Vinyl cyclic acetal, synthesis

Synthesis of a vinyl cyclic acetal monomer is similar to the synthesis of a NVGA but includes a dehydrohalogenation step as shown in Figure 4. Stoichiometric amounts of the appropriate aryl aldehyde and 3-chloropropane-l,2-diol were reacted and worked up as previously described. The chloromethyl cyclic acetal intermediate was dissolved in toluene and added slowly to three equivalents of potassium rm-butoxide in toluene in a round bottom flask cooled in an ice bath. When the addition was complete, the mixture was allowed to warm to room temperature and stirred vigorously overnight. The dark reaction mixture was vacuum filtered through a paper filter covered with a small amount of silica gel. The filtrate was dried and concentrated as before. 

Acetal handle 78 synthesized from Merrifield resin and 4-hydroxy-benzaldehyde was applied to the solid-phase synthesis of carbohydrates and 1-oxacephams (Scheme 41) [90]. For the latter, a 1,3-diol was initially anchored to the support to form a cyclic acetal. A ring opening reaction with DIBAL generated a resin-bound alcohol which was converted to the corresponding triflate for A-alkylation with 4-vinyl-oxyazetidin-2-one. A Lewis acid catalyzed ring closure released 1-oxa-cephams from the support. 

As shown in Scheme 32, when allylilc alcohols are allowed to react with vinyl ethers, the resulting a--bond in oxypalladation intermediate adds intramolecularly to the C=C bond of allylic moiety.f Subsequent (3-Pd—elimination leads to cyclic acetals. With this method, albeit stoichiometric in palladium(II), a unique approach to the synthesis of prostaglandins was attained by Larock and Lee as shown in Scheme 33.1 ... 

The simplest nitroalkene, nitroethene, undergoes Lewis acid-promoted [4+2] cycloaddition with chiral vinyl ethers to give cyclic nitronates with high diastereoselectivity. The resulting cyclic nitronates react with deficient alkenes to effect a face-selective [3+2] cycloaddition. A remote acetal center controls the stereochemistry of [3+2] cycloaddition. This strategy is applied to synthesis of the pyrrolizidine alkaloids (+)-macronecine and (+)-petasinecine (Scheme 8.33).165... 

Base catalysis is not required for conjugate addition. If the nucleophile is sufficiently enolized under the reaction conditions then the enol form is perfectly able to attack the unsaturated carbonyl compound. Enols are neutral and thus soft nucleophiles favouring conjugate attack, and p-dicarbonyl compounds are enolized to a significant extent (Chapter 21). Under acidic conditions there can be absolutely no base present but conjugate addition proceeds very efficiently. In this way methyl vinyl ketone (butenone) reacts with the cyclic P-diketone promoted by acetic acid to form a quaternary centre. The yield is excellent and the triketone product is an important intermediate in steroid synthesis as you will see later in this chapter. 

Homopropargylic alcohols are readily available substrates that can be used for the synthesis of 7-lactones. Cul-catalyzed selenation with PhSeBr at the alkyne terminus affords alkynyl aryl selenides. These react with an excess of /i-toluenesulfonic acid monohydrate, in dichloromethane at 60°C, to form a selenium-stabilized vinyl cation intermediate. The cation is then intramolecularly trapped by the tethered hydroxyl group to afford a cyclic selenoketene acetal, which readily adds a molecule of water to give the 7-lactone products (Scheme 55) <2006SL587>. 

A combination of radical and electron transfer steps mediated by manganese triacetate has been used in the synthesis of 5-acetoxyfuranones 21 through carbox-ymethyl radical addition to mono- and disubstituted alkynes 20, followed by oxidative cyclization of the resulting vinyl radicals 22 (Scheme 2.4). The cyclic intermediate 24 is transformed into the furanone 21 through stepwise one-electron oxidation and capture of the resulting aUyl cation 26 by acetate. 

Cyclic vinyl acetals in organic synthesis 89S721. 

A different outcome in the presence of an additional vinylic oxygen was observed by Overman s group (Scheme 52). The formation of the five-membered cyclic ether (108) is rationalized in terms of an SnCU-mediated acetal ring opening of (105), subsequent cyclization of (106) to (107), followed by a ring contraction to (108) by a pinacol-type rearrangement. This stereocontrolled reaction proved to be applicable to the synthesis of related natural products. ... 

---