Olefin stereoselectivity

Despite the remarkable success of olefin metathesis catalysts in organic applications, one major challenge that remains is the diastereomeric control of olefin geometry. Olefin stereoselectivity is an issue in all metathesis reactions. However, prior to the widespread use of CM processes, it was only pertinent to the RGM of large rings (>8 carbons) and in the backbone structure of ROMP-derived polymers. 

Scheme 5 Olefin stereoselectivity based on allylsilane substituents.

Scheme 6 Allylic substitution effects on CM olefin stereoselectivity.

In 1985, Warwel and Winkelmiiller reported a series of catalyst systems for the CM of either styrene or 4-vinylcyclohexane with unfunctionalized olefins (Scheme 9). Using heterogeneous catalyst systems of RceOy/ AI2O3, among others, the authors demonstrated that both a substrate s electronic and steric properties govern CM product selectivity. Unfortunately, as the stereoselectivities of these reactions were not reported, the effect of a secondary allylic carbon on olefin stereoselectivity was not determined. Nevertheless, the non-statistical product distribution obtained in these reactions constitutes the first example of a product selective CM reaction. 

Within the context of total synthesis, the application of CM to a one-pot sequential protocol has the potential to dramatically simplify the preparation of complex natural products. Trost and co-workers recently demonstrated an elegant example of this, wherein a one-pot CM-Takai olefination reaction was used for the preparation of the antitumor agent callipeltoside A and various analogs (Scheme 21). By using a three-step, two-pot sequence employing this protocol, the synthetic route toward these compounds was shortened by five steps and olefin stereoselectivity was increased (4 1 to >8 1 E/Z) relative to previous syntheses employing a classical Emmons-Wadsworth-Horner approach. 

Discussions of the mechanism of the oxygen transfer to the double bond have led to controversy. Depending on the substrate and additives, the formation of side products with trans stereochemistry points to a radical mechanism, whereas alkyl-substituted olefins stereoselectively give only cis products via a concerted mechanism. 

In the present review the ring systems containing one heteroatom are considered first, except for P-lactams which are given a special section at the end. Interest in azetidines continues to be stimulated by the discovery of the potentially useful trinitro derivative. The requirements for the stereoselective synthesis of substituted oxetane are being explored and derivatives of aluminium are useful in the stereoselective routes to oxetanones. The preparation and subsequent pyrolysis of oxetanones is suggested as an alternative to the Wittig route to olefins. Stereoselective routes to thietanes and thietane 1 -oxides are mentioned. 

In a total synthesis of (+)-brefeldin A, the reagent was elaborated into the a,(3-enone shown, which participated in a palladium-mediated cyclopentene-forming reaction to afford the cxo-olefin. Stereoselectivity in the ring-forming reaction was 3.5 1 in favor of the desired isomer over the alternative trans-cyclopentene. Ozonolysis and reduction of the resulting ketone, followed by protection afforded the MEM ether shown, where all the relevant stereocenters of the final target were established (eq 18). ... 

HWE olefination Stereoselective olefination of aldehydes and ketones using phosphoryl-stabilized carbanions. 212... 

Tomooka, K., Igarashi, T., Kishi, N., Nakai, T. Olefinic stereoselection in the [2,3]-Wittig rearrangement of a,P-disubstituted allylic ethers forming trisubstituted olefins. Tetrahedron Lett. 1999, 40, 6257-6260. 

Triflic acid was also used in the synthesis of dixanthones and poly(dixanthones) by cyclization of 2-aryloxylbenzonitriles at room temperature. Addition of dialkyl disulfides to terminal alkynes is catalyzed by a rhodium-phosphine complex and triflic acid giving (Z)-bis(alkylthio)olefins stereoselectively (eq 50). ... 

Base-induced migration of the double bond in the cyclopropene (863 R = H or Me) to the exocyclic position has been shown to give the -olefin stereoselectively. Methylenecyclopropanes are also synthesized by dehydrochlorination of 1-chloro-1 -methylcyclopropanes. ... 

The presence of the silyl substituent at the olefinic carbon provides an important featnre in the regio- and stereochemical control of the Lewis acid-catalyzed carbonyl-ene reactions which gives 230 (equation 188). The changeover of the olefinic stereoselectivity from trans to cis is observed (c/231a) (eqnation 189). when R is a silyl gronp ". Withont a silyl group (R = H) trans product 231b is obtained predominantly. It is noteworthy... 

Keywords Arenediazonium tetrafluoroborate salts, olefins, palladium acetate, triton X-100, water, room temperature, Pd-nanoparticles, Matsuda-Heck coupling, arylation of olefins, stereoselectivity, aryl substituted olefins... 

Application of this olefin synthesis to the CJH problem began with conversion of methacrolein (27) to allylic alcohol 17 via cyanohydrin 28. Reaction of 17 with ketal 29 provided 31/32 with good olefin stereoselectivity, presumably via allyl vinyl ether intermediate 30. Reduction of 32 with sodium borohydiide gave allylic alcohol 33 and set the stage for the second forced 8 2 reaction. 

The reaction is highly stereoselective eijt/zro-dibromides give trawj-olefins and t/ireo-dibromides give cw-olefins (stereoselectivity > 98% as determined by HNMR). 

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