Allylic iodides synthesis

The synthesis of key intermediate 6 begins with the asymmetric synthesis of the lactol subunit, intermediate 8 (see Scheme 3). Alkylation of the sodium enolate derived from carboximide 21 with allyl iodide furnishes intermediate 26 as a crystalline solid in 82 % yield and in >99 % diastereomeric purity after recrystallization. Guided by transition state allylic strain conformational control elements5d (see Scheme 4), the action of sodium bis(trimethylsilyl)amide on 21 affords chelated (Z)-enolate 25. Chelation of the type illustrated in 25 prevents rotation about the nitrogen-carbon bond and renders... 

For enolates with additional functional groups, chelation may influence stereoselectivity. Chelation-controlled alkylation has been examined in the context of the synthesis of a polyol lactone (-)-discodermolide. The lithium enolate 4 reacts with the allylic iodide 5 in a hexane THF solvent mixture to give a 6 1 ratio favoring the desired stereoisomer. Use of the sodium enolate gives the opposite stereoselectivity, presumably because of the loss of chelation.61 The solvent seems to be quite important in promoting chelation control. 

General procedure for the reaction of an o-substituted aryl iodide with an allylic alcohol. Synthesis of biphenyls containing an oxoalkyl chain. 

The symmetrical Wurtz coupling has been found to give particularly good yields in the case of the higher alkane homologues. Selected illustrative examples (hexane, octane, decane and dodecane) are to be found in Expt 5.7. A related reaction is to be found in the synthesis of hexa- 1,5-diene (Expt 5.7, cognate preparation), which illustrates the symmetrical coupling of two molecules of allyl iodide by the action of sodium metal. 

Selenium-stabilized carbanions can be also generated by 1,4-addition of nucleophilic reagents to a-selanyl a,[3-unsaturated carbonyl compounds. The conjugate addition of trialkylsilyllithium compounds to 133, followed by reaction with allyl iodide, afforded the addition products 134 with good m-stereoselectivity (R = Me dr 86 14 R = Ph dr 94 6) (Scheme 34).214 The addition of lithium dialkylcuprates to 2-phenylselanylcycloalk-2-enones has also been used for the synthesis of natural products.215,216... 

Similar conditions for the formation of a (Z)-configured ketone enolate (6) at low temperature were applied by Myles and coworkers in their total synthesis of (-l-)-discoder-molide (10, equation 3f. Deprotonation of the ethyl ketone 7 with LiHMDS as base at —78 °C and addition of TMEDA delivered a (Z)-configured enolate (8), which was subsequently alkylated with allyl iodide 9. Thereby, chelation of the lithium enolate with the adjacent MOM protecting group led to a conformationally stable chair-like transition-state 8, in which the attack of the alkylation reagent 9 (represented in 8 by E+) could only occur from the site opposite to the bulky group R. Thus, the alkylation prodnct 10 was obtained with a good diastereomeric selectivity at C of 83-85% ds. 

A large number of 3-lactams have been prepared - by this method (equations 56-61). Cycloadditions of CSI with 1,5-hexadiene, allyl iodide and vinyl acetate - yield azetidinones which have been used as starting materials in the synthesis of carbapenems and penems. In some cases the cycloaddition must be conducted at low temperature to avoid open-chain products (equations 61 and 62). 

Intramolecular 1,3-dipolar cycloaddition of azide (81) proceeds through a triazoline and vinyl-aziridine (82) and results in the formation of tetrahydropyrrolizidine (83) and (84). This represents a formal total synthesis of supinidine. Thermolysis of vinyl aziridine (82) leads to pyrrolizidine (84) probably via azomethine ylides, while the nucleophilic opening leads exclusively to (83) through an intermediate allylic iodide (85). The latter is produced as a mixture of (E) and (Z) isomers but is converted to (83) via an equilibrium and recyclization of the (Z)-isomer (Scheme 30) <85TL3523, 85TL3527). 

The key reactions of Mulzer s synthesis [146a,b] involved coupling of sulfone 596 and allyl iodide 597 for the synthesis of (12Z)-olefin, and aldol reaction with ketone 591. The chiral sources of 596, 597, and 591 were derived from (R)-3-hydroxy-2-methylpropionate, (5)-malic acid, and by Kiyooka asymmetric aldol reaction, respectively. The aldehyde 590 was synthesized through addition of sulfone 596 to allyl iodide 597. Aldol reaction of 590 with 591 resulted in a 4 1 ratio... 

SYNTHESIS A solution of 5.8 g of homosyringonitrile (see under E for its preparation), 100 mg decyltriethylammonium iodide, and 13.6 g allyl iodide in 50 mL anhydrous acetone was treated with 6.9 g finely powdered anhydrous K2C03 and held at reflux for 16 h. The color changed from a near-black to a light yellow. The mixture was filtered, the solids washed with acetone, and the solvent from the combined filtrate and... 

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