Enantioselective synthesis iodination

The first enantioselective synthesis of an aflatoxin building block was published in 1993 by Marino (57). He presented a synthesis of 32 in 80% enantiomeric excess and induced the stereospecificity via optically active vinyl sulfoxides (see Scheme 2.14). Catechol (40) was acylated, mono-iodinated and then coupled with chiral vinyl sulfoxide 85 under Stille conditions (- 86). Dichloroketene lactonization under reductive conditions followed by zinc-promoted dechlorination gave the major diastereomer 87. 

Anew methodology for oxazolines was developed based on the unique property of iodine(III) reagents. lodine(III)-based approach is a better alternative to the traditional methods for an enantioselective synthesis of oxazoline scaffold 55. In this reaction, the electrophilicity of iodine(III) reagent, DIB was enhanced by the addition of a Lewis acid (BF3.Et20). The possible mechanistic pathway suggested that an initial conversion of DIB into a more electrophilic aryliodonium ion 56, which reacted with N-allylamides 54 produced the functionalized oxazolines 55 in good yields (Scheme 9) [25]. 

Halogenations. Fluorination of ketones can make use of 7, although the enantioselectivity is only moderate. Of the active methylene compounds, fluorination in the presence of dihydroquinine esters is adequate. A synthesis of p-amino-a-hydroxy acids involves iodination of substrates such as 8, which is attended by spontaneous cyclization. ... 

The oxylactonization of ort/io-alkenylbenzoates with lactate-derived optically active hypervalent iodine(III) reagents proceeds with a high degree of regio-, diastereo- and enantioselectivity leading to the asymmetric synthesis of 3-alkyl-4-oxyisochroman-l-ones [263]. A specific example - the enantioselective oxylactonization of substrate 202 with reagent 203 - is shown in Scheme 3.83. 

In 2003, Trost and Toste presented the first enantioselective total synthesis of aflatoxins Bj (1) and 82a (46) 40, 41). In Scheme 2.6, their synthesis is shown. The starting material for this sequence is catechol 40. A Pechmann condensation with diethyl p-oxoadipate and iodination with iodine chloride gave the lactone 41. 

Alkyl-4-oxy-3,4-dihydroisocoumarins are enantioselectively prepared by oxylactonization ofo-(alk-l-enyl)benzoates promoted by the in situ-generated chiral lactate-based hypervalent iodine(III) catalysts (13EJ07128). Chemoenzymatic synthesis of 3,4-dialkyl-3,4-dihydroisocoumarins involves one-pot dynamic kinetic reductive resolution processes catalyzed by E. co/i/alcohol desidrogenase. This strategy consists in the bioreduction of various racemic ketones to the corresponding enantiopure alcohols followed by intramolecular acidic cyclization (Scheme 71) (130L3872). 

The application of hypervalent iodine(III) mediated and catalyzed amination of hydrocarbon substrates has developed into a useful tool for organic synthesis. Reactions comprise direct amination of sp-, sp -, and sp -hybridized C-H bonds and numerous oxidative transformations of alkenes, butadienes, and allenes. Some of these methods have been developed directly in the form of catalytic transformations, which adds to underline the synthetic potential of the field. Where applicable, the possibility for enantioselective transformations has been demonstrated for some cases. One can be optimistic that hypervalent iodine chemistry is able to complement existing methodology for oxidative amination reactions in a practical manner over the next few years. 

The first ever chiral hypervalent iodine compound, diphenyliodonium tartrate, was reported in 1907 by Pribram [12]. However, the use of hypervalent iodine compounds in asymmetric synthesis has only been explored over the last decade. Access to asymmetric reactions can be obtained either through the use of chiral hypervalent iodine reagents or by using achiral hypervalent iodine compounds in combination with chiral ligands. Hypervalent iodine compounds are utilized in these reactions either in stoichiometric amounts or as catalysts. Various asymmetric transformations are achieved with moderate to excellent enantioselectivity with these reagents. This review is divided into different sections based on the type of transformations involved ... 

Another cinchona alkaloid-catalysed Mannich reaction was reported by Barbas et al, occurring between a thioester and an a-amido sulfone, leading in the presence of KOH to the unti-Mannich product in 79% yield, with both moderate diastereo- and enantioselectivity of 64% de and 45% ee, respectively. Finally, Akiyama et al. have developed a new method for the enantioselec-tive synthesis of y-butenolide derivatives, which involved the vinylogous Mannich-type reaction catalysed by a novel chiral phosphoric acid bearing iodine groups at the 6,6 -positions. Aliphatic as well as aromatic aldimines... 

In 2009, Marinetti and co-workers reported the preparation and structural data of NHC-Pt" complexes and their catalytic activity in model 1,6-enyne cycloisomerization reactions. The elaboration of square planar Pt" complexes bearing symmetric or unsymmetric chiral diphosphines was described in a sequence involving an iodine oxidative addition to a NHC-Pt complex and subsequent complexation of a chiral chelating diphosphine. In this context, the synthesis of a new family of Pt" six-membered metallacyclic NHC complexes was reported. This new platinacyclic complex was then used in an enantioselective 1,6-enyne cycloisomerization to afford, under mild conditions, the expected fused azabicycles in very high enantiomeric excesses and good to excellent yields [eqn (10.45)]. 

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