Diastereoselective hydroboration

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. 

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-... 

High levels of asymmetric induction have been achieved in the hydroboration of 1,3-, 1,4-, and 1,5-dienes with thexylborane (482,483,489,490). The first chiral center is formed by an intermolecular reaction. In the second step, the organoborane intermediate undergoes an intramolecular hydroboration, creating the second chiral center with high diastereoselectivity. 

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. 

Prior literature indicated that olefins substituted with chiral sulfoxides could indeed be reduced by hydride or hydrogen with modest stereoselectivity, as summarized in Scheme 5.10. Ogura et al. reported that borane reduction of the unsaturated sulfoxide 42 gave product 43 in 87 13 diastereomer ratio and D20 quench of the borane reduction mixture gave the product 43 deuterated at the a-position to the sulfoxide, consistent with the hydroboration mechanism [10a]. In another paper, Price et al. reported diastereoselective hydrogenation of gem-disubstituted olefin rac-44 to 45 with excellent diastereoselectivity using a rhodium catalyst [10b],... 

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... 

Albert S.C. Chun of the Hong Kong Polytechnic University reports (J. Org. Chem. 68 1589, 2003) two important transformations. The three-component (Mannich) condensation of 10 with 11 and 12 proceeds with high diastereoselectivity, to give the amino alcohol 13. Hydroboration of the alkyne 14 followed by transmetalation of the intermediate vinyl borane gives a zinc species, which under catalysis by the easily-prepared 3-naphthol 13 adds to aromatic and branched aldehydes with high . The product allylic alcohols are useful intermediates for organic synthesis. 

Hydroboration-oxidation of enecarbamates with borane-dimethylsulfide complex gives reasonable yields of /i-hydn > xycarbarn ales (equation 28) with some diastereoselectivity, depending upon what other functional groups are present in the starting material152. 

PMB calculations indicate that jr-facial diastereoselection in the reaction of 2,3 -endo-disubstituted 7-methylenenorbornanes 285 with electrophiles such as (AcO)2Hg or I+ is determined by electrostatic asymmetry, favouring the electron-richer awti-facial attack 285 -> 286 (with R = F or CC Me)415. In contrast, hydroboration is controlled by orbital interactions giving the syw-addition product 287415. This is an alternative interpretation of the experimental results reported previously30. 

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 ... 

Hupe, E. Calaza, M. I. Knochel, P. Substrate-controlled highly diastereoselective synthesis of primary and secondary diorganozinc reagents by a hydroboration/B-Zn exchange sequence. Chem. Eur. J. 2003, 9, 2789-2796. 

Hydroboration of alkenes1 (15, 91). The Rh(I)-catalyzed hydroboration provides a highly diastereoselective reaction in a synthesis of a poly ether antibiotic. Thus the derivative (1) of an acyclic allylic alcohol is converted to the primary alcohol 2 by hydroboration with catecholborane (CB) catalyzed by ClRh[P(C6H5)3]3 with 94 6 selectivity. Note that hydroboration of 1 with disiamylborane (12, 484) proceeds with the opposite selectivity at Cio (8 92). 

This reaction also proceeds well with a variety of other substituted stilbene derivatives. Thus, the boranes obtained by hydroboration of E and Z stilbenes 80 undergo the thermal boron migration with excellent diastereoselectivity leading to the anti and syn organoboranes 81. After amination of 81 the corresponding benzylic amines (anti and syn 82) were obtained in 66 and 40 % yield and with diastereoselectivity better than 90 10 between C(l) and C(2) (Scheme 16) [7, 8,13],... 

Remarkable regioselectivity was observed in the thermal migration of the tetra-substituted alkene Z-83. Hydroboration of this compound furnishes only the migration product in the direction of the ethyl group. Furthermore, the migration was stereoselective providing, after the standard amination sequence, the benzylic amine 85 in 46% yield. The diastereoselectivity was 95 5 between C(l) and C(2) and >99 1 between C(2) and C(3) (Scheme 17) [7, 8, 13],... 

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