1,3-diols homoallylic alcohol derivatives

II-NMR analysis of derived pinanediol ester. b By 13C-NMR and GC analyses of derived 4-methyl-3-heptanol see text. c 1H-NMR analysis of derived symmetrical diol. The construction of R3 (Section 1.1.2.1.6.) was not totally stcrcospecific and may have been the source of the 12% diastercomeric contaminant. d From the ee of the homoallylic alcohol derivative formed by reaclion with benzaldchyde, measured by GC on a chiral column. 

FORMATION OF 1,3-DIOLS FROM HOMOALLYLIC ALCOHOL DERIVATIVES... 

Asymmetric allylboration has also been applied to y-methoxyallyl derivatives. Isomerically pure (Z)-y-methoxyallyldiisopinocampheylborane (rf31), prepared from Ipc2lSOMe and the lithium anion of allyl methyl ether, reacts with various aldehydes to afford the yyn - j-m e (boxy homoallylic alcohol (32a) in a highly regio- and stereoselective manner17 (Scheme 3.In). This one-pot synthesis of enantiomerically pure 1,2-diol derivatives went as smoothly as the asymmetric Brown crotylation, affording products with uniformly high diastereoselectivity. 

Addition to a-hydroxy aldehydes. The Lewis acid-catalyzed addition of 1 to aldehydes to afford homoallylic alcohols (9, 8) has been extended to the reaction with derivatives of a chiral a-hydroxy aldehyde (2), which can result in the monoderivative of a jyn-diol (3) and/or an anti-d o (4). The diastereoselectivity can be controlled by the... 

Chiral all-syn-l,3-polyols. A reiterative route to these polyols from an optically active epoxide (1) involves ring opening with a cuprate derived from vinyllithium and copper(I) cyanide (11, 366-367) to give an optically active homoallylic alcohol (2). This is converted into the fepoxide (4) via a cyclic iodocarbonate (3) by a known procedure (11, 263). Repetition of the cuprate cleavage results in a homoallylic 1,3-diol (5). The ratio of desired syn- (o anfi-diols is 10-15 1. This two-step sequence can be repeated, with each 1,3-diol unit formed being protected as the acetonide. The strategy is outlined in Scheme (I). 

The use of C2-symmetric 1,2- and 1,3-diols as chiral auxiliaries is a reliable method for asymmetric allylation of acetals [382]. Acyclic acetals derived from homochiral 1-phenylethanol undergo the Hosomi-Sakurai allylation with high diastereoselectivity [383]. Tietze et al. have, on the other hand, reported that the TMSOTf-catalyzed successive acetalization-allylation reaction of aliphatic aldehydes with homochiral silyl ethers 123 and allyltrimethylsilane gives the corresponding homoallyl ethers with complete diastereocontrol these ethers can be readily converted into enantiomerically pure homoallyl alcohols without epimerization (Scheme 10.135) [384]. This method is applicable to asymmetric allylation of methyl ketones [385]. 

Scheme 9 Santonin (41) was converted to the derivative (99), whose conversion to alcohol (100) by metal hydride reduction and Mitsunobu reaction. Diol (102), prepared from (100), on acid catalysed cyclization and followed by subjection to Mitsunobu reaction, gave (104), which was converted to ketone (106), whose transformation to homoallylic alcohol (108), was achieved by standard organic reactions. Phenylselenylation afforded (110), which was finally converted to phytuberin.

Formaldehyde can be coupled to an alkene in the presence of an acid to give a diol (152) or a 1,3-dioxane derivative (154) in what is known as the Prins reaction. l Allylic alcohols such as 153 can also be produced in this reaction. Camphene (155) reacted with formaldehyde and acid to give a 1 1 mixture of allylic alcohol 156 and the acetate 157, in 94% yield. Scandium tiiflate has been used to prepare tetrahydropyran-4-ol derivatives from aldehydes and homoallylic alcohols via a Prins-type cyclization. 3... 

BF3-OEt2 reverses the usual anti selectivity observed in tbe reaction of crotyl organometallic compounds (based on Cu, Cd, Hg, Sn, Tl, Ti, Zr, and V, but not on Mg, Zn, or B) with aldehydes (eq la) and imines (eq lb), so that homoallyl alcohols and homoallylamines are formed, respectively. " The products show mainly syn diastereoselectivity. BF3-OEt2 is the only Lewis acid which produces hydroxy- rather than halo-tetrahydropyrans from the reaction of aUyl-stannanes with pyranosides. The BF3-OEt2 mediated condensations of y-oxygenated allylstannanes with aldehydes (eq Ic) and with activated imines (eq Id) affords vicinal diol derivatives and 1,2-amino alcohols, respectively, with syn diastereoselectivity. The activated imines are obtained from... 

Under catalysis by a ruthenium complex, N-methylmorpholine 7V-oxide rapidly oxidizes most alcohols to the corresponding aldehyde or ketone in high yield at room temperature. Homoallylic alcohols are exceptional, undergoing conversion at a slow rate, if at all. Preferential oxidation of primary, secondary diols at the secondary centre leading to keto-alcohols has been achieved by treatment of the bis-trityl derivative with trityl tetrafluoroborate. ... 

Duan and Smith developed a diastereoselective electrophilic cyclization of carbonates derived from homoallylic alcohols 98 via reaction with iodine monobromide to afford a-iodocarbonates 99 (Figure 25.13). These can further be utilized as intermediates for the synthesis of epoxy alcohols, iodohydrins, diols, triols, cyclic carbonates, and so on ... 

Kitching and co-workers " " developed total syntheses of plakortones C, D, E, and F. Acquisition of plakortone D, the most effective activator of SR-Ca " -pumping ATPase, used stereodefined lactone cores that resulted from asymmetric dihydroxylation of protected homoallylic alcohol 67 (Scheme 15.18). A derived lactone aldehyde was then coupled with an independently generated, sulfone activated side chain unit 68. The 5,6- -double bond, carried through the sequence as a protected, stereodefined diol, was released there by stereospecific sy/j-elimination via an orthoester derivative. Racemic plakortone E was also acquired by using the Pd(II) induced sequence, but in this case, the required, complete acyclic system 69 was assembled first. 

A further application of the carbonylation strategy for construction of 2,3-cis substituted tetrahydrofuran derivatives is shown in Scheme 15.23. Nesbitt and McErlean reported on the synthesis of C19 lipid diols, the enantiomers of the anthelmintic marine natural products. Key steps in the divergent synthesis include a syn selective epoxidation of a homoallylic alcohol, a one-pot alkoxypalladation-lactonization reaction sequence, and diethyl azodicarboxy-late promoted Mitsunobu inversion. 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

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