimethyl derivatives of silicon, germanium and tin. 

The alkylation chemistry of a considerable number of O-trimethylsilyl cyanohydrins derived from aryl and heteroaryl aldehydes has been reported by Hunig and coworkers. Tbe protected cyanohydrins are easily prepared by heating the aldehydes with trimethylsilyl cyanide in the presence of a Lewis acid. The use of dialkyl sulfates and tosylates as alkylating agents was so reported. Hata et alP failed to alkylate the anion of the adduct of trimethylsilyl cyanide and acetaldehyde, suggesting that the trimethylsilyl group is incompatible with the more basic anions derived from aliphatic aldehydes. Ficini et alP... 

Enantiomerically pure cyanohydrins can easily be modified chemically or enzymatically (Scheme 4.12B), providing access to chiral a-hydroxy acids, a-hydroxy amides, 2-aminoalcohols, and epoxides. Replacement of the hydroxyl functionahty by a better leaving group, such as a sulfonyl moiety (e.g. tosylate), allows the introduction of various other nucleophiles with inversion at the stereocenter [51a]. The structures of some bioactive molecules that have been synthesized using a biotransformation step with a hydroxynitrile lyase are depicted in Scheme 4.12B [51a, 52]. 

Special preparations. a-Trialkylsiloxy aldehydes and l-tosyloxy-2-alkanols have been synthesized using DIBALH reduction of cyanohydrin silyl ethers and epoxy tosylates, respectively. Indoles and (Z)-allylic alcohols are acquired after simple manipulations of the primary reduction products of nitriles and a-hydroxy esters, respectively. 

A method of more general application depends on the reduction of iodo derivatives in which the iodine has replaced the hydroxyl of a primary alcoholic group. These are easily obtained by treatment of the tosyl derivatives with sodium iodide in acetone solution (sealed tube) or in refluxing acetonyl-acetone 228) or acetic anhydride 229). The reduction is often carried out by catalytic methods. The 5-deoxy-n-xylose is synthesized from D-xylose by this method, and by application of the cyanohydrin synthesis 6-deoxy-n-gulose is prepared 230). 

An 5n2 displacement of a caesium carboxylate on a remote mesylate group is used in an effective synthesis of / -zearaIenone. This compound has also been prepared by carbon-carbon bond formation using the displacement of a tosylate group by a protected cyanohydrin carbanion. The intramolecular coupling of a terminal vinyl iodide with an enone catalysed by PdCl2(CH3CN)2 has been used as a route to an unsaturated 16-membered macrolide. ... 

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