Hydrazones asymmetric hydroxylation

One-carbon Homologations. SEM-Cl can be used as a formaldehyde equivalent, which upon alkylation affords, directly, a protected hydroxyl. SEM-Cl does not suffer from some of the handling liabilities of formaldehyde (e.g., the need for cracking or the use of aqueous solutions) and as such has shown specific promise in the area of asymmetric alkylations. Asymmetric alkylations of enolates have been accomplished via the employment of chiral auxiliaries including oxazolidinones (eq 26) and RAMP/SAMP hydrazones. Furthermore, Schultz and co-workers have utilized SEM-Cl to trap chiral enolates derived from Birch reductions (eq 27). ... 

Hydrazone Formation ACC hydrazones are typically formed by condensation of the ACC auxiliary and the ketone in the presence of 10 mol% -TsOH x H2O by refluxing in dichloromethane for periods of 6-12 hours (Scheme 7.10A). ° In the case of chiral nonracemic a-hydroxy ketone derivatives, however, a combination of pyridinium p-toluenesulfonate (PPTS) (5 mol%) and MgS04 must be used in place of / -TsOH x H2O to avoid epimerization at the hydroxyl-bearing a-carbon (Scheme 7.10B). When asymmetrical ketones are used. 

A related synthesis of apratoxin began with the preparation of methyl ketone 119, which was then condensed with (R)-55 to obtain hydrazone 120 (Scheme 7.20). ACC hydrazone 120 was then subjected to the a,a-bisalkylation sequence using methyl iodide followed by allyl bromide, which proceeded in excellent overall yield and with excellent stereoselectivity dr > 99 1). At this stage, attempts to remove the auxiliary under standard conditions were unsuccessful. However, it was established that the hydrolysis was effective following deprotection of the a -hydroxyl. The derived ketone 123 then underwent a series of transformations, ultimately leading to the first asymmetric total synthesis of apratoxin D 124. 

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