Homochiral boronate

Directed asymmetric reduction of a ketone has been brought about by the use of an intramolecular homochiral boronate ester250. The latter was readily introduced at a hydroxyl group in the molecule and has allowed the production of the enantiomeric alcohol, from the ketone by use of BH3-complex as the reductant (equation 64). The boronate ester may be readily removed by treatment with hydrogen peroxide-sodium hydroxide, using standard methodology. Other similar reductions have also been reported251-253. 

Equation B5.6 depicts the reaction of an achiral aldehyde with a homochiral boron enolate derived from (5)-mandelic acid. Again the geometry of the enolate controls the relative stereochemistry of C2 and C3 and so only the two erythro isomers are formed. In this case, however, the homochiral centre in the boron enolate results in approach to one face of the aldehyde being strongly preferred over approach to the other face and a product ratio of 2R,3S 2S,3R = 28 1 is observed. 

Addition of a wide range of boronic acids [RB(OH)2] or esters [RB(OR )2] to the pinanediols gives the very stable pinanediol boronic esters. For example, propylboronic acid (available from the addition of propylmagnesium bromide to trimethyl borate followed by acid hydrolysis) and the (s) pinanediol combine to give a homochiral boronic ester as shown in Equation B6.3. 

A homochiral boronate derived from the chiral imidazolidinone template yields various biaryls with little or no loss of stereochemical integrity. Although the amino ester shown in Eq. 38 undergoes partial racemization during biaryl coupling, a recent method of Novartis in USA using Seebach s imidazolidinone made the assessment of the dias-tereoselectivity exceedingly simple (Eq. 70).The imidazolidinones... 

If the face discrimination in the asymmetric hydroboration reaction is high then the optical purity of the chiral molecule produced will also be high. Efficient asymmetric hydroboration reactions followed by stereospecific cleavage of the boron-carbon bonds produced have been used in syntheses of several complex homochiral molecules (see Section B2.1). 

Consider Equation B5.5 which depicts the reaction of a homochiral ddehyde with an achiral boron enolate. The aldol product contains two lew chiral centres at C2 and C3. The boron enolate geometry dictates that the... 

Thus the homochiral aldehyde (-)-dimethylglutaric hemialdehyde in Equation B5.5 and the homochiral (S)-boron enolate of Equation B5.6 both favour formation of the 2R,3S diastereoisomer. When these two molecules are reacted together their stereochemical preferences reinforce one another (they are said to be matched ) and good stereoselectivity is observed (2R,3S 2S,3R = >100 1) (Equation B5.7). 

Reaction of boronic esters, RB(OR )2, with dichloromethyllithium, LiCHCl2, inserts the CHC1 unit into the carbon-boron bond of the boronic ester. This is known as boronic ester homologation. If boronic esters derived from homochiral alcohols are used in this reaction, then new homochiral centres may be generated as will be illustrated below. 

Subsequent addition of either an alkyllithium or a Grignard reagent to B leads to the displacement of the second chlorine atom with clean inversion of configuration at the a centre. The boronic ester may be oxidized at this point to generate a homochiral alcohol or, as C is merely an extension of A, the process may be repeated to build up further chiral centres as illustrated in the applications described below. 

By co-ordinating BH3 to its nitrogen atom and the oxygen atom of the ketone to be reduced to its boron atom, the homochiral catalyst A, depicted below, facilitates the delivery of hydride to one face of the prochiral ketone. 

These ligand combinations were then applied to the asymmetric addition of aryl boronic acid derivatives to 2-cyclohexenone. The results of this study are illustrated in Figure 4. From this data it can be seen that the heterochiral ligand combination LL/L2 exhibited the highest conversion during the 3h evaluation period. Furthermore, the heterochiral complexes LL/L2 and LL/L3 are significantly more enantioselectivity than the homochiral combinations. 

Asymmetric aza-DA reactions using chiral imines derived from a-amino esters an carbohydrates were extensively studied by Waldmann [310] and Kunz [311], re P o tively, at the end of fhe nineteen-eighties. After these significant works Yamamoto e al. reported the utility of homochiral N-(l-phenylefhyl)imines in asymmetric cy dition [219, 312]. In fhe presence of a stoichiometric amount of chiral boron tors 83 and 84, the cycloaddition of Danishefsky s diene 102 to these imines rea iz s almost complete diastereocontrol in the matched cases (Scheme 10.115), a e... 

Stereoselective synthesis of the C28-C46 fragment of phorboxazole A has been achieved. In this approach the correct relative stereochemistry at Csy/Csg was established by use of allylborane which was prepared by transmetalation between allylstannanes and a boron bromide reagent derived from homochiral diamine and BBrj (Scheme 12.24) [62]. 

Methylation and conversion to the boronic acid 232 followed by precipitation from dichloromethane with hexanes yielded the boronic anhydride 233. The isoquinoline portion 234 was synthesized from homochiral 86 by selective demethylation, benzylation and subsequent... 

Homochiral epoxides are versatile intermediates for the synthesis of a variety of natural products. The four-carbon bifiinctional chiron (i )-l- erNbutyldimethylsilyl-3,4-epoxybut-l-yne (228) is conveniently prepared from 141 as shown in Scheme 53. The conversion of 141 to chloride 225 followed by base-induced chloride elimination in liquid ammonia proceeds without any detectable epimerization (as determined by both hplc and nmr analysis of the corresponding Mosher ester) to provide the i -alcohol 226 in good yield. Subsequent silyl protection followed by treatment with boron tribromide results in a highly stereoselective bromination, together with simultaneous debenzylation to the bromohydrin 227, which under mild basic conditions is converted to epoxide 228. The optical purity of 228 (ee = 99%) demonstrates the high selectivity in this new bromination reaction [80,81]. 

In 1993, Cambie et al. published the synthesis of the 9-chloro-9-fluoro derivative [33]. Subsequently, they continued to study the introduction of fluorine at C-9 into an anthracyclinone and later, in 1996, finished the synthesis of 9-fluoro-9-methylanthracyclinone 44 (Fig. 5). The 9-fluoro derivatives were achieved by treating ortho-methallyl-substituted anthraquinonyl homochiral dioxanes with boron trifluoride etherate. In this case, the yields of the fluoro derivatives were better than in the earlier work [36]. 

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