Diastereoselective allylations

Many examples of stereospecific allylation consistent with the above mechanism have been reported. As one example, the regioselective and highly diastereoselective allylation of the lactone 17 with the optically active allylic phosphate 16 proceeded with no appreciable racemization of the allylic part to give the lactones l8 and 19, and the reaction has been used for the synthesis of a polypropionate chain[26]. 

Diastereoselective allylation of aromatic aldehyde. Bulletin of the Chemical Society of Japan, 68, 1523. 

Marquez, R, Llebaria, A., Delgado, A. (2001) Studies on the Diastereoselective Allylation of Aldehydes with Enantiopure 2-Sulfinylallyl Building Blocks. Tetrahedron Asymmetry, 12, 1625-1634. 

Diastereoselective allylation under aqueous Barbier conditions of a-amino aldehydes with the chiral building block (Ss)-3-chloro-2-(p-tolylsulfinyl)-l-propene to give enantiomerically pure sulfinyl amino alcohols in good yields and with high diastereoselectivity was reported (Eq. 8.34).73... 

Scheme 4 Diastereoselective allylic alkylation with protected glycine...

Cyclic hydrocarbons, diastereoselective allylic hydroperoxide formation, 861-3, 864 Cyclic olefins, final ozonides, 718 Cyclic peroxides... 

Indium-mediated diastereoselective allylation of L-glyceraldimines with4-bromo-1,1,1-trifluoro-2-butene provided stereoselectively, after further steps, enantiopure 4,4,4-trifluorovaline or 4,4,4-trifluoroisoleucine." ° Enantiopure hexafluorovahnes have been prepared by separation of the diastereomeric mixture resulting from the Michael addition of a chiral amine onto an ester of bis(trifluoromethyl) acryhc acid. Presence of the two CF3 groups reverses the orientation of the Michael addition (Figure 5.7)." ... 

An interesting 1,2-induced diastereoselective allylation is that of 2-aryl-3-methylbutenolide 33 with allyl bromide24. This reaction is worth noting, in the sense that the enolate was formed with sodium hydride and the reaction temperature never went below 0°C, although the yield and diastereoselectivity were still very good, Although lactone 33 is a special case with its a-aryl substituent, it does seem that very low temperatures are not always really necessary. 

Substrate-induced diastereoselective allylzincations essentially rely on coordination of the alkenylmetal by an appropriately located heteroatom, but a zinc-alkene -interaction23 27 can also exert a remarkable stereodirecting effect. Indeed, the alkenyllithium derived from 248, bearing an appropriately located carbon—carbon double bond, underwent highly diastereoselective allyl- and crotylzincations which led after hydrolysis to the corresponding 1,6-dienes 249 and 250. The stereochemical outcome... 

This alkylation strategy has been successfully implemented to the diastereoselective synthesis of a number of biologically active compounds,17 19 32 72 73 including the orally active HIV protease inhibitor Crixivan (>95% de)17-19 and nucleoside antibiotic (+)-sinefungin (51) (>99% de).72 The C-6 amine stereochemistry of (+)-sinefungin was set by a highly diastereoselective allylation of (lS,2/ )-l-amino-2-indanol-derived oxazolidinone 52 (Scheme 24.10). 

In this chapter, recent applications of (W)-phcnylglycine amide (1) in asymmetric synthesis are presented (Figure 25.2). The first section deals with diastereoselective Strecker reactions for the preparation of a-amino acids and derivatives, whereas the second section focuses on diastereoselective allylation of imines for preparation of enantiomerically pure homoallylamines. This latter class of compounds is a well-known intermediate for the synthesis of, for example, many types of amines, amino alcohols, and P-amino acids. The final section describes reduction of imines providing enantiomerically pure amines. (S)-3,3-Dimethyl-2-butylamine and (S)-l-aminoindane will be presented as leading examples. The results described in this chapter originate from a longstanding cooperation in the field of chiral technology development between DSM Pharma Chemicals and Syncom B.V. 

