41. Aspects of stereochemistry. Part XII. A specific directing effect in the mercuration of some 4-substituted cyclohexenes and cis-hex-3-enol

Abstract

Henbest and Nicholls. 227 41. Aspects of Stereochemistry. Part XII.* A Speci$c Directing Effect in the Mercuration of Some 4-Substituted cycloHexenes and cis-Hex-3 -ewZ. By H. B. HENBEST and B. NICHOLLS.Functional groups can exert a directing effect on the stereochemistry of addition of HgX and OR at a double bond, in at least two ways. In the first, the reactions are completed by a suitably placed acid or alcohol group acting as an intramolecular nucleophile, and lactones or ethers are formed: some new examples are given in the bicydoheptene series and with tvans-hex-3-enol. A second, new directing effect has been encountered with certain 4-substituted cyclohexenes and cis-hex-3-enol : here hydroxyl or other Lewis base groups (OMe, OAc, CO,Me, CH,*OH, CN) promote stereospecific addition of acetoxymercuri-groups and of anions (from solvent) to the double bond. A possible mechanism for these additions is discussed. As the mercuri-groups in these adducts can be removed by reduction, a two-step method for the specific addition of water or methanol to certain double bonds becomes available.

Sulfinylnitriles: Sulfinyl–Metal Exchange–Alkylation Strategies

“…Nucleophilic addition to benzylidene malononitrile, a carbonyl surrogate, [23] proceeds well, as does the addition of the electrophiles propylene oxide and diphenyl disulphide (Table 1, entries [15][16][17]. Cyclohexenone is attacked selectively at the carbonyl carbon (Table 1, entry 11), which is likely a consequence of strong chelation between the alkoxymagnesium intermediate and the p-electrons of the nitrile, [24] which prevents equilibration to the more stable conjugate adduct. [25] With a choice of ketone and alkylbromide electrophilic sites, attack occurs on the carbonyl of 2-bromoacetophenone to afford the epoxide 10 n ( [b] 23 92 [b] 11 86 24 93 [b] 12 91 [b] 25 94 [b] 13 90 [b] [a] Performed by sequential addition of iPrMgCl and the electrophile to a solution of the sulfinyl nitrile in THF at À78 8C, unless otherwise noted.…”

Investigation into the Synthesis of C-25 Oxysterols

“…In conclusion, compared to the method of oxymercuration and hydrodemercuration, [3][4][5][6] we have successfully developed a facile, convenient, attractive and safe process for preparing 25-hydroxycholesterol using mCPBA under mild reaction conditions in the regioselective oxyfunctionalisation of readily available natural compounds such as desmosterol. The reaction affords a promising strategy for large-scale preparations.…”

“…3,4 Charles 5 reported in 1971 the reaction of mercuric acetate with desmosterol (24-dehydrocholesterol) in which yields the 25-hydroxycholesterol. The nuclear Δ 5 double bond, which is quite reactive towards most electrophilic reagents, was left untouched.…”

“…The reaction of mercuric acetate with unsaturated sterols and tetracyclic triterpenes (oxymercuration), followed by reduction with sodium borohydride in sodium hydroxide/ water (hydrodemercuration), is highly selective for the sidechain bonds such as a 24-methylene or 24 (25) double bond. 3,4 Charles 5 reported in 1971 the reaction of mercuric acetate with desmosterol (24-dehydrocholesterol) in which yields the 25-hydroxycholesterol. The nuclear Δ 5 double bond, which is quite reactive towards most electrophilic reagents, was left untouched.…”

Cyclic Metalated Nitriles: Stereoselective Cyclizations to cis‐ and trans‐Hydrindanes, Decalins, and Bicyclo[4.3.0]undecanes

“…[47] Adding excess LiNEt 2 to 38 or 41 first deprotonates the hydroxyl group which prevents subsequent elimination on deprotonation at the adjacent nitrile-bearing carbon. [48] Complexation in the resulting dilithiated nitriles 39 and 42 between the lithium alkoxide [49] and the nitrile π-electrons [50] effectively locks the lithiated nitrile in a pyramidal geometry, the geometry of the chiral carbanion being determined by the configuration of the adjacent alkoxide. [51] For the equatorially oriented hydroxynitrile 38 , the chelate 39 with the axial nitrile is favoured which directs the cyclization exclusively to the trans -decalin 40 .…”