portion of didemnaketal A (Scheme 60). Sharpless asymmetric dihydroxylation of
the meso bis-enone 248 and in situ hemiacetalization followed by conjugate
addition gave the singly anomeric spiroacetal 251 as the only product.
2.9 Double Intramolecular Hetero-Michael Addition
(DIHMA)
Alternatively, a double intramolecular hetero-Michael addition (DIHMA) can be
used to assemble a spiroacetal from an α,β-ynone (Scheme 61).
1 H NMR studies
have shown that, in accordance with Baldwin’s rules, initial 6-endo-dig cyclization
rather than 6-exo-dig is favored. Subsequent 5-exo-trig cyclization furnishes the
5,6-spiroacetal [132]. The corresponding 6,6-spiroacetals are obtained in an analogous manner.
Recent examples of its application include Koskinen et al.’s work toward
calyculin C [132–134] and Forsyth et al.’s report of a simplified okadaic acid
spiroacetal fragment 255 [135] (Scheme 62). Acidic hydrolysis of the TES-ethers
and consequent DIHMA of the ynones afforded the spiroacetals 253 and 255,
respectively.
Scheme 60 Wulff et al.’s oxa-Michael terminated cascade approach toward didemnaketal A [131]
232
M.A. Brimble and L.A. Stubbing
the meso bis-enone 248 and in situ hemiacetalization followed by conjugate
addition gave the singly anomeric spiroacetal 251 as the only product.
2.9 Double Intramolecular Hetero-Michael Addition
(DIHMA)
Alternatively, a double intramolecular hetero-Michael addition (DIHMA) can be
used to assemble a spiroacetal from an α,β-ynone (Scheme 61).
1 H NMR studies
have shown that, in accordance with Baldwin’s rules, initial 6-endo-dig cyclization
rather than 6-exo-dig is favored. Subsequent 5-exo-trig cyclization furnishes the
5,6-spiroacetal [132]. The corresponding 6,6-spiroacetals are obtained in an analogous manner.
Recent examples of its application include Koskinen et al.’s work toward
calyculin C [132–134] and Forsyth et al.’s report of a simplified okadaic acid
spiroacetal fragment 255 [135] (Scheme 62). Acidic hydrolysis of the TES-ethers
and consequent DIHMA of the ynones afforded the spiroacetals 253 and 255,
respectively.
Scheme 60 Wulff et al.’s oxa-Michael terminated cascade approach toward didemnaketal A [131]
232
M.A. Brimble and L.A. Stubbing