Alcohols, homoallylic, chiral aldehydes

In reactions of chiral aldehydes, TiIV compounds work well as both activators and chelation control agents, a- or A-oxygcnated chiral aldehydes react with allylsilanes to afford chiral homoallylic alcohols with high selectivity (Scheme 22).85 These chiral alcohols are useful synthetic units for the synthesis of highly functionalized chiral compounds. Cyclic chiral 0,0- and A/O-acetals react with allylsilanes in the same way.86,87 Allenylsilanes have also been reported as allylation agents. 

Diastereoselective reaction with fl-alkoxy-a-methylpropionaldehydes.1 The reaction of (R,R)-1 with the chiral aldehyde 2a provides the syn-homoallylic alcohol... 

In order to apply tartrate ester-modified allyl- and crotylboronates to synthetic problems,23 Roush and Palkowitz undertook the stereoselective synthesis of the C19-C29 fragment 48 of rifamycin S, a well-known member of the ansamycin antibiotic group24 (Scheme 3.1u). The synthesis started with the reaction of (S,S)-43E and the chiral aldehyde (S)-49. This crotylboration provided the homoallylic alcohol 50 as the major component of an 88 11 1 mixture. Compound 50 was transformed smoothly into the aldehyde 51, which served as the substrate for the second crotylboration reaction. The alcohol 52 was obtained in 71% yield and with 98% diastereoselectivity. After a series of standard functional group manipulations, the alcohol 53 was oxidized to the corresponding aldehyde and underwent the third crotylboronate addition, which resulted in a 95 5 mixture... 

Chiral homoallylic alcohols. The chiral acetals 2 formed from an aldehyde and 1. undergo titanium-catalyzed coupling with allyltrimcthylsilane with marked stereoselectivity. Highest sterco.selectivity is usually obtained with the mixed catalyst TiClj-Ti(0-/-Pr)j (6 5). Cleavage of the chiral auxiliary, effected by oxidation to the ketone followed by -elimination, provides optically active alcohols (4) with —95% ee (equation I). ... 

Chiral homoallylic alcohols, The glycol 1 has been used as the chiral matrbt in an enantioselective synthesis of homoallylic alcohols (4) from aldehydes and allyl-boranes (equation I). 

The homoallylic alcohols (5) are isolated in fair to good yields. Their optical purity often exceeds 95% and the anti diastereomers are produced almost exclusively (>98% ds). Exceptions with up to 33% syn epimer have, however, been obtained for (2f). The reagent controlled stereoselectivity of (R)-(2) and the enantiomers (5)-(2) is best documented by conversions with chiral aldehydes, examples being (6), (7), and (8). ... 

Achiral allylic silanes and chiral aldehydes. The stereochemical course of reaction for simple allylsilanes is largely governed by Cram (Felkin-Anh) [29] or chelation control [lOh]. Two examples which illustrate this phenomenon are shown in Scheme 10-10 [30]. In the first example, the reaction of 2-phenylpropanal 19 with allyltrimethylsilane 20 affords the homoallylic alcohols 22 and 24 with almost no selectivity. However, methallylsilane 21 afforded a much higher syn selectivity under the influence of BF3-OEt2. The reaction of the n-alkoxy aldehyde... 

The stereochemical complexity of the reaction can be further increased when an ( )- or (Z)-2-butenylsilane reacts with a chiral aldehyde. Herein both diastereo-selection processes are operative, relative (between the reacting faces) and internal with respect to the original stereogenic center in the aldehyde. Thus, the reaction of jff-benzyloxy aldehyde 32 and silane ( )-31 with bivalent Lewis acids (SnCU, TiCU) was examined in the presence of an additive, e.g. MgBr2, ZrCp2Cl2, TiCp2Cl2 (Scheme 10-12) [32]. The reactions all afford mixtures of the four possible diastereomeric products, favoring the syn homoallylic alcohol. When the com-... 

The addition of 2-butenyltrifluorosilane 68 to chiral aldehydes has been examined by Roush in the synthesis of the a fi,ant/-dipropionate stereotriad, a common but difficult-to-synthesize subunit in polyketide-derived natural products [54], The synthetic approach involves the 2-butenylation reaction of a-methyl-)9-hydroxy aldehydes 72 with (Z)-68 (Scheme 10-30). Using this approach, the anti,anti-dipro-pionate 73 could be obtained in excellent selectivity. The best selectivity is observed when anti-/]-hydroxy aldehydes are used. When the syn aldehyde is used, a mixture of homoallylic alcohols is produced which may arise from a nonche-lated Zimmenuan-Traxler transition structure. 

