Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 0705 780

Furan or pyrrole rings may be readily formed by the Ti-induced coupling of CO groups, producing an alkene (McMurry reaction)627,628. This reaction gives good yields and can also be used to prepare carbocyclic ring systems629. One example of the use of this reaction is in the synthesis of salvadoricine as shown in equation 175630.

Intramolecular Diels-Alder reaction (with high periselectivity and good yields) of conjugated carbodiimides, catalyzed by Lewis acids, affords a simple procedure for the construction of pyrido[2,3-b]indole and indolo[2,3-b]quinoline ring systems (equation 176)631. This procedure is superior to the often mixed reactions that occur in the absence of the Lewis acid632 635. It is interesting to note that Lewis acids also improve yields and selectivity in intermolecular reactions of this type636.

R R

The formation of -lactones, by intramolecular radical coupling of haloalkenes, is usually a very efficient means of converting acyclic compounds into cyclic target molecules. The reagent of choice for promoting this reaction is usually Bu3SnH637. The replacement of this promotor with samarium(II) iodide allows for a more functionalized target molecule to be produced638,639. In this way, unsaturated haloacetals may be smoothly converted into -lactones upon treatment with SmI2, followed by Jones oxidation, in 50 99% overall yields (equation 177)640.

Br

a useful synthetic reaction which involves single-electron transfer. This process gives particularly good yields when performed at low temperature with ultrasonic irradiation, in the presence of manganese(III) acetate (equation 178)641. In general, the reaction is useful for alkenes possessing electron-donating groups and enol ethers. This reaction gives superior yields for these alkenes as compared with the thermal route642. Notwithstanding this, the thermal route to lactonization has been used as a key step in the synthesis of the ˇ-glucoside paeoniflorin which is a component of the Chinese paeony, widely used

in traditional medicine643.

O

A wide range of 5- and 6-membered lactones may be synthesized in high yields from alkenoic acids upon treatment with palladium(II) acetate, sodium acetate and oxygen (equation 179)644. The reaction has advantages (most notably, higher yields and lower required temperatures) over the normal two-step processes used to form lactones such as halolactonization followed by dehydrohalogenation645, sulfenolactonization followed by oxidation646 or selenolactonization followed by oxidation647 651.

COOH

(179)

O O

Substituted 2-(ˇ-oxoalkyl)tetrahydrofurans have been prepared in acceptable yields by a one-step aldol-type reaction of allyl ketones and 4-methyl-1-phenyl-4-penten-1-one, catalyzed by a rhodium(I) complex tin(II) chloride mixture (equation 180)652. This type of catalyst mixture has also been used for both linear653 and cyclic654 codimers in a similar fashion.

Catalytic oxy-palladation is an extremely useful method for the synthesis of functionalized THF and tetrahydropyran moieties. This reaction is brought about simply by treating a 1,4- or 1,5-hydroxy alkene with 0.1 mol-eq of Pd(II) salts and copper(I) chloride in DMF, with oxygen (equation 181)655. If this reaction is carried out in the presence of carbon monoxide in methanol, then an ester moiety is introduced into the product molecule (equation 182)656 658. If an alkene is introduced in place of the CO, then a tandem vinylation reaction also takes place (equation 183)659.

(181)

short reaction times (equation 187)670.

O

HO

O

(187)

O

I

The [4 C 2] cycloaddition reaction of 2-aminobutadienes with N-silylimines is an extremely useful means by which cyclic eneamines may be produced671 673. The reaction (equation 188) takes place at 80 °C to room temperature and is catalyzed by Lewis acids, such as ZnCl2. Chirality in the 2-amino group is maintained and is useful for further synthetic elaborations. Alternatively, the eneamine moiety may be replaced by a ketone by passing the product through a column of damp silica, thus affording 4-pyridinones as the final synthetic target. A similar reaction can be performed by replacing the amino group on the butadiene with a siloxy group674,675 or by replacing the silylimine with an acyl676 678, sulfonyl679 682 or substituted alkyl683 imine.

