Homoallylic alcohols asymmetric hydrogenation

In the case of tri-substituted alkenes, the 1,3-syn products are formed in moderate to high diastereoselectivities (Table 21.10, entries 6—12). The stereochemistry of hydrogenation of homoallylic alcohols with a trisubstituted olefin unit is governed by the stereochemistry of the homoallylic hydroxy group, the stereogenic center at the allyl position, and the geometry of the double bond (Scheme 21.4). In entries 8 to 10 of Table 21.10, the product of 1,3-syn structure is formed in more than 90% d.e. with a cationic rhodium catalyst. The stereochemistry of the products in entries 10 to 12 shows that it is the stereogenic center at the allylic position which dictates the sense of asymmetric induction... 

A considerable success has been realized for asymmetric hydrogenation of functionalized alkenes since the discovery of BINAP-Ru complexes in the mid-1980s [5]. The details are described in each of the following substrates, enamides, alkenyl esters and ethers, a,/3- and /3,y-unsaturated carboxylic acids, a,/3-unsaturated esters and ketones, and allylic and homoallylic alcohols. 

Asymmetric hydrogenation of allylic and homoallylic unsaturated alcohols was not very efficient until the discovery of the BINAP-Ru catalyst. With Ru(BrNAP)(OAc)2 as catalyst, geraniol 70 and nerol 72 are successfully hydrogenated to give ([S)- or (i )-citronellol (71 and 73, respectively) in high overall yield with good enantioselectivity of 98 and 99% ee.59... 

As one of the fundamental bond constructions, the carbonyl-ene reaction - between an aldehyde and an alkene bearing an allylic hydrogen - attracts considerable attention [1] from the synthetic community. Given the versatile chemistry of the product homoallylic alcohols, both the intra- and intermolecular versions of asymmetric carbonyl-ene reactions are valuable processes. [2] Within the catalytic field, [3] the continuing development of chiral Lewis acids further advances the utility and scope of carbonyl-ene chemistry. We wish to highlight a number of these developments. 

Figure 4.6. Internal asymmetric induction in homogeneous hydrogenation of allylic and homoallylic alcohols.

Mechanistically related to the Mukaiyama aldol reaction, the carbonyl ene reaction is the reaction between an alkene bearing an allylic hydrogen and a carbonyl compound, to afford homoallylic alcohols. This reaction is potentially 100% atom efficient, and should be a valuable alternative to the addition of organometallic species to carbonyl substrates. However, the carbonyl ene reaction is of limited substrate scope and works generally well in an intermolecular manner only with activated substrates, typically 1,1-disubstituted alkenes and electron-deficient aldehydes (glyoxylate esters, fluoral, a,p-unsaturated aldehydes, etc.), in the presence of Lewis acids. The first use of chiral catalyst for asymmetric carbonyl ene was presented by Mikami et al. in 1989. ° By using a catalytic amount of titanium complexes prepared in situ from a 1 1 ratio of (rPrO)2titaniumX2 (X = Cl or Br) and optically pure BINOL, the homoallylic alcohols 70a,b were obtained in... 

High enantioselectivities in asymmetric hydrogenation of 3,3-di-substituted allylic alcohols and related homoallylic alcohols were achieved with iridium complexes of phosphinomethyloxazoline ligands 148 in ethereal solutions (14CEJ2440). 

Allylic alcohols also provide a suitably activated substrate for hydrogenation. Ryoji Noyori s asymmetric reduction of the prochiral geraniol (E-double bond geometry) and nerol (Z-double bond geometry) to enantiomerically pure citronel-lol in the presence of Ru(OAc)2 BINAP is a well-known example. The nonallylic olefin is not reduced appreciably, which indicates the importance that the allylic alcohol functionality plays in this reduction. (Homoallylic alcohols are also reduced by this system, but when the olefin in question is three or more bonds distant from the alcohol moiety, the compound is inert.) Either enantiomer of cit-ronellol is accessible regardless of which substrate is used depending on the chirality of the Ru-BINAP catalyst used (8). This type of relationship implies that the reaction s mechanism possesses high facial selectivity. 

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