Diastereoselective Allylation Reactions of (R)-PGAa (1) with Several Aldehydes (Scheme 25.5)... 

Like their carbon counterparts, silylcuprates and stannylcuprates readily participate in SN2 -substitution reaction with allylic electrophiles.43,51 For example, <37z//-diastereoselective allylic substitution of the vinyl oxiranes 147 with the lower-order cyanocuprate (PhMe2Si)Cu(CN)Li cleanly affords the allylsilanes 148 (Scheme 38).106 Products of this type can be converted into the corresponding diols with retention of configuration by Tamao-Fleming oxidation 53,53a,53b,107... 

A /3-carboxyl group on the aldehyde also influences the diastereoselection. The high diastereoselectivity observed with the y-hydroxy lactone can be rationalized by a chelated transition state with the carboxylic acid group (Scheme 41).174 2-Oxocarboxylic acids also undergo diastereoselective allylation with cinnamyl bromide to provide the corresponding a-hydroxy acids as a single diastereomer (Equation (19)).1... 

Diastereoselective allylation of ct-keto imides derived from Oppolzer s sultam has been realized in aqueous THF (Equation (20)).181... 

The imines generated in situ from 2-pyridinecarboxaldehyde (or 2-quinolinecarboxaldehyde) and arylamines undergo indium-mediated Barbier allylation in aqueous media to provide homoallylic amines. Crotyl and cinnamyl bromides lead to diastereoselective allylation with diastereomeric ratios up to 98 2 (Equation (60)).260... 

Diastereoselective allylation of optically pure sulfinyl dienal complexes using tributyl allyltin can be obtained (Scheme 138). 2,4-Hexadien-1,6-dial iron tricarbonyl complex (88) undergoes nucleophilic addition reactions with diaUcylzincs in the presence of a catalytic amount of an optically active amino alcohol (Scheme 139). Very high enantio-and diastereoselectivity is observed. Related reactions of (88) with chiral allyl boronic esters give allylated alcohols in very high enantiomeric excess. 

Highly diastereoselective allylic sulfoxide rearrangements in larger ring systems were used in syntheses of the natural products ( + )-desmethylcytochalasin D34 and cadinanes35. 

Table 7. TiCl4-assisted diastereoselective allylation of ring systems. Substrate Allylsilane Major product...

The chelation between zinc and heteroatoms allows a diastereoselective allyl- or crotylzincation of secondary y-heterosubstituted vinyl metals. However, the intramolecular interaction between the metal center and an olefinic site was also described in the case of di(4-pentenyl)zinc [114]. This weak dipolar chelation is the result of the inherent polarity of the Zn - C " bond and the polarity of the double bond (having a partial negative charge on the terminal carbon). Such interactions were evidenced by NMR investigations and the spiro structure of di(4-pentenyl)zinc was postulated to interpret this phenomenon (Fig. 7-1). The oxygen chelation described in Scheme 7-95 is now replaced by a jr-chelation between a vinyl organozinc and an cu-olefinic residue. 

Chen, Q, Qiu, X-L. and Qing, F-L. (2006) Indium-mediated diastereoselective allylation of D- and L-glyceraldimines with 4-bromo-l,l,l-trifluoro-2-butene Highly stereoselective synthesis of 4,4,4-trifluoroisoleucines and 4,4,4-trifluorovaline. J. Org. Chem., 71, 2162-2161. 

Table 13-2. Diastereoselective allylations using oxazolidinone auxiliaries.

Highly diastereoselective allylations were also achieved in a slightly different manner through radical addition to chiral oxazolidinone acrylate and trapping with allylstannane [25]. In reactions with a,yS-unsaturated substrates, the Lewis acid... 

Chiral auxiliary-mediated diastereoselective allylations of a-bromoglycine derivatives 65 have also been established. 8-Phenylmenthol has been successfully employed as a chiral auxiliary in glycine allylations (Eq. (13.19)) [29]. The captoda-tive radical intermediate generated in this reaction benefits from the observation that a-amino acid radicals prefer an s-cis geometry about the single bond, presum-... 

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