Spiroketal enol ethers

For substituted lactones this method gave a low yield of the spiroketal 189 (<5%). For 5,6-dimethylvalerolactone a second scheme has been suggested involving treatment of ketoalcohol 190 with potassium carbonate in methanol to form enole ether acetal 191 in quantitative yield (90JOC5894). 

Yaodong Huang, while pursuing the synthesis of ( + )-berkelic acid (69), reported a diastereoselective cycloaddition using method H that leads to another type of 5,6-aryloxy spiroketals (Fig. 4.36).32 For example, addition of three equivalents of t-butyl magnesium bromide to alcohol 70 in the presence of the exocyclic enol ether 71 proceeds in a 72% yield to the spiroketal 72 with a 4.5 1 selectivity favoring the endo approach (Fig. 4.36). Additional experiments suggest the bromine atom decreases the HOMO-LUMO band gap and improves diastereoselectivity. 

In the designed synthesis, gold first catalyzed an exo-addition of an OH group across an alkyne resulting in an enol ether. This transient enol ether could engage a ketal oxygen under protic conditions to form the bis-spiroketal [103]. 

The spiroketal side-chain of diosgenin has been converted into 22-ketocholes-terol (488) by straightforward reactions. The known enol ether (485), prepared by a modification of Marker s method, was selectively saponified at C(26) and converted into (486) by lithium aluminium hydride reduction of the C(26)-tosylate. Lithium bromide-hydrogen bromide opening of the enol ether ring... 

Lewis acid catalyzed aldol coupling of silyl enol ethers with substituted cyclohexanone acetals showed an excellent preference for equatorial attack (95-l(X)%). In accord with this general rule, additions of a silyl enol ether to equatorially or axially substituted chiral spiroketals derived from -menthone gave 00% equatorial attack and formation of a single one of the four possible diastereoisomers (Scheme 9) 3, 4 -pjjjg methodology, followed by protection of the hydroxy group (X = OTHP, (XIPh.i) and alkaline removal of the chiral auxiliary was used for the synthesis of several natural products. ... 

Another scheme utilizing laevoglucosan lead to phosphonium salt 7 which is the precursor for a Wittig olefination product (an exocyclic enol ether) which is perfectly set up for an intramolecular spiroketalization for milbemycin P3 [87,88]. The same approach was modified to synthesize the fragment containing... 

Cl 1-25 of the milbemycins. The intramolecular spiroketalization theme was slightly altered to feature an endocyclic enol ether [86] by condensation of a lithio-2-benzenesulfonyl-tetrahydropyran with a suitable epoxide. An alternative but not enantiospecific approach from lactone B 3 comes from a double Baeyer-Villiger oxidation of bicyclo[2.2.1]heptane-2,5-dione to control [107] the relative stereochemistry in the B ring. The acetylenic partner was in turn derived from two different routes, the more selective being an anti hydroxyl group directed alkylation of a homopropargylic alcohol. 

Different cycloaddition strategies can be used to synthesize spiroketals such as [4+2]-, [3+2]-, [2+2+2]-, and [2+2+l]-cycloadditions (2005JA8260, 2000EJOC873 1995JA6605 2006OL3565 2007CAJ1388). For example, a [3+2]-cycloaddition has been utiHzed to form the bis(benzannulated) spiroketals of y-rubromycin (2011JA6114). The cycloaddition in between diketone 110 and the exocyclic enol ether 111, induced by CAN, led to the 0- andp-quinone spiroketals 112 and 112 in a 1 2 mixture in 58% yield. 

SCHEME 8.1 Synthesis of [n,5]-spiroketals 10 using exocyclic enol ethers 13 as starting materials the last step involves the domino sequence. 

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