3- Methyl- - -octalone

Bellus D, Kearns SR, Schafhier K (1969) Zur Photochemie von a,p-ungesattigen cyclische Ketoene Spezifische Reaktione der n,jt - und x, x -Triplettszustande von O-Acetyl-testosteron und 10-Methyl-octalon-(2). Helv Chim Acta 52 971-1009... 

MONOALKYLATION OF a.p-UNSATURATED KETONES via METALLOENAMINE8 l-BUTYL-10-METHYL-Ai< -2-OCTALONE... 

A. 0-Methyl-ls -2-octalone id,lA-Dimethylhydra2one. A 250-ml., round-bottomed flask equipped with a magnetic stirring bar and a Dean-Stark water separator is maintained under a dry nitrogen atmosphere (Note 1) and eharged with 7.4 g. (0.045 mole) of 10-methyl-A -2-oetalone [2(3 f)-Naphthalenone, 4,4a,5,6,7,8-hexahydro-4a-methyl-] (Note 2), 9.0 g. (0.15 mole) of N,N-dimethylhydrazine, 150 ml. of dry benzene, and 0.02 g. of p-toluenesulfonie aeid. This mixture is refluxed for 10-14 hours, after whieh time no further water separates. Benzene and excess N,A -dimethylhydrazine are then removed by simple distillation, and the residue is distilled under reduced pressure to give 8.1 g. (87%) of the dimethylhydrazone as a pale-yellow liquid, b.p. 94-98 (0.2 mm.) (Notes 3, 4). 

B. -Butyl- a-methyl- >-2-octalone. A 250-ml., three-necked flask equipped with a magnetic stirring bar, a reflux condenser, a 50-ml., pressure-equalizing funnel, and a rubber septum is charged with 1.4 g. (0.032-0.036 mole) of 55-60% sodium hydride dispersion in mineral oil... 

At this point the submitters reported 7.07 g. of crude product which by gas chromatographic analysis on an SE 30 column at 200° showed 1-3% of 10-methyl-A < -2-octalone and 85% of the desired alkylated product. 

Anotheranalogy between the enolate anions derived from a,)3-unsatura ted ketones and the corresponding enamines is encountered in their alkylation reactions (57), which proceed by the kinetically controlled attack at the a-carbon atom. For instance, Stork and Birnbaum (51) found that the alkylation of the morpholine enamine of /J -octalone-2 (117) with methyl iodide gave the C-1 methylated derivative (118). 

The procedure given in the preceding experiment can be applied to the reduction of lO-methyl-J -octalone-2 prepared in Chapter 10, Section VI. The product of the reduction has bp 94-9673 mm. 

Ammonia, anhydrous Matheson Co. 10-Methyl-d < -octalone-2 (Chapter 10, Section VI)... 

Cyclohexanecarbonyl chloride EK Triethylamine MCB, EK N-Methyl-A -nitroso-p-toluenesulfonamide A Isophorone MCB, A d < -Octalone-2 (Chapter 9, Section III)... 

Allenyl Silyl enol ethers, 86 Allyl alcohol trimethylsilyl ether, 84 Allyl carbonates, 114-15 9 Allyl-ay 2 octalone, 34-5 2-Allyl-2 methylcyclohexanone, 106 (Allyldimethylsilyl)methyl chloride, 58, 59 (AUyldimethylsilyl)methylmagnesium chloride, 59... 

Methyl nitroacetate, 57, 60 10-Methyl-A1 (9)-2-octalone, 57, 69 1O-Methyl-A1 (9 )-2-octalone,Ar,iV-dimethyl hydrazone, 57, 69... 

The first enantiospecific total synthesis of (-)-PF1092A, B and C (10- 12) is based on the SnCLf- promoted cyclization of an a-keto methyl sulfone and dimethyl acetal followed by a Stork annulation which gives the octalone core (3) (Scheme 1). 

The presence of substituents on an unsaturated ketonic species can modify product stereochemistry in a variety of ways. When an angular methyl group is present in an octalone ring (e.g., compound XXIII) (33), the formation of the cis product usually predominates. 

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