On the mechanism of ylide-mediated cyclopropanations: evidence for a proton-transfer step and its effect on stereoselectivity.

In this paper, we describe studies on the cyclopropanation of Michael acceptors with chiral sulfur ylides. It had previously been found that semi-stabilized sulfonium ylides (e.g., Ph-stabilized) reacted with cyclic and acyclic enones and substituted acrylates with high ee and that stabilized sulfonium ylides (e.g., ester-stabilized) reacted with cyclic enones again with high ee. The current study has focused on the reactions of stabilized sulfonium ylides with acyclic enones which unexpectedly gave low ee. Furthermore, a clear correlation of ee with ylide stability was observed in reactions with methyl vinyl ketone (MVK): ketone-stabilized ylide gave 25% ee, ester-stabilized ylide gave 46% ee, and amide-stabilized ylide gave 89% ee. It is believed that following betaine formation an unusual proton transfer step intervenes which compromises the enantioselectivity of the process. Thus, following addition of a stabilized ylide to the Michael acceptor, rapid and reversible intramolecular proton transfer within the betaine intermediate, prior to ring closure, results in an erosion of ee. Proton transfer occurred to the greatest extent with the most stabilized ylide (ketone). When the same reactions were carried out with deuterium-labeled sulfonium ylides, higher ee's were observed in all cases since proton/deuteron transfer was slowed down. The competing proton transfer or direct ring-closure pathways that are open to the betaine intermediate apply not only to all sulfur ylides but potentially to all ylides. By applying this model to S-, N-, and P-ylides we have been able to rationalize the outcome of different ylide reactions bearing a variety of substituents in terms of chemo- and enantioselectivity.

Psychological impact of stillbirth on fathers in the subsequent pregnancy and puerperium.

BACKGROUND: Approximately 1 in 200 UK pregnancies ends in stillbirth. Although serious psychological effects of stillbirth on mothers are well established, much less is known about the impact of such loss on fathers. AIMS: To assess the psychological morbidity of fathers in the pregnancy and post-partum year subsequent to a stillbirth, to test within-couple effects and to identify risk factors. METHOD: This was a community-based cohort study of 38 pregnant couples whose previous pregnancy had ended in stillbirth, and 38 pair-matched controls. Psychological assessments took place antenatally and at 6 weeks, 6 months and 1 year postnatally. RESULTS: Fathers in the index group experienced significant levels of anxiety and post-traumatic stress disorder antenatally, but all of their symptoms remitted postnatally (after the birth of a live baby). Fathers' symptom levels were lower than those of mothers at all time points. In contrast to mothers, fathers experienced greater anxiety when a subsequent pregnancy (following stillbirth) was delayed. CONCLUSIONS: The vulnerability of fathers to psychological distress during the pregnancy after a stillbirth needs to be recognised.

The psychological effects of stillbirth and neonatal death on fathers: systematic review.

OBJECTIVE: To review the available evidence on the psychological effects of perinatal death on fathers. METHOD: Electronic search of CINAHL, MEDLINE and PsycINFO databases from 1966-2005. INCLUSION CRITERIA: papers describing at least one psychological outcome for fathers who had experienced stillbirth or neonatal death. EXCLUSION CRITERIA: papers not in English, dissertations, reviews, books without original data, intervention studies, studies of parents without separate results for fathers, studies where perinatal loss was not distinguished from other losses, first person accounts of a single experience, studies reporting on fewer than five fathers. Seventy-seven potential papers were obtained and screened by two authors. Seventeen studies were included. Study quality was rated using a checklist and main findings were summarized. RESULTS: Quality of methodology varied. Qualitative studies described classical grief responses, but less guilt than mothers. Fathers described experiences related to their social role and potential conflict between grieving couples. Quantitative research reported symptoms of anxiety and depression, but at a lower level than mothers. Fathers may develop post-traumatic stress disorder following stillbirth. DISCUSSION: Case prevalence of psychological disorders is unknown. More good quality research is needed. The social role of fathers as carers for their partners needs recognition when planning care for bereaved families.

Psychological aspects of perinatal loss.

PURPOSE OF REVIEW: Parents are attached to their unborn children, and loss around the time of birth is a serious trauma. Parental grief is a normal response, and may last for many months. Clinicians have always sought to implement practices that will help recovery, and for a generation, have advocated that parents have contact with the body of their dead infant, believing that this will facilitate mourning. Review of the literature shows that no previous systematic evidence has ever been offered to support this practice. RECENT FINDINGS: Recent research throws doubt on the therapeutic value of the practice of encouraging contact with the dead infant. These findings are outlined and discussed. SUMMARY: Following an outline of what is already known about the psychological effects of perinatal loss, the paper focuses on the evidence that aspects of psychosocial management are associated with better outcomes. It goes on to describe the cultural context in which psychosocial management changed and parents were first encouraged to see and handle their dead infant, and explores the distinction between the medical and cultural models which may frame this behaviour in very different ways. Finally, it briefly discusses the ethical position of staff who advise parents about their choice to see or not see their infant's body.