Stereoselective synthesis protocols

For stereoselective synthesis of a-aminocarbonyl compounds, a number of protocols have been reported using chiral enolates and A-(alkoxycarbonyl)-0-(arenesulfonyl) hydroxylamines. 

A new protocol for the stereoselective synthesis of (i-lactams [213] has been reported to be performed by a conrotatory ring closure of l-halo-3-aza-4-alkyl-l, 3-dienes, previously prepared by Staudinger methodology, (for the synthesis and chemistry of /V-silyl imines see [214] for [2+2] cycloaddition of /V-silyl imines and ketenes see [215]) in refluxing toluene (Scheme 96). 

It is also important to note that the potential synthetic utility of the asymmetric alkylation protocol discussed in this section has been fruitfully demonstrated by its application to the stereoselective synthesis of various biologically adive natural products possessing unique a-amino acid derivatives as their structural components [27,28]. 

If the olefin is chiral (entries 23-25) high diastereoselectivity has been observed, when the center of asymmetry is at C-3 of cyclic silyl enol ethers (entry 24). Cyclopropanation then occurs trans to the substituent at this carbon 57) exclusively, and due to the very mild cleavage conditions this mww-relationship is preserved in the subsequent ring opening (vide infra). This protocol has been applied to introduce a side chain during the stereoselective synthesis of a prostaglandin58> and of dicranenone A 59). 

Stereoselective synthesis of the C11-C16 fragment of the polyene macro-lide antibiotic, pentamycin, has also been accomplished under the aldolase protocol.45 A formyl and benzyl protected aldehyde, available from D-glucose by chemical methods, reacts with DHAP under the influence of FDP aldolase. After phosphatase hydrolysis the essential C11-C16 skeleton of pentamycin is generated. Removal of an additional hydroxyl group at position 1 and isolation of the C11-C16 fragment as a thioacetal, is accomplished in several steps (Scheme 5.23). 

Renuga S, Gnanadeebam M et al (2007) A novel four-component tandem protocol for the stereoselective synthesis of highly functionalised thiazoles. Tetrahedron 63 10054—10058... 

The same chiral auxiliary has also been used for the stereoselective synthesis of arene-chromium complexes treatment of an aromatic aminal with chromium hexacarbonyl gives the corresponding complex with high diastereomeric excess. This protocol was recently applied in a total synthesis of (—)-lasubine (eq 4). A successful application of 1,2-diaminocyclohexane (as its IR,2R enantiomer) as a chiral auxiliary is illustrated by the di-astereoselective alkylation of the potassium enolate of bis-amide (3) with electrophiles such as benzyl bromide to give bis-alkylated products with excellent diastereoselectivity (eq 5). Lower levels... 

For a review, see Tadano, K, Natural product s3mthesis starting with carbohydrates based on the Claisen rearrangement protocol. In Studies in Natural Products Chemistry, Vol. 10 Stereoselective Synthesis, Part F, Atta-ur-Rahman, Ed., Elsevier, Amsterdam, The Netherlands, pp. 405-455, 1992. 

R.S. Coleman and co-workers have developed a stereoselective synthesis of the 12-membered diene and triene lactones characteristic of the antitumor agent oximidines I and II, based on an intramolecular Castm-Stephens coupling. The effectiveness of this protocol rivals the efficiency of standard macrolactonization. The stereoselective reduction of the internai alkyne afforded the 12-membered ( ,Z)-diene lactone in good yield. 

Over the past decade, our laboratory has been actively involved in developing methods for the preparation and applications of glycosyl iodide donors (36-49) including efficient a-stereoselective glycosylation protocols that work well with various sugars iodides (39-41). Recently, we have applied this methodology in the synthesis a-anomeric glycolipids. 

In this chapter, key studies which have led to the current understanding of the mechanism of this transformation will be discussed, as a basis for dealing with issues of selectivity and choice of experimental variables in subsequent sections. Since the initial development of this reaction, it has evolved in scope to become a primary method for the stereoselective synthesis of epoxides to which an electronegative substituent is directly attached. Several recent variations on the initial protocol which afford functionally diverse molecules are the subject of Section 1.13.3. Section 1.13.5 examines related reactions that afford substituted aziridines instead of epoxides, and Section 1.13.6 examines some recent variants of the re-... 

