Cyanide thexylborane

Section B of the Scheme 9.1 shows several procedures for the synthesis of ketones. Entry 6 is the synthesis of a symmetrical ketone by carbonylation. Entry 7 illustrates the synthesis of an unsymmetrical ketone by the thexylborane method and also demonstrates the use of a functionalized olefin. Entries 8 to 10 illustrate synthesis of ketones by the cyanide-TFAA method. Entry 11 shows the synthesis of a bicyclic ketone involving intramolecular hydroboration of 1,5-cyclooctadiene. Entry 12 is another ring closure, generating a potential steroid precursor. 

An interesting new method for the preparation of the methoxycarbonyl (and related) compound (35) involves the hydroboration-carbon monoxide insertion in bis-alkenic amines (34). The best reagent for this process is thexylborane, followed by cyanidation (82JOC1494). The yields are not very good and seven-membered ring compounds (36) can also be formed, but the procedure is short and simple. 

A synthesis of 5-coniceine by a transannular reaction has been reported (81TL2075). Treatment of N-allyl-N-3-butenyl-N-benzyloxycarbonylamine with thexylborane followed by cyanidation afforded an azacyclanone in 35% yield which could be transformed into 5-coniceine by catalytic reduction (Scheme 28). 

Migration of tertiary alkyl groups in the dichloromethyl methyl ether reaction does however mean that ketones cannot be synthesized using thexylborane and the approach adopted in the carbonylation and cyanidation processes. In order to obtain ketones by this route, boranes bearing chloro or alkoxy groups, i.e. groups of very low migratory aptitude, have to be used as substrates (Equation B3.17). 

Azacyclanones.3 The usual syntheses of medium-sized azacyclanones involve Dieckmann or acyloin cyclization conducted under high dilution. An interesting new approach involves hydroboration-cyanidation (4, 446-447 5, 606-607) of a diunsaturated carbamate such as 1. Hydroboration of 1 with thexylborane followed by cyanidation under standard conditions gives the cyclic ketone 2 in moderate yield in one step. The product can be reductively cyclized to the indolizidine alkaloid <5-coniceine (3). 

While this method is applicable to symmetrical alcohols or ketones, formation of unsymmetrical ketones is difficult unless selective transfer of the alkyl groups can be achieved. Thexylborane provides a solution since it can react sequentially with two different alkenes to generate an unsymmetrical trialkylborane. Reaction of thexylborane with cyclopentene and then arylalkene 172, for example, gave 173. Subsequent reaction with sodium cyanide gave the unsymmetrical ate complex ( 74) and this generated unsymmetrical ketone 175 upon treatment with trifluoroacetic anhydride followed by oxidation. 20b... 

Unsymmetrical cyclic ketones can be formed by the hydroboration of dienes followed by the oxidation sequence just described. In a typical example, Bryson reacted 176 with thexylborane but sodium cyanide was present (in situ) and this mixture generated 177. When this product was treated with trifluoroacetic anhydride... 

Rearrangement by thermolysis of unsymmetrically substituted tricyclic derivatives of 2,6-epi-dioxypiperidine (118) afforded the ketamide (119) (Equation (17)) <90KGS109>. Synthesis of N-substituted 5-azalactanone (121) was accomplished by CO insertion. Thexylborane-cyanidation hydroboration protocol proved to be the most useful method with moderate to high yield (Equation (18)) <82JOC1494>. 

Hydroboration. Metallacycloalkanones have been prepared by the cyclic hydroboration of dialkenyl silanes. In order to obtain one such dialkenyl silane, chlorodimethylvinylsilane was allylated with allyl magnesium bromide (eq 4).3 The dialkenyl silane 6 was then hydroborated sequentially with thexylborane, followed by treatment with potassium cyanide, trifluoroacetic anhydride, and finally hydrogen peroxide in sodium hydroxide to produce the silacycloheptanone 7 (eq 4). Cyclic silylketones were then further reacted to form acyclic compounds with chiral centers that are difficult to introduce without the use of the silicon tether. 

---