Spiroacetals synthesis

Alder (hDA) reaction <00CEJ3755> and the electrochemical oxidation of m-hydroxyalkyl tetrahydropyrans offers a different approach to spiroketals <00TL4383>. The synthesis and stereochemistry of insect derived spiroacetals has been reviewed <00S1956>. 

In TaHe and Kocienski s total synthesis of lacrimin A (272), methoxyallene 268 was easily prepared via consecutive alkylations and subjected to acidic conditions to afford the presumed enone intermediates 269 and 270 (Scheme 19.48) [57]. Enone 269 underwent spontaneous spiroacetal formation to give a single stereoisomer 271 in 78% yield from 268. This compound was taken on to complete a total synthesis of lacrimin A (272). 

Scheme 38. The Chan, Hough, and Richardson s enantioselective synthesis of spiroacetal derivatives from the chloroethyl pyranoside derived from D-fructose (1984).

The synthesis of bis-spiroacetal ring systems has been discussed <99T7661>. An enantioselective synthesis of reveromycin B has been achieved <99JA456> and fungal metabolites containing a 1,8-dihydroxynaphthalene derived spiroacetal unit have been synthesised <99JCS(P1)1073,99JOC1092>. 

The alkylation of metalated imines, hydrazones, 4,5-dihydrooxazoles, 4,5-dihydroisoxazoles, 5,6-dihydro-4/7-1,2-oxazines and 2,5-dialkoxy-3,6-dihydropyrazines (i.e., azaenolates) is a commonly used method in asymmetric synthesis of enantiomerically enriched aldehydes, ketones, spiroacetals, amines, /J-oxo esters, carboxylic acids, lactones, 1,3-amino alcohols, /(-hydroxy ketones and amino acids. 

Research Focus Synthesis of polycarbonates, poly(acetal carbonate)s, poly(spiroacetal)s, polyesters, and polyurethanes using dihydroxyacetone. 

Martin et al. (289) utilized the chiral bicyclic lactone 88 for a total synthesis of (+)-phyllanthocin (Scheme 6.62). Cycloaddition of 88 to acetonitrile oxide, generated in situ from hydroximoyl chloride (89), furnished cycloadduct 90 in 45% yield together with other regio- and stereoisomers. After several steps, methyl glycoside (91) could be obtained. From this, reduction-hydrolysis gave the aldol that was subjected to acid-catalyzed spiroacetalization to produce spiroketal (92), and eventually (+)-phyllanthocin (93) after two additional steps (289). The... 

The cyclofunctionalization of cycloalkenyl systems where the chain containing the nucleophilic functionality is attached at one end of the double bond leads to spirocyclic structures. Cyclizations of cyclic and acyclic enol ethers to generate spiroacetals are shown in equations (66)168 and (67).169 These reactions generate the thermodynamically more stable products based on anomeric and steric factors.170 Spiroacetal products have also been obtained using isoxazolines as the nucleophilic functionality (cf. Table 14).l4lb Studies of steric and stereoelectronic control in selenoetherification reactions which form spirocyclic tetrahydrofurans have been reported.38 An interesting example of stereoelectronic control in the formation of a spirocyclic lactone has been reported in a recent mevinolin synthesis (equation 68).171... 

This process has found occasional use in the synthesis of heterocycles. The major product resulting from the reaction of MeLi on the dibromocarbene adduct (51) is the tetrahydrofuran (52), as shown in equation (105).189 In a novel approach to the synthesis of spiroacetal pheromones, caibene insertion into an acetal C—H bond was studied (equation 106).252 Unfortunately, the reaction proceeds in low yield and the approach is further hampered by the lack of stereocontrol in the ring opening of the cyclopropane. Carbene insertions into N—H and C—H bonds adjacent to nitrogen have been shown to give azabicyclo systems, as shown in equations (107) and (108).188... 

The silyl-Prins reaction between (Z)-4-trimethylsilyl-3-buten-l-ol 255 and aldehydes under mild Lewis acid conditions exclusively provides 2,6-ry -disubstituted 3,6-dihydropyrans 256 (Equation 115) <2002TL7055, 2003JOC7880>. A silyl-Prins reaction is also used to construct a 3,6-dihydropyran intermediate during a synthesis of the bis-spiroacetal moiety of the spirolides B and D in this instance a masked bromoaldehyde 257 is used as the cyclization partner (Equation 116) <2005OL3497>. 

M. A. Brimble, D. P. Furkert, Chemistry of Bis-Spiroacetal Systems Natural Products, Synthesis and Stereochemistry, Curr. Org. Chem. 2003, 7, 1461-1484. 

Allylic alcohols may also be formed from their corresponding halides by reaction with either peracids222 or potassium superoxide and a crown ether223. This latter methodology has been used in the synthesis of a polyether antibiotic, containing an allylic alcohol and a spiroacetal, where other methods have failed223. During allylic halide conversion, allylic... 

A versatile approach to spiro-oxacycles is the use of cyclic a-methylene enol ethers employed by us in an efficient and short enantioselective total synthesis of the mycotoxin talaromycin B (see Sect. 7.1). Later Pale and Vogel [148] employed the same protocol for the preparation of spiroacetals 2-145 using e.g. acrolein 2-78, methyl vinyl ketone and 2-pentenal, respectively with the enol ether 2-143 (Fig. 2-39). In most cases the yields were only modest, however, reaction of 2-143 and 2-78 in benzene in the presence of the mild Lewis acid ZnCl2 gave 2-145 in 70% yield as a single adduct. 

For the synthesis of the a-lithiated 5-methoxy-3,4-dihydro-2H-pyran 642, the deprotonation must be carried out with n-BuLi or f-BuLi at 0 to 50 °C in ether, DME or hexane947,948. For the preparation of hemiacetals947 948 or spiroacetals948, bifunctional electrophiles were used. Scheme 168 illustrates the preparation of the spiroacetal 644 from the alkylated product 643948. 

---