Cyanohydrin ether cyclization

A similar method was used for the synthesis of a cyclic cyanohydrin ether 75. The cyclization took place by the intramolecular displacement of the polymer-supported cyanohydrin 74 by treatment with lithium hexa-methyldisilazide (Scheme 21). Target 75 was obtained in 46% yield. While the yield is moderate, a pure product was obtained after a simple workup procedure. The cyanohydrin ether 75 can be readily converted to a cyclic ketone.46... 

Allylic ethers of cyanohydrins are easily prepared through phase transfer allylation. Deprotonation of these ethers with LDA in THF at -78 °C effects 2,3-rearrangement to transient p. y-unsaturated ketone cyanohydrins, which are transformed during work-up to the ketones (Table 16). In an extension of this work, the mixed acetal cyanohydrin ethers (187), prepared by mild acid treatment of the cyanohydrins with 2-methoxy-1,3-butadiene or 1-f-butoxyallene, rearranged to the keto enol ethers (189 equation 40). Hydrolysis of the enol ethers (189) leads to 1,4-dicarbonyl compounds, which can be cyclized to cyclopentenones. 

Reaction with /1-Hydroxy Ketones and Alcohols. The reaction of dicyanodimethylsilane with diacetone alcohol occurs according to eq 4. The reaction, which is initiated at —78 °C, proceeds by way of the indicated cyanodimethylsilyl ether. When warmed to rt, the intermediate silyl ether cyclizes to give a mixture of the cyanosilylation product and the cyclic enol silyl ether. The cyanosilylation of secondary )3-hydroxy ketones is highly di-astereoselective (eq 5). After desilylation, the cyanohydrins are obtained with high syn selectivity (de > 95%). The stereochemical... 

This Cl homologation of osones proved to be valuable in the preparation of L-ascorbic acid analogues (16) as well as in the preparation of radiolabeled L-ascorbic acid (17-20), This synthesis was greatly improved when aldoses were discovered to be directly oxidized to osones with cupric acetate (Equation 1) (21), Subsequently, the conditions were modified so that D-xylose could be oxidized to D-xylosone in 50-55% yield with cupric acetate in methanol. The intermediacy of the imino ether was proved by the isolation of 7 when D-glucosone was treated with potassium cyanide (16), The initial cyanohydrin adduct (3a) easily undergoes cyclization to the imino ether intermediate (aqueous solution for 10 min at room temperature. Scheme 5). This feature will be compared with the conditions required for the lactonization of other intermediates. 

Starting with, -famesol, a Sharpless asymmetric epoxidation [16] followed by four convenient functional group transformations afforded aldehyde 73 (Scheme 14). Reaction of 73 with 2 equivalents of sodium cyanide gave a mixture of cyanohydrins (1 1) which upon treatment with 5 mol % of tosic acid underwent cyclization to give cyano ether 74 (40%) and the Ci4-epimer (39%). The epimer could be treated with potassium hexamethyldisilazane to afford more of the desired product (74) [46]. 

Dihydrophenanthrene synthesis. Evans et al. have reported a new route to dihydrophenanthrene derivatives based on the condensation of p-quinone mono-ketals (1) or monosilyl cyanohydrin derivatives (5, 721-722) with the enolate of methyl 3-(3,4,5-trimethoxyphenyl)propionate (2) to give p-quinol ketals (3). These undergo acid-catalyzed cyclization to dihydrophenanthrene derivatives (4). A typical example is formulated in equation (I). The choice of the Lewis acid catalyst is sometimes critical for the cyclization. In the case of the cyclization shown above, use of SnCL, CF3COOH and BF3 etherate resulted in much lower... 

---