Bis spiroacetals

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 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. 

Out of numerous endo-type multiple ring closure cascades, only the double cyclization of (98) is mentioned here. This leads to the bis(spiroacetal) entity (99 Scheme 48), which is present in polyether antibiotics, insect pheromones and other important natural products. ... 

The bis-spiroacetal (3) arises by cyclisation of the lactol derived from... 

Li-Yang J, Brimble MA (2010) Synthesis of the bis-spiroacetal C25-C40 moiety of the antimitotic agent sprrastrellolide B using a bis-dithiane depiotectimi/spiFoacetalisation sequence. Chem Cmmnun 46 3967-3969... 

Lee et al. [110] have reported the synthesis of bis(spiroacetals) using an intramolecular aUcyne hydroalkoxylation strategy (Scheme 46). Treatment of diynes 196 with catalytic Ph3PAuCl/AgOTf under microwave irradiation afforded the bis (spiroacetals) 197-198 in moderate to good yield, generally favoring the trans-bis (spiroacetal) 197. 

The 6,5,6- and 6,6,6-bis-spiroacetals 413 and 415 could also be accessed by substituting the TBS-protected alcohol with a second allyl substituent, allowing sequential RRM-RRM reactions (Scheme 99). The 6,5,6-bis(spiroacetal) 413 was obtained in moderate yield, while the yield of the 6,6,6-bis(spiroacetal) 415 was much higher. 

Furkert, D.P. and Brimble, M.A. (2002) Synthesis of the C10-C22 bis-spiroacetal domain of spirolides B and D via iterative oxidative radical... 

Thus, two groups of investigators reported that the irradiation of certain oxygen heterocycles having a hydroxyalkyl side chain in cyclohexane in the presence of (diacetoxyiodo)benzene and iodine at room temperature gave bis-spiroacetals in good yields (Scheme 30). Subsequent work showed that similar reaction conditions could be applied to the synthesis of a number of five- and six-membered cychc acetals from y- and e-hydroxyethers (Scheme 31). The formation of a cychc acetal was also found in the hypoiodite reaction of hydroxysteroid with mercury(ll) oxide and iodine (Scheme 32). 

---