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the proximal olefin of allenyne 38 in a cyclocarbonylation reaction leads to an α-alkylidene
cyclopentenone 39 (Scheme 1.9). Alternatively, the same transformation of the distal double
bond leads to a 4-alkylidene cyclopentenone 40. Furthermore, a cycloisomerization reaction
involving the distal double bond of the allene can lead to a cross-conjugated triene 41.
Scheme 1.9 Skeletal diversity using carbocyclization reactions of allenynes.
38
•
R 2
CH 2R 1
Mo(CO) 6
Rh(I), CO
Rh(I)
Each reaction results in increase of molecular complexity since relatively simple acyclic
precursors are transformed to mono- or bicyclic skeletons. Furthermore, a novel reactive moiety
is generated (enone, cross-conjugated triene) that can be further exploited in diversity generating
transformations. Therefore, implementing a diversity-oriented synthetic strategy based on
transition metal-catalyzed cyclocarbonylation and cycloisomerization reactions of allenes is of
great interest. Herein, the efforts toward this goal are described. In this study, two important
goals have been combined: (1) development of new synthetic methodologies for efficient
assembly of complex small molecules; and (2) synthesis of collections of these compounds
specifically for use as biological probes. At the initiation of the project, we envisioned
employing the three reaction pathways available to a single allenyne (Scheme 1.9). It was
reasoned that other reaction pathways may be available to an appropriately designed precursor.
13
39
40
41
R 2
R 2
R 2
CH 2R 1
O
CH 2R 1
R 1
O