Selectivity control conjugated carbonyl

The formation of a titanium chelate enables regiochemical control of the conjugate addition of a thiol to an a,/3,y,d-dienone, as shown in Eq. (307) [694]. Simple base-catalyzed reaction occurred selectively at the terminal (d) position of the substrate. When, however, a similar reaction was performed in the presence of TiCU, addition occurred exclusively at the position / to the carbonyl group, where the intermediate can take the chelate form, as depicted. The same observation was also noted for the corresponding conjugated trienone. A similar reaction has been applied to the cis —> trans isomerization of conjugated dienoates [695]. 

The general representation of the classic Wittig reaction is presented in equation (21). The ( )- and (Z)-selectivity may be controlled by the choice of the type of ylide (95), the carbonyl derivative (94), the solvent and the counterion for ylide formation. As a general rule, the use of a nonstabilized ylide (95 X and Y are H or alkyl substituents and is phenyl) and salt-free conditions in a nonprotic, polar solvent favors the formation of the (Z)-alkene isomer (96) in reactions with an aldehyde. A stabilized ylide with strongly conjugating substituents such as an ester, nitrile or sulfone forms predominantly the (f -alkene. 

Unlike the Peterson alkenation, which is in principle similar, the phosphine oxide anion addition can be controlled to produce predominantly the erthyro isomer (206). The threo isomer can be obtained by selective reduction of the a-ketophosphine oxide (210), allowing highly stereoselective alkene fonna-tion. Since a two-step sequence is employed, this reaction does not require a stabilizing functionality to be conjugated to the phosphine oxide in order to produce the alkene. In fact, unlike the phosphonate HWE reagents, the reaction of a ketophosphine oxide (211) with a carbonyl derivative does not occur to produce the unsaturated carbonyl (213 Scheme 30). ° The addition step is presumably too rapidly reversible and the elimination of phosphine oxide too slow. 

Lewis acid coordination of carbonyl-conjugated dieno[ iles usually results in vastly improved regio-selectivities on [4 + 2] cycloadditions to nonsymmetrical dienes (Section 4.1.4.1). Medium effects can also be usefully applied to achieve better regiochemical control (Section 4.1.4.2). 

Even when isomeric mixtures of the allylsilane are used, complete stereochemical control is observed for all the stereocenters established in the conjugate addition. The only breakdown in selectivity in the process occurs with the stereocenters adjacent to the carbonyl carbon, which result from protonation on work-up. The less stable cis-fused decalone is readily converted to the trans-fused isomer by treatment with base. Hence, with two steps, complete control over the relative configuration of four contiguous stereogenic centers is achieved. 

A different approach to solving this problem is to attach a chiral auxiliary to the enone substrate. The auxiliary is a chiral material that is attached to an achiral substrate. The asymmetry of the auxiliary controls the selectivity of the reaction and is then removed in a separate chemical step. Posner studied the use of optically pure a-carbonyl-a, 3-ethylenic sulfoxides (465, see sec. 3.9.A.ii for the preparation of optically active sulfoxides)." 29 Conjugate addition of di-(2,2,-dimethylpropyl)magnesium cuprate to the chiral... 

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