Alcohols synthesis from alkenes

Hydroboration was discovered by Professor Herbert C. Brown (1912-2004). This reaction is so useful in synthesis that Brown s work earned him a Nobel Prize in 1979. We will describe here only one practical example of hydroboration, a two-step alcohol synthesis from alkenes. 

Among the simplest syntheses of this type are those of tetrahydro-quinolines or -iso-quinolines based on Friedel-Crafts cyclizations. The use of side-chain halides is shown by the synthesis of 1,2,3,4-tetrahydroisoquinolines (158) (71CC799), and of 3,4-dihydroquinol-2-ones (159) (27CB858). Electrophilic carbon atoms can be developed from secondary or tertiary alcohols, or from alkenes or alkynes. In the synthesis of the tetrahydroisoquinoline... 

Halogenation of an alkane is required here. Iodination of alkanes, however, is not a feasible reaction. We can make alkyl iodides from alcohols or from alkenes by treatment with HI. A reasonable synthesis using reactions that have been presented to this point proceeds as shown ... 

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

Using the catalyst system described above in combination with a rhodium phosphine catalyst Lebel reported the de novo synthesis of alkenes from alcohols [100]. They developed a one-pot process, avoiding the isolation and purification of the potentially instable aldehyde intermediate. They combined the oxidation of alcohols developed by Sigman [89] with their rhodium-catalyzed methylenation of carbonyl derivatives. The cascade process is compatible with primary and secondary aliphatic as well as benzyUc alcohols in good yields. They even added another reaction catalyzed by a NHC complex, the metathesis reaction, which has not been addressed in this review as there are many good reviews, which exclusively and in great depth describe all aspects of the reaction. 

In recent years, dioxiranes have become workhorses for a variety of selective transformations in organic synthesis, from epoxidation of alkenes to the conversion of alcohols into fee corresponding ketones <99CJC308>. Dioxirane-mediated epoxidation continues to be the method of choice for complex substrates wife acid-sensitive functionality. Thus, fee dimethyl-dioxirane (DMD)-mediated epoxidation of the silylated stilbene lactam 159 has been reported as a key step in fee synthesis of protoberberines <99JOC877>. 

Ethers are prepared from alkyl halides by the treatment of metal alkoxide. This is known as Williamson ether synthesis (see Sections 4.3.6 and 5.5.2). Williamson ether synthesis is an important laboratory method for the preparation of both symmetrical and unsymmetrical ethers. Symmetrical ethers are prepared by dehydration of two molecules of primary alcohols and H2SO4 (see Sections 4.3.7 and 5.5.3). Ethers are also obtained from alkenes either by acid-catalysed addition of alcohols or alkoxymercuration-reduction (see Section 5.3.1). 

Ireland-Claisen rearrangements frequently are used for the synthesis of alkenes. This works particularly well if the allyl ester is derived from a secondary allyl alcohol. In this case a stereogenic double bond is formed in the rearrangement. The examples in Figure 14.48 show that the alkene is mostly trans-configured if this C=C bond is 1,2-disubstituted and almost completely is-configured if it is trisubstituted. 

Radical Epoxide Reduction Borane-free Two-step Synthesis of anti-Markownikow Alcohols from Alkenes... 

In combination with the range of standard transformations of alcohols, alkenes, and vinylsulfides, these silicon-tethered additions of functionalized radicals offer a versatile and stereoselective approach to amino alcohol synthesis. Whereas vinyl and 2-oxoethyl radicals have not yet been demonstrated as competent participants in the various intermolecular additions reported in the literature, the temporary tether approach allows such functionalized fragments to be installed in an efficient and stereoselective manner. Synthesis of the aminosugar daunosamine from achiral precursors shows how this concept, employing hydrazone radical acceptors, can be merged with asymmetric catalysis to achieve practical synthetic advances. 

Allylic alcohols from sulfones.1 Polish chemists have extended the Julia synthesis of alkenes (11, 474) to a synthesis of allylic alcohols. In the presence of 1 equiv. of BF3 etherate, a-alkoxy aldehydes react with lithiafed sulfones to form adducts that are converted to allylic alcohols on reduction with sodium amalgam. This reaction was developed specifically for a synthesis of prostaglandins from Corey s lactone-aldehyde, but should have wider application. 

Both chemical and enzymatic synthetic methods for the asymmetric oxidation of the carbon-carbon double bond have been developed [46], but the area of carbon-carbon double bond oxidations has been shaped by the breakthrough discovery of asymmetric epoxidation of allylic alcohols with the Katsuki-Sharpless method [47]. Catalytic asymmetric synthesis of epoxides from alkenes by Jacobsen... 

An important aspect of the metal catalyzed hydroboration reaction is its ability to selectively reduce certain functionalities within a molecule. For instance, a key step in the synthesis of a tripeptide derivative containing the Phe-Arg hydroxyethy-lene dipeptide iosostere is the selective rhodium-catalyzed hydroboration of a lactone. The use of disiamylborane, 9-H-BBN, dicyclohexylborane, and (.9)-alpmeborane, however, gave only low to variable yields of the alcohol due to competitive reduction of the y-lactone to the hemiacetal (equation 8). In another example, hydroboration of the diene illustrated in equation (9) with HBcat and RhCl(PPh3)3 gave exclusive formation of the terminal alcohol derived from reaction of the less substituted alkene. Interestingly, uncatalyzed reactions failed to hydroborate this substrate selectively. ... 

Z)-Trisubstitutedalkenes. Still and Mitra have described an efficient synthesis of alkenes of this type from allylic alcohols by a [2.3] sigmatropic Wittig rearrangement. The alcohol 2 is converted into the allyl stannylmethyl ether (3), which can be isolated if desired. Treatment with n-butyllithium results in tin-lithium exchange and rearrangement to the homoallylic alcohol 4 in 95% overall yield. When 3 is transmetalated and immediately quenched with cyclohexanone, 5 is obtained in 73% yield. 

---