Stereofacial selectivity

Figure 1. Stereofacial selectivity rule for the Sharpless asymmetric epoxidation.

Treatment of a mixture of 76 and 77 with hydrogen fluoride (or fluoride anion) followed by sodium metaperiodate affords the corresponding 2,3-jyn-3-hydroxy-2-methylcarboxylic acids 79 and M in enantiomeric excesses higher than 98%. Therefore, with the proper selection of the ligands attached to the boron atom, the stereofacial selectivity of 74 exceeds 1(X) 1. 

Although it was also Henbest who reported as early as 1965 the first asymmetric epoxidation by using a chiral peracid, without doubt, one of the methods of enantioselective synthesis most frequently used in the past few years has been the "asymmetric epoxidation" reported in 1980 by K.B. Sharpless [3] which meets almost all the requirements for being an "ideal" reaction. That is to say, complete stereofacial selectivities are achieved under catalytic conditions and working at the multigram scale. The method, which is summarised in Fig. 10.1, involves the titanium (IV)-catalysed epoxidation of allylic alcohols in the presence of tartaric esters as chiral ligands. The reagents for this asyimnetric epoxidation of primary allylic alcohols are L-(+)- or D-(-)-diethyl (DET) or diisopropyl (DIPT) tartrate,27 titanium tetraisopropoxide and water free solutions of fert-butyl hydroperoxide. The natural and unnatural diethyl tartrates, as well as titanium tetraisopropoxide are commercially available, and the required water-free solution of tert-bnty hydroperoxide is easily prepared from the commercially available isooctane solutions. 

The origin of stereofacial selectivity in electrophilic additions to methylene-cyclohexanes (2) and 5-methylene-l,3-dioxane (3) has been elucidated experimentally (Table 2) and theoretically. Ab initio calculations suggest that two electronic factors contribute to the experimentally observed axial stereoselectivity for polarizable electrophiles (in epoxidation and diimide reduction) the spatial anisotropy of the HOMO (common to both molecules) and the anisotropy in the electrostatic potential field (in the case of methylenedioxane). The anisotropy of the HOMO arises from the important topological difference between the contributions made to the HOMO by the periplanar p C-H a-bonds and opposing p C—O or C—C cr-bonds. In contrast, catalytic reduction proceeds with equatorial face selectivity for both the cyclohexane and the dioxane systems and appears to be governed largely by steric effects. ... 

All the above examples share high stereofacial selectivity defined by the configuration of the stereogenic center that connects the enone chromophore with the alkenyl side chain. However, chiral induction at the enone and/or the alkenyl tethered must be introduced to achieve stereofacial selectivity in the more general systems in which the alkene is connected at the a-carbon or /1-carbon of the enone. One of the successful early examples is found in Pirrung s120 synthesis of ( )-isocomene 263. Irradiation of 261 afforded the single product 262, which was transformed to isocomene in a two-step sequence. 

The effect of substituents at the a-carbon of the enone on the stereoselectivity was examined on compounds 270, with the stereogenic center located at the alkenyl side chain. Crimmins and DeLoach122 found that the stereoselectivity encountered upon irradiation of 270 depends on the degree of steric hindrance associated with the ester group linked to the double bond. The ratio of the two epimeric centers at the C-9 position varied from 13 1 (R = Me) to 17 1 (R = Et), then 20 1 (R = i-Pr). These results demonstrate that steric effects play an important role in controlling the stereofacial selectivity in these and related systems. Fragmentation of the photoproduced four-membered ring and simple transformations afforded synthesis of ( )-pentalene 274, (i)-pentalenic acid 275 and (i)-deoxypentalenic acid 276 (Scheme 59). 

The effect of substituents on the stereoselectivity of the intramolecular photocycloadditions of alkenes to cyclohexenones was systematically examined by Becker and coworkers84 who obtained high stereofacial selectivity in compounds 283a-c. However, small changes in the position, geometry or steric effect of the substituents have dramatically affected the selectivity, indicating the complexity in predicting the stereoselectivity in such system (Scheme 61). 

The use of an enamine derived from a chiral C2-symmetric amine such as (2R, 5R)-2,5-dimethylpyrrolidine leads to products 30 with high diastereoselectivity as well as high stereofacial selectivity (equation 7)32. In this case the radical addition is thought to take place from the relatively less hindered face of the enamine 29. 

In the acid-catalyzed ortho ester Claisen rearrangement of allylic alcohol (303) with trimethyl orthobutyrate, diastereomers (304), (305) and (306) were isolated in a ratio of 63 30 7 (Scheme 53). The 3,3-sigmatropic rearrangement occuned with a high degree of stereofacial selectivity from the p-face of the allylic alcohol (a >13 1 for Ht). In contrast, Qaisen rearrangement of the enol ether (307) at 135-140 C (PhH, sealed tube) provid the desired -dicarbonyl compound (308) as a single diastereomer at... 

BBN-H tolerates many functional groups, and this, coupled with its high regioselectivity, allows the clean synthesis of a number of functionalized organoboranes e.g. equation 26), including many derived from unsaturated heterocyclic compounds. It also shows impressive stereofacial selectivity in the hydroboration of cyclic alkenes (e.g. equations 27-29), - and sometimes in the cases of acyclic alkenes. ... 

Cyclopropenes with bulky C3 substituent(s) add with high stereofacial selectivity to 1,3-dienes such that exo rather than endo adducts are obtained (Y. Apeloig, personal communication, September, 1986). 

The conjugate addition of allyl tri-n-butylstannane to pyranose 144 occurs in high yield under mild conditions, and exhibits impressive stereofacial selectivity corresponding to axial addition of the nucleophile in 145 to produce the 2,6-fran -pyran 146 (Scheme 5.2.30). 4... 

Scheme 51 illustrate this point.First, the mismatched double asymmetric reaction of (274) and (5,5)-(18) provides the 3A-anti-4,5-anti diastereomer (276) (cf., 137) with only 73% selectivity. This is a substantial drop in stereoselectivity compared to the mismatched reaction of (5,5)-(18) and (254) that provides (137) with 84% selectivity (Table 8, entry 26). Substrate (277) is even more problematic diastereomer (278) predominates with >95 5 selectivity from the reaction with (/ ,/ )-(18), while (279) was the expected product based on the stereochemical preferences of (/ , )-(18). Thus, the intrinsic dia-stereofacial selectivity of (277) totally overwhelmed that of (/ , )-(18) in this attempted mismatched double asymmetric reaction. 

Cainelli, Martelli and coworkers have reported an interesting case of combined syn-anti and dia-stereofacial selectivity using chiral A/-silylimine (199), prepared in situ from (S)-O-TBDMS-lactic aldehyde (198). 2 As shown in Scheme 41, condensation of the lithium enolate of r-butyl butyrate with A -silylimine (199) affords essentially a single p-lactam (2(M)), contaminated with only 4% of the corresponding other trans diastereomeric 3-lactam. The authors propose that the high level of diastereofacial selectivity (14 1) is due to the formation of lithium chelate (201), which undergoes attack by the enolate from the least hindered ir-face of the imine. The authors do not discuss the unusual anti selectivity of this reaction. 

---