Stereoselectivity acyclic systems

Rh+ catalyst is more selective than Ir+ for acyclic stereoselection, Acyclic homoallylic systems ... 

In acyclic systems, the enolate conformation comes into play. p,(3-Disubstituted enolates prefer a conformation with the hydrogen eclipsed with the enolate double bond. In unfunctionalized enolates, alkylation usually takes place anti to the larger substituent, but with very modest stereoselectivity. 

In acyclic systems, the stereochemistry of alkylation depends on steric factors. Stereoselectivity is low for small substituents.71... 

In acyclic systems the 1,4-relative stereoselectivity was controlled by the stereochemistry of the diene. Thus, oxidation of (E,E)- and (E,Z)-2,4-hexadienes to their corresponding diacetates affords dl (>88% dl) and mesa (>95% me so) 2,5-diacetoxy-3-hexene, respectively. A mechanism involving a t vans-accto xy pal I adation of the conjugated diene to give an intermediate (rr-allyljpalladium complex, followed by either a cis or trans attack by acetate on the allyl group, has been suggested. The cis attack is explained by a cis migration from a (cr-allyl)palladium intermediate. The diacetoxylation reaction was applied to the preparation of a key intermediate for the synthesis of d/-shikimic acid, 3,... 

Modern synthetic chemistry has taken up the challenge of acyclic substrate-induced stereoselection302, including auxiliary-directed stereoselectivity. The main principles are 1,2-in-duction, the formation of cyclic intermediates, and intramolecular reactions. Many aspects, rules , and examples of diastereoface-differentiating reactions, both in cyclic and in acyclic systems, are summarized in Section 2.3.5.2. 

Several recent reviews have included specific types of electrophilic cyclofunctionalization reactions.1 Important areas covered in these reviews are halolactonization u cyclofunctionalization of unsaturated hydroxy compounds to form tetrahydrofurans and tetrahydropyrans lb cyclofunctionalization of unsaturated amino compounds lc cyclofunctionalization of unsaturated sulfur and phosphorus compounds ld lf electrophilic heterocyclization of unconjugated dienes 1 synthesis of y-butyrolactones 1 h synthesis of functionalized dihydro- and tetrahydro-furans lj cyclofunctionalization using selenium reagents lk lm stereocontrol in synthesis of acyclic systems 1" stereoselectivity in cyclofunctionalizations lP and cyclofunctionalizations in the synthesis of a-methylenelactones.lq Previous reference works have also addressed this topic.2... 

An Introduction of Chiral Centers into Acyclic Systems Based On Stereoselective Ketone Reduction"... 

The more obvious way to make this epoxide would be by epoxidation of the ester of the original unsaturated acid. However, the stereoselectivity in that reaction is nowhere near as good as in the iodolactonization. We shall return to this subject when we discuss reactions in acyclic systems in the next chapter. 

You have had three chapters in a row about stereochemistry this is the fourth, and it is time for us to bring together some ideas from earlier in the book. We aim firstly to help you grasp some important general concepts, and secondly to introduce some principles in connection with stereoselective reactions in acyclic systems. But, first, some revision. 

Conjugate additions. The silyl cuprate rcapcnt (PhMc,Si),CuLi (1) undergoes conjugate addition to a,(3-unsaturated aldehydes, ketones, or esters to form (3-silyl carbonyl compounds. Methylation of the intermediate enolate in acyclic systems is highly dia-stereoselective in favor of the isomer in which the silyl and methyl groups have the anti-... 

Similar methodology can be used in acyclic systems for the diasteieoselective, and sometimes dia stereoselective (Scheme 18), formation of 1,3-diols. With some substrates, the proportion of products arising from 6 endo-trig cyclization can be significant. 

Stereocontrolled epoxidation of acyclic systems. Stereoselectivity in the epoxi-dation of homoallylic alcohols is usually low. Nonetheless Kishi etal. have observed... 

Alkylation of vinyl lactones. Trost and Klun have reported that alkylation of TT-allylpalladium complexes derived from vinyl lactones provides a stereocontrolled approach to acyclic systems such as the side chains of a -tocopherol and vitamin K. The alkylation of lactones 1-4 proceeds with greater than 95% stereoselectivity. 

The rules that apply to acyclic systems are also applicable to cyclic compounds with an exo-double bond. Thus 3-arylideneflavanones 1 were stereo selectively epoxidized with alkaline hydrogen peroxide and stereospecifically with 3-chloroperoxybenzoic acid20 and potassium hypochlorite21 and, similarly, 6-methoxyaurones 6 were stereoselectively epoxidized with alkaline hydrogen peroxide and stereospecifically with 2-chloroperoxybenzoic acid22. 

The development of reliable methods for the diastereoselective reduction of carbonyl compounds in a wide range of acyclic systems has been an area of explosive growth in recent years. This was prompted by the requirements of modem total synthesis in which redundant diastereoisomers are avoid, - together with enhanced theoretical understanding of stereoselectivity which allows rationalization of the results. 

The issue of stereoselectivity in acyclic systems has not been studied systematically, but a high degree of control is not expected. There is one report of the formation of an ethylideneazacyclohexane with excellent control of stereoselectivity (Scheme 59). No explanation for this dramatic selectivity was offered, nor is one readily apparent. Note also the strong preference for the formation of the more highly substituted regioisomer. 

An instructive example of a 7i-facial, homoallylic OH-directed stereoselective epoxidation in an acyclic system, used for the construction of the natural product monensin, is depicted belowC As expected, the more electron-rich trisubstituted double bond in A would be more susceptible to epoxidation than the terminal double bond. To minimize allylic 1,3-strain between the ethyl group and the CH2CH=CH2 appendage, A should preferentially adopt the conformation B, in which the smallest substituent H (hydrogen) is now in the same plane as the ethyl group. This places the hydroxymethyl moiety (CH2OH) in proximity to the P-face of the double bond, leading, after treatment with mCPBA, to the formation of epoxide diastereomer C. 

The methodology of using allyl alcohols as d -synthons of type (7) has proven to be a very general one, providing an easy and highly stereoselective route to allylic alcohols with exclusive formation of ( )-double bonds in acyclic systems, even in the case of trisubstituted alkenes (Scheme 15). ... 

The cyclic phosphate and phosphoramidate derivatives of v/c-diols undergo a two-step reductive elimination on treatment with Li/NHs, Na-naphthalene, TiCl4-Mg(Hg) or TiClt-K. In acyclic systems the reaction is only moderately stereoselective. The reaction has particular value in the synthesis of tetra-substituted alkenes from highly hindered v/c-diols. Scheme 20 illustrates its use in the synthesis of [10,10]-betweenanene (49). ... 

Enyne titanium complexes are synthesized when enynes are treated with Ti(OPr1)2( 72-propene). These species add aldehydes, ketones, and chiral imines to generate multiple stereogenic centers in an acyclic system. Numerous methods for the stereoselective construction of two stereogenic centers are known, although those for more than three in one asymmetric procedure are less common.195... 

Chamberlin and Reich investigated hydride additions to a,3-unsaturated ketones and the correlation of conformational preferences in enones with the ( )/(Z) stereoselectivity in formation of the corresponding enolates. They found that in acyclic systems s-trans enones gave enolates A and s-cis enones gave enolates B (Scheme 15). The reduction of a,3-unsaturated amides with L-selectride gave the same stereochemical results (Scheme 16). ... 

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