Claisen etherification

Important advances in propargylic etherification have come from the use of copper-based systems that achieve efficient, catalytic O-progargylation of phenols (Scheme 8).245,246 While the mechanism of this transformation remains unclear, the products of these reactions have been readily converted into chromenes through subsequent Claisen rearrangement,... 

The etherification of alcohols or phenols and their subsequent Claisen Rearrangement under thermal conditions makes possible an extension of the carbon chain of the molecule. 

Synthesis.—Reisch, Mester, and co-workers have made important contributions this year by synthesizing the alkaloids furacridone (34) and ( )-rutacridone (37) for the first time. Regioselective etherification of 1,3-dihydroxy-jV-methylacridone (32 R = H) gave the acetal (33), which furnished furacridone (34) as the major product of acid-catalysed cyclization (Scheme 4). Claisen rearrangements of the 3-allyloxy-acridone (32 R = CH2CH=CH2) and the propargyl derivative (32 R = CH2C=CH) were also studied.18... 

In a series of elegant studies, Paquette and coworkers demonstrated the potential of the Claisen rearrangement for the stereocontrolled total synthesis of natural products. Dehydrative coupling of (2)-3-(trimethylsilyl)-2-propen-l-ol with cyclohexanone (51) under Kuwajima s conditions, followed by rearrangement of enol ether (52) in decalin, led in excellent stereoselectivity (>99 1) to aldehyde (53 Scheme 8). Concise construction of the eight-membered core of acetoxycrenulidine was achieved by intramolecular phenylseleno etherification of lactone (54), introduction of the exocyclic vinyl ether double bond by selenoxide elimination and subsequent Claisen rearrangement (Scheme 9, 66% from 54). ... 

Preparation of allyl phenyl ether756 serves as example of Claisen s method of etherification A mixture of phenol (188 g), allyl bromide (242 g), finely powdered potassium carbonate (280 g), and acetone (300 ml) is heated on the water-bath under reflux for 8 h. Potassium bromide separates. After cooling, the mixture is treated with water and extracted with ether. The ethereal solution is shaken with 10% sodium hydroxide solution, dried over potassium carbonate, and evaporated. Distillation of the residue in a vacuum gives the ether (230 g, 86%), b.p. 85°/19 mm. 

On heating methylbutenol (9.21) with 2-methoxypropene (9.27) (which is the methyl enol ether of acetone), a /ra .v-etherification occurs with the elimination of methanol and the formation of the allyl vinyl ether (9.28). This ether is perfectly set up for a Claisen rearrangement, which it undergoes, to produce methylheptenone (9.5). 

Still another method for constructing the carbon skeleton of the southern half is illustrated by the synthesis of optically active synthon 74 by Hirama et al. [122]. Their synthesis begins with 69 (prepared in 5 steps from D-glucose) and uses two aldol reactions and a cylic etherification to establish the basic ring structure. Similarly, an intramolecular Claisen cyclization was the key step in the synthesis of optically active southern half 79 by Williams et al. [123, 124]. 

Sol 9. (c) Sodium borohydride in the presence of CeCls selectively reduces a,P-unsaturated carbonyl compounds into allylic alcohols. It is called Luche s reduction. The selective 1,2-addition is facilitated by the strongly oxophilic Ce " " ion, which coordinates with the carbonyl oxygen. The allylic alcohol I then undergoes mercury catalyzed fran -etherification to give allyl vinyl ether (Claisen substrate), which readily undergoes [3,3] shift on heating to give II. 

For the synthesis of the intermediate of the sesquiterpene ( )-ceratopicanol, the secondary allylic alcohol 7 was converted to a new alcohol 8 via one-pot etherification, Claisen rearrangement and reduction with LiAlH4 (Eq. 3.1.7) [12]. This trans-... 

The addition of acetylene to acetone under Favorski-Babayan conditions gives meth-ylbutynol (43) which can be hydrogenated to methylbutenol (44) using a Lindlar catalyst [25-29]. When this is treated with methyl propenyl ether (the vinyl ether of acetone), trans-etherification takes place to give (45), which then undergoes a Claisen-Cope... 

---