Diastereoselective hydroboration and

Weiss et al. reported a first total synthesis of daphmanidin A type alkaloid, (+)-daphmanidin E [51]. The key features of the strategy involve rapid access to an enantiomerically pure bieyelo-[2.2.2]octadione and elaboration around its periphery through the implementation of two Claisen rearrangements, a diastereoselective hydroboration, and a cobalt -catalyzed alkyl-Heek cyelization (Scheme 1). 

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

The conversion of a thiolactone to a cyclic ether can also be used as a key step in the synthesis of functionalized, stereochemically complex oxacycles (see 64—>66, Scheme 13). Nucleophilic addition of the indicated higher order cuprate reagent to the C-S double bond in thiolactone 64 furnishes a tetrahedral thiolate ion which undergoes smooth conversion to didehydrooxepane 65 upon treatment with 1,4-diiodobutane and the non-nucleophilic base 1,2,2,6,6-pentamethylpiperidine (pempidine).27 Regio- and diastereoselective hydroboration of 65 then gives alcohol 66 in 89 % yield after oxidative workup. Versatile vinylstannanes can also be accessed from thiolactones.28 For example, treatment of bis(thiolactone) 67 with... 

A recently developed application of the Ramberg-Backlund reaction is the synthesis of C-glycosides. The required thioethers can be prepared easily by exchange with a thiol. The application of the Ramberg-Backlund conditions then leads to an exocyclic vinyl ether that can be reduced to the C-nucleoside.95 Entries 3 and 4 in Scheme 10.6 are examples. The vinyl ether group can also be transformed in other ways. In the synthesis of partial structures of the antibiotic altromycin, the vinyl ether product was subjected to diastereoselective hydroboration. 

Halogen-lithium exchange of iodide 71 and subsequent addition of 2-acetyl-furan (72) to the resultant organolithium intermediate yielded two diastereomeric tertiary alcohols (dr=l l), which were converted to (E)-olefin 73 with complete diastereoselectivity upon brief exposure to catalytic amounts of concentrated aqueous hydrogen chloride (Scheme 11) [18]. Diastereoselective hydroboration/oxidation of 73 gave largely the desired stereoisomer 74 due to... 

SCHEME 46. Diastereoselective hydroboration of allylic derivatives and B/Zn exchange... 

Acyclic diastereoselective hydroboration,J Hydroboration-oxidation of terminal alkenes substituted at C4 by a large and a medium alkyl group can proceed asymmetrically with BH3 S(CH,)2 or, even more selectively, with thexylborane. Example ... 

An analogue (126) of the immunosuppressant PA48153 (with a ring methoxy in place of the ethyl group of the natural product) has been prepared from D-galactose derivative 124. Homologation was achieved by Wittig reaction, with subsequent reasonably diastereoselective hydroboration at C-6 and further... 

The first applications in total syntheses started from amide 188. The rearrangement, under standard conditions, led diastereoselectively to amide 189 in 77% yield no traces of other diastereomers were found. Amide 189 was converted into (-)-isoiridomyrmecm 190 via diastereoselective hydroboration. Oxidative work-up and a final lactonization in the presence of a pTsOH (41.4% yield over three steps) (28f. Alternatively, LLAlHj-reduction of 189 resulted in amine 191 (80%), a final five step sequence enabled one to synthesize (-r)- -skytanthine 192 with 60% yield (Scheme 10.42) [28g],... 

The remote activation of C-H bonds is an important synthetic goal and some especially crowded tetrasubstituted olefins undergo such a reaction. Furthermore, in all the examples studied, this activation proceeds with high diastereoselectivity. Thus, the two tert-hutyl substituted olefins 65 and 66 undergo, after the initial hydroboration and migration, an insertion into a remote C-H bond forming the boracycles 67 and 68 which after oxidation furnish the two diols 69 and 70 as one diastereoisomer (Scheme 16) (24). 

Diastereoselective osmylation and hydroboration of, y-unsaturated (V,(V-diisoprop-ylamides (100)-(1 2) have been reported to occur with useful diastereofacial selectivity (Scheme 11). The major diol isomer from (E)-alkenes (100) and (101), in the presence of TMEDA at -78 °C, corresponds to the facial preference shown in transition-state model (103) [(100) gave an 11 1 preference at -78 °C (101) afforded the same ratio at —78 °C, and 6 1 at room temperature], while the opposite preference for (104) is observed with the (Z)-alkene (102) (>20 1 at —78°C and 7 1 at room temperature). Hydroboration with 9-BBN does not show this inversion of diastereofacial selectivity for the (Z)-alkene all of the results correspond to the usual preference for a transition state such as (105). ... 

Although most of the techniques to direct selectivity in acetylene chemistry will also work with olefins, there are some very typical double bond reactions that pose substantial regioselectivity and diastereoselectivity problems and therefore merit detailed treatment in their own right. These are particularly reactions such as allylic substitutions and rearrangements including aUene derivatives, hydroborations, hydroformylations, and cycloadditions. 

Still documented a classic study involving the diastereoselective hydroboration of allylic alcohols (Equation 1) [21]. For example, when allylic alcohol 20 was allowed to react with borane, a 1 1.4 mixture of diols 21 and 22 was isolated. However, the hydroboration of 20 with the bulkier 9-BBN resulted in a pronounced preference for 21 (dr=ll 1). 

An innovative application of these concepts is to be found in Evans synthesis of the potent antifungal agent echinocandin D (68, Scheme 7.11) [27]. When 65 is treated with dicyclohexylborane, diastereoselective hydroboration is followed by reaction of the azide with the organoborane intermediate, resulting in a ring-contraction and the formation of 67 as the sole diastereomer. 

Versatile [3 + 2]-cydoaddition pathways to five-membered carbocydes involve the trimethylenemethane (= 2-methylene-propanediyl) synthon (B.M. Trost, 1986). Palladium(0)-induced 1,3-elimination at suitable reagents generates a reactive n -2-methylene-l,3-propa-nediyl complex which reacts highly diastereoselectively with electron-deficient olefins. The resulting methylenecyclopentanes are easily modified, e. g., by ozonolysis, hydroboration etc., and thus a large variety of interesting cyclopcntane derivatives is accessible. 

---