By appropriate structural modification of known musk odorants, new strong musk odorants have been discovered. Incorporation of supplementary CH, or CH, groups into the basic musk skeleton of type G only slightly modifies the global shape of the molecule but leads to densely packed structures of enhanced lipophilicity. For the construction of these highly substituted 1,2,3,4-tetrahydronaphthalenes, new annulation sequences (intramolecular mono-and dialkylations; see Schemes 3.6, and 8) have been developed and, in certain cases, the design of the target molecules was dictated by both structure-activity-relationship and synthetic considerations (e.g. 46 and 47, Scheme 6). This work also presents an original solution to an analytical problem: the distinction between a C2-and a C,-symmetrical aromatic hydrocarbon (uiz. 7 1 and 72) by conversion into a [Cr(CO),arene]complex.
The novel reagents formed by combination of Crignard reagents (RMgX) with lithium diisopropylamide (LDA) convert non-enolizable or slowly enolizable carboxylic esters or carboxamides into ketones which are protected from further reaction by their in situ conversion into enolates. These enolates can be trapped with electrophiles such as Me3SiC1 and ally1 bromide. The scope of this Grignard mono-addition is illustrated by two direct syntheses of artemisia ketone (14).Recently, we published a procedure for converting non-enolizable or slowly enolizable carboxylic esters or amides into ketones, using [allyl-MgCI, LDA] as reagent (LDA = lithium diisopropylamide) [ 11. This transformation proceeds via rapid deprotonation of the initially formed ketones by their in situ conversion into enolates (Scheme 1) and was applied to efficient syntheses of a -damascone, B-damascone, and P-damascenone.The general preparative value of this transformation which is the synthetic equivalent of a Grignurd mono-addition [2] has prompted us to extend it to other allylic and non allylic Grignurd reagents (Table). [Methallyl-MgC1, LDA] exhibits a reactivity which is very similar to that of [allyl-MgC1, LDA]: thus, methyl a-cyclogeranate [3] (1; Entry I ) is converted into ketone 7 in excellent yield and high selectivity (ketone us. tertiary alcohol 98:2), whereas normal Grignard reaction in the absence of LDA mainly leads to the diallylic alcohol (selectivity ketone us. tertiary alcohol 21 :79). [Crotyl-MgC1, LDA] (Entry 2) undergoes reaction essentially (9: 1) with allylic transposition. Isomerization with AI,O, [4] affords a mixture of propenyl ketones 9 (57 %).The selectivity for ketone formation strongly depends on the ease of deprotonation of the intermediate ketones. Thus, IPhCH,MgCl, LDA] reacts with cyclohexenyl ester 2 [5] (Entry 3) to afford benzyl ketone 10 with high selectivity (97:3), whereas the reaction of ester 2 with [BuLi, LDA] (Entry 4 ) mainly leads to the tertiary alcohol 12. However,
The title reagents convert the hardly or non‐enolizable esters (I), (XI), (XVI), and (XIX) into ketones, which are protected from further reaction by the formation of enolates.
By appropriate structural modification of known musk odorants, new strong analogues such as (IV), (VIII) or (XIII) possessing supplementary CH3 or CH2 groups in the basic musk skeleton are prepared.
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