The functionalities in the previously described reaction may be reorganized so that the imine is part of the diene moiety, which is then reacted with an alkene. This particular arrangement of functionality has been used as one of the key steps in the total synthesis of streptonigrone (equation 189)684.

Diels Alder reactions are a very versatile means of synthesizing several ring systems in a single-step process. This protocol has been used to form octahydroacridine derivatives by taking N-arylimines which contain a nonactivated alkene functionality appropriately

placed within the molecule, and subjecting them to Diels-Alder conditions in the presence of a Lewis acid (equation 190)685. Control of cis versus trans selectivity can be achieved by variation of substituents within the molecule. Previously, electron-rich dienophiles had been required in order for this type of reaction to occur in useful yields686 688.

A similar reaction, with functionalities reorganized, may also be used to form tricyclic compounds. Thus, sulfonylimines (as part of a diene system) react by [4C2] intramolecular cycloaddition with an appropriately placed alkene moiety as shown in equation 191689. Some aromatization of the nitrogen-containing ring also occurs. This problem of a mixed product can be overcome by treating the reaction mixture with DBU/DDQ, which gives the aromatized product in 84% yield.

A nonconcerted pathway by which N-arylimines react with alkenes to give quinolines has been described (equation 192)690. The reaction takes place at room temperature, in acetonitrile, and is catalyzed by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ); final processing involves bubbling ammonia into the reaction mixture. Yields are low (10 65%) but in many cases only a single product is formed, and purification from starting materials is a relatively simple matter.

some unexpected diastereoselectivity, by the copper(I)-catalyzed cyclization of ω-alkenyl trichloroacetates. For example, the reaction shown in equation 196 proceeded in 74% yield, producing only a single diastereomer704. The catalyst, Cu(bpy)Cl, has been used with other substrates to induce radical cyclizations which produce 8- and 9-membered lactones705,706.

Cl

O Cl

ω-Alkenoic acids have also been used to form 7- to 11-membered lactones, in useful yields, in a reaction that is induced by iodine(I) compounds at room temperature (equation 197)707,708. The reaction has been employed as the key step in the formation of a natural product that has been isolated from the East African tree, Conyza hypoleuca, which has yielded some useful bioactive compounds709.

Further, medium-sized lactones have been prepared by a thermal elimination Claisen rearrangement sequence, of unsaturated selenoxide cyclic acetals (equation 198)710. The reaction affords reasonable yields of these useful lactones upon treatment with DBU and a siloxy species at 185 °C. The reaction has been used as the key step in the synthesis of (C)-laurencin, which contains an 8-membered cyclic ether moiety711.

OBn

Finally, using a variant of the Claisen rearrangement (Malherbe Bellus712), ninemembered lactones may be synthesized in reasonable yields with some stereocontrol.

a heterocyclic system, then useful tricyclic compounds may be produced (equation 207).

υ-Sultones are useful heterocycles which may be synthesized, in up to 80% yield, simply by treatment of conjugated dienes with sulfur trioxide at low temperatures

(equation 208)723. Other alkene-containing molecules react with sulfur trioxide to give ˛- and ˇ-sultones724.

SO3

(208)

SO2

O

Finally, 1,3,5-trioxanes are heterocyclic systems that are seeing increasing use in industrial chemical applications, for example as stabilizers in color photography725 and in polymers726. Many syntheses of these compounds give low yields under rather extreme conditions. A new, mild and high yielding synthesis has been developed for symmetrical 1,3,5-trioxanes which simply involves treatment of aldehydes with bentonitic earth (equation 209)727.

VI. ACKNOWLEDGMENTS

The author wishes to thank his students and colleagues (especially the Head of the Chemistry and Soil Science Department, A. Robin Robinson) at the Nova Scotia Agricultural College for their moral support. Also, the help and assistance of the science staff at the Killam Library at Dalhousie University is greatly appreciated. Finally, I would especially like to thank my wife, Niki Hoyle, for all her help and encouragement and for just being there when it mattered.