This group has recently reported the CAB-promoted additions of 2-butenylstan-nanes to branched and chiral aldehydes [88]. The reactions were optimized using cyclohexanecarboxaldehyde and ( )-85 in the presence of the CAB catalyst and trifluoroacetic anhydride. Under optimized conditions, the reaction affords a 92/8 mixture ot syn/anti homoallylic alcohols in 71% yield and the syn diastereomer is obtained in 93% ee. 

The chiral allyl- and 2-butenylboronates derived from tartrate esters (Chart 10-5) have been used in combination with a wide variety of chiral aldehydes to produce homoallylic alcohols in high yield and moderate to high enantioselectivity [124], The results obtained from reaction of selected chiral aldehydes (Chart 10-6) with the tartrate-modified allylboronates 195 and 197 (Chart 10-5) are shown in Table 10-20. As with the achiral aldehydes, the highest enantioselectivities are obtained when the chiral aldehydes are combined with allylboronate 197. A strong reagent-induced selectivity is apparent, but is nevertheless dependent on the intrinsic bias of the aldehyde. 

Achiral allylic indium reagents and chiral aldehydes. Allylindium reagents generated in water react smoothly with aldehydes and ketones (Scheme 10-99) [196], The reaction of achiral aldehydes and a-oxygenated aldehydes 290 with the allyl indium reagents proceeds smoothly to homoallylic alcohols without the need for external promoters. It is interesting to note that the a-hydroxyl aldehyde was se-leetive for the syn (chelation-eontrolled) product even in water. 

The preference for the (Z)-crotylboronate reagent 4 to generate the anti-Felkin homoallylic alcohols 31 and 38 in reaction with a-methyl chiral aldehydes 25 and 32 (Table 11-1) is rationalized by transition state 43, where the R substituent of the aldehyde occupies the least sterically demanding a-carbon position, anti to the forming C-C bond, while the hydrogen occupies the most sterically demanding... 

From the range of synthetic applications of Brown s pinene-derived allyl- and crotylborane reagents illustrated in these selected examples, it is clear that they are excellent reagents for the synthesis of chiral homoallylic alcohols from chiral and achiral aldehydes alike. That so many researchers have applied these reagents in their research also attests to the great utility of these reagents in organic synthesis. 

The reactions of aldehydes with y-alkoxystannanes 2.81 are catalyzed by BF3 Et20, and they are more selective toward syn E-homoallyl alcohols 6.62 than the previous examples [1214, 1217] (Figure 6.56). This holds for the reactions with prochiral or a-chiral aldehydes provided that the reagents are matched [569], Transition-state model Aj accounts for this selectivity. This method has been applied by Yamamoto and coworkers [1223] to the reaction of aromatic aldehydes with y-(tetrahydropyranyk>xy)-allylstannanes under AICI3 catalysis. 

Since the introduction of this reagent in 1983 (/2), it has been utilized in key steps in several syntheses. The reagent can be prepared by the treatment of allyl Grignard reagent with either B-chlorodiisopinocampheylborane (DIP-Chloride M) 34, 35) or B-methoxydiisopinocampheylborane 12). A variety of aldehydes, including perfluoroalkyl 36) and heterocyclic aldehydes (57) have been tested with this reagent to demonstrate its capability. In all of the cases examined thus far the product homoallyl alcohols were obtained in >92% ee (Scheme 2). It has been established that in the case of chiral aldehydes, the reagent controls the diastereoselectivity 38). 

While the chiral aldehydes or allyl nucleophiles are based on stoichiometric amounts for the control of diastereoselectivity [74, 77], it has been found that catalytic amounts of titanium complexes derived from BINOL can mediate the enantioselective addition of allyl stannanes to aldehydes, giving the homoallyl alcohols high enantioselectivity. Mikami reported that the BINOL-Ti complexes prepared in situ in the presence of 4A molecular sieves (MS) catalyze the carbonyl addition reaction of allyl silanes or stannanes to afford the syn product in high enantiomeric excess [78] (Scheme 14.21). 

Nokami reported a study that documents the asymmetric rearrangement of chiral oxonium ions (Scheme 16.19) [97]. These reactive intermediates are generated upon condensation of optically active alcohols and aldehydes. The requisite alcohol 158 was prepared by diastereoselective addition of cro-tylmagnesium chloride 156 to menthone 157. Subsequent treatment of the alcohol with an aldehyde such as PhSCH2CH2CHO under acidic conditions induced formation of 159. The ensuing [3,3]-rearrangement gave 160, and in situ hydrolysis of the chiral auxiliary afforded the secondary homoallylic alcohol with excellent optical purity (99% ee). 

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