Iodolactonization examples

Stereoselective iodolactonization stereoselective epoxidation. lodolactoniza-tion of 7,8- and 8,c-unsaturated acids with iodine in the presence of NaHCOs exhibits only slight stereoselectivity (kinetic control). In the absence of base, equilibration occurs to ive the more stable rrans-isomers. Epoxides are formed in quantitative yield on methanolysis (CH3OH + NazCOs) of the iodolactones. Examples ... 

Because the Corey synthesis has been extensively used in prostaglandin research, improvements on the various steps in the procedure have been made. These variations include improved procedures for the preparation of norbomenone (24), alternative methods for the resolution of acid (26), stereoselective preparations of (26), improved procedures for the deiodination of iodolactone (27), alternative methods for the synthesis of Corey aldehyde (29) or its equivalent, and improved procedures for the stereoselective reduction of enone (30) (108—168). For example, a catalytic enantioselective Diels-Alder reaction has been used in a highly efficient synthesis of key intermediate (24) in 92% ee (169). 

Under kinetic conditions, iodolactonization reflects reactant conformation. Several cases illustrate how the stereoselectivity of iodolactonization can be related to reactant conformation. For example, the high stereoselectivity of 1 corresponds to proximity of the carboxylate group to one of the two double bonds in the preferred reactant... 

Entries 15 to 18 are examples of use of iodocyclization in multistep syntheses. In Entry 15, iodolactonization was followed by elimination of HI from the bicyclic lactone. In Entry 16, a cyclic peroxide group remained unaffected by the standard iodolactonization and subsequent Bu3SnH reductive deiodination. (See Section 5.5 for... 

Examples of iodolactonization and related iodocyclizations can be found in Scheme... 

Examples of 1,3-asymmetric induction in cyclizations to 8-lactones have been observed. Iodolactonization of 3-methyl-5-hexenoic acid to a 8-lactone under equilibrating conditions showed reasonable stereoselectivity (6 1 cis trans).l20b Recent studies have examined the formation of 8-lactones from cyclization of 5-hexenoic acids with a homoallylic oxygen substituent at C-3.135 Selenolactonization of 3-hydroxy-5-hexenoic acid under conditions of kinetic control provided the trans lactone in modest yield (40%) and high stereoselectivity.13515 Equilibrating conditions led to a slight preponderance of the cis... 

The illustrative preparative example is the conversion of cyclohex-1 -en-l-yl-acetic acid into the y-iodolactone (12) (cis-l-iodo-7-oxabicyclo[4.3.0]nona-8-one,188 Expt 5.172). In general the simpler iodolactones tend to be unstable the preparative sequence therefore recommends conversion into the unsaturated lactone by a dehydrohalogenation reaction. 

Iodolactonization of y, o-unsaturated alcohols results in preferential formation of tram-2, 5-disubstituted tetrahydrofuranes. However, the corresponding benzyl ethers cyclize preferentially to the cis-isomers. The alkyl group must be bulky enough to exert a steric effect, but not to prevent cyclization. Substituted benzyl ethers are particularly useful. Examples of this steric control are illustrated for the preparation of tram- and c/s-linalyl oxide (equations I and II).10... 

An enantioselective reduction of an a-iodolactone under radical conditions has been reported [95CC481]. Treatment of 207 with tin hydride, magnesium(II) iodide and in the presence of a chiral amine gave the 8-lactone 208 in good yield and moderate enantioselectivity. This is one of the first examples of chiral Lewis acid mediated enantioselective radical reactions. 

Intramolecular cyclization is a useful method for the preparation of lactones and cyclic ethers.39 The most common examples are iodolactonization and iodoetherification, the difference being that... 

Intramolecular cohalogenation is a related process which leads to halogenation with cyclization. Recent examples are the polymer supported synthesis of 2,5-disubstituted tetrahydrofuran (equation 54)459 and the iodolactonization of co-unsaturated carboxylic acids (equation 55)460. 

Every example of electrophilic addition of a halogen to an alkene that we have shown you so far has been with bromine. This is quite representative bromine is the most widely used halogen for electrophilic addition, since its reactivity is second only to iodine, yet the products are more stable. However, in these lactonization reactions, iodine is the more commonly used reagent, and the products of iodolactonizations are important intermediates (you will meet them again in Chapter 33). In the next example, the iodolactonization product is treated with sodium methoxide, which appears (a) to hydrolyse the lactone, and (b) to substitute the iodide for OMe. In fact, there is a little more to this than meets the eye. 

In fact, this is not such a good example because the aldol product is normally dehydrated and the second stereogenic centre is lost. More important examples are those in which a ring is formed but can later be cleaved, and among the best of this type of reaction are iodolactonizations, which you first met in Chapter 20. To remind you, iodolactonization involves treating a nonconjugated unsaturated acid with iodine in aqueous NaHC03. The product is an iodolactone. 

The following cyclic example illustrates the stereoselective aspect of iodolactonization. 

One of the simplest open-chain examples is 2-methylbut-3-enoic acid, which cyclizes in >95% yield to a single iodolactone with three stereogenic centres. Two come from stereospecific trans addition to the E-alker "ut the third reveals that iodine attacked the face of the alkene opposite the green methyl group in the conformation that can cyclize. 

We have said little in this chapter about the stereospecific transformation of one ring into another but we now have an opportunity to remedy that defect. Iodolactonization of a terminal alkene with a stereogenic centre next to it is as stereoselective as (if not more than) the example we have just seen. The two side chains on the ring end up trans to one another as we should expect. This is a purely stereoselective process as the alkene has no geometry. 

Iodolactonization has a similar mechanism notice how in these two examples the geometry of the double bond in the starting material defines the relative stereochemistry highlighted in black in the product. 

Hoshino et al. [33] reported the first example of an enantioselective radical reaction employing a chiral Lewis add complex. The enantioselective reduction of a-methoxy-methyl-a-iodolactone 41 with tributyltin hydride (BusSnH) in the presence of stoichiometric amounts of the chiral complex of a chiral diamine 42 and Mgl2, gave the reduced product 43 in 88 % yield with 62 % ee (Sch. 17). Reaction using Mg(C104)2, TiCU, Znl2,... 

A radical protocol was developed using CI4 with base. Cyclohexane could be iodinated, for example, with CI4 in the presence of powdered NaOH. The reaction led to the use of iodoform on solid NaOH as the iodination reagent of choice, a-lodo ethers and ot-iodolactones have been prepared from the parent ether or lactone via treatment with Et4N 4 HF under electrolytic conditions. 

A superb example of the synthetic utility of the iodolactonization reaction in organic synthesis is the conversion of the bicyclo[2.2.1]heptenone below into the Corey lactone. The latter compound possesses four contiguous stereogenic centers and is an important precursor for the synthesis of prostaglandins. 

Intramolecular cyclization is a useful method for the preparation of lactones and cyclic ethers [34], The most common examples are iodolactonization and iodoetherification, the former using a carboxylic acid derivative as the nucleophile and the latter relying on a hydroxy group. Thus, butyrolactones are available from Y, -unsaturated carboxylic acid derivatives [1,35,36], while unsaturated alcohols lead to cyclic ethers [37-40], Lactones are also available from a wide variety of nucleophiles such as carbonates [41], orthoesters [42], or carbamates [43,44], which can all be used in place of a carboxylate anion [44,45],... 

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