Alcohols halocyclization

The halocyclization of unsaturated alcohols leading to bicyclic compounds is of interest because bicyclic tetrahydrofurans are building blocks for the synthesis of a number of prostaglandins and prostacyclins. The cyclization is performed with bromine or iodine under kinetic conditions and the bicyclic products are obtained in good yield. The stereochemical outcome of this haloetherification reaction is determined by steric interactions and the formation of the exo-isomer is generally favored52-56. 

The halocyclization of cyclic unsaturated alcohols to give fused 2,6-disubstituted tetrahydro-2//-pyrans proceeds quite predictably since the equatorial disubstituted isomer is generally formed whenever possible. The yields arc moderate to good and (V-iodosuccinimide and iodine have been employed as halonium sources. When the cyclization is performed under kinetic control with vV-iodosuccinimide in dichloromethane, and a tertiary carbocation is the intermediate in the reaction, electronic factors are responsible for tetrahydro-2//-pyran ring formation76. 

O-Allylic and O-homoallylic trichloroacetimidates are readily obtained in quantitative yield by treatment of allylic or homoallylic alcohols with a catalytic amount of sodium hydride, followed by reaction with trichloroacetonilrile at O C141. Halocyclization of O-all ylic and O-homoallylic trichloroacetimidates is a useful method for the nitrogen functionalization of a C—C double bond. 

Both 4,5-dihydrooxazoles 3 and 5,6-dihydro-4f/-l,3-oxazines 2 obtained by halocyclization of imidates are cleaved under neutral Or acidic conditions to give trichloroacetamides or amino alcohols which constitute building blocks for the total synthesis of antibiotics and natural products with biological activity144. 

Intramolecular participation of an appropriately placed nucleophile promises to be a useful strategy for the stereocontrolled synthesis of acyclic systems. Thus, halocyclization of unsaturated carboxylic acids, alcohols and functionalized alcohols (123) can be effected by a variety of electrophilic halogenating... 

Halocyclization of y,(5-unsaturated alcohols and the corresponding O-alkylated derivatives also gives tetrahydrofurans (Equation (87)) <81JA3963, B-84MI207-02,85TL1943,87X3309,92XU747>. 

Guided addition of the elements of ammonia to an allylic alcohol has been demonstrated in syntheses of 3-amlno-2,3-dideoxy-sugars. Thus, two groups employed the halocyclization of the 4- -trichloro-acetimido-derlvatlve (16) in the synthesis of methyl a-L-ristosaminide (17) (Scheme while a daunosamlne derivative. 

Both phosphates [164, 165] and carbonates [166, 167] have been investigated as nucleophiles in stereoselective halocyclization reactions, as illustrated for the transformations of 221 (Equation 36) [164] and 223 (Equation 37) by Bartlett and Cardillo [166], respectively. The approach provides a general strategy for preparation of 1,3-ds diols from acyclic homoallylic alcohols. 

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