A useful protocol for effecting the stereoselective synthesis of masked 3,3 -dihydroxy ketones and compounds derived therefrom has recently been developed (Schemes 17 and 18). The process features the metallation of enantiomerically pure 3-p-tolylsulfinylmethyl-4,5-dihydroisoxazoles such as (36), followed by reaction with an aldehyde to give the intermediate adducts (37). The diastereomeric ratio of the... 

The reaction between a carbanion derived from alkyl 3,5-bis(trifluoromethyl)phenyl sulfones and aldehydes affords, with good yields and stereoselectivities, the corresponding 1,2-disubstituted alkene through the Julia-Kocienski olefination reaction. This one-pot protocol can be performed using the phosphazene base at —78 °C and has been successfully used in a high yielding and stereoselective synthesis of various stilbenes such as resveratrol [47] (Scheme 5.28). 

For the stereoselective synthesis of C-glycosides, deoxygenation of hemiketals, obtained from Wacker oxidation of sngar-derived olefin alcohols, was envisaged as an easy and efficient protocol. In our earlier study on the synthesis of 4-epiethisolide, attempted PdCV mediated conversion of the terminal olefin (1), obtained from sugar chiron into a methyl ketone (2) resulted in the exclnsive formation of an anti-Markovnikov product (3), which happened to be the first report in the literature (Scheme 22.1). 

This convenient oxidation protocol has been used in several syntheses of complex organic molecules. In the stereoselective synthesis of (-)-tetrodotoxin by Du Bois and coworkers, the protected pentaol 810 was oxidized with PhI02/Py2Se2 to afford the unsaturated carbonyl compound 811 in a good yield (Scheme 3.319) [1112],... 

This reaction was first reported by Johnson et al. in 1970. It is a highly stereoselective synthesis of y,5-unsaturated esters from the reaction between allylic alcohols and an orthoester in the presence of a trace amount of weak acid, such as propionic acid. Because this reaction is the modification or variant of the Claisen Rearrangement, it is often referred to as the Johnson orthoester Claisen rearrangement. Occasionally, this reaction is also known as the Claisen-Johnson orthoester rearrangement, " or Johnson orthoester protocol. This reaction involves the formation of mixed orthoester from allyl alcohol and the added orthoester, which loses an alcoholic component to form a ketene acetal then migrates to unsaturated carbonyl compounds via the Claisen Rearmagement with high syn selectivity. Posner further extended this reaction to use sulfonyl orthoester. Overall, this reaction has been applied to the synthesis of a variety of complicated natural products, such as squalenes. ... 

Hassner and coworkers reported a one-pot protocol for the stereoselective synthesis of isoxazolines fused to five- and six-membered carbocycles 204 (Scheme 49) [151]. The method involves conjugate addition of Grignard... 

An unprecedented protocol for the stereoselective synthesis of stracturally diverse electron-deflcient alkenes in moderate to excellent yields from readily accessible A-sulfonyl imines and stabilized phosphonium ylides has been reported. The oleflna-tion reaction of (V-sulfonyl imines with nitrile-stabilized phosphonium ylides affords an array of a./S-unsaturated nitriles with high Z selectivity, and the reactions with ester-, amide-, and ketone-stabilized phosphonium ylides afford a,)3-unsaturated esters, amides, and ketones with high E selectivity, respectively (Scheme 3). 

A highly (>98%) stereoselective synthesis of vitamin A [116a, 127] employing an alkyne ZMA-Pd-catalyzed alkenylation protocol (Eq. (1), Scheme 3.27) was followed by an exceedingly efficient and selective synthesis of fS- and y-carotenes [116a] (Eqs. (2) and (3), Scheme 3.27). In the latter, the use of ( )-ICH=CHBr as a two-carbon linchpin should be noted. Although no rigorous comparisons were attempted, the overall superiority of the Pd-catalyzed alkenylation route over the conventional carbonyl olefination route [128] appears to be rather clear. 

Similarly, Paquette s stereoselective synthesis of a marine sesquiterpene from the capnellene family utilizes this addition/rearrangement protocol/ Alcohol 50, produced by lithium acetylide addition to 49, underwent smooth rearrangement to provide 51 in excellent yield. 

Sulfur substituted 1,3-butadienes are valuable synthons, particularly in Diels-Alder reactions, where they impart an added level of reactivity and regioselec-tivity [35]. Pearson et al [36] have reported the stereoselective synthesis of 2-(phenylthio)-1,3-butadiene by the protocol delineated in Scheme 24.12. 

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