Stereoselective synthesis iodination

Alkenyl(phenyl)iodonium salts have attracted a significant interest recently as stable and readily available powerful alkenylating reagents. Several convenient, general procedures for the stereoselective synthesis of alkenyliodonium salts from silylated or stannylated alkenes and the appropriate hypervalent iodine reagents are known [5]. The chemistry of alkenyliodonium salts has been extensively covered in several recent reviews [42 - 45]. 

Using other hypervalent iodine compounds or different reagent combinations, various functional groups can be introduced in the a-position of ketones. a-Tosylations of ketones can be achieved directly using [hydroxy(tosyloxy)-iodo]benzene 6. The major drawback is the low regioselectivity observed in these reactions, although the a-tosylation of silyl enol ethers circumvents this problem. In the last few years some efforts have been done in the synthesis of chiral hypervalent iodine compounds [48, 53-55,113-117], but only a few of them have been used successfully in stereoselective synthesis. With chiral derivatives of type 59 it is possible to a-tosylate propiophenone with about 40% ee [56,118,119]. 

Fig. 13.17. Alkenylation of a dienylboronic acid with an iodinated triene stereoselective synthesis of vitamin A. The enyne (top left) is added to catecholborane to prepare the tra/rs-configured boronic ester in a chemoselective fashion. The latter affords trans-dienylboronic acid A upon acid-catalyzed hydrolysis.

Addition of BuiSnLi to cyclohex-2-enone followed by enolate trapping with n-decyl iodide proceeded with high diastereoselectivity to provide the 2,3-rrdiR5-stannyl ketone (16), which could be equilibrated with the cis diastereomer (17) upon treatment with base. LAH reduction, followed by separation of the diasteteomers, afforded samples of the 2-alkyl-3-stannylcyclohexanols as shown in Scheme 17. Iodine(III)-mediated fragmentation was shown to proceed in a stereospecific anti manner, with either of the rrdiRr-2,3-cyclohexanols affording ( )-enal (18), and the cir-2,3-alcohol the (Z)-enal (19 Scheme 17). Enal (18) was then utilized in a stereoselective synthesis of the mosquito pheromone, erythro-6-asx-toxyhexadiecan-S-olide (20 Scheme 18). ... 

Analogously, after enolization with Ihmds, hypervalent iodine compounds such as PhI(OAc)2 have been used for the stereoselective synthesis of 2,3-disubstituted succinates by using the chiral oxazolidinone auxiliary (45 )-4-(phenylmethyl)-2-oxazolidinone (equation 19) . 

Copper-catalyzed carbomagnesation of propargylic alcohols with allylmagnesium bromide regio- and stereoselcctively gives a trans-addition product which, after hydrolysis or iodine oxidation, leads to stereodefined allylic alcohols 51617. These products are used as starting materials in the stereoselective synthesis of e.vo-alkylidene carbocycles and heterocycles8-18. 

If the oxidation is performed in the presence of an external dienophile, the respective products of [4+2] cycloaddition are formed [351-356]. Typical examples are illustrated by a one-pot synthesis of several silyl bicyclic alkenes 283 by intermolecular Diels-Alder reactions of 4-trimethylsilyl substituted masked o-benzoquinones 282 generated by oxidation of the corresponding 2-methoxyphenols 281 [351] and by the hypervalent iodine-mediated oxidative dearomatization/Diels-Alder cascade reaction of phenols 284 with allyl alcohol affording polycyclic acetals 285 (Scheme 3.118) [352]. This hypervalent iodine-promoted tandem phenolic oxidation/Diels-Alder reaction has been utilized in the stereoselective synthesis of the bacchopetiolone carbocyclic core [353]. 

J. Org. Chem. 2(X)4, 69,4(X)5—4(X)6. Iodine as a very powerful catalyst for three-component synthesis of protected homoal-lylic amines, (c) J.-R. Ella-Menye, W. Dobbs, M. BUlet, P. Klotz, A. Mann, Tetrahedron Lett. 2005, 46, 1897-19(X). Unexpected 1,2 syn diastereoselectivity in the three-component aza Sakurai-Hosomi reaction, (d) M. Sugiura, K. Hirano, S. Kobayashi, J. Am. Chem. Soc. 2004, 126, 7182-7183. a-Aminoallylation of aldehydes with ammonia stereoselective synthesis of homoallylic primary amines, (e) M. BiUet, P Klotz, A. Mann, Tetrahedron Lett. 2(X)1,42, 631-634. Syn diastereoselectivity in the synthesis of homoallylamine using crotylsilane in the three-component reaction, (f) L. Niimi,... 

In recent years, chiral hypervalent iodine(III) reagents have received immense attention and have been applied extensively in the stereoselective synthesis of heterocycles. In 2010, Fujita et al. [53, 54] documented an enantiodifferentiating ewiio-selective oxylactonization of ort/io-alkenylbenzoates 55 by using a series of optically active lactate-derived iodine(III) reagents such as 57 (Scheme 14). This stereocontrolled transformatirai allowed efficient access to optically active 4-oxyisochromanones 56. 

Abstract This chapter describes recent developments in stereoselective synthesis using h5tpervalent iodine reagents. 

Stereoselective synthesis of highly functionalized azatricycles (e.g., 75) has been achieved by copper-catalysed Henry reaction of enals with nitromethane, zinc reduction of the nitro group and subsequent tosylation, followed by iodocyclization. The iodine is easily removed afterwards by hydrogenation, or can be used to introduce other functionality, such as by epoxidation of the adjacent alcohol. 

Togo, H., Aoki, M., and Yokoyama, M., Facile radical decarboxylative alkylation of heteroaromatic bases using carboxylic acids and trivalent iodine compounds, Tetrahedron Lett., 32, 6559, 1991. Togo, H., Aoki, M., and Yokoyama, M., Alkylation of aromatic heterocycles with oxalic acid monoalkyl esters in the presence of trivalent iodine compounds, Chem. Lett., 1691,1991. Vismara, E., Torri, G., Pastori, N., and Marchiandi, M., A new approach to the stereoselective synthesis of C-nucleosides via homolytic heteroaromatic substitution. Tetrahedron Lett., 33, 7575, 1992. 

Stereoselective Alkene Synthesis. Terminal alkynes can also be alkylated by organoboranes. Adducts are formed between a lithium acetylide and a trialkylborane. Reaction with iodine induces migration and results in the formation of the alkylated alkyne.24 25... 

In contrast, cyclizations of /V-alkoxy derivatives with iodine are much less selective (Table 30, entry 3), and similar results are observed with systems containing internal double bonds of either ( )- or (Z)-configuration.238 The stereoselectivity of the aminomercuration reaction of /V-methyl derivatives has been reported to be controlled by the choice of mercury(II) salt and solvent (entries 6 and 7).244 Cyclization with platinum salts showed little selectivity (entry 8).239 An iodocyclization of a complex N-alkyl system has been used in a recent synthesis of (+)-croomine.238... 

This synthesis featured a four-component coupling involving an oxidative dimerization process. Treatment of homochiral acyl silane 56 with vinyl lithium at low temperature, followed by the addition of half an equivalent of iodine to the reaction mixture, furnished tetraene 58 in high yield and with a very high level of stereoselectivity. The TBS ether was then converted to its triflate equivalent 59 in a... 

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