Intermolecular cycloadditions ketone derivation

Intermolecular [2+2] Cycloaddition Reactions of Ketone Derived Silyl Enol Ethers Takasu s group moved to investigate the intermolecular version of the cycloaddition reaction by using silyl enol ethers 4a-6a and a,(3-unsaturated esters 7 (Table 4.2). 

In 1999, Hashimoto and coworkers demonstrated the first successM examples of the intermolecular cycloadditions of carbonyl ylides derived from a-diazo ketones with dimethyl acetylenedicarboxylate (DMDA) using fV-benzene-fitsed phthaloyl-(5)-valine-derived Rh catalyst, Rh2(5-BTPV)4 with high enantioselectivity (up to 92% ee) (Scheme 7.21) [57]. 

In intermolecular PET processes, radical ions are formed either as close pairs or as free species from neutral molecules (Sch. 1) [2,6]. Most commonly, carbonyl compounds or related derivatives as for example enol ethers, cyclopropyl ketones, and siloxycyclopropanes are used for intramolecular cyclization reactions. With the exception of cycloadditions the ring-building key step is always an intramolecular bond formation. In PET... 

In contrast to intermolecular photoaldols, which can be manipulated with facility, intramolecular cycloadducts undergo retro-[2 + 2] cycloaddition when subjected to hydrolytic conditions. In an alternative protocol, oxymercuration of (229) afforded a-mercurio ketone (230 42%) which was acetylated under standard conditions to provide 1,4-diketone (231) quantitatively. Similarly, epoxidation of (229) provided functionalized photoaldol (232), which was hydrolyzed and acetylated to form a-acetoxy derivative (233). Finally, hydrolysis of (234) (4 1 THF/0.1 N HCl) gave lactol (235) in nearly quantitative yield, illustrating the utility of the intramolecular furan carbonyl photocycloaddition in spirocycle formation. 

Even though the use of (S)-proline (1) for the synthesis of the Wieland-Miescher ketone, a transformation now known as the Hajos-Parrish-Eder-Sauer-Wiechert reaetion, was reported in the early 1970s, aminocatalysis - namely the catalysis promoted by the use of chiral second-aiy amines - was rediscovered only thirty years later. The renaissance of aminocatalysis was prompted by two independent reports by List et al. on the asymmetric intermolecular aldol addition catalysed by (S)-proline (1) and by MacMillan et al. on the asymmetric Diels-Alder cycloaddition catalj ed by a phenylalanine-derived imidazolidinone 2. These two reactions represented the archetypical examples of asymmetric carbonyl compound activation, via enamine (Figure ll.lA) and iminium-ion (Figure 11.IB), respectively. 

Under enyne cross-metathesis conditions, the intermolecular reaction of the a,(D-dienes 153, derived from the MBH reaction, with different terminal alkynes 154 afforded triene intermediates that cyclized spontaneously under the reaction conditions to give substituted cis-hexahydro-l/f-indenes 155 (Scheme 4.45), which can be further transformed into steroid analogues via TBS deprotection and oxidation. However, metathesis reactions starting with 156 only furnished trienes 157 [as EfZ) mixtures] and no spontaneous intramolecular cycloaddition occurred. Even at elevated reaction temperatures, trienes 157 cyclized only slowly to give octahydronaphthalene diastereomers. With deprotection of the TBS and subsequent Dess-Martin oxidation, trienes 157 could be converted exclusively into cw-fused 7-substituted 6,7-dehy-drodealone-l-one-lO-carboxylic esters 158 in 50-60% yields. Moreover, c ross-metathesis of TBS-unprotected MBH adduct 159 with alkynes 154 along with treatment with Dess-Martin periodinane (DMP) in one pot could conveniently produce the corresponding bicyclic ketones 160 in moderate yields. ... 

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